Trends in the use of aspirin and nonsteroidal anti-inflammatory drugs in the general U.S. population.
The objective of this study was to describe trends in the prevalence of regular aspirin and nonsteroidal anti-inflammatory drug (NSAID) use among adults in the United States during 2005 and 2010, and to identify characteristics of regular users. Data from the 2005 and 2010 National Health Interview Survey (NHIS) were analyzed to estimate the prevalence of regular use of aspirin and NSAIDs among U.S. adults aged 18 years and older. Results were stratified by demographics and self-reported medical conditions and extrapolated to provide U.S. population estimates. In 2010, around 43 million adults (19.0%) took aspirin at least three times per week for more than 3 months (i.e. regular users), and more than 29 million adults (12.1%) were regular users of NSAIDs. Compared with 2005, this was an overall increase of 57% in aspirin use and 41% in NSAID use. These increases were consistent across the strata of age, sex, race, and selected medical conditions, including cardiovascular disease (CVD), arthritis, peptic ulcers, cancer, and severe headache, except for Asian Americans. Large increases in the use of both aspirin and NSAIDs were observed over a 5 year period. The increase may be the result of increasing media attention reporting that regular aspirin use lowers the risk of CVD and related deaths, and may also prevent cancer. Moreover, safety concerns related to alternative medications such as acetaminophen and selective COX-2 inhibitors may influence users of these drugs to switch to aspirin and NSAIDs.


[Aicardi syndrome with favorable outcome].
Aicardi syndrome is usually associated with a very poor outcome. We report a particular case of Aicardi syndrome characterised by a partial agenesis of the corpus callosum associated with an arachnoidal interhemispheric cystic formation, and by a complete control of epilepsy and a favorable outcome regarding visual and psychomotor performances. A better prognosis could be expected in Aicardi syndrome when spasms occur lately and are not preceded by partial seizures, when agenesis of corpus callosum is partial and especially when chorioretinal lacunae are small, isolated, few and spare the macula.


Effects of a wheelchair ergometer training programme on spinal cord-injured persons.
Before and after investigation of the effects of a wheelchair ergometer Training programme. To investigate the effects of an original interval-training programme on work capacity and cardiorespiratory variables with spinal cord-injured persons (SCIP's) on a wheelchair-specific ergometer. BESANCON, FRANCE. Seven SCIP's (male) performed 45 min of wheelchair ergometry three times per week, for 6 weeks. Training effects on maximal dynamic performance and endurance capacity were studied by comparison of performance and cardiorespiratory responses observed during both a maximal progressive test (10 W/2 min) and the same training session performed before and after training. Training induced significant improvements in maximal tolerated power (+19.6%), in peak oxygen consumption (VO2,+16%), and in oxygen pulse (O2p,+18.7%). At ventilatory threshold, significant improvements were also observed in power output (+63%), VO2VT(+ 34.1), ventilation VEVT(+ 37.1%), and V2pVT(+ 19.9% ). Heart rate and ventilation were significantly lower (-11 and -14.6%, respectively) after training at the same work rate, while VO2 was unchanged. Between the first and the last training session, the total physical work was improved by 24.7%, whereas heart rate was unchanged. An interval-training programme individualised to each paraplegic subject using a wheelchair ergometer can significantly improve the fitness level and endurance capacity.


Commissioning of a PTW 34070 large-area plane-parallel ionization chamber for small field megavoltage photon dosimetry.
This study investigates a large-area plane-parallel ionization chamber (LAC) for measurements of dose-area product in water (DAPw ) in megavoltage (MV) photon fields. Uniformity of electrode separation of the LAC (PTW34070 Bragg Peak Chamber, sensitive volume diameter: 8.16 cm) was measured using high-resolution microCT. Signal dependence on angle α of beam incidence for square 6 MV fields of side length s = 20 cm and 1 cm was measured in air. Polarity and recombination effects were characterized in 6, 10, and 18 MV photons fields. To assess the lateral setup tolerance, scanned LAC profiles of a 1 × 1 cm2 field were acquired. A 6 MV calibration coefficient, ND,w,LAC , was determined in a field collimated by a 5 cm diameter stereotactic cone with known DAPw . Additional calibrations in 10 × 10 cm2 fields at 6, 10, and 18 MV were performed. Electrode separation is uniform and agrees with specifications. Volume-averaging leads to a signal increase proportional to ~1/cos(α) in small fields. Correction factors for polarity and recombination range between 0.9986 to 0.9996 and 1.0007 to 1.0024, respectively. Off-axis displacement by up to 0.5 cm did not change the measured signal in a 1 × 1 cm2 field. ND,w,LAC was 163.7 mGy cm-2 nC-1 and differs by +3.0% from the coefficient derived in the 10 × 10 cm2 6 MV field. Response in 10 and 18 MV fields increased by 1.0% and 2.7% compared to 6 MV. The LAC requires only small correction factors for DAPw measurements and shows little energy dependence. Lateral setup errors of 0.5 cm are tolerated in 1 × 1 cm2 fields, but beam incidence must be kept as close to normal as possible. Calibration in 10 × 10 fields is not recommended because of the LAC's over-response. The accuracy of relative point-dose measurements in the field's periphery is an important limiting factor for the accuracy of DAPw measurements.


Haemodynamic and renal effects of urodilatin in healthy volunteers.
Urodilatin (ANF(95-126)), an analogue of the atrial natriuretic factor (ANF(99-126)), has recently been isolated from human urine. To study haemodynamic and renal effects of synthetic urodilatin, 18 healthy male volunteers (age 26.1 +/- 0.8 years; X +/- SEM) received i.v. bolus injections of urodilatin at doses of 1, 2 or 4 micrograms kg-1 body weight (bw) (n = 6 per dosage group). Urodilatin dose-dependently increased heart rate and cardiac index. A dose-dependent increase in plasma cyclic GMP levels was also observed. Urinary cyclic GMP excretion, urine flow and natriuresis increased 7-fold, 5-fold and 4-fold, respectively. Renal effects were not different between dosage groups. Compared with ANF(99-126), after urodilatin the reduction in mean pulmonary arterial pressure (PAP) was more pronounced (2 micrograms kg-1, n = 6; ANF -1.8 +/- 0.5, URO: -5.5 +/- 1.1 mmHg, P less than 0.05). Furthermore, after urodilatin the reduction of PAP lasted continuously from 2 up to 90 min after injection, while ANF(99-126) produced only a transient decrease of PAP. Similarly the reduction of pulmonary capillary wedge pressure (PCWP) by urodilatin from 9.3 +/- 1.2 to 3.8 +/- 0.9 mmHg (P less than 0.05) was also sustained up to 90 min post administration. These data in healthy volunteers suggest that, due to prolonged reduction of PAP and PCWP with increases of cardiac index and reduction of systemic vascular resistance, urodilatin might exhibit beneficial effects in cardiovascular disease.


Isolation and characterization of a novel serine proteinase complexed with alpha 2-macroglobulin from porcine gastric mucosa.
Porcine stomach mucosa was found to contain a 740-kDa protein having endopeptidase activity toward peptide 4-methylcoumaryl-7-amide substrates and low molecular mass peptides. This protein was purified to an apparent homogeneity by a series of chromatographic steps on DEAE-cellulose, Sepharose CL-4B, hydroxylapatite, and fast protein liquid chromatography Mono Q columns. The protein was shown to be a complex of the plasma proteinase inhibitor alpha 2-macroglobulin and a 25-kDa endopeptidase. The enzyme activity was completely inhibited by diisopropyl fluorophosphate, p-amidinophenylmethanesulfonyl fluoride, leupeptin, antipain, bovine pancreatic trypsin inhibitor, soybean trypsin inhibitor, and ovomucoid, indicating that the entrapped enzyme is a serine proteinase. The proteinase could be released from alpha 2-macroglobulin by mild acid treatment and the released enzyme showed activity toward protein substrates. Substrate specificity studies using synthetic and peptide substrates indicated that the enzyme preferentially hydrolyzes Arg-X bonds and, to a much lesser extent, Lys-X bonds, and is apparently distinct from thrombin, kallikrein, plasmin, and other trypsin-like proteinases so far reported including tryptase. Thus, the present enzyme is thought to be a novel type of serine proteinase. The proteinase associated with alpha 2-macroglobulin was also found in porcine intestinal mucosa, but not in plasma.


Chronic lymphocytic leukaemia CD20 expression is dependent on the genetic subtype: a study of quantitative flow cytometry and fluorescent in-situ hybridization in 510 patients.
CD20 is an important therapeutic target in chronic lymphocytic leukaemia (CLL). In order to examine the relationship between CD20 expression and cytogenetic abnormalities, we correlated the fluorescent in-situ hybridization (FISH) genetic subtype of 510 treatment-naïve patients with CD20 expression as measured by quantitative flow cytometry. Patients were classified using the Dohner hierarchial classification. The median numbers of CD20 antigen sites by FISH subtypes were: 17p- (n = 26), 9341 per cell; 11q- (n = 42), 5886 per cell; +12 (n = 93), 23 603 per cell; negative FISH (n = 153), 8828 per cell; and 13q- (n = 196), 10 781 per cell. Compared to cases with negative FISH, 11q- cases had significantly lower CD20 expression (P = 0.001), and +12 cases had significantly higher CD20 expression (P < 0.001). The significance of trisomy 12 and high CD20 expression was maintained after multivariate analysis accounting for other disease characteristics. Fifty-nine patients received the combination of rituximab and granulocyte-macrophage colony-stimulating factor as frontline therapy; responses were observed in 13 of 14 (93%) patients with +12, in two of four (50%) patients with 11q-, and in 30 of 41 (73%) patients with negative FISH, 13q- or 17p- CLL. Leukemic CD20 expression differed significantly between FISH subtypes. Patients with trisomy 12 CLL showed strong leukemic cell CD20 expression and had a high rate of response to rituximab-based therapy.


Effects of Previous Acoustic Experience on Behavioral Responses to Experimental Sound Stimuli and Implications for Research.
Ambient noise differs considerably between habitats. Increased ambient noise can affect the physiology and behavior in a variety of taxa. Previous acoustic experience can modify behavior and potentially affect research conclusions in natural and laboratory environments. Acoustic conditions should thus be accounted for, especially in experiments involving experimental sound stimuli. Methods sections should contain acoustic specifications, and a consensus should be achieved over which measurements to include for comparability between researchers. Further investigation of how previous and repeated exposure to sound affects behavior and research conclusions is needed to improve our knowledge of acoustic long-term effects in animal welfare and conservation.


In vivo intranasal delivery of coagulation factor IX: a proof-of-concept study.
Hemophilia B (HB) is a bleeding disorder characterized by coagulation factor (F) IX (FIX) deficiency. The current standard-of-care for severe HB is prophylaxis with long-term repetitive intravenous (i.v.) infusions of recombinant FIX (rFIX) with standard half-life or extended half-life. Unmet needs remain regarding the development of non-invasive administration routes for coagulation factors. The aim of this study was to evaluate the effectiveness of intranasal delivery (IND) of rFIX and rFIX fused to Fc fragment (rFIX-Fc) in mice. Drops of rFIX and rFIX-Fc were deposited in the nostrils of wild-type, FcRn knock-out, FcRn humanized, and FIX knock-out mice. rFIX mucosal uptake was evaluated by measuring plasma FIX antigen and FIX activity (FIX:C) levels, and by performing histologic analysis of the nasal mucosa following IND. After IND, both rFIX and rFIX-Fc were equally delivered to the blood compartment, irrespective of the mouse strain studied, mostly through a passive mechanism of transportation across the mucosal barrier, independent of FcRn receptor. Both plasma FIX antigen and FIX:C activity levels increased following IND in FIX knock-out mice. This proof-of-concept study describes evidence supporting the nasal route as an alternative to FIX i.v. infusion for the treatment of HB.


Forecasting in humanitarian operations: Literature review and research needs.
Forecasting research in the humanitarian context is scarce. In this literature review, our goal is not only to show why forecasting research is important for the humanitarian sector, but also to identify what has been done so far, and where are the needs for further research. We conducted a structured literature search in Scopus, Web of Science, ABI Inform, and Google Scholar resulted in only 38 papers published between 1990 and 2018. Based on our findings we highlight three case studies as exemplary research in forecasting within the humanitarian context and list seven future research streams with specific research needs identified in each stream.


RAG1 and RAG2: nuclear genes involved in the dependence/independence on mitochondrial respiratory function for growth on sugars.
The analysis of five independent isolates of Kluyveromyces lactis shows that CBS 2359, CBS 683 and CBS 4574 could grow in the presence of mitochondrial inhibitors (antimycin A, oligomycin or erythromycin) and that CBS 2360 and CBS 141 were unable to grow in the presence of drugs. The resistant growth was observed only on glucose and not on other fermentable carbon sources (galactose, lactose). The phenotype 'growth on glucose in the presence of mitochondrial inhibitors' was called Rag+. This phenotype was found to be controlled by two unlinked nuclear genes: RAG1 and RAG2. Either of their recessive alleles, rag1 and rag2, led to the Rag- phenotype (i.e. the failure of growth on glucose in the presence of antimitochondrial drugs). Rag- strains represent the case in which fermentative growth becomes absolutely dependent on the functioning of the normal respiratory chain.


Ethanol(nitrato)[tris-(4-cyano-3-phenyl-1H-pyrazol-1-yl)hydroborato]nickel(II).
The synthesis and structure is reported of TpPh,4CNNi(NO3)(EtOH) or [Ni(C30H19BN9)(NO3)(C2H6O)], the first half-sandwich complex of a cyano-scorpionate ligand. The pseudo-octa-hedral coordination sphere of the NiII ion is comprised of a tridentate tris-(4-cyano-3-phenyl-pyrazol-yl)borate ligand, a bidentate nitrate ligand and a neutral ethanol ligand. The phenyl substituents on the TpPh,4CN ligand are relatively parallel to the planes of the ethanol and nitrate ligands. An inter-molecular hydrogen-bonding inter-action is evident between the ethanol OH group and the pyrazole CN substituent. The ethanol ligand was modeled with a 0.572 (13)/0.428 (13) disorder of the methyl C atom.


A study of emotion and behaviour in children attending a normal school in an urban area.
Anxiety, depression, self-esteem, behavioural deviance and prosocial behaviour were studied in children attending a normal school in a disadvantaged urban area, using self-rated and teacher-rated questionnaires. The prevalence of depression was rated as 5%. 15% described frequent suicidal thoughts. 40% scored as behaviourally deviant. Significant correlations were found between the variables studied. The rates of depression and behavioural deviance were higher than in comparable British populations.


Case of round pneumonia: pulmonary infarct and a rare situation that is similar with the lung cancer.
Round pneumonia (RP) is a rare radiological presentation of a subtype of lobar pneumonia that arises because of a developmental defect in connective tissues (pores of Köhn and channels of Lambert). The round appearance on chest X-ray (CXR) is thought to occur from an infectious process that spreads from small peripheral alveoli centrifugally through interalveolar channels via the pores of Kohn and the canals of Lambert. This explains the nonsegmental distribution and shape of RP. The pathogenesis of RP is unknown. An alternative theory holds that RP in children occurs because of underdeveloped pores of Kohn and the absence of canals of Lambert, limiting the spread of the organism and resulting in a focal, round mass seen on radiographs. As a result of this developmental defect, dissemination of infection remains in a limited area. While this is a well-known entity in childhood, it has been described infrequently in adults. Lesions of RP are not necessarily round; oval lesions can also be seen. It is a radiological subtype of the pneumonia subtype and presents as a solitary nodule or a mass lesion in CXR. We presented two cases of RP. One mimicked and was mistaken for pulmonary infarction because of triangular pleural-based density and the other mimicked pulmonary malignancy because of a homogeneous triangular opacity based on the pleura on the posteroanterior radiography and computed tomography. These cases were presented because of RP's importance, and RP should be considered a part of differential diagnosis of pulmonary infarct and lung tumor.


What a Difference a Drink Makes: Determining Associations Between Alcohol-Use Patterns and Condom Utilization Among Adolescents.
This study aimed to identify differences in condom use among adolescents by alcohol consumption patterns using the 2017 Youth Risk Behavior Survey. Results suggest significant increased risk of condomless sex among binge drinking youth. Surprisingly, no significant difference in condom utilization was identified between non-drinkers and only moderate drinkers. Findings highlight the need to tailor STI preventative measures accordingly.


Erectile dysfunction: the need to be evaluated, the right to be treated.
Erectile dysfunction (ED) is commonly associated with cardiovascular disease, which has potentially fatal consequences if not managed appropriately. Physicians and patients for a number of reasons commonly ignore ED. Increased awareness of the health consequences of ED would encourage men and health care professionals to address this condition more freely, permitting appropriate screening and treatment of cardiovascular disease. Concerns about the risks of treating ED in the cardiac patient should not prevent ED from being discussed and we suggest that early acknowledgment of ED might prevent cardiovascular morbidity and even mortality. Specific guidelines for the management of ED in cardiac patients, produced by 2 expert panels, can also be applied to men without known cardiovascular disease.


Composition and toxicity of diethyl ether soluble lipids from Nocardia asteroides GUH-2 and Nocardia asteroides 10905.
Virulent Nocardia asteroides GUH-2 and avirulent N. asteroides 10905 contained 8.2% and 10.6% of diethyl ether soluble lipids (DESL) per dry cell mass, respectively. Intraperitoneal (i.p.) inoculation of 250 micrograms of DESL from GUH-2 dissolved in mineral oil was toxic to mice, resulting in weight loss and death of 100% of the animals (20/20) within 20 days. In contrast, DESL from 10905 had very little toxicity, and only one mouse (1/10) died within 30 days. Three fractions resulted from DESL by silicic acid column chromatography: (1) neutral lipids and fatty acids (NFA); (2) glycolipids (GL); and (3) phospholipids (PL). Each fraction dissolved in mineral oil was inoculated into mice as described above. The NFA and PL were not toxic. GL from 10905 had low toxicity (30% of the animals died, 3/10) whereas GL from GUH-2 expressed high toxicity (100% of the animals became cachetic and died, 10/10). GL from 10905 represented a minor component (0.6% of dry cell weight) whereas GL from GUH-2 was more prominent (1.5% of dry cell wt.). Approximately 95% of GL from GUH-2 had properties of an authentic trehalose-6,6'-dimycolate standard. Infrared spectrum of the major glycolipid (GUH-2 GL) had characteristic absorptions in the fingerprint region between 800 cm-1 and 1500 cm-1. Upon alkaline hydrolysis GUH-2 GL released 76% mycolic acids in the C50 size range plus 24% trehalose.(ABSTRACT TRUNCATED AT 250 WORDS)


Analysis of the mylohyoid nerve in elderly Japanese cadavers for dental implant surgery.
Injury to the mandibular nerve (MN) branches may cause pain and irregular occlusal movement during mastication after mandibular dental treatments. Growing evidence indicates that the calcitonin gene-related peptide (CGRP) plays a key role in the development of peripheral sensitization and the associated enhanced pain, suggesting it may be a sign to ensure a safe and reliable dental implant treatment. Our focus was on the distribution of the MN branches and their communication with the lingual nerve (LN), the localized expression of CGRP, and the identification of a pain area related to the mylohyoid muscle (MM) fascia in the mandibular floor. In this study, MM samples from 440 sides of 303 human cadavers aged 61-103 years were examined microscopically and immunohistochemically. These data were further evaluated by the use of principal component analysis. A complex but weak attachment site was identified for the fascia of the MM. CGRP expression was mainly located in small vessels and was scattered throughout the whole fascia of the MM. Communication between the MN and LN was found in 62.5% (275/440) of the samples. The results from the principal component analysis showed that the positive contributions were from the descending branch in the premolar region (correlation coefficient value R = 0.665), the ascending branch in the molar region (R = 0.709) and the intermediate branch of the digastric branch (R = 0.720) in component 1. In the fascia off the MM, strongly labeled CGRP-positive cells were also found around the blood vessels and the nerve. The findings reported in this study indicate that there is a risk of damage when pulling the fascia off the MM at the border of the molar and premolar regions during dental implant surgery.


The inter-rater reliability of the 13-point manual muscle test in people with spinal cord injury.
Objective: To determine the inter-rater reliability of the 13-point manual muscle test (MMT) in two upper limb muscle groups of people with tetraplegiaSetting: The study was conducted at three spinal cord injury (SCI) units.Participants: Sixty people with complete or incomplete tetraplegia.Methods: The inter-rater reliability of the 13-point MMT was investigated. Strength of the elbow flexors and/or wrist extensors in people with tetraplegia was measured by two physiotherapists on the same day.Results: The weighted kappa coefficient (95% confidence interval) reflecting the agreement between the two strength assessments by two different assessors for the wrist extensors and elbow flexors were 0.96 (0.93 to 0.99) and 0.94 (0.89 to 0.99), respectively. Repeat measurements by different physiotherapists were within 1 of 13 points of each other 82% of the time for wrist extensors and 87% of the time for the elbow flexors.Conclusion: The 13-point MMT is a reliable measure of strength in the wrist extensors and elbow flexors of people with tetraplegia.


Low-pressure headaches following foramen magnum decompression secondary to absorption of cerebrospinal fluid into the venous system of the diploic space.
We describe a case of a patient who suffered low-pressure headaches secondary to absorption of cerebrospinal fluid into the venous system of the diploic space following a foramen magnum decompression. This case is important as it describes a physiologically plausible but previously undescribed complication of a common surgical intervention. A nine-year-old boy underwent a foramen magnum decompression for a Chiari malformation (Type I). Five years after his initial decompression, his original symptoms returned and he underwent further decompression with short-term relief of symptoms. He then began to describe low-pressure headaches. Comprehensive investigations revealed a small posterior pseudomeningocoele that had extended into the diploic space at the site of the previous surgery to the occipital bone. It was postulated that the diploic space may be acting as an additional site for reabsorption of his CSF, and as a result of this, he was experiencing consistently low-pressure symptoms. His symptoms have completely resolved following surgical intervention to seal the site of communication with the diploic space. We review recent literature that supports this theory through an understanding of the anatomy of the diploic venous system and also its physiological behaviour as demonstrated in recent cadaveric and porcine studies.


An effective method of DNA extraction for bioleaching bacteria from acid mine drainage.
An effective and versatile method for microorganism lysis and direct extraction of DNA from bioleaching bacteria was developed using pure cultures and an acid mine drainage (AMD) sediment sample. In the described method, microorganisms are treated at three different incubation temperatures: boiling water incubation for 6-10 min, followed by 60 +/- 5 degrees C for 30 min, then 72 degrees C for 30 min. The extracted DNA is purified using a phenol/chloroform/alcohol mixture and precipitated in absolute alcohol. The 16S ribosomal RNA (rRNA) and gyrB genes of the pure cultures were amplified using the polymerase chain reaction (PCR) and differentiated using repetitive intergenic DNA sequences amplification (Rep-PCR). For the AMD sediment sample, the 16S rRNA and gyrB genes of the amplicons were digested with Hin6I and MspI, and the restriction fragment length polymorphism analysis patterns were used as a fingerprint to discern community diversity. The results indicated that this method is a versatile, reproducible, effective, and rapid technique for routine DNA extraction from bioleaching bacteria. The low cost of this method also makes it attractive for large-scale studies.


Collagen type IV of Drosophila is stockpiled in the growing oocyte and differentially located during early stages of embryogenesis.
We have developed and characterized a battery of specific polyclonal antibodies directed against specific portions of the alpha-chain of collagen type IV synthesized in Drosophila by the gene DCg1. Here, we describe the use of these antibodies together with in situ hybridization experiments in an attempt to study the expression and localization of collagen type IV during Drosophila oogenesis and early embryogenesis. The results clearly demonstrate that DCg1 is maternally expressed by follicle cells and that the collagen type IV chain produced is stockpiled in the growing oocyte. During the gastrulation stages, this component of Drosophila basement membranes concentrated on cells involved in the gradual invaginations leading to morphogenetic furrows. The presence of collagen type IV, which is an RGD-bearing molecule, during early stages of Drosophila development is discussed in comparison with the crucial, active role its vertebrate counterpart is supposed to play in morphogenetic processes.


Minimal intervention for neurofibromatosis type I manifestations: A case report.
Neurofibromatosis type I (NF1, OMIM: 162200) is a benign, autosomal dominant, tumorigenic predisposing syndrome with variable manifestations. Both neurofibromatosis and soft tissue sarcomas are associated with the formation of hematomas. Moreover, skeletal manifestations of NF1 include focal or generalized forms and expansive or infiltrative growth types. A 19-year-old NF1 female patient presented with an expanding post-traumatic facial hematoma that resembled a soft-tissue tumor at initial presentation. A congenital neck mass was noted ipsilateral to her craniofacial skeletal deformities. Multiple imaging modalities were used to aid diagnosis, and urgent surgical intervention of the expanding facial lesion was performed. Her neck lesion and skeletal deformities were monitored, and her recovery was uneventful at 1-year follow-up, with no progression. A palpable, non-pulsatile soft tissue mass is a common clinical presentation with a diverse differential diagnosis. Despite the low incidence of post-traumatic vascular injuries and lesions in the maxillofacial region, neurofibromatosis-associated vasculopathy remains an underestimated and serious manifestation of NF1. The reported zygomatic arch deformity is believed to be unique. However, the NF1 tumor-associated skeletal malformations are not linearly related. NF1 is a multisystem disorder necessitating an early multidisciplinary team approach. Minimal intervention can help convert an emergent operation into an urgent one and preclude the need for major surgery. The case illustrated a rare example of simultaneous affection of soft tissue and jaw bones in NF1 patients.


Mechanical Ventilation in Critical Care Transport.
Although the benefit of transferring patients with hypoxemic respiratory failure to tertiary care centers has been shown, transporting hypoxemic patients remains controversial, given the risk of desaturation in transit. We performed a retrospective analysis of a database of critical care transports (CCTs) of patients with hypoxemic respiratory failure to quantify the number, types, and effects of ventilator changes performed by the CCT teams. We evaluated the changes in fraction of inspired oxygen (FiO2), positive end-expiratory pressure (PEEP), tidal volume, both FiO2 and PEEP, and the administration of a neuromuscular blocking medication to assess for an association with an improvement in the arterial partial pressure of oxygen (PaO2) from the sending to the receiving hospitals. Ventilator changes were made in 211 (89%) of the 237 identified transports, with significant changes in the tidal volume, PEEP, and FiO2. Analysis of variance revealed a significant relationship between changes in FiO2, PEEP, tidal volume, FiO2 and PEEP, and the administration of neuromuscular blocking agents and change in PaO2 (F5,1037 = 119.6, P < .001). Multivariable regression analyses showed a significant association between an increase in PaO2 and increasing FiO2, increasing FiO2 and PEEP, and the administration of a neuromuscular blocking medication. The CCT team performed multiple changes to ventilators. Complex ventilator management was associated with a higher PaO2 on arrival.


Endoplasmic reticulum stress signals in the tumour and its microenvironment.
Protein handling, modification and folding in the endoplasmic reticulum (ER) are tightly regulated processes that determine cell function, fate and survival. In several tumour types, diverse oncogenic, transcriptional and metabolic abnormalities cooperate to generate hostile microenvironments that disrupt ER homeostasis in malignant and stromal cells, as well as infiltrating leukocytes. These changes provoke a state of persistent ER stress that has been demonstrated to govern multiple pro-tumoural attributes in the cancer cell while dynamically reprogramming the function of innate and adaptive immune cells. Aberrant activation of ER stress sensors and their downstream signalling pathways have therefore emerged as key regulators of tumour growth and metastasis as well as response to chemotherapy, targeted therapies and immunotherapy. In this Review, we discuss the physiological inducers of ER stress in the tumour milieu, the interplay between oncogenic signalling and ER stress response pathways in the cancer cell and the profound immunomodulatory effects of sustained ER stress responses in tumours.


Carcinogenicity of flour infested with Tribolium castaneum using the Egyptian toad Bufo regularis as a biological test animal.
Feeding the Egyptian toad Bufo regularis for 14 weeks with flour infested for 1 year with Tribolium castaneum, at a dose level of 200 mg/50 g body weight, induced neoplasms in 22 out of 100 toads. These neoplasms comprise 22 primary hepatocellular carcinomas and 6 tumours in the kidney due to metastases from the primary hepatocellular carcinoma. It is speculated that the carcinogenicity of the flour used in this work is due to quinone derivatives secreted by the defensive glands of T. castaneum.


Food cravings during acute hypoglycaemia in adults with Type 1 diabetes.
Food craving is defined as an intense desire to eat a specific foodstuff. It may be distinguished from the sensation of hunger, which is relieved by nonspecific foodstuffs. No controlled studies have examined the effects of hypoglycaemia on food cravings. Thus, the aim of this study was to examine change in cravings for eight specified food types during euglycaemia and insulin-induced hypoglycaemia. Thirteen adults with Type 1 diabetes attended two experimental sessions where acute hypoglycaemia was induced with either insulin aspart or human soluble insulin. Food cravings were assessed, using a questionnaire, at baseline and at the onset of the autonomic reaction to hypoglycaemia ("R"). The mean arterialised blood glucose concentration at baseline was 6.0+/-0.3 mmol l(-1) and at R was 1.9+/-0.4 mmol l(-1) (P<.01). Fifteen percent of subjects reported having a craving for food during euglycaemia. The prevalence increased to 65% during hypoglycaemia (P<.01). Cravings for seven of the eight food types increased during hypoglycaemia, but the greatest effect sizes (>1.0 standard deviations) were observed for three food types that had a high carbohydrate content. In people with Type 1 diabetes, acute hypoglycaemia produces a highly reliable generalised increase in cravings for food, particularly foodstuffs with a high content of carbohydrate. The mechanisms behind this response remain to be elicited.


High-performance thin-layer hydrogel composite membranes for ultrafiltration of natural organic matter.
Thin-layer hydrogel composite (TLHC) ultrafiltration (UF) membranes were synthesized by photo-grafting of either poly(ethylene glycol) methacrylate (PEGMA) or N,N-dimethyl-N-(2-methacryloyloxyethyl-N-(3-sulfopropyl) ammonium betaine (SPE) onto commercial polyethersulfone (PES) UF membranes. The performance of TLHC UF membranes was evaluated for natural organic matter (NOM) filtration and compared to commercial PES UF membranes. The fouling evaluation was done by investigation of membrane-solute interactions (adsorptive fouling) and membrane-solute-solute interactions (UF). The results suggest that the TLHC membranes convincingly displayed a higher adsorptive fouling resistance than unmodified PES UF membranes. In long-term stirred dead-end UF, a much lower fouling was observed for TLHC membranes than for commercial membranes with the same flux and rejection. Further, water flux recovery was also much higher. An analysis using an existing blocking model was performed in order to elucidate the effect of a polymer hydrogel layer on fouling mechanism as well as cake layer characteristics. The TLHC membranes synthesized by photo-grafting of PEGMA (40 g/L) and PEGMA with a low concentration of cross-linker monomer in the reaction mixture (ratio: 40/0.4 (g/L)/(g/L)) showed a much better performance than the other composite membranes. Those membranes could reduce the cake resistance on the membrane surface. This work has relevance for the design of high-performance UF membranes for applications in water treatment.


Immunohistochemical detection of intra-neuronal VZV proteins in snap-frozen human ganglia is confounded by antibodies directed against blood group A1-associated antigens.
Varicella-zoster virus (VZV) causes chickenpox, establishes latency in trigeminal (TG) and dorsal root ganglia (DRG), and can lead to herpes zoster upon reactivation. The VZV proteome expressed during latency remains ill-defined, and previous studies have shown discordant data on the spectrum and expression pattern of VZV proteins and transcripts in latently infected human ganglia. Recently, Zerboni and colleagues have provided new insight into this discrepancy (Zerboni et al. in J Virol 86:578-583, 2012). They showed that VZV-specific ascites-derived monoclonal antibody (mAb) preparations contain endogenous antibodies directed against blood group A1 proteins, resulting in false-positive intra-neuronal VZV staining in formalin-fixed human DRG. The aim of the present study was to confirm and extend this phenomenon to snap-frozen TG (n=30) and DRG (n=9) specimens of blood group genotyped donors (n=30). The number of immunohistochemically stained neurons was higher with mAb directed to immediate early protein 62 (IE62) compared with IE63. The IE63 mAb-positive neurons always co-stained for IE62 but not vice versa. The mAb staining was confined to distinct large intra-neuronal vacuoles and restricted to A1(POS) donors. Anti-VZV mAb staining in neurons, but not in VZV-infected cell monolayers, was obliterated after mAb adsorption against blood group A1 erythrocytes. The data presented demonstrate that neuronal VZV protein expression detected by ascites-derived mAb in snap-frozen TG and DRG of blood group A1(POS) donors can be misinterpreted due to the presence of endogenous antibodies directed against blood group A1-associated antigens present in ascites-derived VZV-specific mAb preparations.


The Effects of Ephedrine and Phenylephrine on Placental Vascular Resistance During Cesarean Section Under Epidual Anesthesia.
The purpose of this article is to study the effect of ephedrine and phenylephrine on placental vascular resistance during cesarean section under epidural anesthesia via Doppler ultrasonography. Sixty female subjects, scheduled for elective cesarean section and had an intrathecal injection of bupivacaine, were randomly divided into two groups to receive phenylephrine (50 μg/min) or ephedrine (4 mg/min) via titration to maintain systolic blood pressure at baseline. Doppler ultrasonography was used to measure baseline vascular resistance values prior to administration of anesthesia, and resistance index (RI) and systolic peak velocity/diastolic velocity (S/D) values of umbilical artery and uterine artery were measured at each time point within first 20 min following intrathecal injection. Blood samples were collected from umbilical artery and umbilical vein during delivery to assess the blood gas values. No significant differences in RI and S/D values of umbilical artery and uterine artery after intrathecal injection were found between two groups. RI and S/D values of uterine artery slightly increased in both groups at each time point after anesthesia, but remained within the normal range. No significant differences were observed in blood gas values and the total amount of vasoconstriction drugs between two groups. In contrast to previous reports that used animal models, our study did not show increased placental vascular resistance in patients following phenylephrine (50 μg/min) or ephedrine (4 mg/min) infusion, as well as no significant differences in the effect of either of these two. The discrepancy between the results of human and animal studies may be related to species differences and the mechanism of human placental vascular remodeling.


Role of phosphodiesterase-4 on ethanol elicited locomotion and narcosis.
The cAMP signaling pathway has emerged as an important modulator of the pharmacological effects of ethanol. In this respect, the cAMP-dependent protein kinase has been shown to play an important role in the modulation of several ethanol-induced behavioral actions. Cellular levels of cAMP are maintained by the activity of adenylyl cyclases and phosphodiesterases. In the present work we have focused on ascertaining the role of PDE4 in mediating the neurobehavioral effects of ethanol. For this purpose, we have used the selective PDE4 inhibitor Ro 20-1724. This compound has been proven to enhance cellular cAMP response by PDE4 blockade and can be administered systemically. Swiss mice were injected intraperitoneally (i.p.) with Ro 20-1724 (0-5 mg/kg; i.p.) at different time intervals before ethanol (0-4 g/kg; i.p.) administration. Immediately after the ethanol injection, locomotor activity, loss of righting reflex, PKA footprint and enzymatic activity were assessed. Pretreatment with Ro 20-1724 increased ethanol-induced locomotor stimulation in a dose-dependent manner. Doses that increased locomotor stimulation did not modify basal locomotion or the suppression of motor activity produced by high doses of this alcohol. Ro 20-1724 did not alter the locomotor activation produced by amphetamine or cocaine. The time of loss of righting reflex evoked by ethanol was increased after pretreatment with Ro 20-1724. This effect was selective for the narcotic effects of ethanol since Ro 20-1724 did not affect pentobarbital-induced narcotic effects. Moreover, Ro 20-1724 administration increased the PKA footprint and enzymatic activity response elicited by ethanol. These data provide further evidence of the key role of the cAMP signaling pathway in the central effects of ethanol.


Cardiac tumors.
Cardiac tumors are great imitators in cardiovascular disease. Common clinical presentations include arrhythmias, congestive heart failure, pericardial effusion, pulmonary or systemic embolic disease, valvular dysfunction and constitutional symptoms, such as fever, malaise and weight loss. M-mode and two-dimensional echocardiography have simplified diagnosis, but the physician must have a high index of suspicion.


Variability in the phenotypic expression of abnormal sarcosine metabolism in a family.
A retarded child with hypersarcosinemia and his family were studied by loading tests to determine the probable site of his defect. On the basis of his response to folate treatment, a partially-reversible defect in the formation of activated formaldehyde in the reaction catalyzed by sarcosine dehydrogenase was considered to be the most likely site. During a glycine loading test, sarcosine levels in the plasma and urine increased, indicating that the direct transmethylation of glycine to sarcosine could occur in this patient. The father of the proband tolerated a load of sarcosine poorly, resembling the proband in his plasma sarcosine levels. No evidence that glycine could be transmethylated to sarcosine was found in the father, despite the fact that his peak glycine level was four times higher than the proband's. These findings provide indirect evidence that sarcosine formation may be affected by two additional components besides the apo moiety of sarcosine dehydrogenase, the availability of tetrahydrofolic acid as a one carbon unit carrier and the integrity of the transmethylase which catalyzes the direct transmethylation of glycine to sarcosine.


Is there a relationship between estimated fetal weight and umbilical artery Doppler impedance indices?
To establish whether there is a relationship between estimated fetal weight (EFW) and umbilical artery Doppler waveform impedance indices in the third trimester. The pulsatility index (PI) and S/D (systolic/diastolic) ratio were obtained together with the EFW from 274 low-risk pregnancies. Measurements were made at fortnightly intervals from 30 weeks' gestation until delivery. A relationship between the two impedance indices and EFW was sought at gestational age ranges of 30-32, 33-35, 36-38 and 39-41 weeks. There were 918 pairs of PI (with S/D) and EFW available for analysis. The mean of the impedance indices decreased with advancing gestational age as expected. There was no clinically relevant correlation between impedance indices and EFW within any of the gestational age ranges. Impedance indices from the umbilical artery Doppler waveform decrease with advancing gestational age due, at least partially, to expansion of the placental vascular tree. Within narrow gestational age ranges in the third trimester, there is no meaningful correlation between fetal weight and impedance indices. It is therefore not necessary to adjust umbilical artery Doppler impedance indices to account for fetal size.


Potential advantages of robotic total gastrectomy for gastric cancer: a retrospective comparative cohort study.
Laparoscopic total gastrectomy (LTG) is a highly technical surgery that can lead to postoperative complications. Whether the recently introduced robotic surgery overcomes the drawbacks of laparoscopic surgery in total gastrectomy remains controversial. Therefore, we aimed to elucidate the potential benefits of robotic total gastrectomy (RTG) and compare the short-term outcomes of RTG and LTG. We retrospectively analyzed 56 patients with primary gastric or esophagogastric junction cancer who underwent RTG or LTG between June 2017 and July 2021. The groups were compared in terms of operative outcomes and postoperative complications. Potential risk factors associated with postoperative complications were assessed by performing multivariable analysis using logistic regression models via the exact method. Operation time was significantly longer, and postoperative hospital stay was significantly shorter in the robotic group (550 vs. 466 min, P < 0.001; 13 vs. 18 days, P = 0.013, respectively). The incidence of overall postoperative complications of Clavien-Dindo grade ≥ II was 18.5% and 24.1% in the RTG and LTG groups, respectively. Pancreatic fistulas were not observed, but other local complications were observed in 0% and 17.2% of the RTG and LTG groups, respectively (P = 0.052). In the multivariable analysis, the independent risk factors for local complications were laparoscopic surgery (odds ratio [95% confidence interval] 8.542 [1.065-∞], P = 0.045) and esophagogastric junction cancer (16.646 [2.559-∞], P = 0.005). Compared with LTG, RTG was associated with fewer local complications (mainly anastomotic leakage), especially in cases of esophagogastric junction cancer with high anastomotic sites.


The citrulline generation test: proposal for a new enterocyte function test.
The amino acid citrulline is mainly produced by enterocytes from conversion of glutamine. As fasting plasma citrulline proved disappointing as a biomarker for enterocyte dysfunction in clinical practice, we propose a citrulline generation test (CGT) to assess enterocyte function. To assess the feasibility of a CGT in healthy subjects and patients with decreased enterocyte mass. Nineteen healthy subjects, 16 patients with intestinal villous atrophy and nine patients with short bowel syndrome (SBS) were given an oral bolus of 20 g of the dipeptide alanine-glutamine. Subsequent changes in plasma citrulline and other amino acid concentrations were determined using reverse-phase high-performance liquid chromatography. Following the oral bolus of alanine-glutamine, plasma citrulline concentrations showed a time dependent rise in healthy subjects of 44 +/- 13% (38-55 micromol/L, P < 0.0001). The slope from baseline plasma citrulline to peak concentrations was 0.22 +/- 0.08, 0.13 +/- 0.04 and 0.09 +/- 0.04 micromol/L/min in healthy subjects, patients with coeliac disease (CeD) and refractory CeD, respectively (healthy subjects vs. CeD P < 0.05, healthy subjects vs. refractory CeD P < 0.001). In patients with SBS, the CGT was able to distinguish between non-adapted and adapted SBS by means of the incremental area under the CGT curve till 90 min (iAUC T90). The iAUC T90 was 447 +/- 179 and 1039 +/- 178 micromol/L/min in non-adapted and adapted SBS, respectively (P = 0.04). An oral bolus of alanine-glutamine induces a time-dependent rise in plasma citrulline concentration to an extent dependent on the existence of villous atrophy or enterocyte hyperplasia in CeD, and adapted SBS, respectively.


[Bevacizumab in thoracic oncology: results and practical aspects].
Bevacizumab (Avastin(®)) is the first antiangiogenic therapy approved in non-small cell lung cancer (NSCLC). It is also currently the only agent in this family approved in NSCLC. This review focuses on results of clinical trials assessing bevacizumab in thoracic oncology. It also provides to clinicians practical advices for its prescription.


Endoscopic Submucosal Dissection Improves Bloody Stool Associated with Polypoid Type Mucosal Prolapse Syndrome: A Case Series.
Mucosal prolapse syndrome (MPS) is a benign inflammatory disease of the rectum that causes bloody stool. Endoscopic treatment for MPS has not been established. We herein report a consecutive case series of endoscopic submucosal dissection (ESD) for MPS. There were four cases treated with ESD alone. All lesions were on the dentate line, and all were polypoid. The median procedure time was 77 minutes. No complications were observed. The median observation period was 1,108 days, and bloody stool and endoscopic recurrence of MPS were not observed.ESD for polypoid-type MPS was an effective treatment for improving bloody stool and suppressing endoscopic recurrence.


Pediatric glioblastoma cell line shows different patterns of expression of transmembrane ABC transporters after in vitro exposure to vinblastine.
Resistance to drug is a major cause of treatment failure in pediatric brain cancer. The multidrug resistance (MDR) phenotype can be mediated by the superfamily of adenosine triphosphate-binding cassette (ABC) transporters. The dynamics of expression of the MDR genes after exposure to chemotherapy, especially the comparison between pediatric brain tumors of different histology, is poorly described. To compare the expression profiles of the multidrug resistance genes ABCB1, ABCC1, and ABCG2 in different neuroepithelial pediatric brain tumor cell lines prior and following short-term culture with vinblastine. Immortalized lineages from pilocytic astrocytoma (R286), anaplasic astrocytoma (UW467), glioblastoma (SF188), and medulloblastoma (UW3) were exposed to vinblastine sulphate at different schedules (10 and 60 nM for 24 and 72 h). Relative amounts of mRNA expression were analyzed by real-time quantitative polymerase chain reaction. Protein expression was assessed by immunohistochemistry for ABCB1, ABCC1, and ABCG2. mRNA expression of ABCB1 increased together with augmenting concentration and time of exposure to vinblastine for R286, UW467, and UW3 cell lines. Interestingly, ABCB1 levels of expression diminished in SF188. Following chemotherapy, mRNA expression of ABCC1 decreased in all cell lines other than glioblastoma. ABCG2 expression was influenced by vinblastine only for UW3. The mRNA levels showed consistent association to protein expression in the selected sets of cell lines analyzed. The pediatric glioblastoma cell line SF188 shows different pattern of expression of multidrug resistance genes when exposed to vinblastine. These preliminary findings may be useful in determining novel strategies of treatment for neuroepithelial pediatric brain tumors.


An experimental reunion of psychoanalytic theory with perceptual vigilance and defense. Reply to Blum.
Methodological criticisms are answered, and additional reasons for questioning Blum's theory and method are offered.


A sero-epidemiological study of Leptospira interrogans serovar Balcanica in four brush-tailed possum populations in Victoria, Australia.
The microscopic agglutination (MA) test was utilised to study the prevalence of antibodies to Leptospira interrogans serovar hardjo in 4 populations of brush-tailed possums (Trichosurus vulpecula). The overall antibody prevalence varied from 14% to 66%; however, the age distribution of MA test titres was remarkably similar in all 4 populations. Antibody prevalence was similar in both males and females and demonstrable antibodies were limited to sexually mature animals. The greater prevalence of high titres (greater than or equal to 1:128) in the 18- to 24-month age group suggested that primary infections were acquired at this age. The findings suggested that infection was maintained in possum populations by direct transmission, probably associated with breeding. Focal interstitial nephritis was observed in kidneys of possums greater than 18 months of age and was associated with MA titres to hardjo (P less than 0.001). Serovar balcanica was isolated from possum kidneys from 2 of these populations, suggesting that balcanica infections were responsible for most of the hardjo titres. However, agglutinin-absorption tests indicated that some possums may be infected with a leptospire more closely related to hardjo than to balcanica.


Depolarizing agents regulate the phosphorylation of myelin basic protein in rat optic nerves.
The regulation of the state of phosphorylation of myelin basic protein has been studied in intact rat optic nerves incubated in vitro. For this purpose the endogenous state of phosphorylation was preserved and the "back-phosphorylation" technique was used to determine the amount of dephosphorylated protein present in extracts of the nerves. Our results indicate that when nerves were incubated in the presence of depolarizing agents, the state of phosphorylation of myelin basic protein was increased. This effect was calcium-dependent and was partly inhibited by chlorpromazine.


Phototoxicity of bituminous tars-correspondence between results of 3T3 NRU PT, 3D skin model and experimental human data.
Bituminous tars (Ichthammol and Ichthyol Pale) are widely used in pharmaceutical, veterinary and cosmetic industries for their anti-microbial, anti-inflammatory and anti-pruritic effects. In contrast to coal tar, no phototoxicity of bituminous tars has been reported in man, although both Ichthammol and Ichthyol Pale exhibit UV absorption which is higher and broader for the former. The validated 3T3 NRU phototoxicity test indicated phototoxic potential of both substances. The phototoxicity test in a 3D human skin model (EpiDerm) only confirmed phototoxicity for Ichthammol. Human data on Ichthammol phototoxicity are missing. A photopatch test in human volunteers was performed in order to clarify the discrepancy between the phototoxicity found in the skin model and the absence of reported human phototoxicity. Following 4h exposure to 5% and 10% aqueous solutions of Ichthammol and Ichthyol Pale the test sites were irradiated with a UVA dose of 5 J/cm(2). Early phototoxic reaction (erythema) within 4-6h after irradiation was only elicited by Ichthammol and not by Ichthyol Pale. These data correspond well with those from the 3D skin model test and suggest the necessity to employ several test systems for final phototoxicity assessment. In addition to the results obtained in 3T3 NRU PT, further testing on 3D skin models may better reflect bioavailability of a given chemical in the skin, relevant to the situation in humans.


Assessment of the potential reproductive and subchronic toxicity of EDS coal liquids in Sprague-Dawley rats.
The EDS direct coal liquefaction process is one of several methods of producing liquid fuels from coal which have reached the pilot or demonstration stage of development. Relatively high levels of polycyclic aromatic hydrocarbons are present in distillate fractions boiling above approximately 370 degrees C, and unrefined coal-derived liquids which contain substantial amounts of material from this boiling range are relatively potent dermal carcinogens. Because coal-derived liquids containing high boiling (i.e., greater than 370 degrees C) material may pose a variety of toxic hazards, efforts have been made to evaluate the potential effects on biological endpoints other than cancer. The present studies assessed the potential for reproductive and subchronic toxicity following repeated oral administration of 2 coal-derived liquids, recycle solvent and fuel oil, which contained substantial amounts of high boiling material. Few biologically important differences were found in any of the experimental parameters. In the reproductive toxicity study, frequency of fertilization and implantation, mean number of live births, fraction of litter surviving through the lactation period and mean weight gain of the litters during the lactation period were not affected by treatment; in addition, there was no evidence of increased frequency of malformation. In the subchronic toxicity study, weight gain was reduced in animals from the high dose groups, but was not significantly different from controls. Liver weights were significantly elevated, but there was no microscopic evidence of pathologic changes. Erythrocyte counts, hemoglobin levels and hematocrits were significantly reduced suggesting a tendency towards anemia. These findings suggested that repeated exposure to EDS recycle solvent and fuel oil at levels of up to 0.5 g/kg per day had no detectable effect on reproductive capacity or performance and did not induce substantial systemic toxicity.


Purification of human lymphoblastoid cell-derived interferon-alpha by controlled-pore glass bead adsorption chromatography and molecular sieving.
Human lymphoblastoid cell-derived interferon-alpha has been purified by a combination of chromatography on controlled-pore glass 350, gel filtration on Ultrogel AcA 54 and hydrophobic chromatography on Phenyl-Sepharose CL-4B. Specific activities of greater than 10(7) units/mg have been obtained. Controlled-Pore Glass has the advantages of accommodating large volumes of induced medium in an "in-line" process giving high recoveries of interferon and removing most of any contaminating DNA.


Neuropathological characterization of Lemur tyrosine kinase 2 (LMTK2) in Alzheimer's disease and neocortical Lewy body disease.
Alzheimer's disease (AD) and neocortical Lewy body disease (LBD) are the most common neurodegenerative dementias, with no available curative treatment. Elucidating pathomechanism and identifying novel therapeutic targets are of paramount importance. Lemur tyrosine kinase 2 (LMTK2) is involved in several physiological and pathological cellular processes. Herewith a neuropathological characterization is presented in AD and neocortical LBD samples using chromogenic and fluorescent LMTK2 immunohistochemistry on post-mortem brain tissues and compared them to age-matched controls (CNTs). LMTK2 immunopositivity was limited to the neuronal cytoplasm. Neurons, including tau-positive tangle-bearing ones, showed decreased chromogenic and immunofluorescent labelling in AD in every cortical layer compared to CNT and neocortical LBD. Digital image analysis was performed to measure the average immunopositivity of groups. Mean grey values were calculated for each group after measuring the grey scale LMTK2 signal intensity of each individual neuron. There was significant difference between the mean grey values of CNT vs. AD and neocortical LBD vs. AD. The moderate decrease in neocortical LBD suggests the effect of coexisting AD pathology. We provide neuropathological evidence on decreased neuronal LMTK2 immunolabelling in AD, with implications for pathogenesis.


Resilience in the context of dementia family caregiver mental health: A concept analysis.
Resilience has been identified as a key concept for dementia family caregiver mental health; however, the concept is not well defined. A concept analysis examining dementia caregiver resilience was conducted using Rodger's Evolutionary Method. The aim of this concept analysis was to describe the historical perspective, attributes, antecedents, and consequences of resilience as it relates to dementia caregiver mental health. Key attributes of dementia caregiver resilience were acceptance, coping strategies, social support, self-appraisal, and spirituality. The results from this concept analysis provide the foundation for the development of resilience-based interventions to support the well-being of dementia family caregivers.


Evoked potential and preferential looking estimates of visual acuity in pediatric patients.
Pattern visual evoked potentials (VEPs) and behavioral visual acuity measured with forced-choice preferential looking techniques (FPL) were obtained from 172 pediatric patients between the ages of 4 months and 10 years. More children younger than 2 years of age successfully completed monocular testing by pattern VEP than by FPL methods. For children older than 2 years, we were equally successful in completing each of the two tests. Of those children who completed both tests, the VEP results agreed with Snellen, Allen, and "E" acuity measures more often (66%) than did the FPL results (50%). Both tests were more sensitive than Allen single characters in detecting interocular acuity differences in children younger than 3 years of age.


An investigation of dopaminergic metabolites in the striatum and in the substantia nigra in vivo utilising radiolabelled L-DOPA and high performance liquid chromatography: a new approach in the search for transmitter metabolites.
Although the major routes of dopamine metabolism seem to be established, at least in terminal regions such as the striatum, it is important to search for previously unknown metabolites and to investigate the relevance of previously suggested minor alternative pathways. An urgent issue is to verify and quantify the transformation of dopamine to putative toxic species, another is to further explore metabolism of dopamine located in cell bodies/dendrites, e.g. in the substantia nigra. We have developed a new method in order to widen the search for alternative metabolites of dopamine. The method is based on systemic injection of tritiated L-DOPA to rats in vivo. Brain tissue was homogenised and centrifuged and the resulting supernatant fractioned following passage through a liquid chromatography system. The radioactivity of each fraction was measured using a scintillation system. By identifying fractions containing major catecholamines and metabolites, according to a standard solution, novel metabolites can be searched for in the remaining fractions. It was possible to obtain sufficient radioactivity in separate fractions of supernatant of homogenised tissue, even from such a small brain nucleus as substantia nigra. Radioactivity was obtained in those fractions that contained the major catecholamines and their metabolites, as well as in other fractions where it may represent previously unknown metabolites of L-DOPA/dopamine. The method was used to evaluate the possibility that cytochrome P450 2E1 is involved in the metabolism of dopamine in the substantia nigra. Significant changes in the radioactivity pattern were induced by inhibition of the enzyme but conclusions about whether cytochrome P450 2E1 is involved in the metabolism of dopamine or not requires further studies. The method can be used to study the metabolism of dopamine and can be extended, by using other radiolabelled precursors, also to evaluate metabolism of other transmitters, e.g. serotonin.


Genetic determinants of plasma lipoproteins.
The search for common genetic determinants of plasma lipoproteins began in the early 1980s. Despite some exceptions, these efforts have not yet yielded a set of biological markers that can be used in clinical practice. By contrast, successes in defining the molecular basis of rare single-gene disorders, such as familial hypoalphalipoproteinemia, have shown the value of experimental designs that focus on genomic analysis of individuals within the tails of Gaussian distributions of quantitative lipoprotein traits. For example, this strategy showed that a small but relevant proportion of individuals within the <5% tail of plasma HDL-cholesterol distribution have mutations in genes that cause familial hypoalphalipoproteinemia. The value of clinical testing for genomic variants as an adjunct to a biochemical measurement of plasma lipoproteins, however, is at best questionable. A more direct impact of genetic studies is that definitions of 'common' and 'large genetic effects' have become more tempered, reflecting perhaps the biological reality that plasma lipoproteins are probably determined by the aggregate of numerous modest and occasional large genetic effects in addition to environmental factors. Here, we review recent progress on genomic variants and cholesterol metabolism, and discuss the impact these genetic studies will have on clinical cardiology.


Two new species and a new phyllobothriid cestode genus from sharks of the genus Negaprion Whitley (Carcharhiniformes).
Alexandercestus n. g. (Cestoda: Tetraphyllidea) is erected for two cestode species found parasitising the two known species of lemon sharks (Carcharhiniformes: Negaprion spp.). This new genus differs from all other phyllobothriid genera except for Hemipristicola Cutmore, Theiss, Bennett & Cribb, 2011, Marsupiobothrium Yamaguti, 1952, Nandocestus Reyda, 2008, Orectolobicestus Ruhnke, Caira & Carpenter 2006, Orygmatobothrium Diesing, 1863, Paraorygmatobothrium Ruhnke, 1994 and Phyllobothrium van Beneden, 1849 in possessing uniloculate bothridia with an apical sucker and neck scutes. Alexandercestus differs from Orectolobicestus and Nandocestus in lacking marginal loculi on the bothridia, from Paraorygmatobothrium in possessing uninterrupted vitelline follicles at the level of the ovary and from Phyllobothrium in being euapolytic as opposed to anapolytic and in lacking posteriorly bifid bothridia. The new genus lacks the central accessory bothridial organ seen in specimens of Orygmatobothrium, and lacks the central bothridial accessory sucker of specimens of Marsupiobothrium. Alexandercestus spp. compare most favourably with specimens of Hemipristicola, especially with respect to aspects of proglottid morphology, but differ in possessing aristate gladiate spinitriches rather than serrate gladiate spinitriches on the proximal bothridial surface. In addition, the bothridia of Alexandercestus spp. are comparatively more fleshy and foliose than those in specimens of Hemipristicola. Two new species of Alexandercestus n. g. are described, Alexandercestus gibsoni n. sp. from Negaprion acutidens, collected from off northern Australia and the Marshall Islands, and Alexandercestus manteri n. sp. from N. brevirostris, collected off the islands of Bimini and the Florida Keys. The two new species differ in total length and vitelline follicle distribution. Bayesian inference and parsimony analysis of the D1-D3 region of the large nuclear ribosomal DNA of 17 published and seven novel sequences placed A. gibsoni as the sister taxon to a clade containing Hemipristicola gunterae Cutmore, Theiss, Bennett & Cribb, 2011 and species of Paraorygmatobothrium. This result supports the erection of Alexandercestus as a genus separate from Hemipristicola and Paraorygmatobothrium. At the present time, species of Alexandercestus are known only from hosts of the carcharhinid genus Negaprion Whitley; examination of extensive survey data suggests this may be the extent of the host distribution of this genus.


Functional monocyte-derived dendritic cells can be generated in chronic lymphocytic leukaemia.
Chronic lymphocytic leukaemia (CLL) remains an incurable disease. Although modern available treatments are able to induce disease regression, relapse almost inexorably occurs. Therefore, novel therapeutic strategies aimed at reducing the disease relapse rate are very much needed. Among these, the induction of tumour-associated antigen-specific cytotoxic T lymphocytes (CTL), through either DNA vaccines or injection of idiotype pulsed dendritic cells (DCs), has been actively investigated with encouraging preliminary results in B-cell malignancies. As the CLL B lymphocyte characteristically expresses low amounts of surface immunoglobulin (Ig) and T cells from these patients have been reported to display impaired functional activity, there are concerns related to the possibility of generating specific cytotoxic antitumoral T cells in this disease. In addition, no information is presently available regarding the functional ability of CLL-derived DCs. In the present work, freshly purified monocytes from CLL patients and normal donors were induced to differentiate in granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 serum-free medium and compared for their morphological, phenotypic and functional characteristics. Our results demonstrate that: (1) functional DCs can be generated from CLL patients with similar phenotype and function to those observed from normal donors; (2) in contrast to normal control subjects, monocyte-derived DCs from CLL patients spontaneously secrete endogenous IL-10; and (3) interferon (IFN)-gamma in combination with CD40L plays a major role in priming DCs from CLL patients for IL-12 and IL-15 production. Overall, these results indicate that it is possible to derive functionally competent DCs from circulating monocytes in CLL patients.


Design of a polarization-insensitive superconducting nanowire single photon detector with high detection efficiency.
Superconducting nanowire single photon detectors (SNSPDs) deliver superior performance over their competitors in the near-infrared regime. However, these detectors have an intrinsic polarization dependence on the incident wave because of their one-dimensional meander structure. In this paper, we propose an approach to eliminate the polarization sensitivity of SNSPDs by using near-field optics to increase the absorption of SNSPDs under transverse magnetic (TM) illumination. In addition, an optical cavity is added to our SNSPD to obtain nearly perfect absorption of the incident wave. Numerical simulations show that the maximum absorption of a designed SNSPD can reach 96% at 1550 nm, and indicate that the absorption difference between transverse electric (TE) and TM polarization is less than 0.5% across a wavelength window of 300 nm. Our work provides the first demonstration of the possibility of designing a polarization-insensitive and highly efficient SNSPD without performing device symmetry improvements.


Diabetes remission after bariatric surgery is characterized by high glycemic variability and high oxidative stress.
To evaluate glycemic variability (GV) and oxidative stress in patients who achieved type 2 diabetes (T2DM) remission after bariatric surgery (BS). Twenty-two patients (M/F10/12, age 50 ± 9 years, BMI 31 ± 6 kg/m2) who were in remission of T2DM (T2DM remitters) after BS since at least 1 year and 22 age-, sex- and BMI-matched control subjects were studied. Of the BS group, eleven subjects had undergone Roux-en-Y gastric bypass (RYGB) and eleven subjects sleeve gastrectomy (SG). Oral glucose tolerance test (OGTT), 7 days-continuous glucose monitoring, 24-h urinary excretion of 8-isoprostaglandin F2α (8-isoPGF2α) and dietary intake evaluation were performed. According to general linear model for repeated measures, glucose and insulin response during OGTT were significantly different in T2DM remitter than in control subjects (p < 0.001, for both). All measures of GV (standard deviation, coefficient of variation and mean amplitude of glucose excursions) were significantly higher in T2DM remitters than in controls, (p < 0.001 for all). These indexes were higher among RYGB than SG patients (p < 0.05). The time spent out of the 60-160 mg/dl range was significantly longer in T2DM remitters undergoing RYGB than in controls (p < 0.02). Mean 24-h urinary 8-isoPGF2α excretion was significantly higher in T2DM remitters than that of control subjects (p = 0.04). All GV indexes were directly correlated with blood glucose levels at 30 and 60 min during OGTT (p < 0.05-0.001). Remission of T2DM after BS is characterized by high GV and high oxidative stress in the face of fasting blood glucose and HbA1c within the normal range.


Bromocriptine potentiates the behavioural effects of directly and indirectly acting dopamine receptor agonists in mice.
After an initial period of depression which lasted up to 90 min following injection, bromocriptine (BRC, 5-20 mg/kg, IP) produced dose-dependent and long lasting (7 h) locomotor stimulation in mice. The locomotor stimulation was antagonised by reserpine, alpha-methyl-p-tyrosine (AMPT) or haloperidol. The blockade by AMPT of BRC's locomotor stimulant effect was reversed by prior treatment of the mice with a low, behaviourally inactive dose of L-Dopa plus benserazide. In mice pretreated with reserpine, BRC enhanced the stimulant action of d-amphetamine. Moreover, in mice pretreated with reserpine plus AMPT, BRC significantly enhanced the locomotor stimulant effect of apomorphine. This ability of BRC to enhance the effect of apomorphine commenced as soon as 20 min after BRC administration and lasted for at least 8 h. The dopamine (DA) uptake inhibitor and DA receptor agonist nomifensine potentiated and prolonged the stimulant effect of BRC while inhibitors of the neuronal uptake of noradrenaline (desipramine) and 5-hydroxytryptamine (fluoxetine) were without marked effect. The results clearly show that BRC, in behavioural terms, has no efficacy per se at the postsynaptic DA receptor and that it requires either DA or the administration of an exogenous agonist such as apomorphine for the expression of its effects.


A two kilograms euthyroid goiter in Singida Regional Referral Hospital, Central Tanzania: Case report.
Multinodular goiter (MNG) is a clinic pathological entity characterized by an increased volume of the thyroid gland with formation of nodules. Goiter is defined as a thyroid gland weighing over 20-25 g or with a volume of over 19 ml in women and 25 ml in men. In developed countries where iodination of food is common and health services are available and accessible, hardly will you see a goiter of up to 0.2 kg while in areas where poverty is high and health services not available, there identification of goiter of up to 4 kg. Therefore each member of theatre team must be competent and experienced to anticipate any complications which may occur during thyroidectomy of such huge goiter. Awareness on the operation of such huge multinodular goiter is the sincere aim of this work due to the fact that these are rare findings in today's surgical clinics. A 35 M.O.S years old female presented with complain of swelling of the anterior neck for 10 years. Laboratory and radiological investigations reveals nontoxic multinodular goiter with no suspicion of malignance. After successful thyroidectomy, a 2 kg multinodular goiter was removed and taken for histological diagnosis. Post-operative care was uneventful and patient discharged day five post-operative. No complication observed during follow up. The case report presented a patient with huge goiter of 2 kg, which was not compressing the trachea. After physical examination, radiological imaging and laboratory investigation of thyroid hormones confirm as nontoxic goiter. The subtotal thyroidectomy was successful and after follow up of 60 days there was no complication reported. Currently, hardly will you find goiter weighing a kg and thus skills for thyroidectomy in such case is hardly available. Special complications like trachealmalacia and difficult intubation which need one to be aware of fiber optic intubation and be prepared for tracheostomy require experienced operating team.


Spectrum of morphologic alterations of regression in cutaneous melanoma--potential for improving disease prognosis.
Regression occurs as a complex interaction between tumor cells and host's immune response; neither biologic mechanisms, nor regression prognostic significance are deciphered to date but promising anti-cancer vaccine strategies were thus developed. We analyzed 127 superficial spreading melanomas identifying melanoma with regression (segmentary (SR), partial (PR) and segmentary & partial (SR-PR)) or without regression (AR). Several histopathologic parameters were registered; statistical analysis was performed (level of significance P < 0.05). Regression was present in 52% cases, less frequently in pT4 melanomas. Ulceration and vascular invasion were similarly present in pT2-pT4 melanomas with regression and significantly less in pT1 ones; their incidence increased with stage in AR (P < 0.001). SR and SR-PR melanomas showed significantly more tumor infiltrating lymphocytes within the non-regressed tumor than AR melanomas (P < 0.05). SR melanomas presented significantly less frequent mitoses than PR (P = 0.04), SR-PR (P = 0.04) or AR ones (P = 0.03). Marked inflammation and more numerous melanophages were present regressed areas advanced stage melanomas. More numerous plasma cells were identified in advanced stages; in SR and SR-PR melanomas less numerous plasma cells were present in pT1 than in advanced stages. Vascular hyperplasia was significantly higher in SR than SR-PR cases. Differences in perception of regression might be the result of labeling with similar name of various processes comprising inflammation and tumor cells destruction; at least in thin melanomas, PR and SR seem to belong to different spectrum of alteration, SR bearing a more favorable potential. Further studies will be performed in order to further elucidate the mechanisms involved in regression in melanoma.


Crystal structures of cyclomaltoheptaose (beta-cyclodextrin) complexed with ethylene glycol.8.0H2O and glycerol.7.2H2O.
Single-crystal X-ray diffraction studies were carried out for the title compounds at room temperature. The crystal packings are of the cage-type and isomorphous to that of beta-cyclodextrin (beta CD) hydrate. In both crystal structures, disorder and extensive thermal vibrations of the complexed guest molecules are observed. In beta CD-ethylene glycol.8H2O, one ethylene glycol molecule (disordered over two discrete sites) and three water molecules (four discrete sites) are included in the beta CD cavity. Within the beta CD cavity, all oxygen sites (ordered and disordered) are in positions occupied by water molecules in beta CD.12H2O; this is only possible because the ethylene glycol molecule adopts the low-energy conformation with the O-C-C-O torsion angle approximately 60 degrees and an O...O separation of 2.9 A, in which its hydroxyl groups can directly substitute for two hydrogen-bonding water molecules. In beta CD-glycerol.7.2H2O, one glycerol molecule (disordered over two discrete sites) and two water molecules (two fully occupied sites) are included in the beta CD cavity. The general situation in both compounds parallels that found earlier in beta CD-ethanol.8H2O. It is assumed that the disorder is dynamic, i.e., associated with jumps between the partially occupied molecular sites.


Development and characterization of agonistic antibodies targeting the Ig-like 1 domain of MuSK.
Muscle-specific kinase (MuSK) is crucial for acetylcholine receptor (AChR) clustering and thereby neuromuscular junction (NMJ) function. NMJ dysfunction is a hallmark of several neuromuscular diseases, including MuSK myasthenia gravis. Aiming to restore NMJ function, we generated several agonist monoclonal antibodies targeting the MuSK Ig-like 1 domain. These activated MuSK and induced AChR clustering in cultured myotubes. The most potent agonists partially rescued myasthenic effects of MuSK myasthenia gravis patient IgG autoantibodies in vitro. In an IgG4 passive transfer MuSK myasthenia model in NOD/SCID mice, MuSK agonists caused accelerated weight loss and no rescue of myasthenic features. The MuSK Ig-like 1 domain agonists unexpectedly caused sudden death in a large proportion of male C57BL/6 mice (but not female or NOD/SCID mice), likely caused by a urologic syndrome. In conclusion, these agonists rescued pathogenic effects in myasthenia models in vitro, but not in vivo. The sudden death in male mice of one of the tested mouse strains revealed an unexpected and unexplained role for MuSK outside skeletal muscle, thereby hampering further (pre-) clinical development of these clones. Future research should investigate whether other Ig-like 1 domain MuSK antibodies, binding different epitopes, do hold a safe therapeutic promise.


Identifying factors affecting the safety of mid-block bicycle lanes considering mixed 2-wheeled traffic flow.
Electric bikes (e-bikes) have been one of the fastest growing trip modes in Southeast Asia over the past 2 decades. The increasing popularity of e-bikes raised some safety concerns regarding urban transport systems. The primary objective of this study was to identify whether and how the generalized linear regression model (GLM) could be used to relate cyclists' safety with various contributing factors when riding in a mid-block bike lane. The types of 2-wheeled vehicles in the study included bicycle-style electric bicycles (BSEBs), scooter-style electric bicycles (SSEBs), and regular bicycles (RBs). Traffic conflict technology was applied as a surrogate measure to evaluate the safety of 2-wheeled vehicles. The safety performance model was developed by adopting a generalized linear regression model for relating the frequency of rear-end conflicts between e-bikes and regular bikes to the operating speeds of BSEBs, SSEBs, and RBs in mid-block bike lanes. The frequency of rear-end conflicts between e-bikes and bikes increased with an increase in the operating speeds of e-bikes and the volume of e-bikes and bikes and decreased with an increase in the width of bike lanes. The large speed difference between e-bikes and bikes increased the frequency of rear-end conflicts between e-bikes and bikes in mid-block bike lanes. A 1% increase in the average operating speed of e-bikes would increase the expected number of rear-end conflicts between e-bikes and bikes by 1.48%. A 1% increase in the speed difference between e-bikes and bikes would increase the expected number of rear-end conflicts between e-bikes/bikes by 0.16%. The conflict frequency in mid-block bike lanes can be modeled using generalized linear regression models. The factors that significantly affected the frequency of rear-end conflicts included the operating speeds of e-bikes, the speed difference between e-bikes and regular bikes, the volume of e-bikes, the volume of bikes, and the width of bike lanes. The safety performance model can help better understand the causes of crash occurrences in mid-block bike lanes.


The consortium of heterogeneous cobalt phthalocyanine catalyst and bicarbonate ion as a novel platform for contaminants elimination based on peroxymonosulfate activation.
The design of catalytic oxidation processes with high efficiency has attracted considerable attention for a long while in environmental catalysis. In this work, a novel oxidation system, CFs-CoPc/PMS, was developed by coupling cellulosic fibers-bonded cobalt phthalocyanine (CFs-CoPc) with peroxymonosulfate (PMS). CFs-CoPc/PMS system could effectively decolorize azo dyes such as Acid Red 1 (AR1) with almost 100% decolorization efficiency in 35 min, suggesting that the CFs-CoPc/PMS system was a highly efficient oxidation process. In addition, bicarbonate ion (HCO3(-)) was further introduced to CFs-CoPc/PMS to construct a combined system, CFs-CoPc/PMS/HCO3(-). Remarkably, this system turned the negative effect of HCO3(-) observed in most reported Co/PMS systems into a positive one, which enhanced the AR1 decolorization with over 2-fold increase of the rate constant. The main factor responsible for the enhancement was high-valent cobalt-oxo intermediates (PcCo(IV)=O), which was presumably generated via the heterolytic cleavage of the PMS OO bond by CoPc-HCO3(-) complex. It is noteworthy that high-valent cobalt-oxo intermediates as the major active species is different from most reported mechanisms in Co/PMS systems, in which hydroxyl and sulfate radicals are recognized as the dominant active species. This study paves an avenue for developing highly efficient catalytic oxidation technology for wastewater remediation.


Synchronous resection of pancreatic serous cystadenocarcinoma and liver metastasis: First reported case and review of literature.
Cystic neoplasms account for approximately 10-20% of all pancreatic cysts and 1% of pancreatic cancers. Serous cystadenomas are considered benign tumors with almost no malignant potential, and thus the management is typically only observation with serial imaging. According to the current World Health Organization classification, cases with distant metastases are defined as serous cystadenocarcinomas. To date, only 17 such cases with concomitant synchronous or metachronous liver metastasis have been described in the literature, and eight of these reports described treatment of secondary liver lesions. This report describes the first case of synchronous resection of pancreatic serous cystadenocarcinoma and liver metastasis in a 56-year-old female patient. The patient is currently well after 30 months of follow-up with no tumor recurrence or new metastatic liver nodules based on magnetic resonance imaging.


The influence of secreted factors and extracellular vesicles in ovarian cancer metastasis.
Ovarian cancer cells mainly metastasise within the peritoneal cavity, the lethal consequence of tumour progression in this cancer type. Classically, changes in tumour cells, such as epithelial to mesenchymal transition, involve the down-regulatinon of E-cadherin, activation of extracellular proteases and integrin-mediated adhesion. However, our current understanding of ovarian tumour progression suggests the implication of both intrinsic and extrinsic factors. It has been proposed that ovarian cancer metastases are a consequence of the crosstalk between cancer cells and the tumour microenvironment by soluble factors and extracellular vesicles. Characterisation of the alterations in both the tumour cells and the surrounding microenvironment has emerged as a new research field to understand ovarian cancer metastasis. In this mini review, we will summarise the most recent findings, focusing our attention on the role of secreted factors and extracellular vesicles in ovarian cancer metastasis.


Imaging strategies for MR of the brain.
MR has emerged as the imaging modality of choice for the brain in patients presenting with seizures, chronic headaches, progressive neurologic deficits, ataxia, vertigo, hearing loss, visual loss, congenital abnormalities, signs of increased intracranial pressure, dementia, suspected multiple sclerosis, and in the vast majority of other elective neurologic problems. CT should currently be considered the primary imaging modality in patients with acute neurologic deficits (stroke), acute onset of severe headaches, and when fine bone detail is required. Acutely injured patients are more readily studied with CT. The vast majority of patients in whom CT is preferred are seen in emergent situations, frequently in hospital emergency rooms. The effects of trauma beyond the acute stage are best evaluated with MR. In the future, MR is likely to become the procedure of choice in even more clinical situations than at present. A summary of currently recommended primary imaging modalities in various clinical situations is provided in Table 1.


Subunit Mobility and the Chaperone Activity of Recombinant alphaB-Crystallin.
The comparison of the chaperone-like activity of native and covalently cross-linked human alphaB-crystallins has confirmed the important role of the subunit mobility in the chaperoning mechanism. Our data clearly demonstrate that the chaperone-like activity of alpha-crystallin is not only a surface phenomenon as was suggested by some researchers.


Lasers in otology.
The author describes the use of lasers in over 2500 tympanomastoid surgical procedures. The advantages of using laser energy in microsurgery, which include fewer complications and the possibility of outpatient treatment, are presented.


The international role of a U.S. medical school in developing health services.
This paper discusses the educational approach taken by the Department of Community Medicine of the Mount Sinai School of Medicine in providing technical assistance in foreign countries. Using a specific project in the Dominican Republic as an example, the paper describes the role and different functions assumed by the department in planning and developing a health care system in the eastern region of that country.


Accurate relaxation parameters for large proteins.
The practical applicability, performance, and robustness of three-way decomposition (TWD) for the extraction of relaxation parameters are demonstrated for a large protein with 370 residues, the maltose binding protein. An ordinary set of seven relaxation-modulated (15)N HSQC spectra, recorded at another site, is systematically analyzed. For all 341 assigned backbone amide groups, including 21 pairs and one group of three overlapped peaks, T1 decay values were determined. On isolated peaks, TWD extracts T1 values with systematically lower error bounds compared to conventional tools, although for these simple cases the improvements remain limited. However, in the presence of spectral artifacts, the decrease in errors can become significant, demonstrating the higher robustness of TWD. For about half of the peaks in overlapped regions, the decomposition allowed separation of the signals, yielding significantly different T1 values between overlapping signals. For the rest, similarity of the decay times for the two or three overlapping signals could be confirmed within usually low error bounds. The use of TWD thus leads to a significant increase in the number of accessible relaxation probes in large proteins. With a newly implemented graphical user interface, the application of TWD requires merely a peak list, and thus no additional effort compared to conventional approaches is needed.


In vivo and in vitro studies on the protective effects of 9 beta-methylcarbacyclin, a stable prostacyclin analogue, in galactosamine-induced hepatocellular damage.
Early treatment with prostacyclin (PGI2) was previously shown to reduce mortality in the galactosamine model of acute hepatic failure in the rat, with a decreased release of hepatic cytosolic and lysosomal enzymes. In this study, 9 beta-methylcarbacyclin, a chemically stable analogue of PGI2, had similar protective effects to PGI2 in vivo but required approximately 100-fold higher concentrations (2 mg kg-1). These effects were only obtained when 9 beta-methylcarbacyclin was given early (0 to 6 h post-galactosamine) but not later (24 to 30 h). In isolated rat hepatocytes in vitro galactosamine up to a concentration of 100 mM caused a dose-dependent inhibition of L-[U-14C] leucine incorporation into protein and increase in the release of the cytoplasmic enzyme lactate dehydrogenase. Studies on the short-term effects of 9 beta-methylcarbacyclin using isolated hepatocytes treated with galactosamine (5 mM) showed that this agent, at an optimum concentration of 30 ng ml-1, was capable of significantly reducing the inhibition of protein synthesis caused by galactosamine but did not alter the rate of release of lactate dehydrogenase. The results demonstrate that the protective effects of 9 beta-methylcarbacyclin occur early in the time course of galactosamine action, and include direct effects on the hepatocytes.


The interaction between spatial variation in habitat heterogeneity and dispersal on biodiversity in a zooplankton metacommunity.
It is hypothesized that biodiversity is maintained by interactions at local and regional spatial scales. Many sustainability plans and management practices reflect the need to conserve biodiversity, yet once these plans are implemented, the ecological consequences are not well understood. By learning how management practices affect local environmental factors and dispersal in a region, ecologists and natural resource managers can better understand the implications of management choices. We investigated the interaction of local and regional scale processes in the built environment, where human-impacts are known to influence both. Our goal was to determine how the interaction between spatial variation in habitat heterogeneity in algal management of urban ponds and dispersal shape biodiversity at local and regional spatial scales. A twelve-week mesocosm study was conducted where pond management and dispersal were manipulated to determine how spatial variation in habitat and dispersal from various source pools influence zooplankton metacommunities in urban stormwater ponds. We hypothesized that dispersal from managed or unmanaged source pools will lead to community divergence and local management practices will act as an environmental filter, both reducing beta diversity between managed ponds and driving compositional divergence. Our results suggest that zooplankton dispersal from managed or unmanaged source pools was important to explaining divergence in community composition. Furthermore, local management of algae marginally reduced compositional turnover of zooplankton among ponds but did not lead to significant divergence in community composition. Management practices may act as strong environmental filters by reducing beta diversity between ponds. As hypothesized, source pool constraints led to compositional divergence and local management practices resulted in reduced compositional turnover between ponds. The results of this study suggest that sustainability and management plans may have complex effects on biodiversity both within and across spatial scales.


A functionally integrated thermoplastic microdevice for one-step solid-phase-based nucleic acid purification and isothermal amplification for facile detection of foodborne pathogen.
In this study, we fabricate a functionally integrated monolithic thermoplastic microdevice for continuous operation of nucleic acid purification and amplification using polycarbonate (PC). A solid-phase-based purification and subsequent isothermal amplification, specifically, thermal helicase-dependent amplification (tHDA), was performed in a single operation in a valve-free manner. PC microdevice was assembled using modified thermal bonding process under relatively low temperature and pressure condition, realized by surface chemical modification of PC into hydrophilic property using amine-bearing polyethyleneimine (PEI). After the device sealing, only the microchannel parts were selectively modified to be hydrophobic, using epoxy-terminated poly(dimethylsiloxane) (PDMS) (epoxy-PDMS) on amine-coated surface for stepwise introduction of multiple reagents in a valve-free manner. Using the integrated PC microdevice, nucleic acids from genetically modified Escherichia coli (E. coli) O157:H7 were captured inside a chamber bearing amine functionality, by electrostatic interaction, and were subsequently amplified isothermally in the same chamber. Purified DNA captured inside the microchamber was detected directly inside the chamber by fluorescence measurement, and a 92-bp long EaeA gene, inserted into the E. coli O157:H7, was successfully amplified using the integrated PC microdevice in less than 90 min, paving the way for facile identification of foodborne pathogens with simple operation and reduced peripheral operations applicable for portable healthcare purposes. Biotechnol. Bioeng. 2016;113: 2614-2623. © 2016 Wiley Periodicals, Inc.


Evaluation of iron metabolism in hospitalized COVID-19 patients.
Iron metabolism dysregulation may play a role in organ failure observed in Coronavirus disease 2019 (COVID-19). This study aimed to explore the whole iron metabolism in hospitalized COVID-19 patients and evaluate the impact of tocilizumab. We performed an observational multicentric cohort study, including patients with PCR-provenCOVID-19 from the intensive care unit (ICU) (n = 66) and medical ward (n = 38). We measured serum interleukin-6 (IL-6), ferritin, glycosylated ferritin (GF), transferrin, iron, and hepcidin. The primary outcome was death. Among the 104 patients, we observed decreased median GF percentage (35 %; IQ 23-51.5), low iron concentration (7.5 μmol/L; IQ 4-14), normal but low transferrin saturation (TSAT; 21%; IQ 11-33) and increased median hepcidin concentration (58.7 ng/mL; IQ 20.1-92.1). IL-6, ferritin, and GF were independently and significantly associated with death (p = 0.026, p = 0.023, and p = 0.009, respectively). Surprisingly, we observed a decorrelation between hepcidin and IL-6 concentrations in some patients. These findings were amplified in tocilizumab-treated patients. Iron metabolism is profoundly modified in COVID-19. The pattern we observed presents differences with a typical inflammation profile. We observed uncoupled IL-6/hepcidin levels in some patients. The benefit of additive iron chelation therapy should be questionable in this setting.


Adoptive transfer of metabolically reprogrammed macrophages for atherosclerosis treatment in diabetic ApoE -/- mice.
Atherosclerosis is characterized by inflammation in the arterial wall, which is known to be exacerbated by diabetes. Therapeutic repression of inflammation is a promising strategy for treating atherosclerosis. In this study, we showed that diabetes aggravated atherosclerosis in apolipoproteinE knockout (ApoE -/-) mice, in which increased expression of long-chain acyl-CoA synthetase 1 (Acsl1) in macrophages played an important role. Knockdown of Acsl1 in macrophages (Mφ shAcsl1 ) reprogrammed macrophages to an anti-inflammatory phenotype, especially under hyperglycemic conditions. Injection of Mφ shAcsl1 reprogrammed macrophages into streptozotocin (STZ)-induced diabetic ApoE -/- mice (ApoE -/-+ STZ) alleviated inflammation locally in the plaque, liver and spleen. Consistent with the reduction in inflammation, plaques became smaller and more stable after the adoptive transfer of reprogrammed macrophages. Taken together, our findings indicate that increased Acsl1 expression in macrophages play a key role in aggravated atherosclerosis of diabetic mice, possibly by promoting inflammation. Adoptive transfer of Acsl1 silenced macrophages may serve as a potential therapeutic strategy for atherosclerosis.