Bilateral optic nerve edema presenting as initial manifestation of thyroid eye disease.
A 48-year-old smoker with a history of hyperthyroidism treated 10 years prior to presentation with radioactive iodine ablation of the thyroid gland presented to his ophthalmologist with a 2-week history of transient loss of vision in the right eye occurring for 1 to 2 hours each morning. He denied ocular pain, diplopia or change in the prominence of one or both eyes. Examination revealed 2 mm of relative proptosis on the right, bilateral temporal flare and lower lid retraction. There was minimal upper lid retraction and no evidence of lid lag. Ocular motility was full. Dilated fundoscopic examination revealed bilateral optic nerve edema, right more than left. CT of the orbit demonstrated enlargement of the extraocular muscles bilaterally with marked enlargement of the right medial rectus and left inferior rectus muscles resulting in crowding at the orbital apex bilaterally. Laboratory testing revealed the patient to be hyperthyroid. The patient was treated with high dose oral steroids followed by orbital radiation. Hyperthyroidism was managed by the patient's primary care physician. Visual symptoms rapidly improved with oral steroids and orbital radiation. Optic nerve edema completely resolved. Repeat CT imaging demonstrated a reduction in the enlargement of the extraocular muscles with relief of bilateral optic nerve compression.


On the relationship between autistic traits and executive functioning in a non-clinical Dutch student population.
We examined the association between autistic traits and different aspects of executive functioning (EF), using non-clinical Social Science and Science students as participants. Autistic traits, and associated personality traits, were measured using the Autism Quotient (AQ) and the Temperament and Character Inventory (TCI), respectively. EF was examined by means of a random number generation test and a phonemic fluency test. Using appropriate dependent measures, the following EF components were examined: 1) inhibition of prepotent responding, 2) simple output inhibition, 3) working memory monitoring and updating, and 4) switching. No significant relationship was found between the AQ and each of the four components of EF. However, two TCI subscales were reliably correlated with either the working memory or the shifting component. These results were discussed in view of the concept of an autism spectrum with respect to executive abilities.


Silver impregnation of the prefrontal cortices in the brains with long postmortem delay.
Silver impregnation was performed histologically on the prefrontal parts of brains, which had long postmortem delay of one month while under 4 degrees C refrigeration. The brains were from individuals from 60+- to 80+-years old. It was evident from these specimens that, as a whole, the outer layers of the brains degenerated first while the inner layers remained to be silver stainable and had near normal morphology after silver impregnation, even in the oldest specimens. Comparatively, the postmortem degeneration was worse in the outer cortical layers of the older individual when compared with the younger.


Discrete and infinite cage-like frameworks with inclusion of anionic and neutral species and with interpenetration phenomena.
Complex [Ag(tpba)N(3)] (1) was obtained by reaction of novel tripodal ligand N,N',N"-tris(pyrid-3-ylmethyl)-1,3,5-benzenetricarboxamide (TPBA) with [Ag(NH(3))(2)]N(3). While the reactions between 1,3,5-tris(imidazol-1-ylmethyl)-2,4,6-trimethylbenzene (TITMB) and silver(I) salts with different anions and solvent systems give six complexes: [Ag(3)(titmb)(2)](N(3))(3).CH(3)OH.4 H(2)O (2), [Ag(3)(titmb)(2)](CF(3)SO(3))(2)(OH).5 H(2)O (3), [Ag(3)(titmb)(2)][Ag(NO(3))(3)]NO(3).H(2)O (4), [Ag(3)(titmb)(2)(py)](NO(3))(3).H(2)O (py=pyridine) (5), [Ag(3)(titmb)(2)(py)](ClO(4))(3) (6), and [Ag(3)(titmb)(2)](ClO(4))(3).CHCl(3) (7). The structures of these complexes were determined by X-ray crystallography. The results of structural analysis of complexes 1 and 2, with the same azide anion but different ligands, revealed that 1 is a twofold interpenetrated 3D framework with interlocked cage-like moieties, while 2 is a M(3)L(2) type cage-like complex with a methanol molecule inside the cage. Entirely different structure and topology between 1 and 2 indicates that the nature of organic ligands affected the structures of assemblies greatly. While in the cases of complexes 2-7 with flexible tripodal ligand TITMB, they are all discrete M(3)L(2) type cages. The results indicate that the framework of these complexes is predominated by the nature of the organic ligand and geometric need of the metal ions, but not influenced greatly by the anions and solvents. It is interesting that there is a divalent anion [Ag(NO(3))(3)](2-) inside the cage 4 and an anion of ClO(4)(-) or NO(3)(-) spontaneously encapsulated within the cage of complexes 5, 6 and 7.


Growth suppression of human cancer cells by polyphenolics from sweetpotato (Ipomoea batatas L.) leaves.
Sweetpotato leaves (Ipomoea batatas L.) contain a high content of polyphenolics that consist of caffeic acid, chlorogenic acid, 3,4-di-O-caffeoylquinic acid, 3,5-di-O-caffeoylquinic acid, 4,5-di-O-caffeoylquinic acid, and 3,4,5-tri-O-caffeoylquinic acid. We investigated the suppression of the proliferation of selected human cancer cells by phenolic compounds isolated from sweetpotato leaf. The human cancer cells used in this research included a stomach cancer (Kato III), a colon cancer (DLD-1), and a promyelocytic leukemia cell (HL-60). Caffeic acid and di- and tricaffeoylquinic acids dose-dependently depressed cancer cell proliferation, and the difference in sensitivity between caffeoylquinic acid derivatives and each kind of cancer cell was observed. Specifically, 3,4,5-tri-O-caffeoylquinic acid effectively depressed the growth of three kinds of cancer cells, and caffeic acid had an exceptionally higher effect against HL-60 cells than other di- and tricaffeoylquinic acids. In attempting to clarify the mechanism of growth suppression with the addition of the apoptotic inhibitor N-ethylmaleimide, we observed that the nuclear granulation in 3,4,5-tri-O-caffeoylquinic acid-treated HL-60 cells suggested apoptosis induction. This effect was confirmed by DNA fragmentation, an increase of caspase-3 activity, and expression of c-Jun. Growth suppression of HL-60 cells by 3,4,5-tri-O-caffeoylquinic acid was determined to be the result of apoptotic death of the cells. These results indicate that 3,4,5-tri-O-caffeoylquinic acid may have potential for cancer prevention.


Pendrin expression in nodular and non-nodular thyroid tissues.
Different mechanisms for the expression of pendrin which is an apical iodide transporter have been reported in nodular thyroid tissues compared to normal thyroid. The aim of the present study was to determine the alterations of pendrin expression in nodular and surrounding non-nodular thyroid tissues and clarify the role of pendrin in the functional behaviour of nodular lesions. Twenty-six nodular and paired non-nodular normal thyroid tissues were collected at the same centre. Patients were divided into two groups based on the function of the dominant thyroid nodule; hot nodules (n = 18) and cold nodules (n = 8). mRNA levels of pendrin were evaluated by quantitative RT-PCR. Pendrin protein expression was determined by immunohistochemical analysis. Results of dominant nodules were compared to non-nodular thyroid tissue of the same patient. No statistically significant difference was found with respect to qualitative and quantitative measurements of pendrin expression between hot and cold nodules. However, percent immunohistochemical staining of pendrin was significantly higher in both hot and cold nodules compared to non-nodular thyroid tissue of the same patients. RT-PCR revealed comparable mRNA levels of pendrin gene between hot nodules and corresponding normal thyroid tissues. However, in cold nodules, significantly decreased mRNA levels of pendrin were observed compared to normal thyroid tissue. mRNA levels of pendrin showed significant positive correlation with TSH in corresponding non-nodular thyroid tissues. The present study demonstrates that expression of pendrin could not be influenced by TSH in thyroid nodules and expression level of pendrin seems not to have an effect on nodule function.


Atomic imaging and spectroscopy of low-dimensional materials with interrupted periodicities.
Identification of individual atoms and examination of their electronic properties in materials are the ultimate goal of all microscopy-based analytical techniques. Here, we demonstrate successful single-atom imaging and spectroscopy in low-dimensional materials using (scanning) transmission electron microscopy together with electron energy-loss spectroscopy (EELS). Edges and point defects in single-layered materials such as graphene, hexagonal boron nitride and WS(2) nanoribbons are investigated by annular dark-field imaging and EELS fine-structure analysis. Individual dopant atoms are unambiguously identified in nano-peapods. It is noteworthy that irradiation damage and specimen contamination even at the single-atom level are crucial issues in these experiments.


Role of the Forkhead Transcription Factors Fd4 and Fd5 During Drosophila Leg Development.
Appendage development requires the coordinated function of signaling pathways and transcription factors to pattern the leg along the three main axes: the antero-posterior (AP), proximo-distal (PD), and dorso-ventral (DV). The Drosophila leg DV axis is organized by two morphogens, Decapentaplegic (Dpp), and Wingless (Wg), which direct dorsal and ventral cell fates, respectively. However, how these signals regulate the differential expression of its target genes is mostly unknown. In this work, we found that two members of the Drosophila forkhead family of transcription factors, Fd4 and Fd5 (also known as fd96Ca and fd96Cb), are identically expressed in the ventro-lateral domain of the leg imaginal disc in response to Dpp signaling. Here, we analyze the expression regulation and function of these genes during leg development. We have generated specific mutant alleles for each gene and a double fd4/fd5 mutant chromosome to study their function during development. We highlight the redundant role of the fd4/fd5 genes during the formation of the sex comb, a male specific structure that appears in the ventro-lateral domain of the prothoracic leg.


IgG4-related disease in Singapore: a description of two cases and review of the literature.
We describe a 42-year-old man who presented with painless obstructive jaundice, organomegaly and lymphadenopathy. Biopsy of the ampulla of Vater revealed the presence of increased populations of plasma cells which stained positively for immunoglobulin G4. He was treated with prednisolone and demonstrated significant clinical improvement 1 month later. A further case is described and a review of the literature is also provided.


Minimally Invasive Versus Transcatheter Aortic Valve Replacement: An Updated Meta-Analysis and Systematic Review.
Transcatheter aortic valve replacement (TAVR) has arisen as a viable alternative to surgery. Similarly, minimally invasive surgical aortic valve replacement (mini-SAVR), such as ministernotomy and minithoracotomy, have also gained interest. We conducted a pairwise meta-analysis to further investigate the efficacy of TAVR versus mini-SAVR. Medical databases were comprehensively searched for studies comparing TAVR with a mini-SAVR modality, defined as minimally invasive aortic surgery, ministernotomy, minithoracotomy, or rapid-deployment or sutureless SAVR. Random-effects meta-analysis was conducted using the generic inverse variance method. Primary outcomes included 30-day mortality, midterm mortality, 30-day stroke, acute kidney injury (AKI), paravalvular leak (PVL), new permanent pacemaker (PPM), new-onset atrial fibrillation, and postintervention mean and peak valve pressure gradients and were pooled as risk ratio (RR), mean difference (MD), or hazard ratio (HR) with 95% confidence interval (CI). A total of 5,071 patients (2,505 mini-SAVR vs 2,566 TAVR) from 12 studies were pooled. Compared with TAVR, mini-SAVR showed significantly lower rates of both 30-day (RR = 0.63, 95% CI: 0.42 to 0.96, P = 0.03) and midterm mortality at 4 years of follow-up (HR = 0.76, 95% CI: 0.67 to 0.87, P < 0.001). Furthermore, mini-SAVR was protective against 30-day PVL (RR = 0.07, 95% CI: 0.04 to 0.13, P < 0.001) and new PPM (RR = 0.25, 95% CI: 0.11 to 0.57, P < 0.001). Conversely, TAVR was protective against 30-day AKI (RR = 1.67, 95% CI: 1.20 to 2.32, P = 0.002) and postinterventional mean gradients (MD = 1.65, 95% CI: 0.25 to 3.05, P = 0.02). No difference was observed for 30-day stroke (RR = 0.84, 95% CI: 0.56 to 1.24, P = 0.38), new-onset atrial fibrillation (RR = 1.79, 95% CI: 0.93 to 3.44, P = 0.08), or postinterventional peak gradients (MD = 3.24, 95% CI: -1.10 to 7.59, P = 0.14). Compared with TAVR, mini-SAVR was protective against 30-day and midterm mortality, 30-day PVL, and new permanent pacemaker, while TAVR patients had lower 30-day AKI. Future randomized trials comparing the efficacy of mini-SAVR approaches with TAVR are needed.


The metabolism of berberine and its contribution to the pharmacological effects.
Berberine, a bioactive alkaloid isolated from several herbal substances, possesses multiple pharmacological effects, including antimicrobial, antidiabetic, anticancer activities. Meanwhile, berberine undergoes extensive metabolism after oral administration which results in its extremely low plasma exposure. Therefore, it is believed that the metabolites of berberine also contribute a lot to its pharmacological effects. Along these lines, this review covers the metabolism studies of berberine in terms of its metabolic pathways and metabolic organs based on the identified metabolites, and it also covers the pharmacological activities of its active metabolites. In brief, the predominant metabolic pathways of berberine are demethylation, demethylenation, reduction, hydroxylation and subsequent conjugation in vivo. Active metabolites such as columbamine, berberrubine and demethyleneberberine also exhibit similar pharmacological effects by comparison with berberine, such as antioxidant, anti-inflammatory, antitumor, antimicrobial, hepatoprotective, neuroprotective, hypolipidemic and hypoglycemic effects. Overall, berberine together with its metabolites formed the material basis of berberine in vivo.


The Effect of Intraoperative Transesophageal Echocardiography Probe Placement on the Endotracheal Tube Cuff Pressure in Adult Patients Undergoing On-Pump Cardiac Surgery.
The study was directed toward documentation of the effect of transesophageal echocardiography (TEE) probe insertion on the endotracheal tube cuff pressure (CP) in adult patients undergoing on-pump coronary bypass surgery. The primary objective of this study was to assess whether CP reaches supranormal pressures during the different stages of intraoperative TEE examination. The secondary objective was to observe the effect of TEE probe placement on the ventilation parameters. A prospective observational study. At a tertiary care cardiac center. Thirty-four cardiac surgical patients older than 18 years of age who required intraoperative TEE examination. TEE probe insertion. Following the induction of general anesthesia and tracheal intubation, a TEE probe was introduced. The endotracheal tube CP was recorded at 5 time zones: Before TEE probe insertion, during the insertion of the probe, during probe manipulation, probe in the transgastric position, and during removal of the probe. A nonparametric test was used for comparing intracuff pressure between pairs of time zones. There was a statistically significant difference in CP values between the baseline and those during different time zones (chi-square test = 134.77, degrees of freedom = 4, p = 0.001). There was a statistically significant difference in the peak pressure between different time points compared to baseline (p = 0.0001). TEE probe placement in patients with tracheal intubation may be associated with a significant increase in CP well above the baseline pressure. With the possibility of the mean arterial pressures during cardiopulmonary bypass being substantially lower than expected, the findings of the current study raised the concern of predisposing the tracheal mucosa to hypoperfusion, with subsequent temporary or permanent tracheal damage. Hence, at least a baseline estimation of the endotracheal tube CP at the time of tracheal intubation, with the help of a pressure gauge in the operating room, may be considered as a safe practice.


[Treatment with transcutaneous electric stimulation in chronic pain. Long-term study of 100 cases].
The Authors report the experience about 100 cases of patients affected by chronical pain syndromes where the medical treatment has been uneffective. After a follow-up of 2 years about, only in 14% of the patients treated by S.E.N.T., the benefit has been clear and prolonged.


[Research on the relationship between atmospheric inhalable particulate matter and cardiovascular diseases burden in Tianjin].
Objective: To evaluate the association between atmospheric inhalable particulate matter (PM(10)) concentration and cardiovascular diseases burden in Tianjin. Methods: The data on daily mean concentrations of main pollutants (PM(10), nitrogen dioxide(NO(2)) and sulfur dioxide(SO(2))), meteorological factors (temperature and relative humidity) and population death monitoring data in Tianjin, from January 1, 2001 to December 31, 2010, were collected and analyzed in this study. The death counts and years of life lost were simultaneously used as the indicators of disease burden. The generalized additive model was used to assess the associations between PM(10) and daily death counts and years of life lost due to cardiovascular system diseases in Tianjin by adjusting the confounding factors such as long-term trend, seasons, meteorological factors and other factors related to the long-term variability. Results: The daily average concentration of PM(10) was 117.6 μg/m³ in Tianjin during 2001 to 2011. The daily average number of deaths of cardiovascular system diseases, cerebrovascular diseases and ischemic heart diseases in Tianjin were 38.4, 14.8 and 17.2 people respectively, and the daily average years of life lost were 776.8, 306.5 and 326.1 person years respectively. The effects of PM(10) on the daily death counts of the three diseases categories were statistically significant (all P<0.01) in Tianjin and the maximum effect occurs at the moment when PM(1)0 was at moving average concentration of today and lagged 1-day (Lag01). The effects of decreasing order were ischemic heart diseases, cardiovascular system diseases and cerebrovascular diseases, excess risks were 0.53% (95% CI 0.35%-0.71%), 0.40% (95%CI 0.28%-0.53%) and 0.38% (95%CI 0.19%-0.56%). The effects of atmospheric PM(10) on the years of life lost of the three diseases were also statistically significant on the different lag days (all P<0.01) in Tianjin and the maximum effect of PM(10) appeared in Lag01. The effects from the largest to the lowest were 2.86 (95%CI 1.79-3.93) person years for cardiovascular system diseases, 1.59 (95%CI 0.95-2.23) person years for ischemic heart diseases and 1.07 (95%CI 0.43-1.71) person years for cerebrovascular diseases, respectively. In multi-pollutant models, after controlling SO(2), the effect of PM(10) on the daily life loss of above 3 kinds of diseases was higher than that of single pollutant model. In contrast, after controlling SO(2) or SO(2) with NO(2), the effect was lower. After controlling NO(2), the effect of PM(10) on the daily life loss of cerebrovascular disease was no longer statistically significant (P>0.05). Conclusions: Exposure to atmospheric PM(10) can significantly increase the cardiovascular diseases burden in Tianjin, especially for ischemic heart diseases. These results suggested that particular attention should be paid to reduce the exposure to atmospheric inhalable particulate matter for patients with ischemic heart diseases.


Histamine skin test reactivity following single and multiple doses of azelastine nasal spray in patients with seasonal allergic rhinitis.
To determine whether azelastine nasal spray suppresses the dermal response to epicutaneous histamine in allergic patients and the duration of suppression after azelastine use is discontinued. Seventy-eight patients with seasonal allergic rhinitis were entered into this randomized, double-blind, parallel-group, placebo-controlled study. Patients received either azelastine nasal spray (2 sprays per nostril twice daily) or placebo nasal spray for 14 days. Skin tests were performed 5 hours after the first dose of study drugs to determine the effect of a single dose of azelastine nasal spray on the wheal-and-flare response to histamine. At the end of the 14-day treatment period, skin tests were performed 5 hours after the last dose of study drugs and at 24-hour intervals thereafter, until each patient's wheal-and-flare response to histamine (1.0 and 5.0 mg/mL) returned to within 20% of baseline values. A single dose of azelastine nasal spray did not significantly alter the wheal-and-flare response to histamine. The wheal response was within 20% of the baseline value in 82% and 88% (1.0 and 5.0 mg/mL of histamine, respectively) of the patients 5 hours after discontinuing 14 days of treatment with azelastine nasal spray. Wheal responses were within 20% of baseline values 48 hours after treatment was discontinued, whereas flare responses returned to within 20% of baseline within 48 hours in 92% of the patients. Azelastine nasal spray should be discontinued for at least 48 hours before beginning allergy skin test procedures.


Transcatheter closure of an unligated vertical vein with an Amplatzer Vascular Plug-II device.
: The usual surgical practice after repair of a Total Anomalous Pulmonary Venous Connection (TAPVC) is to ligate the vertical vein (VV). Many surgeons find it expedient to leave the VV unligated to reduce pulmonary arterial pressure, decrease perioperative pulmonary hypertensive crisis, provide better hemodynamics postoperatively (1), and enable the adaptation of cardiac chambers to a new workload. Afterwards, the unligated VV may cause significant left-to-right shunt, likewise an atrial septal defect, mandating later surgical ligation or device closure (2). This report details transcatheter occlusion of a patent VV using a device Amplatzer Vascular Plug II, after TAPVC repair in early infancy. The transcatheter occlusion of an unligated VV after repair of supracardiac TAPVC represents an effective alternative to surgical redo. The device Amplatzer Vascular Plug II achieves great results.


Parenchymal alterations in cirrhotic livers in patients with hepatopulmonary syndrome or portopulmonary hypertension.
Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPH) are distinct pulmonary vascular complications of cirrhosis. Little is known about possible associated hepatic histopathological features. Explanted livers from patients clinically diagnosed with HPS (n = 8) or PPH (n = 7) and cirrhotic explants from controls (n = 30) without HPS or PPH were evaluated with trichrome histochemistry, anti-glutamine synthetase (anti-GS), and anti-CD34 immunohistochemistry (IHC). Trichrome stains were characterized by cirrhotic nodules (CNs) of various sizes, including incomplete septal cirrhosis (ISC). ISC was overrepresented in the HPS (4/8 or 50%) and PPH livers (3/7 or 43%); in addition, neither group had micronodular cirrhosis. The control explants showed the entire spectrum of nodules: micronodular, macronodular, mixed CNs, and ISC (P = 0.04). The variability of cirrhosis severity was shown with the Laennec grading system (0-6). The cirrhosis of the majority of the HPS (6/8) and PPH livers (6/7) was scored as mild, whereas the control explants were more evenly distributed across the mild (14/30) and moderate/severe grades (16/30). GS positivity was retained in a perivenular location as the dominant pattern in each explant group. CD34 staining detected capillarized sinusoids of CNs as well as vascular channels within septa, but no significant differences were found between the groups. None of the observed light microscopy or histochemistry and IHC patterns showed a correlation with the underlying liver disease. Although our results demonstrate variable architectural and vascular remodeling within and between explant livers regardless of the presence or types of pulmonary complications, there were differences in explants with HPS or PPH versus controls that correlated with less severe cirrhosis.


[Effect of tumor vascular invasion upon cardio-pulmonary exercise functions in patients with lung cancer].
To investigate the correlation between the tumor vascular invasion and the change of cardio-pulmonary exercise function in patients with lung cancer. The cardio-pulmonary exercise test was performed in 405 patients with lung cancer (293 with vascular invasion and 112 without). The peak load indices examined included maximal work power (measured value/predicted value, W%), maximal oxygen uptake per weight (VO(2)/kg), anaerobic threshold (AT), maximal oxygen pulse (measured value/predicted value, VO(2)/HR%), maximal minute ventilation (V(E)), maximal breath reserve (BR), maximal breath frequency (BF) and maximal tidal volume during expiration (VTex). (1) W%, VO(2)/kg, AT, VO(2)/HR% of patients with vascular invasion [(73 +/- 18)%, (17 +/- 5) ml * min(-1) * kg(-1), (51 +/- 14)%, (79 +/- 18)% respectively] decreased than those without vascular invasion [(86 +/- 20)%, (19 +/- 5) ml * min(-1) * kg(-1), (55 +/- 14)%, (88 +/- 20)% respectively, all P < 0.01) while BF increased [(32.1 +/- 6.1)/min vs (30.6 +/- 5.1)/min, P < 0.05). (2) The patients were divided according to TNM stage, number, kind of tumor vascular invasion and its relationship with tumor, W%, VO(2)/HR% decreased in the groups of 1-, 2- and >or= 3-vessel invasion versus the control group (P < 0.01), AT decreased in the groups of 1- and >or= 3-vessel invasion versus the control group (P < 0.05, P < 0.01), VO(2)/kg decreased in the groups of 2- and >or= 3-vessel invasion versus the control group (P < 0.05, P < 0.01), VO(2)/kg decreased in the group of >or= 3-vessel invasion versus 1- and 2-vessel invasion (P < 0.05 or P < 0.01), VO(2)/HR% decreased in the group of >or= 3-vessel invasion versus 1-vessel invasion (P < 0.01), VTex decreased in the group of >or= 3-vessel invasion versus the control group and 1-vessel invasion (P < 0.05). There was correlation between VO(2)/HR% and the number of tumor invaded vessels (r = 0.220, P < 0.01). The amount of oxygen uptake, exercise ability and cardiac function during exercise decrease in patients of lung cancer with tumor vascular invasion. The main reason is the number of the invaded vessels.


Sucrose rescues seedling establishment but not germination of Arabidopsis mutants disrupted in peroxisomal fatty acid catabolism.
The Arabidopsis acyl-CoA oxidase (ACX) family comprises isozymes with distinct fatty acid chain-length specificities that together catalyse the first step of peroxisomal fatty acid beta-oxidation. We have isolated and characterized T-DNA insertion mutants in the medium to long-chain (ACX1) and long-chain (ACX2) acyl-CoA oxidases, and show that the corresponding endogenous activities are decreased in the mutants. Lipid catabolism during germination and early post-germinative growth was unaltered in the acx1-1 mutant, but slightly delayed in the acx2-1 mutant, with 3-day-old acx2-1 seedlings accumulating long-chain acyl-CoAs. In acx1-1 and acx2-1, seedling growth and establishment in the absence of an exogenous supply of sucrose was unaffected. Seedlings of the double mutant acx1-1 acx2-1 were unable to catabolize seed storage lipid, and accumulated long-chain acyl-CoAs. The acx1-1 acx2-1 seedlings were also unable to establish photosynthetic competency in the absence of an exogenous carbon supply, a phenotype that is shared with a number of other Arabidopsis mutants disrupted in storage lipid breakdown. Germination frequency of the double mutant was significantly reduced compared with wild-type seeds. This was unaffected by the addition of exogenous sucrose, but was improved by dormancy-breaking treatments such as cold stratification and after-ripening. We show that the acx1-1, acx2-1 and acx1-2 acx2-1 double mutants and the ketoacyl-CoA thiolase-2 (kat2) mutant exhibit a sucrose-independent germination phenotype comparable with that reported for comatose (cts-2), a mutant in a peroxisomal ABC transporter which exhibits enhanced dormancy. This demonstrates an additional role beyond that of carbon provision for the beta-oxidation pathway during germination or in dormant seeds.


The hidden costs of caring: what managers need to know.
Vicarious trauma, compassion fatigue, and secondary traumatic stress all have negative costs associated with them that managers of health care agencies need to know about. This article describes the causes and effects of vicarious trauma, compassion fatigue, and secondary traumatic stress on frontline staff. It also examines the negative impact on the functioning of an organization and suggests some intervention strategies that leadership might utilize to mitigate these negative factors.


Abnormal behaviour of allenylsulfones under Lu's reaction conditions: synthesis of enantiopure polyfunctionalised cyclopentenes.
Formal [3+2] cycloadditions of 5-alkoxyfuran-2(5H)-ones 1 and 2 with allenylsulfones 3-5, promoted by different nucleophiles, afford 3-alkoxy-5-arylsulfonyl-3,3 a,6,6 a-tetrahydro-1H-cyclopenta[c]furan-1-ones in good yields with complete control of both regio- and pi-facial selectivity. The incorporation of a sulfinyl group on the furanone ring enhances the reactivity of the furanones and allows the synthesis of optically pure, bicyclic adducts in good yields. Allenylsulfones evolve through a different mechanism to that proposed for allenoates (Lu's reaction) and afford bicyclic adducts in which the sulfonyl group is joined to C-5. This has advantages on the stereochemical control of further reactions leading to enantiomerically pure polyfunctionalised cyclopentenes and cyclopentanes.


The spectral sensitivity of the lens eyes of a box jellyfish, Tripedalia cystophora (Conant).
Box jellyfish, or cubomedusae (class Cubozoa), are unique among the Cnidaria in possessing lens eyes similar in morphology to those of vertebrates and cephalopods. Although these eyes were described over 100 years ago, there has been no work done on their electrophysiological responses to light. We used an electroretinogram (ERG) technique to measure spectral sensitivity of the lens eyes of the Caribbean species Tripedalia cystophora. The cubomedusae have two kinds of lens eyes, the lower and upper lens eyes. We found that both lens eye types have similar spectral sensitivities, which likely result from the presence of a single receptor type containing a single opsin. The peak sensitivity is to blue-green light. Visual pigment template fits indicate a vitamin A-1 based opsin with peak sensitivity near 500 nm for both eye types.


Guidelines to Statistical Analysis of Microbial Composition Data Inferred from Metagenomic Sequencing.
Metagenomics, the application of high-throughput DNA sequencing for surveys of environmental samples, has revolutionized our view on the taxonomic and genetic composition of complex microbial communities. An enormous richness of microbiota keeps unfolding in the context of various fields ranging from biomedicine and food industry to geology. Primary analysis of metagenomic reads allows to infer semi-quantitative data describing the community structure. However, such compositional data possess statistical specific properties that are important to be considered during preprocessing, hypothesis testing and interpreting the results of statistical tests. Failure to account for these specifics may lead to essentially wrong conclusions as a result of the survey. Here we present a researcher introduced to the field of metagenomics with the basic properties of microbial compositional data including statistical power and proposed distribution models, perform a review of the publicly available software tools developed specifically for such data and outline the recommendations for the application of the methods.


Cystic pancreatic neuroendocrine tumors: is preoperative diagnosis possible?
Pancreatic neuroendocrine tumors rarely undergo cystic degeneration leading to a radiologic appearance, which is often interpreted as a pancreatic mucinous cystadenoma or pseudocyst. We reviewed our experience with 38 neuroendocrine tumors, four of which were cystic, and 24 other cystic pancreatic tumors (mucinous cystadenoma [n = 5], cystadenocarcinoma [n = 6], serous cystadenoma [n = 3], solid/cystic papillary neoplasm [n = 3], intraductal papillary mucinous tumor [n = 6], and mucinous adenocarcinoma [n = 1]) managed operatively between 1990 and 2000. This review was undertaken to identify clinical and pathologic features useful for preoperative diagnosis of cystic neuroendocrine tumors. Two of the four patients with cystic neuroendocrine tumors presented with abdominal pain, one patient was asymptomatic, and one patient had hypoglycemia. Three of the four cystic neuroendocrine tumors were identified by CT scan, and none were biopsied preoperatively. Preoperative diagnoses included mucinous cystadenoma in two patients (n = 2), pancreatic cystic neoplasm in one patient, (n = 1) and insulinoma in one patient (n = 1). All four cystic neuroendocrine tumors were benign and were completely resected (distal pancreatectomy [n = 2], enucleation [n = 2]). Cystic neuroendocrine tumors are difficult to diagnose preoperatively because the majority of these tumors are nonfunctional, and CT does not differentiate these tumors from other cystic neoplasms. Cystic neuroendocrine tumors represent a subgroup of pancreatic cystic and neuroendocrine tumors with malignant potential. Their high resectability rate further supports the role of surgical exploration and resection in the treatment of pancreatic cystic neoplasms.


Measurement of DNA Length Changes Upon CpG Hypermethylation by Microfluidic Molecular Stretching.
Abnormal DNA methylation in CpG-rich promoters is recognized as a distinct molecular feature of precursor lesions to cancer. Such unintended methylation can occur during in vitro differentiation of stem cells. It takes place in a subset of genes during the differentiation or expansion of stem cell derivatives under general culture conditions, which may need to be monitored in future cell transplantation studies. Here we demonstrate a microfluidic device for investigating morphological length changes in DNA methylation. Arrayed polymer chains of single DNA molecules were fluorescently observed by parallel trapping and stretching in the microfluidic channel. This observational study revealed that the shortened DNA length is due to the increased rigidity of the methylated DNA molecule. The trapping rate of the device for DNA molecules was substantially unaffected by changes in the CpG methylation.


Mastomys natalensis, Cricetomys gambianus and Taterillus sp. were found PCR positive for Leishmania major in Burkina Faso, West Africa.
Ouagadougou, the capital city of Burkina Faso, was recognized as a focus of zoonotic cutaneous leishmaniosis in April 2000. Leishmania major was the only strain isolated in this focus. We conducted a prospective study to detect L. major in rodents, animals which are described as reservoir of the parasite. Rodents were caught in five city areas from November 2005 to October 2006. Giemsa stained smears were realized from the cutaneous lesions when present after macroscopic examination of external lesions. The spleen of each rodent was sterilely removed and split into 3 parts for microscopic examination of smears, culture on NNN media and PCR, respectively. A total of 101 rodents belonging to 9 genera were trapped. All the direct examinations and cultures were negative. By using PCR of lesions and spleen samples, three animals were found infected by L. major: one out of 24 (4.2%) Mastomys natalensis; one out of 8 (12.5%) Taterillus sp. and one out of three Cricetomys gambianus. This is the first detection of L. major in rodent species in Burkina Faso. Further studies are needed to confirm their role as reservoirs of L. major.


Critical behavior of nonequilibrium phase transitions to magnetically ordered states.
We describe nonequilibrium phase transitions in arrays of dynamical systems with cubic nonlinearity driven by multiplicative Gaussian white noise. Depending on the sign of the spatial coupling we observe transitions to ferromagnetic or antiferromagnetic ordered states. We discuss the phase diagram, the order of the transitions, and the critical behavior. For global coupling we show analytically that the critical exponent of the magnetization exhibits a transition from the value 1/2 to a nonuniversal behavior depending on the ratio of noise strength to the magnitude of the spatial coupling.


Factors influencing measurement of serum iron concentration in dogs: diurnal variation and hyperferritinemia.
We evaluated diurnal variation and hyperferritinemia as factors that influence the values of serum iron concentration in dogs, using the International Committee for Standardization in Hematology (ICSH) colorimetric method. Serum iron levels were significantly higher in the morning than in the evening in 6 clinically healthy beagle dogs, and the maximum decrease in serum iron concentration was 47.3%. Moreover, the change in serum iron concentrations in 22 clinical canine cases with various serum ferritin levels was evaluated by immunoprecipitation of ferritin. The rate of decline in the serum iron concentrations positively correlated with serum ferritin levels (r=0.48, P=0.024). These results show that it is necessary to consider the sampling time and serum ferritin level for accurate interpretation of serum iron concentrations in dogs.


Comparison of the transcriptome between two cotton lines of different fiber color and quality.
To understand the mechanism of fiber development and pigmentation formation, the mRNAs of two cotton lines were sequenced: line Z128 (light brown fiber) was a selected mutant from line Z263 (dark brown fiber). The primary walls of the fiber cell in both Z263 and Z128 contain pigments; more pigments were laid in the lumen of the fiber cell in Z263 compared with that in Z128. However, Z263 contained less cellulose than Z128. A total of 71,895 unigenes were generated: 13,278 (20.26%) unigenes were defined as differentially expressed genes (DEGs) by comparing the library of Z128 with that of Z263; 5,345 (8.16%) unigenes were up-regulated and 7,933 (12.10%) unigenes were down-regulated. qRT-PCR and comparative transcriptional analysis demonstrated that the pigmentation formation in brown cotton fiber was possibly the consequence of an interaction between oxidized tannins and glycosylated anthocyanins. Furthermore, our results showed the pigmentation related genes not only regulated the fiber color but also influenced the fiber quality at the fiber elongation stage (10 DPA). The highly expressed flavonoid gene in the fiber elongation stage could be related to the fiber quality. DEGs analyses also revealed that transcript levels of some fiber development genes (Ca(2+)/CaM, reactive oxygen, ethylene and sucrose phosphate synthase) varied dramatically between these two cotton lines.


Sphingolipid metabolism in brain insulin resistance and neurological diseases.
Sphingolipids, as members of the large lipid family, are important components of plasma membrane. Sphingolipids participate in biological signal transduction to regulate various important physiological processes such as cell growth, apoptosis, senescence, and differentiation. Numerous studies have demonstrated that sphingolipids are strongly associated with glucose metabolism and insulin resistance. Insulin resistance, including peripheral insulin resistance and brain insulin resistance, is closely related to the occurrence and development of many metabolic diseases. In addition to metabolic diseases, like type 2 diabetes, brain insulin resistance is also involved in the progression of neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. However, the specific mechanism of sphingolipids in brain insulin resistance has not been systematically summarized. This article reviews the involvement of sphingolipids in brain insulin resistance, highlighting the role and molecular biological mechanism of sphingolipid metabolism in cognitive dysfunctions and neuropathological abnormalities of the brain.


Deafness and Diversity: Early Intervention.
earlier identification has increased the number of infants identified with hearing loss. A significant and growing proportion of children who are D/deaf or hard of hearing have a disability (DWD). Literature related to infants and toddlers who are DWD is scarce because of the heterogeneity of the population and because many disabilities may go undiagnosed until a child is older. Service availability, professional preparation, and use of evidence-based practices must improve to best meet the needs of these children and their families. An examination of theory, research, and practice in early intervention for children who are DWD revealed a lack of qualified professionals and a need for targeted instruction in teacher preparation programs and for technological advances paired with treatment (e.g., telepractice). Increased transdisciplinary collaboration and technology utilization in teacher preparation hold promise as ways of improving service provision to young children who are DWD.


The 4-hook anchor coaxial needle with scaled suture is superior to the double spring coil for preoperative localization.
Preoperative localization of small size pulmonary nodules is challenging, but it is necessary for surgical resection of early lung cancer. As a new device for preoperative localization, the 4-hook-anchor coaxial needle with scaled suture was tentatively applied in our department to improve the effect of preoperative localization. However, double spring coil, as a proven positioning technology, used to be our preferred method in the past. We did a retrospective single-centre research driven by the interest on which one should be the first choice for preoperative localization among these two approaches. We performed a retrospective analysis on 100 patients undergoing surgery with the new coaxial needle from 2019 to 2020, and 98 patients undergoing double spring coil from 2017 to 2019. The duration of localization, success rate, operation time, intraoperative bleeding, and positioning-related complications of these two groups of patients were examined in this study. There were no significant differences between the two groups of patients in terms of the success rate. However, the new coaxial needle seemed to be able to shorten the duration of preparative localization and operation time by accelerating the efficiency of exploring small nodules intraoperatively, and also decreased the risk of positioning-related pneumothorax and pulmonary hemorrhage. The logistic analysis indicated that the puncture depth was an independent risk factor for overall complications. Meanwhile, previous lung diseases and positioning time were independent risk factors for pneumothorax, besides pneumorrhagia and depth of penetration as well. The new coaxial needle can save time for both radiologists and thoracic surgeons, while reducing the risk of positioning-related complications. We support its application clinically instead of the double spring coil.


Unravelling the pivotal role of Alix in MVB sorting and silencing of the activated EGFR.
Endosomal sorting complex required for transport (ESCRT)-III-mediated membrane invagination and scission are a critical step in multivesicular body (MVB) sorting of ubiquitinated membrane receptors, and generally thought to be required for degradation of these receptors in lysosomes. The adaptor protein Alix is critically involved in multiple ESCRT-III-mediated, membrane-remodelling processes in mammalian cells. However, Alix knockdown does not inhibit degradation of the activated epidermal growth factor receptor (EGFR) in mammalian cell lines, leading to a widely held notion that Alix is not critically involved in MVB sorting of ubiquitinated membrane receptors in mammalian cells. In the present study, we demonstrate that, despite its non-essential role in degradation of the activated EGFR, Alix plays a critical role in its MVB sorting and silencing Epidermal growth factor (EGF) stimulation of mammalian cell lines induces Alix's interaction with the ubiquitinated EGFR via the Alix V domain, and increases Alix's association with membrane-bound charged multivesicular body protein 4 (CHMP4) via the Alix Bro1 domain. Under both continuous and pulse-chase EGF stimulation conditions, inhibition of Alix's interaction with membrane-bound CHMP4, inhibition of Alix dimerization through the V domain or Alix knockdown dramatically inhibits MVB sorting of the activated EGFR and promotes sustained activation of extracellular-signal regulated kinase (ERK)1/2. Under the continuous EGF stimulation conditions, these cell treatments also retard degradation of the activated EGFR. These findings indicate that Alix is critically involved in MVB sorting of ubiquitinated membrane receptors in mammalian cells.


Cells involved in the immune response. XXIX Establishment of optimal conditions for the primary and secondary immune responses by rabbit lymphoid cells in vitro.
Attempts were made to initiate the primary and secondary humoral immune responses to sheep red blood cells (SRBC) in vitro as determined by the hemolytic plaque-forming cell (PFC) response, with cell suspensions prepared from a variety of lymphoid organs of the rabbit- thymus, bone marrow, spleen, appendix, sacculus rotundus, Peyer's patches, popliteal lymph node and circulating leukocytes. A number of different media and gaseous phases were utilized in order to establish the optimal conditions for the immune response in vitro. The induction of a secondary PFC response was consistently obtained with 'memory' spleen cells obtained from rabbits 3-6 months following intravenous immunization with SRBC but not with cells of any of the other lymphoid organs, and this response probably represents the activity of memory cells which reside in the rabbit spleen. A primary response was observed only with 'normal' spleen cells, and the medium which faciliated the response was different from that which facilitated the induction of the secondary response in vitro. It was also observed, using a medium in which normal spleen cells were incapable of generating PFC', that mixed cultures of normal spleen and normal appendix or bone marrow cells could give a marked PFC reponse in vitro. Whether the PFC response to SRBCs obtained with the lymphoid cells of normal, unimmunized rabbits represent a true primary response, a secondary response, or a response of a different nature as a consequence of continuous subthreshold immunization of the rabbit with enteric microorganisms which cross-react with the antigen, remains to be determined. However, out initial successes with cultures consisting of cells of at least two distinct lymphoid organs in cases where the cells of any one of these organs could not respond, suggest that interaction of at least two functionally distinct cells is required and that the repsonse observed in vitro is probably a primary immune response.


Release of heparin-like substance and histamine from basophilic leucocytes separated by counterflow centrifugation elutriation.
Separation of basophilic granulocytes from peripheral blood was carried out by counterflow centrifugation elutriation using a JE-6B roter. The release of histamine and heparin-like substance from basophilic leucocytes was estimated in healthy and asthmatic subjects. 1. The number of basophils was maximal (0.74 x 10(5] at a flow rate of 4.5 ml/min, and the purity reached a peak (11.8 +/- 2.0%) at a flow rate of 9 ml/min. 2. The content of histamine paralleled the number of basophils in each fraction. 3. The release mechanism of histamine induced by anti-IgE was similar to that of the heparin-like substance. 4. The release of histamine and the heparin-like substance was significantly higher in atopic asthmatics than in non-atopic cases.


Evaluation of early and late postoperative flow capacity of internal thoracic artery bypass by means of stress Doppler echocardiography.
Arterial revascularization with the internal thoracic artery (ITA) has shown exceptional long-term results, even though early hypoperfusion can occur and can cause ischemia and contractile dysfunction. Therefore, it is still controversial as to whether the bypass vessel can guarantee the required demand for blood flow during the early postoperative (EPO) phase or whether this is only possible a long time after the operation. This question is important particular in the early postoperative phase to manage afterload and reduce left ventricular oxygen demand. Therefore, stress Doppler echocardiography was performed to assess EPO and late postoperative (LPO) flow capacity after minimal-invasive coronary artery bypass grafting (MIDCAB) in subjects with single vessel disease. Doppler echocardiography was performed after MIDCAB in 15 patients (mean age 65 years+/-12 standard deviation) in the EPO (15 days) and LPO (266 days) at rest and under stress. The mean diastolic velocity (MDV) as a measure for the coronary perfusion in the bypass-graft was comparable (30.9+/-14.5 EPO to 30.8+/-13.9 cm/s LPO, P>0.05) for both settings (early vs. late). In both tests, the stress reactions by means of handgrip maneuver lead to comparable increases in blood flow: MDV 65.0+/-54.4% (EPO) to 62.5+/-53.7% n.s. (LPO). The flow increase in the bypass graft was just as similar [48.2+/-46.2% (EPO) to 51.1+/-41.6% n.s. (LPO)]. The stress echocardiography revealed for the first time that the ITA-graft after MIDCAB-operation is able to produce the same flow reserve through the EPO phase as well as the LPO phase. Restrictions to a maximum early flow adaptation are not justified. Thus, particularly a patient with severe comorbidities or higher age should be mobilized in the EPO phase to minimize the postoperative complications without risk of myocardial ischemia caused by impaired early blood flow through recent implanted ITA. This method for assessment of ITA blood flow allows for long-time observations and can detect disturbances in perfusion at an early stage.


Revealing topological superconductivity in extended quantum spin Hall Josephson junctions.
Quantum spin Hall-superconductor hybrids are promising sources of topological superconductivity and Majorana modes, particularly given recent progress on HgTe and InAs/GaSb. We propose a new method of revealing topological superconductivity in extended quantum spin Hall Josephson junctions supporting "fractional Josephson currents." Specifically, we show that as one threads magnetic flux between the superconductors, the critical current traces an interference pattern featuring sharp fingerprints of topological superconductivity-even when noise spoils parity conservation.


Institutionalization of personalized medicine in India: analysis of research trends and government interventions.
The biggest challenges that any country faces are affordability and accessibility of quality healthcare. Technological advancements can address these challenges. One such advancement is personalized medicine (PM). This paper discusses the implementation and institutionalization of PM. Using the sectoral innovation system framework, this work describes government interventions with research trends in PM in India. The Web of Science database was used to analyze research trends. Indian government-funded interventions to institutionalize PM were compiled and analyzed. Results suggest that India's healthcare sector is dynamic. The framework discusses some specifics, including the research network, boundaries and government initiatives to promote PM adoption. Based on the policy gaps, this paper further proposes an integrated policy framework for incorporating PM into India's healthcare system.


Plasma concentrations of parathyroid hormone-related protein in dogs with potential disorders of calcium metabolism.
The plasma concentrations of total calcium, ionised calcium, albumin, parathyroid hormone and parathyroid hormone-related protein (PTHrp) were measured in 25 dogs with lymphoma, nine dogs with primary hyperparathyroidism and seven dogs with adenocarcinoma of the apocrine gland of the anal sac. Plasma total calcium, ionised calcium, albumin and parathyroid hormone-related protein were measured in 18 clinically normal control dogs. The concentration of PTHrp was high in 12 of the 14 dogs that were hypercalcaemic because of an underlying malignancy but was within the reference range in all the control dogs, in the 17 normocalcaemic dogs with lymphoma and in the seven dogs which were hypercalcaemic because of a parathyroid adenoma.


The role of sensory network dynamics in generating a motor program.
Sensory input plays a major role in controlling motor responses during most behavioral tasks. The vestibular organs in the marine mollusk Clione, the statocysts, react to the external environment and continuously adjust the tail and wing motor neurons to keep the animal oriented vertically. However, we suggested previously that during hunting behavior, the intrinsic dynamics of the statocyst network produce a spatiotemporal pattern that may control the motor system independently of environmental cues. Once the response is triggered externally, the collective activation of the statocyst neurons produces a complex sequential signal. In the behavioral context of hunting, such network dynamics may be the main determinant of an intricate spatial behavior. Here, we show that (1) during fictive hunting, the population activity of the statocyst receptors is correlated positively with wing and tail motor output suggesting causality, (2) that fictive hunting can be evoked by electrical stimulation of the statocyst network, and (3) that removal of even a few individual statocyst receptors critically changes the fictive hunting motor pattern. These results indicate that the intrinsic dynamics of a sensory network, even without its normal cues, can organize a motor program vital for the survival of the animal.


Enhanced breakdown of bovine articular cartilage proteoglycans by conditioned synovial medium. The effect of serum and dextran sulphate.
Medium from cultured bovine synovial membrane when applied to articular cartilage from the same animal enhanced proteoglycan breakdown, as measured by the release of [35S]sulphate from prelabelled cartilage, principally by activating chondrocytes to secrete or activate their own enzymes. This effect persisted whether or not the synovium was cultured in medium containing fetal calf serum. The release of proteoglycans from cartilage was markedly enhanced when the synovium was cultured in the presence of dextran sulphate (200 micrograms/ml), while dextran sulphate had no effect upon cartilage alone or when added together with medium cultured in the absence of dextran sulphate. Since the release of the proteoglycan breakdown products from frozen and thawed cartilage was not stimulated by dextran sulphate, this agent appeared to be enhancing the indirect chondrocyte-mediated effect of synovial medium rather than the direct proteolytic enzyme-induced effect. A possible mechanism for the production of a substance responsible for the chondrocyte-mediated matrix degradation is proposed, involving monocyte-like or macrophage-like cells, either resident in the synovial tissue or derived from the circulation.


Negative feedback regulation is responsible for the non-linear modulation of photosynthetic activity in plants and cyanobacteria exposed to a dynamic light environment.
Photosynthetic organisms exposed to a dynamic light environment exhibit complex transients of photosynthetic activities that are strongly dependent on the temporal pattern of the incident irradiance. In a harmonically modulated light of intensity I approximately const.+sin(omegat), chlorophyll fluorescence response consists of a steady-state component, a component modulated with the angular frequency of the irradiance omega and several upper harmonic components (2omega, 3omega and higher). Our earlier reverse engineering analysis suggests that the non-linear response can be caused by a negative feedback regulation of photosynthesis. Here, we present experimental evidence that the negative feedback regulation of the energetic coupling between phycobilisome and Photosystem II (PSII) in the cyanobacterium Synechocystis sp. PCC6803 indeed results in the appearance of upper harmonic modes in the chlorophyll fluorescence emission. Dynamic changes in the coupling of the phycobilisome to PSII are not accompanied by corresponding antiparallel changes in the Photosystem I (PSI) excitation, suggesting a regulation limited to PSII. Strong upper harmonic modes were also found in the kinetics of the non-photochemical quenching (NPQ) of chlorophyll fluorescence, of the P700 redox state and of the CO(2) assimilation in tobacco (Nicotiana tabaccum) exposed to harmonically modulated light. They are ascribed to negative feedback regulation of the reactions of the Calvin-Benson cycle limiting the photosynthetic electron transport. We propose that the observed non-linear response of photosynthesis may also be relevant in a natural light environment that is modulated, e.g., by ocean waves, moving canopy or by varying cloud cover. Under controlled laboratory conditions, the non-linear photosynthetic response provides a new insight into dynamics of the regulatory processes.


An immune cell infiltration-related gene signature predicts prognosis for bladder cancer.
To explore novel therapeutic targets, develop a gene signature and construct a prognostic nomogram of bladder cancer (BCa). Transcriptome data and clinical traits of BCa were downloaded from UCSC Xena database and Gene Expression Omnibus (GEO) database. We then used the method of Single sample Gene Set Enrichment analysis (ssGSEA) to calculate the infiltration abundances of 24 immune cells in eligible BCa samples. By weighted correlation network analysis (WGCNA), we identified turquoise module with strong and significant association with the infiltration abundance of immune cells which were associated with overall survival of BCa patients. Subsequently, we developed an immune cell infiltration-related gene signature based on the module genes (MGs) and immune-related genes (IRGs) from the Immunology Database and Analysis Portal (ImmPort). Then, we tested the prognostic power and performance of the signature in both discovery and external validation datasets. A nomogram integrated with signature and clinical features were ultimately constructed and tested. Five prognostic immune cell infiltration-related module genes (PIRMGs), namely FPR1, CIITA, KLRC1, TNFRSF6B, and WFIKKN1, were identified and used for gene signature development. And the signature showed independent and stable prognosis predictive power. Ultimately, a nomogram consisting of signature, age and tumor stage was constructed, and it showed good and stable predictive ability on prognosis. Our prognostic signature and nomogram provided prognostic indicators and potential immunotherapeutic targets for BCa. Further researches are needed to verify the clinical effectiveness of this nomogram and these biomarkers.


Search for varicella zoster virus and herpes simplex virus-1 in normal human cerebral arteries.
Virological confirmation of varicella zoster virus (VZV) vasculopathy is provided by presence of virus in the cerebral arteries, frequently associated with inflammation. Yet, cerebral arteries from normal subjects have never been studied for VZV DNA or antigen. We analyzed 63 human cerebral arteries from 45 subjects for VZV DNA and antigen, control herpes simplex virus (HSV)-1 DNA and antigen, and leukocyte-specific CD45 antigen. No cerebral arteries contained VZV or HSV-1 DNA or antigen; eight arteries from seven subjects contained leukocytes expressing CD45. Thus, the presence of VZV antigen in cerebral arteries of patients with stroke is likely to be clinically significant.


Shear bond strength of novel calcium aluminate-based cement (EndoBinder) to root dentine.
To evaluate the shear bond strength of a novel calcium aluminate-based cement, EndoBinder (EB), to dentine in comparison with Grey and White Mineral Trioxide Aggregate (MTA). Root canal hemi-sections obtained from 30 extracted molar teeth were embedded in self-polymerized acrylic resin and were grounded wet in order to obtain a flat dentine surface. Next, the roots were randomly assigned into three groups (n = 10), according to the cement used, as follows: EB: EndoBinder; WMTA: White MTA and GMTA: Grey MTA. The shear bond strength test was performed using a Universal Testing Machine (0.5 mm/min) and the data were submitted to statistical analysis (1-way ANOVA and Tukey tests, P < 0.05). EB presented the highest shear bond strength values; however, there was no statistically significant difference in comparison with GMTA (P > 0.05). WMTA presented the lowest mean values, which were significant in comparison with EB (P < 0.05). The novel calcium aluminate-based cement presented higher shear bond strength than WMTA, and should be considered as a promising alternative in endodontic therapy.


Dynamic Headspace Sampling as an Initial Step for Sample Preparation in Chromatographic Analysis.
This work represents a brief summary of the use of dynamic headspace (DHS) as a technique for sample preparation in chromatographic analysis. Despite numerous developments in the area of analyte isolation and enrichment, DHS remains one of the fundamental methods used with GC. In our opinion, interest in this technique will not diminish significantly because it conforms to stipulations of green analytical chemistry. Moreover, DHS fulfills the need for methods that facilitate detection and determination of analytes present at ultratrace levels in complex matrixes. The main focus of this work was placed on the theoretical fundamentals of this method. Also described herein were DHS development, the advantages and disadvantages of this technique compared with other headspace sampling techniques, and selected examples of its applications in food and environmental analyses.


Heterologous expression of mouse cytochrome P450 2e1 in V79 cells: construction and characterisation of the cell line and comparison with V79 cell lines stably expressing rat P450 2E1 and human P450 2E1.
A V79 Chinese hamster cell line was constructed for stable expression of mouse cytochrome P450 2e1 (Cyp2e1), as an addition to the existing cell battery consisting of cell lines stably expressing rat CYP2E1 and human CYP2E1 (V79 Cell Battery). The aim was to establish a cell battery that offers the in vitro possibility of investigating species-specific differences in the toxicity and metabolism of chemicals representing substrates for CYP2E1. The newly established cell line (V79m2E1) effectively expressed Cyp2e1 in the catalytically active form. The expression of catalytically active CYP2E1 in V79m2E1 cells was maintained over several months in culture, as demonstrated by Western Blotting and chlorzoxazone (CLX) 6-hydroxylase activity. The cells exhibited CLX 6-hydroxylase activity with a Km of 27.8 microM/l and Vmax of 40 pmol/mg protein/minute, compared with a Km of 28.2/28.6 microM/l and a Vmax of 130/60 pmol/mg protein/minute from V79r2E1/V79h2E1 cells. Furthermore, the CYP2E1-dependent mutagenicity of N-nitrosodimethylamine could be demonstrated in the V79m2E1 cells. Therefore, the new cell battery permits the interspecies comparison of CYP2E1-dependent toxicity and of metabolism of chemicals between humans and the two major rodent species--the rat and the mouse--that are usually used in classical toxicity studies.


Alpha-glucosidase inhibitory constituents from Duranta repens.
Three C-alkylated flavonoids 7-O-alpha-D-glucopyranosyl-3,5-dihydroxy-3'-(4"-acetoxyl-3"-methylbutyl)-6,4'-dimethoxyflavone (1), 7-O-alpha-D-glucopyranosyl-3,4'-dihydroxy-3'-(4"-acetoxyl-3"-methylbutyl)-5,6-dimethoxyflavone (2), 3,7,4'-trihydroxy-3'-(8"-acetoxy-7"-methyloctyl)-5,6-dimethoxyflavone (3) and a trans-clerodane type diterpenoid (-)-6beta-hydroxy-5beta,8beta,9beta,10alpha-cleroda-3,13-dien-16,15-olid-18-oic acid (4) are reported from Duranta repens along with (+)-hardwickiic acid (5) and (+)-3,13-clerodadien-16,15-olid-18-oic acid (6), isolated for the first time from this species. Their structures were established on the basis of the spectral methods, especially two dimensional (2D) NMR spectroscopy.


Repeat domains of melanosome matrix protein Pmel17 orthologs form amyloid fibrils at the acidic melanosomal pH.
Most amyloids are pathological, but fragments of Pmel17 form a functional amyloid in vertebrate melanosomes essential for melanin synthesis and deposition. We previously reported that only at the mildly acidic pH (4-5.5) typical of melanosomes, the repeat domain (RPT) of human Pmel17 can form amyloid in vitro. Combined with the known presence of RPT in the melanosome filaments and the requirement of this domain for filament formation, we proposed that RPT may be the core of the amyloid formed in vivo. Although most of Pmel17 is highly conserved across a broad range of vertebrates, the RPT domains vary dramatically, with no apparent homology in some cases. Here, we report that the RPT domains of mouse and zebrafish, as well as a small splice variant of human Pmel17, all form amyloid specifically at mildly acid pH (pH ∼5.0). Protease digestion, mass per unit length measurements, and solid-state NMR experiments suggest that amyloid of the mouse RPT has an in-register parallel β-sheet architecture with two RPT molecules per layer, similar to amyloid of the Aβ peptide. Although there is no sequence conservation between human and zebrafish RPT, amyloid formation at acid pH is conserved.


Clinical efficacy of piracetam in cognitive impairment: a meta-analysis.
A meta-analysis has been performed including nineteen double blind, placebo controlled studies with piracetam in patients suffering from dementia or cognitive impairment in the elderly. These studies had as common outcome measure a clinical global impression of change, a measure of clinically meaningful improvement. The meta-analysis of this global outcome followed the methodology set forward by the Cochrane Collaboration. This article describes the studies, the patient populations and the methods of data extraction. The results of the meta-analysis demonstrate a difference between those individuals treated with piracetam and those given placebo, both as significant odds ratio and as a favourable number needed to treat. While there may be problems in meta-analyses and the interpretation of the statistical results, the results of this analysis provide compelling evidence for the global efficacy of piracetam in a diverse group of older subjects with cognitive impairment.


Evolving concepts of chemical sensitivity.
Chemical sensitivity appears to be an elusive phenomenon. Studies on individual differences in susceptibility may provide glimpses into the range of sensitivity in a population, which can be used for further study. Preliminary evidence in laboratory animals suggests the range of sensitivity to manufactured chemicals may span orders of magnitude. Determining the reasons that underlie individual differences in sensitivity is a more difficult enterprise. Conditioning of adverse physiological effects of airborne chemicals may play a vital role in the etiology of chemical sensitivity, and it provides a rigorous laboratory model by which to investigate some aspects of this elusive phenomenon.


Purification of an acid alpha-glucosidase by dextran-gel filtration.
1. The behaviour of rat liver alpha-glucosidases on dextran gel (Sephadex G-100) columns was studied. A ;retardation' of an acid alpha-glucosidase activity was observed. This activity was identified as lysosome alpha-(1-->4)-glucosidase. A single gel-filtration step resulted in a 700-fold purification of the enzyme. The same technique was also used to purify the acid alpha-glucosidase of human kidney. 2. The acid alpha-glucosidases of both tissues show very similar pH optima when tested with maltose or glycogen as substrate.


The PI3K/AKT signaling pathway regulates ABCG2 expression and confers resistance to chemotherapy in human multiple myeloma.
Side population (SP) cells are involved in the development of multidrug resistance (MDR) in human multiple myeloma (MM), due to their cancer stem cell (CSC)‑like phenotypes. ATP‑binding cassette (ABC) drug transporter proteins have been reported to be closely associated with MDR in leukemia; however, the correlation between ABC proteins and the progression of MM remains unclear. The present study used MM cell lines and clinical samples to determine the role of ABC subfamily G member 2 (ABCG2) in MM via flow cytometry, reverse transcription‑quantitative polymerase chain reaction and western blotting. SP cells sorted from MM cell lines, including NCI‑H929 cells, via fluorescence‑activated cell sorting, exhibited CSC‑like phenotypes and expressed high levels of ABCG2. Expression of ABCG2 and activation of the phosphatidylinositol 3‑kinase (PI3K)/AKT serine/threonine kinase (AKT) signaling pathway was positively associated with the proportion of SP cells in the NCI‑H929 cell line. In addition, suppression of the PI3K/AKT pathway using LY294002 or rapamycin counteracted the protective effects of ABCG2 against chemotherapeutic drug treatment. Mechanistically, PI3K/AKT signaling may regulate ABCG2 expression, and ABCG2 may regulate phosphatase and tensin homolog expression via a potential negative feedback loop. Furthermore, SP cell proportion, ABCG2 expression and PI3K/AKT pathway activation were associated with disease progression in patients with MM. These findings indicated the critical roles of ABCG2 and PI3K/AKT signaling in controlling stemness of MM cells, and suggested a novel strategy for targeting ABCG2 and PI3K/AKT signaling to treat MM with MDR.


Tumor location of the lower-inner quadrant is associated with an impaired survival for women with early-stage breast cancer.
There is growing evidence that tumors of the inner quadrants (especially the lower-inner quadrant) metastasize more often to the internal mammary chain (IMC). As these metastases are not investigated, patients with lower-inner quadrant tumors have an increased risk of being under-staged and under-treated and may therefore have a higher risk of death from breast cancer. We identified all 1522 women operated for stage I breast cancer between 1984 and 2002 recorded at the population-based Geneva Cancer Registry. We compared breast cancer mortality risk by tumor location with multivariate Cox regression analysis that accounted for all factors linked to tumor location and survival. Ten-year disease-specific survival was 93% (95%CI: 91-94%). Patients with breast cancer of the lower-inner quadrant (n = 118; 7.8%) had an importantly increased risk of dying of breast cancer compared to women with breast cancer of the upper-outer quadrant (multiadjusted Hazard Ratio: 2.3, 95%CI: 1.1-4.5, P = 0.0206). The over-mortality associated with this quadrant was particularly evident for tumors >10 mm (multiadjusted HR: 3.6, 95%CI: 1.6-7.9, P = 0.0016). There was no increased breast cancer mortality risk for tumors located in other quadrants. Tumor location in the lower-inner quadrant is an independent and important prognostic factor of stage I breast cancer. Further research is needed to evaluate if the over-mortality of patients with stage I cancer of the lower-inner quadrant is indeed a result of under-treatment due to undetected IMC metastases. If so, patients with stage I breast cancer of the lower-inner quadrant are good candidates for systematic IMC investigation.


Measurement of shear bond strength to intact dentin.
Previously, we reported that the integrity of a resin composite restoration deteriorated when the dentin cavity wall was decalcified by conditioning. In this study, to evaluate the bonding between dentin adhesive and non-decalcified dentin surface, we experimented with a novel method of using a high-pressure water spray device to prepare smear layer-free dentin surfaces. When the smear layer was removed, shear bond strength significantly increased regardless of the removal method employed. Further, with glyceryl monomethacrylate (GM) priming, no significant differences in bond strength were observed among these smear layer removal methods: ethylenediamine tetraacetic acid (EDTA) conditioning, phosphoric acid conditioning, and removal by water spray. It was also found that GM priming was key to achieving marginal integrity, whereas contraction gap width increased with phosphoric acid conditioning. It was thus concluded that the efficacy of a dentin adhesive should be evaluated by consistently observing the contraction gap in three-dimensional cavities rather than by mere measurement of bond strength to a flat dentin surface.


Surfactant-free miniemulsion polymerization of n-BA/S stabilized by NaMMT: films with improved water resistance.
The use of sodium montmorillonite clay as a stabilizer in the surfactant-free emulsion polymerization of n-butyl acrylate/styrene (n-BA/S) was assessed. It was shown that the use of the clay alone did not yield the desired armored latex particles. A functional comonomer, that is, a phosphate ester of poly(ethylene glycol) monomethacrylate, was used to improve the interaction between the polymer and clay, thus allowing for the clay platelets to adhere to the surface of the polymer particles. The morphology of the films obtained for these two different scenarios was similar and resembled a honeycomb structure. However, their water-resistance properties differed drastically. The water absorption and water vapor permeation rate were much lower in the hybrid n-BA/S/clay films in the presence of the functional monomer than in the films obtained without the functional monomer.


Structural basis for the complex DNA binding behavior of the plant stem cell regulator WUSCHEL.
Stem cells are one of the foundational evolutionary novelties that allowed the independent emergence of multicellularity in the plant and animal lineages. In plants, the homeodomain (HD) transcription factor WUSCHEL (WUS) is essential for the maintenance of stem cells in the shoot apical meristem. WUS has been reported to bind to diverse DNA motifs and to act as transcriptional activator and repressor. However, the mechanisms underlying this remarkable behavior have remained unclear. Here, we quantitatively delineate WUS binding to three divergent DNA motifs and resolve the relevant structural underpinnings. We show that WUS exhibits a strong binding preference for TGAA repeat sequences, while retaining the ability to weakly bind to TAAT elements. This behavior is attributable to the formation of dimers through interactions of specific residues in the HD that stabilize WUS DNA interaction. Our results provide a mechanistic basis for dissecting WUS dependent regulatory networks in plant stem cell control.


SweetSEQer, simple de novo filtering and annotation of glycoconjugate mass spectra.
The past 15 years have seen significant progress in LC-MS/MS peptide sequencing, including the advent of successful de novo and database search methods; however, analysis of glycopeptide and, more generally, glycoconjugate spectra remains a much more open problem, and much annotation is still performed manually. This is partly because glycans, unlike peptides, need not be linear chains and are instead described by trees. In this study, we introduce SweetSEQer, an extremely simple open source tool for identifying potential glycopeptide MS/MS spectra. We evaluate SweetSEQer on manually curated glycoconjugate spectra and on negative controls, and we demonstrate high quality filtering that can be easily improved for specific applications. We also demonstrate a high overlap between peaks annotated by experts and peaks annotated by SweetSEQer, as well as demonstrate inferred glycan graphs consistent with canonical glycan tree motifs. This study presents a novel tool for annotating spectra and producing glycan graphs from LC-MS/MS spectra. The tool is evaluated and shown to perform similarly to an expert on manually curated data.


Modelling the effect of temperature on the biology and demographic parameters of the African coffee white stem borer, Monochamus leuconotus (Pascoe) (Coleoptera: Cerambycidae).
The African coffee white stem borer Monochamus leuconotus (Pascoe) (Coleoptera: Cerambycidae) is a destructive insect pest of Arabica coffee trees in African highlands. Our study aims to provide information on the pest biology as influenced by temperature, determine thermal thresholds, and provide life table parameters for M. leuconotus reared in the laboratory. The life cycle of M. leuconotus was studied at seven constant temperatures in the range 15-35 °C, with 80 ± 5% RH and a photoperiod of L:D 12:12. Linear and nonlinear models were fitted to laboratory data to describe the impact of temperature on M. leuconotus development, mortality, fecundity and senescence. The complete life cycle was obtained between 18 and 30 °C, with the egg incubation period ranging 10.8-29.2 days. The development time was longest for the larva, with 194.2 days at 30 °C and 543.1 days at 18 °C. The minimum temperature threshold (Tmin) was estimated at 10.7, 10.0 and 11.5 °C, for egg, larva and pupa, respectively. The maximum temperature threshold (Tmax) was estimated at 37.4, 40.6 and 40.0 °C for egg, larva and pupa, respectively. The optimum temperature for immature stage survival was estimated between 23.0 and 23.9 °C. The highest fecundity was 97.8 eggs per female at 23 °C. Simulated life table parameters showed the highest net reproductive rate (Ro) of 11.8 daughters per female at 26 °C and maximal intrinsic rate of increase (rm) between 26 and 28 °C, with a value of 0.008. Our results will help understanding M. leuconotus biology as influenced by temperature and may be used to predict the distribution and infestation risk under climate warming for this critical coffee pest.


Neuropathy and Dysautonomia in Patients with Obstructive Sleep Apnea Syndrome.
The aim of our study is to search for the existence of neuropathy, dysautonomia and to identify the correlations of sickness level of patients with Obstructive Sleep Apnea Syndrome (OSAS). The research is based on the real cases at Dokuz Eylul University of Medicine Sleep and Epilepsy Center, observed during September 2008-May 2009. The patients were selected by polysomnography samples based on 20 persons at same ages with following criteria; high leveled OSAS (AHİ≥30), low OSAS (5≤AHİ<30) and healthy participants. Classical ENMG protocol, symphatic skin response and R-R interval variation test were performed on these samples. High and low leveled OSAS patients had a statistically significant (p<0.05) decrease in the average velocity of motor conduction in right tibialis posterior when compared to the control group. Besides we observed an statistically significant (p<0.05) increase in the average amplitud of symphatic skin responses in high leveled OSAS patients than control group. OSAS indicates a risk of possible peripheral neuropathy and autonomic dysfunction risk increases in positive correlation with level of OSAS.


Calcitonin as a marker for diethylnitrosamine-induced pulmonary endocrine cell hyperplasia in hamsters.
Immunoreactive calcitonin (iCT) has been localized in solitary endocrine cells and in clusters of these cells, called neuroepithelial bodies, in human and hamster lungs. It has been demonstrated that hyperplasia of hamster lung endocrine cells occurs following exposure to diethylnitrosamine (DEN), a systemic carcinogen. In the present study we have investigated iCT as a hormonal correlate of DEN-induced pulmonary endocrine cell hyperplasia in hamsters. Hamsters were given 3 mg of DEN per animal, subcutaneously, twice a week and then serially sacrificed at 2, 4, 8, and 12 weeks. By immunocytochemistry, iCT-containing cells could be demonstrated in thyroids, tracheal glands, and throughout the airway epithelium. At 8 or 12 weeks of DEN exposure, one to eight neuroepithelial bodies with iCT-containing cells were identified per square centimeter of lung sections, in contrast to zero to one neuroepithelial bodies/cm2 in control hamsters. By radioimmunoassay, pulmonary iCT increased significantly at 8 weeks of DEN exposure, amounting to 3.5-fold the control values at 12 weeks. Serum iCT increased at 4 weeks of exposure and by 12 weeks had tripled (183 +/- 62 pg/ml, mean +/- SD, p less than 0.001), as compared with control animals. Subsequently, DEN was stopped for 4 weeks, and the levels of both serum and lung iCT decreased, although they remained higher than those of controls. The serum and lung iCT of control hamsters was constant throughout the experiment (49 +/- 26 pg/ml and 1754 +/- 489 pg/gm of wet weight, mean +/- SD, respectively). Thyroidal iCT levels of exposed hamsters did not differ from those of the controls; both increased progressively. The DEN-exposed animals had retarded growth as compared with the controls. Column chromatography using superfine Sephadex G-75 demonstrated that both DEN-exposed and control lungs contained iCT with a predominant molecular size corresponding to the dimer of synthetic human calcitonin; whereas thyroidal iCT was mostly monomeric (approximately 3,500 daltons). The increase of pulmonary iCT correlates well with the 4-fold increase of pulmonary endocrine cells, reported earlier following similar DEN exposure. We conclude that iCT levels of hamster sera and lungs can be used as a biochemical parameter to monitor hyperplasia of the pulmonary endocrine cells in these animals.


Spatial, temporal, and quantitative manipulation of intracellular hydrogen peroxide in cultured cells.
Hydrogen peroxide (H2O2) is produced endogenously in a number of cellular compartments, including the mitochondria, the endoplasmic reticulum, peroxisomes, and at the plasma membrane, and can play divergent roles as a second messenger or a pathological toxin. It is assumed that the tuned production of H2O2 within neuronal and nonneuronal cells regulates a discreet balance between survival and death. However, a major challenge in understanding the physiological versus pathological role of H2O2 in cells has been the lack of validated methods that can spatially, temporally, and quantitatively modulate H2O2 production. A promising means of regulating endogenous H2O2 is through the expression of peroxide-producing enzyme d-amino acid oxidase (DAAO from Rhodotorula gracilis lacking a peroxisomal targeting sequence). Using viral vectors to express DAAO in distinct cell types and using targeting sequences to target DAAO to distinct subcellular sites, we can manipulate H2O2 production by applying the substrate d-alanine or permeable analogs of d-alanine. In this chapter, we describe the use of DAAO to produce H2O2 in culture models and the real-time visual validation of this technique using two-photon microscopy and chemoselective fluorescent probes.


Modulation of the population density of identifiable epidermal Langerhans cells associated with enhancement or suppression of cutaneous immune reactivity.
The epidermis on the backs or ears of DBA/2 mice treated for 7 days with a 20% concentration of monobenzyl ether of hydroquinone (MBEH) had a significantly greater population density of ATPase- and Ia-positive cells compared with control mice treated with diluent. There was no decrease or increase in ATPase- or Ia-positive cells at sites distal from the treated tissue. This increase in population density of Langerhans cells was associated with a significant increase in functional afferent immune reactivity measured by allergic contact hypersensitivity. We also found evidence for enhanced efferent immune reactivity. Animals treated on the ears for 7 days with MBEH were sensitized to DNFB on untreated back. MBEH treated ears with more Ia-positive Langerhans cells demonstrated a threefold greater increase in swelling after the DNFB challenge than the control mice. Results of other studies suggest that the afferent and efferent enhanced immune reactivity produced by MBEH are local effects. We postulated that MBEH produced its effects by activating the oxidation of arachidonic acid (AA) to prostaglandins. To test this, we applied AA to mouse skin. AA has a biphasic effect on epidermal Langerhans cells: in low doses it increases their number; in high amounts it decreases the number of identifiable cells with either the Ia or the ATPase technique. An increased population density of identifiable epidermal Langerhans cells induced with AA was correlated with an increase in afferent and efferent immune reactivity. In contrast, reduction of Langerhans cells with larger amounts of AA suppress the afferent and efferent limb of the immune response. DNFB applied to skin with decreased Langerhans cell density from AA induced a state that mimics immune tolerance. The findings are significant because we report the only method to either increase or decrease the population density of Langerhans cells: and to modulate up or down the afferent or efferent limbs of the cutaneous immune response. Our results also suggest that the Langerhans cell may be involved in the efferent limb of the immune efferent response. These effects may be modulated in part by products of AA metabolism.


Falls and Depression in Men: A Population-Based Study.
The link between falls and depression has been researched in the elderly; however, little information is available on this association in younger adults, particularly men. This study sought to investigate the link between major depressive disorder (MDD) and falls in a population-based sample of 952 men (24-97 years). MDD was diagnosed utilizing the Structured Clinical Interview for DSM-IV-TR Research Version, Non-Patient edition, and categorized as 12-month/past/never. Body mass index and gait were measured; falls, smoking status, psychotropic medication use, and alcohol intake were self-reported as part of the Geelong Osteoporosis Study 5-year follow-up assessment. Thirty-four (3.6%) men met criteria for 12-month MDD, and 110 (11.6%) for past MDD. Of the 952 men, 175 (18.4%) reported falling at least once during the past 12 months. Fallers were older (66 [interquartile range: 48-79] vs. 59 [45-72] years, p = .001) and more likely to have uneven gait ( n = 16, 10% vs. n = 31, 4%, p = .003) than nonfallers. Participants with 12-month MDD had more than twice the odds of falling (age-adjusted odds ratio: 2.22, 95% confidence interval [1.03, 4.80]). The odds of falling were not associated with past depression ( p = .4). Further adjustments for psychotropic drug use, gait, body mass index, smoking status, blood pressure, and alcohol did not explain these associations. Given the 2.2-fold greater likelihood of falling associated with depression was not explained by age or psychotropic drug use, further research is warranted.


Super-Radiant SERS Enhancement by Plasmonic Particle Gratings.
Despite recent developments, surface-enhanced Raman spectroscopy (SERS) applications face challenges in achieving both high sensitivity and uniform Raman signals over a large area. Using the directional self-assembly of plasmonic nanoparticles in lattice structures, we show how one can increase the SERS signal 43-fold over randomly aligned gold nanoparticles without relying on the photoluminescence of Rhodamine 6G. For this study, we have chosen the lattice constant for an off-resonant case that matches the lattice resonance and super-radiant plasmon mode along the particle chain. Supported by electromagnetic simulations, we systematically analyze the radiative components of the plasmon modes by varying the particle size while keeping the lattice periodicity constant. We perform polarization-dependent SERS measurements and compare them with other standard SERS excitation wavelengths. Using the self-assembled plasmonic particle lattice, we have developed an effective SERS substrate that provides a significantly higher signal with 73% less surface coverage. This colloidal approach enables the cost-effective and scalable fabrication of highly sensitive, uniform, and polarization-dependent SERS substrates.


Ethical problems and moral sensitivity in physiotherapy: a descriptive study.
This study identified and described ethical problems encountered by physiotherapists in their practice and physiotherapists' moral sensitivity in ethical situations. A questionnaire-based survey was constructed to identify ethical problems, and the Moral Sensitivity Questionnaire Revised version was used to measure moral sensitivity. Physiotherapists (n = 116) working in public health services responded to the questionnaire. Based on the results, most of the physiotherapists encounter ethical problems weekly. They concern mainly financial considerations, equality and justice, professionalism, unethical conduct of physiotherapists or other professions and patients' self-determination. The dimension of moral strength was emphasised in physiotherapists' self-evaluations of their moral sensitivity. As a conclusion, ethical problems do occur not only at individual level but also at organisational and society level. Physiotherapists seem to have moral strength for speaking on behalf of the patient. Scarce resources make them feel insufficient but much could still be done to provide quality care in co-operation with other health-care professionals.


Antimicrobial potential, phytochemical profile, cytotoxic and genotoxic screening of Sedum praealtum A. DC. (balsam).
Sedum praealtum has been used for a long time in traditional medicine as an analgesic and anti-inflammatory agent. Its beneficial effects have been known since ancient times, when Latinos used it to treat sore and swollen eyes. This research evaluated the antimicrobial potential, the cytotoxic and genotoxic effects, and some chromatographic profiles of the hydroethanolic extract of leaves, stems and roots of S. praealtum. The antimicrobial activities were carried out by broth microdilution and agar diffusion. In vitro cytotoxicity was evaluated by cell cultures of Aedes albopictus and the selectivity index (SI) was estimated: SI=CI50/MIC. Genotoxic and systemic toxic effects of S. praealtum leaves were analyzed by micronucleus assay in mice bone marrow. Chromatographic profiles and mass spectra were investigated by GC-MS. Gram-positive (B. subtilis, B. cereus, M. luteus, E. faecalis and S. aureus) and gram-negative (E. coli, E. aerogenes, S. marcescens, P. aeruginosa, P. mirabilis and S. typhimurium) bacteria exhibited MICs ranging from 12.5-50 and 0-50 mg/ml, respectively. Sedum praealtum showed no efficacy against M. tuberculosis and M. bovis. Cytotoxicity (CI50) of S. praealtum was 4.22 and 5.96 mg/ml for leaves and stems, respectively, while its roots showed no cytotoxicity. Micronucleated polychromatic erythrocytes (MNPCEs) analyzes showed no differences between treatment doses (0.5-2 g/kg) and negative control (NaCl), but the PCE/NCE ratio (polychromatic erythrocyte/normochromatic erythrocyte) showed significant differences. Phytochemical screening identified thirteen compounds in the leaves, stems and roots of S. praealtum potentially associated with their biological activities. This research comprises a first scientific study on genotoxicity, cytotoxicity and antimicrobial effects of S. praealtum (Balsam), and it provides an initial theoretical foundation for its comprehensive use. Results showed antibacterial action of S. praealtum against gram-positive bacteria and some gram-negative species (depending on the plant anatomical part), but ineffective antimycobacterial action. However, S. praealtum leaves and stems display potential cytotoxicity, contributing to the SI < 1 values. In addition, S. praealtum leaves exhibit no clastogenic and/or aneugenic effects, but it has systemic toxicity dose-independent.


Rare-Earth-metal methylidene complexes.
Transition-metal carbene complexes have been known for about 50 years and widely applied as reagents and catalysts in organic transformations. In contrast, the carbene chemistry of the rare-earth metals is much less developed, but has attracted the research interest in the recent years. In this field rare-earth-metal alkylidene, especially methylidene, compounds are an emerging class of compounds with a high synthetic potential for organometallic chemistry and maybe in the future also for organic chemistry.


Analysis of hemoglobin in bloodstains using high-performance liquid chromatography.
Hemoglobin (Hb) extracted from bloodstains was investigated using cation-exchange high-performance liquid chromatography (HPLC). Among the HbA1 fractions, the amount of HbA1d increased linearly as the ages of the bloodstains increased, although the amount of HbA1c remained virtually unchanged. As HbA1 fractions are Hb modified with glucose or glycolytic intermediates, the total Hb were separated into glycated and non-glycated Hb fractions using affinity chromatography to investigate the effects of glucose on the age-induced Hb changes. The amounts of glycated Hb increased in proportion to the blood glucose level, and the increased glycated Hbs were eluted at retention times that corresponded to those of HbA1d and HbA0, although HbA1c peak area was virtually unchanged. The amounts of both glycated and non-glycated HbA1d increased with bloodstain aging, and the proportion of non-glycated HbA1d relative to the total HbA1d was greater than that of glycated HbA1d. These findings show that glucose has little effects on the elevation of HbA1d in bloodstains that occurs as they age. Furthermore, measuring HbA1d levels in bloodstains using HPLC may prove useful for the determination of their ages.


A Dynamic Bioinspired Neural Network Based Real-Time Path Planning Method for Autonomous Underwater Vehicles.
Real-time path planning for autonomous underwater vehicle (AUV) is a very difficult and challenging task. Bioinspired neural network (BINN) has been used to deal with this problem for its many distinct advantages: that is, no learning process is needed and realization is also easy. However, there are some shortcomings when BINN is applied to AUV path planning in a three-dimensional (3D) unknown environment, including complex computing problem when the environment is very large and repeated path problem when the size of obstacles is bigger than the detection range of sensors. To deal with these problems, an improved dynamic BINN is proposed in this paper. In this proposed method, the AUV is regarded as the core of the BINN and the size of the BINN is based on the detection range of sensors. Then the BINN will move with the AUV and the computing could be reduced. A virtual target is proposed in the path planning method to ensure that the AUV can move to the real target effectively and avoid big-size obstacles automatically. Furthermore, a target attractor concept is introduced to improve the computing efficiency of neural activities. Finally, some experiments are conducted under various 3D underwater environments. The experimental results show that the proposed BINN based method can deal with the real-time path planning problem for AUV efficiently.


Hydrogels for potential colon drug release by thiol-ene conjugate addition of a new inulin derivative.
Inulin was chosen as a starting polymer for biocompatible, pH-sensitive and biodegradable hydrogels. Three INUDVSA-TT hydrogels were obtained by crosslinking inulin derivatives with trimethylolpropane tris(3-mercaptopropionate) under varying conditions. The resulting hydrogels were cell compatible, as demonstrated by MTS and trypan blue exclusion assays acting on Caco-2 cells, and were biodegraded by inulinase and esterase, thus suggesting their use as colonic drug delivery systems. 2-Methoxyestradiol, an anti-cancer drug, was soaked in INUDVSA-TT hydrogels and its in vitro release and apoptotic effect on Caco-2 cells were evaluated.


Gangrenous cutaneous mucormycosis in a child with a solid organ transplant: a case report and review of the literature.
Infections by members of the Phycomycetes class of fungi typically arise in patients with substantial underlying immunosuppression. Several clinical presentations, including that of gangrenous cellulitis, have been described. In the pediatric population, critically ill premature newborns and older children with underlying hematopoietic malignancies and/or bone marrow transplantation are affected. Presentation in children with solid organ transplants is rare. Successful therapy for this condition includes aggressive debridement of infected tissue and systemic administration of amphotericin B.


Measurement of absolute left ventricular volume by radionuclide angiography: a technical review.
Absolute left ventricular volumes have important clinical implications in the evaluation of cardiac performance. Several invasive and noninvasive techniques have been reported, none of which can be considered ideal for this purpose. Contrast angiography, echocardiography and radionuclide ventriculography are open to criticism. Different radioisotopic approaches are described with emphasis on the importance of accurate separation of left ventricular activity, the selection of background activity, and the correction for photon attenuation by body tissues. Improper use of statistics and validation techniques have obscured the value of these techniques. In the absence of a 'gold standard' there should be a 'radioisotopic' left ventricular volume with established independent characteristics, repeatability and reproducibility by which new approaches can be judged.