Aphasia for Morse code: a comment on Wyler and Ray (1986).
A. R. Wyler and R. W. Ray (1986, Brain and Language, 27, 195-199), present a case of aphasia for Morse code; they relate the deficit to the inability to detect high-speed auditory temporal sequences. Based on a personal observation of transient aphasia for Morse code, we proposed that at least three different abilities participate in recognizing and producing Morse code messages: (1) a specific linguistic ability, (2) a praxic skill, and (3) an auditory discrimination skill. Our patient presents difficulties in the first and second abilities, Wyler and Ray's in the third ability.


Evolutionary dynamics in Barrett oesophagus: implications for surveillance, risk stratification and therapy.
Cancer development is a dynamic evolutionary process characterized by marked intratumoural heterogeneity at the genetic, epigenetic and phenotypic levels. Barrett oesophagus, the pre-malignant condition to oesophageal adenocarcinoma (EAC), is an exemplary system to longitudinally study the evolution of malignancy. Evidence has emerged of Barrett oesophagus lesions pre-programmed for progression to EAC many years before clinical detection, indicating a considerable window for therapeutic intervention. In this Review, we explore the mechanisms underlying clonal expansion and contraction that establish the Barrett oesophagus clonal mosaicism over time and space and discuss intrinsic genotypic and extrinsic environmental drivers that direct the evolutionary trajectory of Barrett oesophagus towards a malignant phenotype. We propose that understanding and exploiting the evolutionary dynamics of Barrett oesophagus will identify novel therapeutic targets, improve prognostic tools and offer the opportunity for personalized surveillance programmes geared to prevent progression to EAC.


Implementing a "Do-Not-Resuscitate" (DNR) policy in a nursing home.
During implementation of a new Do-Not-Resuscitate (DNR) policy in New York State, decisions by 233 nursing home patients of their surrogates were evaluated. Eighteen patients with capacity (mean age +/- SD = 76.4 +/- 12.1 years) chose DNR; 30 patients with capacity (mean age +/- SD = 76.2 +/- 10.7 years) chose to be resuscitated (CODE); 54 patients without capacity, (mean age +/- SD = 86.1 +/- 9.1 years) had surrogates who chose DNR; and 131 patients without capacity and with surrogates (mean age +/- SD = 81.9 +/- 9.8 years) remained CODE. Most patients with capacity who chose DNR had multiple sclerosis, while most choosing CODE had strokes. Most patients who lacked capacity had dementia. Forty-five percent of surrogates did not respond regarding CODE status during the three-month study interval, and 10% wanted additional time to decide. Patient age appeared to be a factor in surrogate choice for DNR but not in patients with capacity making their own decision. Reasons for patients with capacity choosing DNR are discussed; perceived quality of life and premorbid feelings by patients help in the decision-making process.


Beyond visual acuity: new and complementary tests of visual function.
Visual acuity is an essential component of the routine ophthalmic examination and the most common measure of visual function. There is increasing recognition, however, of the need to evaluate visual function beyond the limited extent afforded by visual acuity. The primary objective of this article is to introduce a variety of new and lesser-used techniques for measuring visual function that complement visual acuity assessment, each of which has been shown to detect visual dysfunction in patients with normal visual acuity.


Misplaced tracheoesophageal voice prosthesis: A case of foreign body aspiration.
Foreign body aspiration (FBA) is a rare, but potentially fatal condition frequently seen in the emergency department. Bronchoscopy plays a major role in its diagnosis and treatment. In patients with laryngectomy, the strategies for airway maintenance and foreign body retrieval are limited. We describe management of a patient with laryngectomy presenting with aspiration of a tracheoesophageal voice prosthesis (TEP). The TEP was not initially seen in chest radiography; however, computed tomography showed it within the right lower bronchus. Successful extraction of the TEP was achieved through bronchoscopy with forceps and retrieval basket. Otolaryngology placed a larger TEP and secured it with sutures. TEP migration is rare, but represents a risk for FBA. Initial imaging in the emergency department can be misleading, requiring a high degree of suspicion, as the TEP device may not be seen in standard chest radiography. Flexible bronchoscopy under moderate sedation in conjunction with forceps and retrieval basket may be appropriate for treatment of FBA in patients with laryngectomy and can be performed in the emergency department, preventing hospital admission.


Overexpression of Akt1 upregulates glycogen synthase activity and phosphorylation of mTOR in IRS-1 knockdown HepG2 cells.
Insulin receptor substrate (IRS) proteins are important docking proteins in mediating the insulin signaling cascade. We have investigated the effect of short interfering RNA (siRNA) mediated knockdown of IRS-1 on insulin signaling cascade in primary human hepatocellular carcinoma HepG2 cell line and HepG2 cells overexpressing Akt1/PKB-alpha (HepG2-CA-Akt/PKB). IRS-1 knockdown in both cell lines resulted in reduction of insulin stimulated Akt1 phosphorylation at Ser 473. In parental HepG2 cells, IRS-1 knockdown resulted in reduction (ca. 50%) in the basal level of phosphorylated mTOR (Ser 2448) irrespective of insulin treatment. In contrast, HepG2-CA-Akt/PKB cells showed an upregulation in the basal level of phosphorylated mTOR (Ser 2448) (ca. 40%). Insulin mediated phosphorylation of mTOR was reduced. IRS-1 knockdown also reduced the cell proliferation of parental HepG2 cells by ca. 30% in the presence/absence of insulin, whereas in HepG2-CA-Akt/PKB the cell proliferation was reduced by 15% and treatment of insulin further reduced it to ca. 50% (vs. control). IRS-1 knockdown also reduced the glycogen synthase (GS) activity in parental HepG2 cells, however, it was upregulated in HepG2-CA-Akt/PKB cells. These results suggest that knockdown of IRS-1 abolished basal as well as insulin mediated phosphorylation/activity of proteins involved in cell proliferation or glycogen metabolism in the parental Hep2 cells. IRS-1 knockdown in cells overexpressing constitutively active Akt1/PKB-alpha either did not change or upregulated the basal levels of phosphorylated/active proteins. However, insulin mediated response was either not altered or downregulated in these cells.


Limits on bilingualism.
Speech, in any language, is continuous; speakers provide few reliable cues to the boundaries of words, phrases, or ther meaningful units. To understand speech, listeners must divide the continuous speech stream into portions that correspond to such units. This segmentation process is so basic to human language comprehension that psycholinguists long assumed that all speakers would do it in the same way. In previous research, however, we reported that segmentation routines can be language-specific: speakers of English do not. French has relatively clear syllable boundaries and syllable-based timing patterns, whereas English has relatively unclear syllable boundaries and stress-based timing; thus syllabic segmentation would work more efficiently in the comprehension of French than in the comprehension of English. Our present study suggests that at this level of language processing, there are limits to bilingualism: a bilingual speaker has one and only one basic language.


Management of headwaters based on macroinvertebrate assemblages and environmental attributes.
The ecosystem function of headwaters is important and increasingly well-recognized, but institutional structures to administer their protection and management are lacking or poorly developed. Although the reasons for this mismatch are various, one of practical concern is the potential administrative burden imposed by the sizable number of headwaters. Two essential components of an administrative framework for managing waters is classification by type so that proper expectations can be set, and development of indicators that measure whether those expectations are being met. Ordinations of macroinvertebrate assemblages sampled from 1016 sites in 934 headwater streams draining <13 km2 across Ohio, USA, revealed a highly distinct subset of sites characterized by a combination of taxa having an affinity for cold water and sensitivity to environmental disturbance. Bayesian Network (BN) modeling revealed that several environmental variables, notably water temperature, percent forest cover, and drainage area predict membership in this subset. More generally across all streams, macroinvertebrate assemblages signaled ecological status along a stressor gradient defined by habitat quality and intensity of land uses. Collectively, these results suggest a hierarchical administrative framework wherein stream habitat quality, as measured by summary habitat index scores, can screen and assign protections to waters generally expected to support assemblages consistent with good ecological status. Forest cover and water temperature can serve as an additional screen to assign higher levels of protection consistent with higher ecological status. In cases where levels of protection based on screening are questioned or likely to be contentious, assessment of the macroinvertebrate assemblage can demonstrate the appropriate level.


Exploring the binding pattern between pepsin and deferasirox using detailed experimental and computer simulation methods.
Steady-state fluorescence spectroscopy indicated that a ground state complex was formed between deferasirox (DFX) and pepsin. The binding parameters and thermodynamic parameters of pepsin-DFX complex formation suggested the presence of only one high affinity binding site in the binding process of DFX and pepsin and that the binding process was hydrogen bond dominated. According to the MD simulation optimal pepsin-DFX binding model analysis, the binding force between DFX and pepsin was mainly hydrogen bonding, and the hydrophobic interaction was supplemented. Synchronous fluorescence spectroscopy and 3D fluorescence spectroscopy indicated that the binding of DFX to pepsin had minor effect on the protein structure and function. Circular dichroism spectra showed that DFX had no significant effect on the main secondary structure of pepsin. MD analysis also showed that DFX did not affect the looseness of pepsin and the overall secondary structure, but it affected the amino acid residue sequence Leu48-Ala49-Cys50-Ser51-Asp52. Pepsin enzyme activity test showed that the addition of DFX had a slight enhancement effect on the activity of pepsin. Combined with the MD results, DFX bound to pepsin and was closer to the pepsin active site Asp-215, which may affect the electrical environment of Asp-215 residues and enhance the activity of pepsin.


Caldesmon has two calmodulin-binding domains.
Chicken gizzard caldesmon was cleaved with chymotrypsin or CNBr, and the calmodulin-binding fragments were isolated using an affinity column. Limited chymotryptic digestion gives rise to a 38 kDa calmodulin-binding fragment (CT40) as described previously (Szpacenko, A. & Dabrowska, R., FEBS Lett. 202, 182-186, 1986; Fujii, T., Imai, M., Rosenfeld, G. C. & Bryan, J., J. Biol. Chem. 261, 16155-16160, 1987; Yazawa, M., Yagi, K. & Sobue, K., J. Biochem. 102, 1065-1073, 1987). In the case of CNBr cleavage a 37 kDa calmodulin-binding fragment (CB40) was obtained. Both CT40 and CB40 contain a reactive thiol group, but these thiols are apparently in different environments as judged by the responses of attached fluorescent labels to calmodulin-binding. A comparison of the N-terminal sequences of CB40 and CT40 with the complete sequence of caldesmon shows that the two calmodulin-binding fragments in fact originate from different parts of the parent molecule. Thus there exist two calmodulin-binding sites in caldesmon, one in the N-terminal half and the other in the C-terminal half of the molecule. This is consistent with the recent finding that up to two calmodulin molecules can be crosslinked to each caldesmon molecule (Wang, C.-L.A., Biochem. Biophys. Res. Commun., 156, 1033-1038, 1988).


Anti-mycobacterial diynes from the Canadian medicinal plant Aralia nudicaulis.
Aralia nudicaulis, or wild sarsaparilla, is used as a traditional medicinal plant for the treatment of various illnesses by many of the Canadian First Nations. Iroquois and Algonquin First Nations of Eastern Canada use a tea prepared from dried Aralia nudicaulis rhizome as a cough medicine and for the treatment of tuberculosis. Previous investigations of aqueous extracts of Aralia nudicaulis rhizomes have shown it to possess antimycobacterial activity. To isolate and identify antimycobacterial constituents from Aralia nudicaulis rhizomes. Methanolic extracts of Aralia nudicaulis rhizomes were subjected to bioassay guided fractionation using the microplate resazurin assay (MRA) to assess inhibitory activity against Mycobacterium tuberculosis strain H37Ra. The antimycobacterial constituents were identified by NMR, MS and polarimetry. Two C17 polyacetylenes with significant antimycobacterial activity were isolated from the Aralia nudicaulis rhizome extract. The polyacetylenes were identified as (3R)-falcarinol and (3R, 9R, 10S)-panaxydol. Falcarinol and panaxydol displayed MICs of 25.6μM and 36.0μM and IC(50)s of 15.3μM and 23.5μM against Mycobacterium tuberculosis H37Ra. Falcarinol and panaxydol were identified as the principal constituents responsible for the antimycobacterial activity of Aralia nudicaulis rhizomes validating an ethnopharmacological use of this plant by the Canadian First Nations.


Pathophysiology of the progressive optic neuropathy of glaucoma.
Glaucoma is the most common chronic optic neuropathy. Although traditionally considered a disease of elevated intraocular pressure, it is now clear that glaucoma is primarily a distinctive optic neuropathy. This article discusses the distinctive features of glaucoma: disk morphology, visual field patterns, and disease progression. The primary goal is to distinguish glaucoma from other optic neuropathies and, in so doing, to suggest some hypotheses for its etiology.


The orientation of the primary donor in bacterial photosynthesis.
The triplet state EPR spectra of magnetically aligned whole cells of Rhodopseudomonas viridis and Rhodopseudomonas palustris display a marked dependence on the orientation of the static EPR field with respect to the alignment field direction. This observation implies that the primary donor species on which the triplets are localized are ordered within the membranes. We have developed a theoretical model for the system to enable calculation of the orientation of the magnetic axes of the primary donor species with respect to the membranes in which they reside. The triplet state spectra are generated by an ensemble of partially ordered magnetic systems and a computer simulation of the experimental results. The triplet orientation is very similar for the two organisms studied, where one axis lies predominantly in the plane of the membrane and the other two axes have approximately equal projections onto the normal to the membrane.


Isolation and cloning of the endoglucanase gene from Bacillus pumilus and its expression in Deinococcus radiodurans.
With the aim of engineering a strain of bacteria that could be used for bioremediation of cellulosic waste in radioactive environments, the gene for the secreted endoglucanase enzyme of Bacillus pumilis was decided to be cloned into the radiotolerant bacterium, Deinococcus radiodurans. The endoglucanase gene from B. pumilus was PCR amplified and cloned into Escherichiacoli DH5α using a pDrive vector. It was subsequently sub-cloned into E.coli-Deinococcus shuttle vector pRAD1 downstream of the Deinococcus heat-shock promoter, groESL, and the construct was inserted into D. radiodurans. Functional endoglucanase enzyme was expressed in both E.coli and D.radiodurans.


Provider Perceptions of a Humanizing Intervention for Health Care Workers-A Survey Study of PPE Portraits.
Reports from patients and health care workers dealing with coronavirus disease 2019 (COVID-19) underscore experiences of isolation and fear. Some of this experience results from the distancing effect of masks, gloves, and gowns known as personal protective equipment (PPE). One approach to bridging the divide created by PPE is the use of PPE portraits, postcard-sized pictures affixed to PPE. Our confidential electronic mail-based survey aimed to quantify provider attitudes toward PPE portraits. PPE portraits were piloted at an academic safety-net health system experiencing a COVID-19 patient surge during April-May 2020, necessitating use of full PPE for COVID-positive patients and surgical masks in all hospital settings. Our survey assessed staff exposure to PPE portraits, attitudes toward PPE portraits, and potential program expansion. For staff wearing PPE portraits, we also assessed perceptions of interactions with other staff and patients/families and impact on personal well-being. The University of Massachusetts Medical School's Institutional Review Board designated this as a quality improvement project (#H00020279). More than half of survey respondents (n = 111 of 173; 64%) reported exposure to PPE portraits. Attitudes toward PPE portraits were positive overall, with agreement that PPE portraits were a good idea (89%), improved provider mood (79%), enhanced perception of team connection (72%), and more positive among those who reported exposure. Open-ended responses (n = 41) reinforced positive survey data and also raised concerns about infection control (n = 6), cost/logistics (n = 5), and provider vulnerability (n = 3). Providers report that PPE portraits may represent a positive patient-centered idea that helps reassure patients, is well received by interdisciplinary staff, and may enhance patient and team interactions. Potential adaptations to address concerns include photo pins and donor/patient and family experience department support for costs.


The role of submerged macrophytes in phytoremediation of arsenic from contaminated water: A case study on Vallisneria natans (Lour.) Hara.
Arsenic contamination of water is a global concern due to its heavy threat to human health. In this study, the submerged macrophyte Vallisneria natans (Lour.) Hara was used to remove environmentally relevant concentrations of arsenic in the binary As(III)/As(V) system. The concentrations of total arsenic (tAs) and As(III) in water dropped rapidly within 3 days, while As(V) first increased slightly within 3 days and then gradually decreased. About 1.2% dimethylarsinate (DMA) was detected at the 14th day of treatment. These findings indicated that As(III) could be oxidized to As(V) and methylated to DMA in water with V. natans. In relation to V. natans, both tAs and As(V) were much higher in roots compared to leaves. Arsenate was the predominant species (≥ 95.65 ± 0.10%) in roots, and As(III) was only found at the 14th day (3.45-6.96 mg kg-1). In leaves, As(III) significantly increased (P < 0.05) as the treatment duration increased. The proportions of As(V) (27.99-40.03%) were lower than those of As(III) and arsenobetaine (AsB) was detected (0.52-1.87 mg kg-1) after 7 d. The results of arsenic speciation demonstrated that the transformation of arsenic species in V. natans included As(V) reduction and As(III) methylation to AsB. There were a decrease in chlorophyll content, and an increase in MDA level and antioxidant enzymes (SOD, CAT, and POD) activities. The MDA level was much higher in leaves than roots, whereas the activities of SOD, CAT, and POD were the opposite, suggesting their possible role in arsenic resistance and detoxification. Our results indicate the potential of V. natans in phytoremediation of arsenic-contaminated water.


Huntington's disease in children.
Huntington's disease (HD) is a dominantly inherited, fatal neurodegenerative disease. This incurable illness is characterized by a triad of a movement disorder, cognitive decline and psychiatric manifestations. Although most patients with HD have disease onset in the adult years, a small but significant proportion present with pediatric HD. It has been long known that patients with early-onset HD commonly exhibit prominent parkinsonism, known as the Westphal variant of HD. However, even among patients with pediatric HD there are differential clinical features depending on the age of onset, with younger patients frequently presenting diagnostic challenges. In his chapter, the characteristics of patients with childhood- and adolescence-onset HD are discussed, focusing on the differential clinical features that can aid the clinical reach a correct diagnosis, the indications and rational use of genetic testing and the currently available options for symptomatic treatment.


Zeolite-based nanocomposite as a smart pH-sensitive nanovehicle for release of xylanase as poultry feed supplement.
Xylanase improves poultry nutrition by degrading xylan in the cell walls of feed grains and release the entrapped nutrients. However, the application of xylanase as a feed supplement is restricted to its low stability in the environment and gastrointestinal (GI) tract of poultry. To overcome these obstacles, Zeozyme NPs as a smart pH-responsive nanosystem was designed based on xylanase immobilization on zeolitic nanoporous as the major cornerstone that was modified with L-lysine. The immobilized xylanase was followed by encapsulating with a cross-linked CMC-based polymer. Zeozyme NPs was structurally characterized using TEM, SEM, AFM, DLS, TGA and nitrogen adsorption/desorption isotherms at liquid nitrogen temperature. The stability of Zeozyme NPs was evaluated at different temperatures, pH, and in the presence of proteases. Additionally, the release pattern of xylanase was investigated at a digestion model mimicking the GI tract. Xylanase was released selectively at the duodenum and ileum (pH 6-7.1) and remarkably preserved at pH ≤ 6 including proventriculus, gizzard, and crop (pH 1.6-5). The results confirmed that the zeolite equipped with the CMC matrix could enhance the xylanase thermal and pH stability and preserve its activity in the presence of proteases. Moreover, Zeozyme NPs exhibited a smart pH-dependent release of xylanase in an in vitro simulated GI tract.


Machine learning directed discrimination of virgin and recycled poly(ethylene terephthalate) based on non-targeted analysis of volatile organic compounds.
The use of non-decontaminated recycled poly(ethylene terephthalate) (PET) in food packages arouses consumer safety concerns, and thus is a major obstacle hindering PET bottle-to-bottle recycling in many developing regions. Herein, machine learning (ML) algorithms were employed for the discrimination of 127 batches of virgin PET and recycled PET (rPET) samples based on 1247 volatile organic compounds (VOCs) tentatively identified by headspace solid-phase microextraction comprehensive two-dimensional gas chromatography quadrupole-time-of-flight mass spectrometry. 100% prediction accuracy was achieved for PET discrimination using random forest (RF) and support vector machine (SVM) algorithms. The features of VOCs bearing high variable contributions to the RF prediction performance characterized by mean decrease Gini and variable importance were summarized as high occurrence rate, dominant appearance and distinct instrument response. Further, RF and SVM were employed for PET discrimination using the simplified input datasets composed of 62 VOCs with the highest contributions to the RF prediction performance derived by the AUCRF algorithm, by which over 99% prediction accuracy was achieved. Our results demonstrated ML algorithms were reliable and powerful to address PET adulteration and were beneficial to boost food-contact applications of rPET bottles.


Treating lower extremity malperfusion syndrome in acute type A aortic dissection with endovascular revascularization followed by delayed aortic repair.
To assess the outcomes of emergency revascularization with endovascular fenestration/stenting followed by delayed open aortic repair in patients with acute type A aortic dissection with lower extremity (LE) malperfusion syndrome (MPS); that is, necrosis and dysfunction of the lower extremity. From 1996 to 2019, among 760 consecutive acute type A aortic dissection patients 512 patients had no malperfusion syndrome (Non-MPS), whereas 26 patients had LE-MPS with/without renal MPS and underwent endovascular fenestration/stenting, open aortic repair, or both. Patients with coronary, cerebral, mesenteric, and celiac MPS, or managed with thoracic endovascular aortic repair, were excluded (n = 222). All patients with LE-MPS underwent upfront endovascular fenestration/stenting except 1 patient (with signs of rupture) who initially underwent emergency open aortic repair. Among the LE-MPS patients, 17 (65%) had LE pain, 15 (58%) had abnormal motor function with 8 (31%) having paralysis, 10 (38%) had LE pallor, 17 (65%) had LE paresthesia, and 20 (77%) had LE pulselessness. Of the 25 patients undergoing upfront endovascular fenestration/stenting, 16 went on to open aortic repair, 3 survived to discharge without aortic repair, and 6 died before aortic repair (3-aortic rupture and 3-organ failure). In-hospital mortality among all patients was significantly higher in the LE-MPS group (31% vs 6.3%; P = .0003). Among those undergoing open aortic repair, postoperative outcomes were similar between groups, including operative mortality (18% vs 6.5%; P = .10). LE-MPS was a significant risk factor for in-hospital mortality (odds ratio, 6.0 [1.9, 19]; P = .002). In acute type A aortic dissection, LE-MPS was associated with high in-hospital mortality. Emergency revascularization with endovascular fenestration/stenting followed by delayed open aortic repair may be a reasonable approach.


Specific method for determining uric acid in serum using high-performance liquid chromatography and gas chromatography-mass spectropmetry.
A method using a combination of high-performance liquid chromatography and stable-isotope dilution-mass spectrometry is described for the specific quantitation of uric acid in serum. The procedure involves addition of a known amount of [1,3,9-15n]uric acid, as intenral standard, to the serum sample followed by equilibration with the endogenous analyte. After separation from serum proteins, cationic and neutral compounds by anion-exchange chromatography, the purified uric acid is converted into its tetraethyl derivatives. High-performance liquid chromatography is used to isolate the three major isomeric derivatives for measurement of the isotope ratio m/e 280 to m/e 283. This ratio gives the relative abundances of the molecular ions of natural and of labelled tetraethyluric acid, and from it the amount of uric acid in the original serum specimen is determined. Effective separation of tetraethyluric acid isomers can be achieved by adsorption or reversed-phase high-performance liquid chromatography using n-heptane-isopropanol (80:1, v/v) and methanol-water (3:2, v/v), respectively, as solvent systems.


Non-uniform fine structural alteration in the sinus node after cessation or reduction of blood flow.
The sinus node of the dog was examined, using a large-specimen resin-embedding method for combined light and electron microscopy, after 30-240 min of total in vitro ischaemia and after 15-180 min of reduced blood flow in hearts with 2:1 AV block. Although progressive fine structural alteration was observed in the in vitro series, not all cells developed changes at the same rate. Complete loss of glycogen stores and swelling of organelles could be seen in many after only 30 min, whilst others retained their glycogen and showed minimal alteration even after 90 min. Despite relatively severe alteration throughout the node after 120 or more min, some groups of cells showed more extreme degrees of swelling and surface bleb formation than others. In the partially ischaemic in vivo series focal alteration, consisting chiefly of mitochondrial swelling and/or gross dilatation of sarcoplasmic reticulum vesicles, was detectable after 20 min and increased little in extent or degree during longer periods of reduced blood flow. This non-uniform response of sinus nodal cells to ischaemic injury parallels that of contractile atrial muscle cells.


Bovine platelet myosin. II. Fluorescence of the tryptophanyl groups.
The intrinsic fluorescence of bovine platelet myosin was found to change upon addition of the substrate or its analogs in a manner similar to that of rabbit skeletal muscle myosin. The result suggests that the mechanism of ATP cleavage is analogous for myosins from diverse origins.


[Value of cardiac MRI for intraventricular thrombi's diagnosis].
Intraventricular thrombosis is a serious event, generally complicating a wide myocardial infarction. It requires an adapted therapy, based on the oral anticoagulants. The diagnosis is generally carried out by trans-thoracic echocardiography but with an insufficient sensitivity and a specificity. In this context, the place of cardiac MRI remains to be explored. We carried out a retrospective registry of all cardiac MRI done in our hospital since 2003, for assessment of an intracardiac mass or an cerebral stroke. The aim was to compare the results of cardiac MRI with those of echocardiography and contrast ventriculography. Our registry includes 26 cases of intraventricular thrombi, confirmed by cardiac MRI. Our results confirm the lack of sensitivity of echocardiography and the ventriculography. The Kappa correlation coefficient of echocardiography and ventriculography, with respect to the MRI, are very weak, respectively of -0.08 and 0.16. The values of echocardiography and contrast ventriculography seem limited. The realization of a complementary cardiac MRI must be recommended as often as possible in case of doubt or high risk disease.


Lipid hydroperoxide formation in the retina: correlation with retinal degeneration and light damage in a rat model of Smith-Lemli-Opitz syndrome.
The Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disease presenting with multiple congenital anomalies, caused by a defect in cholesterol biosynthesis that results in abnormally elevated levels of 7-dehydrocholesterol (7DHC). Progressive retinal degeneration has been demonstrated in a rat model of SLOS, which is markedly exacerbated by intense light, far more so than occurs in normal albino rats under the same conditions. Herein, we demonstrate that, by six postnatal weeks, retinas in the SLOS rat model contain levels of lipid hydroperoxides (LPOs) comparable to those found in light-damaged albino rats (twice the normal steady-state levels), and that intense light exposure results in a three-fold elevation of LPOs with concomitant severe retinal degeneration. These results suggest a correlation between retinal degeneration and LPO levels. We propose that the presence of 7DHC in the SLOS rat retina potentiates LPO formation, and promotes the observed hypersensitivity to light-induced retinal degeneration.


Measurement of vessel wall strain using cine phase contrast MRI.
To determine the feasibility of using magnetic resonance imaging (MRI) to non-invasively measure strain in the aortic wall. Cine phase contrast MRI was used to measure the velocity of the aortic wall and calculate changes in circumferential strain over the cardiac cycle. A deformable vessel phantom was used for initial testing and in vitro validation. Ultrasonic sonomicrometer crystals were attached to the vessel wall and used as a gold standard. In the in vitro validation, MRI-calculated wall displacements were within 0.02 mm of the sonomicrometer measurements when maximal displacement was 0.28 mm. The measured maximum strain in vitro was 0.02. The in vivo results were on the same order as prior results using ultrasound echo-tracking. Results of in vivo studies and measurement of cyclic strain in human thoracic and abdominal aortas demonstrate the feasibility of the technique.


The Impact of a Multifaceted Simulation Education and Feedback Program for Community Emergency Departments on Pediatric Diabetic Ketoacidosis Management.
We sought to determine if general emergency departments (GEDs) were managing pediatric diabetic ketoacidosis (DKA) correctly and if management could be improved using a multilayered educational initiative. We hypothesized that a multifaceted program of in situ simulation education and formal feedback on actual patient management would improve community GED management of pediatric DKA. This study combined a prospective simulation-based performance evaluation and a retrospective chart review. A community outreach simulation education initiative was developed followed by a formal patient feedback process. Fifteen hospitals participated in simulation sessions and the feedback process. All hospitals were scored for readiness to provide care for critically ill pediatric patients using the Emergency Medical Services for Children (EMSC) Pediatric Readiness Assessment. Six of the 15 have had a second hospital visit that included a DKA scenario with an average performance score of 60.3%. A total of 158 pediatric patients with DKA were included in the chart review. The GEDs with higher patient volumes provided best practice DKA management more often (63%) than those with lower patient volumes (40%). Participating in a DKA simulated scenario showed a trend toward improved care, with 47.2% before participation and 68.2% after participation ( P = 0.091). Participating in the formal feedback process improved best practice management provided to 68.6%. Best practice management was further improved to 70.3% if the GED participated in both a DKA simulation and the feedback process ( P = 0.04). A multifaceted program of in situ simulation education and formal feedback on patient management can improve community GED management of pediatric patients with DKA.


Digging up the recent Spanish memory: genetic identification of human remains from mass graves of the Spanish Civil War and posterior dictatorship.
The Spanish Civil War (1936-1939) and posterior dictatorship (until 1970s) stands as one of the major conflicts in the recent history of Spain. It led to nearly two hundred thousand men and women executed or murdered extra-judicially or after dubious legal procedures. Nowadays, most of them remain unidentified or even buried in irretraceable mass graves across Spain. Here, we present the genetic identification of human remains found in 26 mass graves located in Northern Spain. A total of 252 post-mortem remains were analyzed and compared to 186 relatives, allowing the identification of 87 victims. Overall, a significant success of DNA profiling was reached, since informative profiles (≥ 12 STRs and/or mitochondrial DNA profile) were obtained in 85.71% of the remains. This high performance in DNA profiling from challenging samples demonstrated the efficacy of DNA extraction and amplification methods used herein, given that only around 14.29% of the samples did not provide an informative genetic profile for the analysis performed, probably due to the presence of degraded and/or limited DNA in these remains. However, this study shows a partial identification success rate, which is clearly a consequence of the lack of both appropriate family members for genetic comparisons and accurate information about the victims' location. Hence, further perseverance in the exhumation of other intact graves as well as in the search of more alleged relatives is crucial in order to facilitate and increase the number of genetic identifications.


Toward cardiac tissue characterization using machine learning and light-scattering spectroscopy.
The non-destructive characterization of cardiac tissue composition provides essential information for both planning and evaluating the effectiveness of surgical interventions such as ablative procedures. Although several methods of tissue characterization, such as optical coherence tomography and fiber-optic confocal microscopy, show promise, many barriers exist that reduce effectiveness or prevent adoption, such as time delays in analysis, prohibitive costs, and limited scope of application. Developing a rapid, low-cost non-destructive means of characterizing cardiac tissue could improve planning, implementation, and evaluation of cardiac surgical procedures. To determine whether a new light-scattering spectroscopy (LSS) system that analyzes spectra via neural networks is capable of predicting the nuclear densities (NDs) of ventricular tissues. We developed an LSS system with a fiber-optics probe and applied it for measurements on cardiac tissues from an ovine model. We quantified the ND in the cardiac tissues using fluorescent labeling, confocal microscopy, and image processing. Spectra acquired from the same cardiac tissues were analyzed with spectral clustering and convolutional neural networks (CNNs) to assess the feasibility of characterizing the ND of tissue via LSS. Spectral clustering revealed distinct groups of spectra correlated to ranges of ND. CNNs classified three groups of spectra with low, medium, or high ND with an accuracy of 95.00 ± 11.77 % (mean and standard deviation). Our analyses revealed the sensitivity of the classification accuracy to wavelength range and subsampling of spectra. LSS and machine learning are capable of assessing ND in cardiac tissues. We suggest that the approach is useful for the diagnosis of cardiac diseases associated with changes of ND, such as hypertrophy and fibrosis.


Short- and long-term outcomes of single-port versus multiport laparoscopic radical gastrectomy for gastric cancer: a meta-analysis of propensity score-matched studies and randomized controlled trials.
At present, there is no convincing evidence-based medical basis for the efficacy of single-port laparoscopic gastrectomy. To make a high-quality comparison of the short- and long-term outcomes of single-port laparoscopic gastrectomy versus multiport laparoscopic gastrectomy, we performed this meta-analysis, which only included propensity score-matched studies and randomized controlled trials comparing single-port laparoscopic gastrectomy with multiport laparoscopic gastrectomy for patients with gastric cancer. Data were retrieved from the electronic databases PubMed, EMBASE, Medline, Cochrane Library, CNKI, Wanfang and VIP up to January 2023, and the data included the outcomes of treatment after single-port laparoscopic gastrectomy and multiport laparoscopic gastrectomy. The primary outcomes were early complications, survival rate after surgery at 1 year, and survival rate after surgery at 5 years. The secondary outcomes were number of pain medications, mean operation time, estimated blood loss, hospital mortality, time to first soft fluid diet, time to first flatus, hospital stay after surgery, and retrieved number of lymph nodes. The Jadad score and Newcastle‒Ottawa scale were used to assess the quality of the included studies. After screening, 9 studies were finally included, including 988 patients. The meta-analysis results showed that estimated blood loss (MD=-29.35, 95% CI: -42.95-15.75, P < 0.0001), hospital stay (MD=-0.99, 95% CI:-1.82~-0.17, P = 0.02), and number of pain medications(MD=-0.65, 95% CI:-1.07~-0.23, P = 0.002) in the single-port laparoscopic gastrectomy group were better than those in the multiport laparoscopic gastrectomy group. There is no significant difference between the single-port laparoscopic gastrectomy group and the multiport laparoscopic gastrectomy group in mean operation time(MD = 5.23,95% CI:-16.58~27.04,P = 0.64), time to first soft fluid diet(MD=-0.06,95% CI: -0.30~0.18,P = 0.63), time to first flatus(MD=-0.18,95% CI:-0.43~0.07,P = 0.16), early complication(OR = 0.73,95% CI:0.50~1.09,P = 0.12), hospital mortality(OR = 1.00,95% CI:0.09~11.16,P = 1.00), retrieved number of lymph nodes(MD=-1.15, 95% CI:-2.71~0.40, P = 0.15), survival rate after surgery 1 year(OR = 2.14,95% CI:0.50~9.07,P = 0.30), and survival rate after surgery 5 year(93.7 vs. 87.6%; p = 0.689). This meta-analysis showed that single-port laparoscopic gastrectomy is both safe and feasible for laparoscopic radical gastrectomy for gastric cancer, with similar operation times and better short-term outcomes than multiport laparoscopic gastrectomy in terms of hospital stay, postoperative pain, and estimated blood loss. There was no significant difference in long-term outcomes between single-port laparoscopic gastrectomy and multiport laparoscopic gastrectomy.


Systemic Administration of Human Bone Marrow-Derived Mesenchymal Stromal Cell Extracellular Vesicles Ameliorates Aspergillus Hyphal Extract-Induced Allergic Airway Inflammation in Immunocompetent Mice.
An increasing number of studies demonstrate that administration of either conditioned media (CM) or extracellular vesicles (EVs) released by mesenchymal stromal cells (MSCs) derived from bone marrow and other sources are as effective as the MSCs themselves in mitigating inflammation and injury. The goal of the current study was to determine whether xenogeneic administration of CM or EVs from human bone marrow-derived MSCs would be effective in a model of mixed Th2/Th17, neutrophilic-mediated allergic airway inflammation, reflective of severe refractory asthma, induced by repeated mucosal exposure to Aspergillus hyphal extract (AHE) in immunocompetent C57Bl/6 mice. Systemic administration of both CM and EVs isolated from human and murine MSCs, but not human lung fibroblasts, at the onset of antigen challenge in previously sensitized mice significantly ameliorated the AHE-provoked increases in airway hyperreactivity (AHR), lung inflammation, and the antigen-specific CD4 T-cell Th2 and Th17 phenotype. Notably, both CM and EVs from human MSCs (hMSCs) were generally more potent than those from mouse MSCs (mMSCs) in most of the outcome measures. The weak cross-linking agent 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride was found to inhibit release of both soluble mediators and EVs, fully negating effects of systemically administered hMSCs but only partly inhibited the ameliorating effects of mMSCs. These results demonstrate potent xenogeneic effects of CM and EVs from hMSCs in an immunocompetent mouse model of allergic airway inflammation and they also show differences in mechanisms of action of hMSCs versus mMSCs to mitigate AHR and lung inflammation in this model. There is a growing experience demonstrating benefit of mesenchymal stromal cell (MSC)-based cell therapies in preclinical models of asthma. In the current study, conditioned media (CM) and, in particular, the extracellular vesicle fraction obtained from the CM were as potent as the MSCs themselves in mitigating Th2/Th17-mediated allergic airway inflammation in a mouse model of severe refractory clinical asthma. Moreover, human MSC CM and extracellular vesicles were effective in this immunocompetent mouse model. These data add to a growing scientific basis for initiating clinical trials of MSCs or extracellular vesicles derived from MSCs in severe refractory asthma and provide further insight into the mechanisms by which the MSCs may ameliorate the asthma.


Relationship between helix-coil transition and gene organization of ColE1 plasmid DNA. Differential scanning calorimetric and theoretical studies.
Differential scanning calorimetry (DSC) was carried out to analyze the transition of helix to coil state of DNA, using ColE1 DNA molecules digested with EcoRI. The DSC curves showed multimodal transition, consisting of nine to 11 peaks over a temperature range, depending on the ionic strength of the DNA solution. These DSC curves were essentially in good agreement with the optical melting curves of ColE1 DNA. The theoretical melting profiles of ColE1 DNA were predicted from calculations based on the helix-coil transition theory and the nucleotide sequence of the DNA. These profiles resembled the DSC curves and made it possible to assign the peaks seen in the DSC curves to the helix-coil transition of particular regions of the nucleotide sequence of ColE1. The helix-coil transition of each of the small genes gave rise to a single peak in the DSC curve, while the helix-coil transition of large genes contributed to two or more peaks in the DSC curve. This multimodal transition within a single coding region might correspond to the melting of individual segments encoding the different domains of the proteins. The helix-coil transition at the specific sites including ori, the origin of replication of ColE1, was also found to occur in a particular temperature range. DSC, a simple method, is thus useful for analyzing the multimodal helix-coil transition of DNA, and for providing information on the genetic organization of DNA.


[The fluorescein dilaurate serum test following metoclopramide and secretin stimulation for evaluating pancreatic function. Contribution to the diagnosis of chronic pancreatitis].
A new method of exocrine pancreatic function testing is described. After oral administration of a standard meal containing fluorescein dilaurate (FDL) metoclopramide (10 mg) and secretin (1 U/kg) are given as intravenous bolus injection. The best discrimination between normal and abnormal pancreatic function was found to be the individual peak serum fluorescein concentration within 180 minutes. 184 patients were studied and divided into 4 groups according to the final diagnosis: group 1: 44 healthy controls; group 2: 87 patients with chronic pancreatitis; group 3: 21 patients with different pancreatic diseases; group 4: 32 patients with different gastrointestinal disorders. Sensitivity of the FDL serum-test in detecting chronic pancreatitis was 87%, specificity was 97%. Considering patients with different gastrointestinal disorders specificity dropped to 77%. FDL serum-test revealed superior as compared to the FDL urine test. Correlation between FDL serum-test and secretin ceruletide test was significant (r = 0.72, p less than 0.001).


Assembly and preliminary analysis of a genotoxicity data base for predicting carcinogens.
With a view to developing methodologies for predicting the carcinogenicity of chemicals on the basis of the results of short-term assays and selecting highly predictive batteries of short-term tests, a data base was assembled. The present is a compilation of data extracted from the reports of Gene-Tox working groups, Salmonella mutagenicity data obtained from the U.S. National Toxicology Program and the Environmental Mutagen Information Center and results from BHK21 transformation assays.


The effects of exposure to different clastogens on the pattern of chromosomal aberrations detected by FISH whole chromosome painting in occupationally exposed individuals.
The pattern of chromosomal aberrations (CA) was studied by fluorescence in situ hybridization (FISH) technique (whole chromosomes #1 and #4 painting) in workers occupationally exposed to any of the four following conditions: acrylonitrile (ACN), ethyl benzene (EB), carcinogenic polycyclic aromatic hydrocarbons (c-PAHs), and irradiation in nuclear power plants (NPP), respectively. Decrease in the relative frequency of translocations was observed in EB group, and an increase in reciprocal translocations in ACN and NPP-exposed groups. An increase in a relative number of insertions was registered under all four conditions (significant at ACN, EB, c-PAHs, quasisignificant at NPP-exposed groups). Significant differences in the percentage of lymphocytes with aberrations on chromosome #1 (58.8+/-32.7%, versus 73.8+/-33.6% in the controls, P < 0.05), and chromosome #4 (47.0+/-34.1%, versus 29.4+/-32.2%, P < 0.01) were found in workers exposed to ACN. Similarly, a decrease in the proportion of cells with aberration on chromosome #1 (61.0+/-24.0%, versus 73.8+/-33.6%, P < 0.05) and an increase on chromosome #4 (45.6+/-24.6%, versus 29.4+/-32.2%, P < 0.05) were observed in workers exposed to EB. Frequency of aberrant cells (%AB.C.) as well as genomic frequency of translocations (F(G)/100) increased with age (P < 0.001). Aging also increased the percentage of translocations and reciprocal translocations (P < 0.05), but decreased the relative number of acentric fragments (P < 0.01). Smoking led to significantly increased F(G)/100 (P < 0.05), but did not affect the pattern of chromosomal aberrations. Our results seem to indicate that different carcinogens may induce a different pattern of chromosomal aberrations.


Immunocytochemical identification of luteinizing hormone-releasing hormone-positive fibres and terminals in the olfactory system of the rat.
Luteinizing hormone-releasing hormone immunoreactivity was studied in the olfactory system of the rat in combination with acetylcholinesterase histochemistry. Neuronal perikarya containing luteinizing hormone-releasing hormone lie in the medial septal nucleus, the vertical limb of the diagonal band of Broca, the olfactory tubercule and the ganglionated plexus of the terminal nerve. Labelled fibres spread in the superficial layers of the main and accessory olfactory bulbs, some encompassing the strongly acetylcholinesterase-positive atypical glomeruli. Others are observed on the medial side of the bulb, running along the terminal nerve bundles and ganglia. These fibres join the vomeronasal nerve branches and proceed distally towards the nasal cavity. In the septal submucosa, immunoreactive fibres are partly associated with the terminal nerve network. Conspicuous endings filled with luteinizing hormone-releasing hormone are observed on blood vessels of the olfactory mucosa. Such well-differentiated terminals might be the neurosecretory afferents of a new neurohemal area. Immunoreactive terminals are also observed around the excretory ducts of the anterior medial glands. We have failed to observe any labelled fibres in the olfactory and vomeronasal epithelia. The results of the present study are discussed with respect to possible functional interpretations. It is suggested that significant amounts of luteinizing hormone-releasing hormone could be released in the submucosal capillaries in spite of the scarcity of immunoreactive fibres. Similar afferents could also modulate the secretory activity of some nasal glands. Synaptic events involving the neuropeptide might occur in the olfactory bulb, particularly in atypical glomerular areas previously characterized by their high acetylcholinesterase content. Finally, no anatomical support for a chemosensory function of fibres containing luteinizing hormone-releasing hormone has been brought out by our work.


Poly Implant Prothèse™ (PIP) experience in the United Kingdom: A prospective cohort study into the accuracy of diagnostic imaging findings in comparison to operative findings of 1029 implants.
The Poly Implant Prosthèse™ (PIP) implants were withdrawn from market use in the United Kingdom on 31st March 2010 following Government issued advice. In June 2012 a final Government report was issued and during this period the majority of patients elected to have their prostheses removed. This study presents the operative findings of three surgeons. 517 patients were identified retrospectively from the implant database as having received PIP implants with a total of 1029 implants. 62 patients (124 implants) declined explantation after consultation and imaging. The data was recorded prospectively for all patients and included the clinical, imaging and operative findings. A total of 905 implants were removed of which 129 were ruptured at the time of explantation (14.25%). 27 implants were intact but the presence of liquid surrounding the prosthesis was noted. 93 implants were reported as being ruptured after diagnostic imaging but were intact operatively resulting in a test sensitivity of 0.82 and a specificity of 0.92 yielding a positive predictive value of 0.59 and a negative predictive value of 0.97 overall. Capsule formation was noted in 27 breasts (3%). Our study showed that the prevalence of PIP ruptures is comparable to other manufacturers. The prevalence of implant rupture predictably increased over time and the prevalence of abnormal capsule formation was similar to other manufacturers.


Author Correction: Possible role of L-form switching in recurrent urinary tract infection.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Combined acute traumatic aortic injury and left main bronchus transection in a 5-year-old child.
Blunt traumatic aortic and tracheobronchial injuries are extremely rare in children. We report a case of a 5 year old male who suffered both of these rare injuries (traumatic aortic rupture and left mainstem bronchus transaction). To our knowledge this combination of injuries has not been previously described in a child. CT with multiplanar images was critical for the detection of both injuries.


Balloon dilatation and stent placement of suprahepatic caval anastomotic stenosis following liver transplantation.
We present an unusual case of suprahepatic caval anastomotic stenosis after adult liver transplantation in the early postoperative period. Color flow Doppler sonography and cavography were used to confirm the clinical diagnosis. Successful nonoperative treatment of the obstruction was achieved by balloon dilatation and subsequent implantation of a vascular stent.


Strength and Nature of Host-Guest Interactions in Metal-Organic Frameworks from a Quantum-Chemical Perspective.
Metal-organic frameworks (MOFs) offer a convenient means for capturing, transporting, and releasing small molecules. Their rational design requires an in-depth understanding of the underlying non-covalent host-guest interactions, and the ability to easily and rapidly pre-screen candidate architectures in silico. In this work, we devised a recipe for computing the strength and analysing the nature of the host-guest interactions in MOFs. By assessing a range of density functional theory methods across periodic and finite supramolecular cluster scale we find that appropriately constructed clusters readily reproduce the key interactions occurring in periodic models at a fraction of the computational cost. Host-guest interaction energies can be reliably computed with dispersion-corrected density functional theory methods; however, decoding their precise nature demands insights from energy decomposition schemes and quantum-chemical tools for bonding analysis such as the quantum theory of atoms in molecules, the non-covalent interactions index or the density overlap regions indicator.


[Effect of corticosteroids on content of amino acids in liver tissue during muscular activity].
Metabolism of amino acids in the liver in connection with the adrenocortical functions of the adrenals was studied in rats as affected by 3-hour swimming. This load causes an increase in the content of corticosterone in blood, in the activity of alanine aminotranspherase as well as the decrease in the amount of free amino acids in the liver tissue. These changes are absent in adrenalectomized rats and appear again when corticosterone is administered to adrenalectomized animals before swimming.


Enhanced recovery after posterior deep infiltrating endometriosis surgery: a national study.
To evaluate the impact of the implementation of a national enhanced recovery after surgery (ERAS) program for posterior deep infiltrating endometriosis (DIE) surgery on the length of hospital stay, the rate of postoperative complications, and readmission within 30 days. Comparative exposed/nonexposed observational study. Study based on the French national medicoeconomic database of the Program of Medicalization of Information System. Seven hundred and sixty-four women who underwent DIE surgery were involved and matched (1:3 ratio) into two groups: ERAS group for the year 2019 and non-ERAS group for the year 2015. Surgical management for posterior DIE. The length of hospital stay, the rate of postoperative complications during the initial hospital stay, and readmission within 30 days. The ERAS group included 191 women, and the non-ERAS group included 573 women. The mean length of hospital stay was shorter in the ERAS group than in the non-ERAS group (4.28 ± 3.80 days vs. 5.42 ± 4.04 days, respectively). The rate of postoperative abdominal or pelvic pain syndromes was lower in the ERAS group than in the non-ERAS group (5/191 (2.62%) vs. 48/573 (8.38%), respectively; relative risk, 0.31 [0.125-0.7969]). The rate of postoperative complication and the rate of readmission within 30 days were not different between the two groups. The implementation of ERAS has a significant positive impact on patient outcomes after DIE surgery. The length of hospital stay and abdominal or pelvic pain syndromes were reduced without increasing complications or readmission within 30 days.


Could local surgery improve survival in de novo stage IV breast cancer?
Resection of the primary tumor is recommended for symptom relief in de novo stage IV breast cancer. We explored whether local surgery could provide a survival benefit in these patients and attempted to characterize the population that could benefit from surgery. Metastatic Breast cancer patients (N = 313) with intact primary tumor between January 2006 and April 2013 were separated into two groups according to whether or not they had undergone surgery. The difference in characteristics between the two groups was analyzed using chi-square test, Fisher's exact test and Mann-Whitney test. Univariable and multivariable Cox regression and stratified survival analysis were used to assess the effect of surgery on survival. Of the 313 patients, 188 (60.1%) underwent local surgery. Patients with local surgery had a 47% reduction in mortality risk vs. those with no surgery (median survival 78 months vs. 37 months; HR = 0.53; 95% CI, 0.36-0.78) after adjustment for clinical and tumor characteristics. Stratified survival analysis showed that patients with bone metastasis alone (and primary tumor ≤5 cm), soft tissue metastasis, or ≤ 3 metastasis sites benefit from surgery. Surgical resection of the primary tumor can improve survival in selected de novo stage IV breast cancer patients.


Reproducibility and reliability of pressure flow parameters in women.
The aim of this study was to evaluate the intra- and inter-rater reliability of pressure flow parameters in women. A prospective study. Tertiary referral unit in a London teaching hospital. Urodynamic traces of 621 women were studied to assess the reproducibility and reliability of pressure flow parameters. Women with lower urinary tract symptoms were studied prospectively. Opening detrusor pressure (ODP), detrusor pressure at maximum flow rate P(detQ(max)), maximum flow rate (Q(max)) and closure detrusor pressure (CDP) were measured by the same observer twice, one week apart. Pressure flows were compared using different media for filling (saline and contrast). All parameters were also measured in nine women from multiple voids during ambulatory urodynamics to assess their reproducibility and finally were remeasured by a second observer. There was good intra-observer agreement for all pressure flow parameters except detrusor pressure at maximum flow rate and good inter-observer agreement for opening detrusor pressure, closure detrusor pressure and detrusor pressure at maximum flow rate. There was no significant difference between parameters using saline or contrast (P > 0.05, independent samples t test). Pressure flow parameters appear to be reproducible and consistent urodynamic measurements in women.


Clove essential oil loaded chitosan nanocapsules on quality and shelf-life of blueberries.
In this study, the formation of clove essential oil loaded chitosan nanocapsules (CEO/CS-NCs) was achieved by the ionotropic gelation technology. The spherical shape and core-shell structure of CEO/CS-NCs were characterized by SEM, TEM, and FT-IR. CEO/CS-NCs have a reasonable encapsulation efficiency rate of 39 % and an average size of 253.63 nm. The simulated release of CEO/CS-NCs in a citric acid buffer solution shows that the nano-encapsulation technology could control the sustained release of clove essential oil (CEO). The shelf life of untreated blueberries at room temperature is only about 3 days, while CEO/CS-NCs combined with low-temperature storage can extend the shelf life to about 12 days. The quality characteristic of blueberries, including fruit firmness and moisture content, were effectively maintained, and the rotting rate of blueberries was significantly reduced with CEO/CS-NCs. As a natural preservative, CEO/CS-NCs have a good antioxidant activity close to the commercial antioxidant butylated hydroxytoluene (BHT) and a high antibacterial activity against pathogenic bacteria (PB) isolated from naturally occurring blueberries. Therefore, this study not only gives a theoretical basis for the development of CEO as a commercial preservative but also provides a practical solution to solve the protection challenge of preserving blueberries.


An integrated framework for targeting functional networks via transcranial magnetic stimulation.
Transcranial magnetic stimulation (TMS) is a powerful investigational tool for in vivo manipulation of regional or network activity, with a growing number of potential clinical applications. Unfortunately, the vast majority of targeting strategies remain limited by their reliance on non-realistic brain models and assumptions that anatomo-functional relationships are 1:1. Here, we present an integrated framework that combines anatomically realistic finite element models of the human head with resting functional MRI to predict functional networks targeted via TMS at a given coil location and orientation. Using data from the Human Connectome Project, we provide an example implementation focused on dorsolateral prefrontal cortex (DLPFC). Three distinct DLPFC stimulation zones were identified, differing with respect to the network to be affected (default, frontoparietal) and sensitivity to coil orientation. Network profiles generated for DLPFC targets previously published for treating depression revealed substantial variability across studies, highlighting a potentially critical technical issue.


Fibrils connect microtubule tips with kinetochores: a mechanism to couple tubulin dynamics to chromosome motion.
Kinetochores of mitotic chromosomes are coupled to spindle microtubules in ways that allow the energy from tubulin dynamics to drive chromosome motion. Most kinetochore-associated microtubule ends display curving "protofilaments," strands of tubulin dimers that bend away from the microtubule axis. Both a kinetochore "plate" and an encircling, ring-shaped protein complex have been proposed to link protofilament bending to poleward chromosome motion. Here we show by electron tomography that slender fibrils connect curved protofilaments directly to the inner kinetochore. Fibril-protofilament associations correlate with a local straightening of the flared protofilaments. Theoretical analysis reveals that protofilament-fibril connections would be efficient couplers for chromosome motion, and experimental work on two very different kinetochore components suggests that filamentous proteins can couple shortening microtubules to cargo movements. These analyses define a ring-independent mechanism for harnessing microtubule dynamics directly to chromosome movement.


Estimation of thyroid doses and health risks resulting from the intake of radioactive iodine in foods and drinking water by the citizens of Tokyo after the Fukushima nuclear accident.
The release of radioactive materials from the Fukushima nuclear power plant after the Great East Japan Earthquake on 11 March 2011 poses health risks. In this study, the intake of iodine 131 (I-131) in drinking water and foods (milk, dairy products, and vegetables) by citizens of Tokyo was estimated. The effects of countermeasures (restrictions on the distribution of foods and the distribution of bottled water for infants) on reducing intake were also evaluated. The average thyroid equivalent doses without countermeasures from 21 March 2011 were 0.42 mSv in adults, 1.49 mSv in children, and 2.08 mSv in infants. Those with countermeasures were 0.28, 0.97, and 1.14 mSv respectively, reductions of 33%, 35%, and 45%. Drinking water contributed more to intake by adults and children than foods. The intake of I-131 within the first 2 weeks was more than 80% of the estimated intake, owing to its short half-life, indicating that rapid countermeasures are important in reducing intake. The average risks of cancer incidence and mortality due to I-131 for infants were estimated to be 3×10(-5) and 0.2×10(-5), respectively, lower than the annual risks of traffic accidents, naturally occurring radioactive material (potassium 40), and environmental pollutants such as diesel exhaust particles.


Parenteral Nutrition in the Neonatal Intensive Care Unit: Intravenous Lipid Emulsions.
Intravenous lipid emulsions (ILEs) are a source of nonprotein calories and fatty acids and help promote growth in preterm infants and infants with intestinal failure. An ILE dose and oil source determines its fatty acid, phytosterol, and vitamin E delivery. These factors play a role in the infant's risk for essential fatty acid deficiency and cholestasis, and help modulate inflammation, immunity, and organ development. This article reviews different ILEs and their constituents and their relationship with neonatal health.


Low uptake of [3H]2-deoxy-D-glucose by cultured rat Schwann cells.
[3H]2-Deoxy-D-glucose (2-DG) was used to investigate the glucose uptake in cultured rat Schwann cells from postnatal Sprague-Dawley rat sciatic nerves. The glucose uptake of Schwann cells slightly increased in a time- and dose-dependent manner. However, the maximal uptake level was much lower than that of ethylnitrosourea (ENU)-induced transformed rat schwannoma-like cells and fibroblasts. By autoradiography of the cultured system, we were able to visualize the accumulation of [3H]2-DG grains in the schwannoma-like cells and fibroblasts, but not in Schwann cells.


Expression of ezrin, CD44, and VEGF in giant cell tumor of bone and its significance.
This research aimed to study the role of ezrin, CD44, and VEGF in invasion, metastasis, recurrence, and prognosis of giant cell tumor of bone (GCTB) and its association with the clinical and pathological features of GCTB. Expression status of ezrin, CD44, and VEGF in 80 GCTB tissues and its adjacent noncancerous tissue samples were measured with immunohistochemical and Elivison staining. Their correlation with the clinical and pathologic factors was statistically analyzed by chi-square test. The expression status of ezrin, CD44, and VEGF were significantly higher in GCTB tissue samples than in its adjacent noncancerous tissue samples and in GCTB at Campanacci stage III than in Campanacci stages I and II (P < 0.05). No significant difference was found in age and sex of the patients and locations of the tumor (P > 0.05). Survival analysis showed that the expression status of ezrin, CD44, VEGF, and Campanacci clinical stages of GCTB were positively associated with the survival rate of GCTB patients and negatively associated with ezrin and Campanacci stages of GCTB, indicating that ezrin, CD44, VEGF, and Campanacci clinical stages of GCTB are the independent factors for GCTB. Ezrin, CD44, and VEGF are over-expressed in GCTB tissue and its adjacent noncancerous tissue samples and may play an important role in the occurrence, invasion, metastasis, and recurrence of GCTB. Measurement of ezrin, CD44, and VEGF expression status may contribute to the judgment of prognosis of GCTB patients.


Carbohydrate content of human red cell membrane in patients with cirrhosis of the liver.
The protein and carbohydrate contents of red cell membranes from 12 patients with liver cirrhosis were compared to those from 12 normal donors. Protein content was significantly higher and surface sialic acid and neutral hexoses were similar, whereas surface fucose and hexosamine were significantly lower in the cirrhotic red cells. The role of these membrane modifications is discussed.


Suppression of cytokines and nitric oxide production, and protection against lethal endotoxemia and viral myocarditis by a new NF-kappaB inhibitor.
Nuclear factor kappa B (NF-kappaB) is activated by several factors, which increase the inflammatory response, and this activation, in turn, leads to the expression of several genes such as cytokines, and may play an important role in cardiovascular diseases. The aim of the study is to examine the effect of SUN C8079, a newly synthesized NF-kappaB inhibitor in vitro and in vivo. We examined the effects of SUN C8079 on the transcriptional responses of NF-kappaB, on activation of NF-kappaB in electrophoretic mobility shift assay, and on the gene expressions of tumor necrosis factor (TNF)-alpha and iNOS. We also studied effects of SUN C8079 on lethal endotoxemia and viral myocarditis in mice. SUN C8079 inhibited the lipopolysaccharide (LPS)-induced expression of the genes of TNF-alpha and iNOS by inhibiting the activation of NF-kappaB in vitro. SUN C8079 inhibited the systemic release of TNF-alpha and improved mortality in LPS-treated mice. In addition to protecting mice against lethal endotoxemia, SUN C8079 prevented the development of myocarditis due to the encephalomyocarditis virus (EMCV), and inhibited the expressions of proinflammatory cytokines and the iNOS gene in cardiac tissues. These findings suggest that the activation of NF-kappaB plays an important role in the pathogenesis of endotoxemia and viral myocarditis, and that the NF-kappaB inhibitor, SUN C8079, may be therapeutic in these disorders.


Anterior mediastinal lymphoma arising after resection of an invasive thymoma and immunosuppressive therapy for complicated myasthenia gravis.
We present the case of a 56-year-old woman with an anterior mediastinal tumor who has past history of myasthenia gravis and invasive thymoma. Furthermore, she had superior vena cava syndrome that was caused by a rapidly growing tumor. A biopsy proved diffuse large B-cell lymphoma. After 8 courses of chemotherapy, remission of the lymphoma was achieved. Because a second primary malignancy, including lymphoma, can occur in patients with thymoma, a biopsy is necessary for tumors located in the anterior mediastinum, particularly in patients with a history of treatment for thymoma, to distinguish between recurrence and a second primary malignancy.


Supporting autonomy for people with dementia living in nursing homes: A rapid realist review.
For people with dementia living in nursing homes, autonomy is important. However, they experience difficulty with being heard as an autonomous person, as well as with expressing their preferences and choices. The question is how to support their autonomy. Despite extensive efforts to support autonomy in daily care for people with dementia living in nursing homes, we do not know exactly what works for whom, in which context, how and why. The objective of this realist review is to explore what is known in literature on autonomy support interventions for people with dementia in nursing homes. A rapid realist review of literature. To understand how autonomy is supported, a realist approach was applied that entailed identifying the research question, searching for information, performing a quality appraisal, extracting data, synthesizing the evidence and validating the findings with a panel of experts. Causal assumptions were derived from articles found in four bibliographic databases (PubMed, PsychInfo, Cochrane and CINAHL) leading to context (C)-mechanism (M)-outcome (O) configurations. Data extraction from the included articles ultimately resulted in sixteen CMO configurations on four themes: a. preferences and choice: interventions for supporting autonomy in nursing homes and their results, b. personal characteristics of residents and family: people with dementia and their family being individuals who have their own character, habits and behaviors, c. competent nursing staff each having their own level of knowledge, competence and need for support, and d. interaction and relationships in care situations: the persons involved are interrelated, continuously interacting in different triangles composed of residents, family members and nursing staff. The findings showed that results from interventions on autonomy in daily-care situations are likely to be just as related not only with the characteristics and competences of the people involved, but also to how they interact. Autonomy support interventions appear to be successful when the right context factors are considered.


Atrial natriuretic peptide suppresses isoprenaline and dibutyryl cyclic adenosine monophosphate-induced cell growth in cultured renin-secreting human nephroblastoma cells. Comparison with forskolin-induced renin secretion.
Renin secretion in response to long-term exposure to isoprenaline, dibutyryl cyclic adenosine monophosphate (dbcAMP), forskolin and atrial natriuretic peptide (ANP) was measured in cultured human nephroblastoma cells. Human nephroblastoma cells in culture were treated long-term (1-12 days) with isoprenaline, dbcAMP or forskolin, alone or in combination with ANP; renin release and cell growth were studied. The increase in renin output caused by isoprenaline and dbcAMP could be accounted for by stimulation of cell growth. The effect of isoprenaline was blocked by propranolol. Forskolin stimulated renin secretion per cell. ANP increased extracellular cyclic guanosine monophosphate and suppressed basal renin output. Suppression of basal renin output was due to a reduced secretion rate per cell, without a change in cell growth. ANP suppressed isoprenaline-induced and dbcAMP-induced renin output by blocking increased cell growth, and forskolin-induced renin output by blocking renin secretion. These results suggest that beta-receptor agonists and ANP interact within the kidney to control renin secretion, by helping to determine the number of renin-secreting cells.


[Non invasive methylergometrine test should be carried out after cardiac arrest due to coronary spasm?].
A 59-year-old man was admitted after cardiac arrest with successful reanimation. There was no significant coronary lesion. We conclude to the diagnosis of coronary spasm after the occurrence of a chest pain with anterior ST elevation reversible with intravenous nitrates. One month later, non-invasive methylergometrine test was carried out and complicated by a cardiac arrest due to complete heart block and asystole treated by chest compression, molsidomine and epinephrine. No cardiac event occurred within the following six months. Technique (invasive versus not invasive) and indication of methylergometrine test for the follow-up of severe manifestations of coronary spasm should be better specified in international guidelines.


[The in vitro study on Polistes mandarinus' effects on cariogenic bacteria].
To study the role of Polistes mandarinus on the growth,acid generation and water insoluble glucan(WIG) production of Streptococcus mutans, Streptococcus sanguis and Actinomyces viscosus as a preparation for screening an effective agent ot medicate the balance of oral microflora. Streptococcus mutans 3a3, Streptococcus sanguis SB 179 and Actinomyces viscosus ATCC 19246 were chosen as the experimental bacteria. The effects of Polistes mandarinus on the growth, acid generation and glucan production were observed. Polistes mandarinus can inhibit the growth and acid generation of S.mutans,S.sanguis and A.viscosus, and the water-insoluble glucan production of S.mutants and S.sanguis effectively. Polistes mandarinus can inhibit the growth, acid generation and glucan production of oral bacteria effectively.


Opposite influences of dopaminergic pathways to the prefrontal cortex or the septum on the dopaminergic transmission in the nucleus accumbens. An in vivo voltammetric study.
Modulation of dopaminergic transmission in the nucleus accumbens by the dopaminergic pathways reaching the prefrontal cortex (anteromedian and the suprarhinal parts) and the lateral septum was investigated. Changes in dopaminergic transmission in the nucleus accumbens were assessed by in vivo voltammetry using pretreated carbon fiber electrodes. This technique allows the selective detection of 3,4-dihydroxyphenylacetic acid, the main presynaptic metabolite of dopamine. Dopaminergic transmission in the prefrontal cortex (anteromedian and suprarhinal parts) and the lateral septum was altered by local injection of the dopaminergic agonist (d-amphetamine) and the dopaminergic antagonists (alpha-flupenthixol and sulpiride). Pharmacological interventions, either stimulation or blockade, in the anteromedian and suprarhinal parts of the prefrontal cortex induced, respectively, a decrease or an increase in extracellular 3,4-dihydroxyphenylacetic acid in the nucleus accumbens. The same pharmacological interventions in the lateral septum had exactly opposite effects in the nucleus accumbens. The inhibitory action of the mesocortical and mesorhinal dopaminergic projections and the facilitatory action of the mesoseptal dopaminergic projection on dopaminergic input in the nucleus accumbens were shown to rely on the activity of inhibitory fugal pathways which could be blocked by local injection of tetrodotoxin in the three structures. In a previous work, it was demonstrated that dopaminergic projections in the amygdala exert an inhibitory influence on dopaminergic transmission in the nucleus accumbens. Thus the present results suggest that functional interdependence between the different dopaminergic pathway arising in the ventral mesencephalon is a general property of this neuronal group. Data obtained after manipulation of dopaminergic transmission in these various projection areas may need to be interpret in a different light. Similarly, neurological and psychiatric observations may need to be reconsidered in view of the interdependence of the dopaminergic mesencephalic pathways.


The diagnosis related groups enhanced electronic medical record.
The introduction of Diagnosis Related Groups as a basis for hospital payment in Germany announced essential changes in the hospital reimbursement practice. A hospital's economical survival will depend vitally on the accuracy and completeness of the documentation of DRG relevant data like diagnosis and procedure codes. In order to enhance physicians' coding compliance, an easy-to-use interface integrating coding tasks seamlessly into clinical routine had to be developed. A generic approach should access coding and clinical guidelines from different information sources. Within the Electronic Medical Record (EMR) a user interface ('DRG Control Center') for all DRG relevant clinical and administrative data has been built. A comprehensive DRG-related web site gives online access to DRG grouping software and an electronic coding expert. Both components are linked together using an application supporting bi-directional communication. Other web based services like a guideline search engine can be integrated as well. With the proposed method, the clinician gains quick access to context sensitive clinical guidelines for appropriate treatment of his/her patient and administrative guidelines for the adequate coding of the diagnoses and procedures. This paper describes the design and current implementation and discusses our experiences.


Psychosis, apathy, depression and anxiety in Parkinson's disease.
Psychiatric symptoms are important non-motor features in PD, which occur at high frequency and have significant impact on health related quality of life. This review concentrates on the prevalence, pathophysiology, diagnosis and treatment of depression, anxiety, apathy and psychosis. The pathophysiology of these disorders is complex, reflecting the widespread brainstem and cortical pathology in PD, with involvement of several neurotransmitters, including dopaminergic, serotonergic, noradrenergic and cholinergic systems. The diagnosis of psychiatric conditions, in particular affective disorders, is challenging because of the overlap of somatic features of psychiatric disorders and underlying movement disorder. The pathogenesis is likely to differ considerably from non-PD patients, and treatments used in general psychiatry services may not be as effective in PD and will require clearer clarification in well-designed clinical studies. Management strategies include adjustment of dopaminergic medication, use of psychotropic treatments and behavioural and psychological approaches. However, the future challenge will be to develop treatments developed specifically for the pathogenesis of these disorders in PD.


[A new ultrasonic method for studying the status of the blood supply to the optic nerve].
For investigation of the state of optic nerve blood supply a duplex ultrasound scanning was used. It is known that such equipment begins to gain popularity in general diagnostics. A special method for investigation of the state of optic nerve blood supply (both of the disc and its orbital part) was worked out and allowed to receive 7 hemodynamic parameters characterizing the state of hemodynamics in norm and in optic nerve atrophy or its suspicion. Thus, a pulsatile index being 1.57 +/- 0.21 in norm, increased to 2.11 +/- 0.13 in atrophy. Systolic-diastolic ratio in norm 5.01 +/- 0.21 increased to 7.25 +/- 0.13 in atrophy. The peak systolic rate of blood supply in norm 32.7 +/- 1.8 cm/c decreased to moderate indices 16.9 +/- 1.3 cm/c. Maximum and moderate rates were also decreased twice as compared with norm. Volume rate of blood flow being 5.02 ml/min. in norm, decreased to 2.05 +/- ml/min. in atrophy. The data obtained are statistically authentic. Thus, duplex equipment can be used for investigation of the state of hemodynamics in short posterior ciliary arteries that nourish the optic nerve.


New kids on the block: FOS and FOSB gene.
FOS and FOSB proto-oncogens are involved in a wide variety of tumourigenic processes. FOS and FOSB gene rearrangements are observed in epithelioid haemangioma, pseudomyogenic haemangioendothelioma, osteoid osteoma/osteoblastoma/cementoblastoma and proliferative myositis/fasciitis. In this review, we provide an overview of FOS and FOSB, including their functions and the differences between lesions with known FOS/FOSB gene rearrangements. Additionally, we discuss the use of FOS/FOSB immunohistochemistry as a diagnostic tool for these lesions.


A novel predictive model of outcome in de novo AML based on S-phase activity and proliferative response of blast cells to haemopoietic growth factors.
This study assesses whether the kinetic response of AML cells to HGFs might help to predict initial clinical outcome of treatment in de novo AML in association with age, FAB type and karyotype. Best subset regression analysis indicated optimal variables to develop models to predict prognosis. High S-phase in surviving cells following 7 days incubation in SFM, resistance to stimulation by G+GM-CSF and poor karyotype taken in combination correctly predicted outcome in 83% of patients. The importance of high SFM S-phase may be to indicate autonomous proliferation therefore a leukemic clone more likely to regenerate following therapy at the expense of normal haemopoiesis. Kinetic studies of AML cells may be a useful predictor of outcome in addition to other more established prognostic factors.


Staggerer-specific protein SP47: a unique species among age- and genotype-dependent cerebellar proteins.
Genotype- and age-specific proteins are found in the developing cerebellum of wildtype and staggerer (sg/sg) mutant mice by analysis of silver-stained one- and two-dimensional protein patterns. The methods used are suitable for gross inspection of protein patterns without previous purification, labeling, or immunochemistry. SP47, a polypeptide of 47 kD with a pI of 6.0, appears in the mature staggerer cerebellum, but not in the wildtype. SP47 is different from the astrocytic glial fibrillary acidic protein (GFAP) as shown by immunoblotting. Four polypeptides have been identified with distinct development- and genotype-dependent patterns in the cerebellum. Some of the changes are correlated with events during postnatal histogenesis.


Analytical threshold and stability results on age-structured epidemic models with vaccination.
This paper examines mathematical models for common childhood diseases such as measles and rubella and in particular the use of such models to predict whether or not an epidemic pattern of regular recurrent disease incidence will occur. We use age-structured compartmental models which divide the population amongst whom the disease is spreading into classes and use partial differential equations to model the spread of the disease. This paper is particularly concerned with an analytical investigation of the effects of different types of vaccination schemes. We examine possible equilibria and determine the stability of small oscillations about these equilibria. The results are important in predicting the long-term overall level of incidence of disease, in designing immunisation programs and in describing the variations of the incidence of disease about this equilibrium level.


A novel photobioreactor structure using optical fibers as inner light source to fulfill flashing light effects of microalgae.
In this work, a novel photobioreactor structure using optical fibers being fixed vertically to culture flow direction as inner light source was proposed to fulfill flashing light effects (FLE) of microalgae, so as to obtain high light efficiency. Three types of optical-fiber photobioreactor fulfilling FLE of microalgae, i.e. air-driven panel, pump-driven panel and stirred tank type, were proposed and a 130 L airlift panel one was practically constructed on which both cold (light profile, liquid velocity) and hot model tests were carried out. Results demonstrated that it could produce uniformed light/dark frequencies being over 10 Hz and microalgae productivity increased by 43% and 38% for Spirulina platensis and Scenedesmus dimorphus respectively, compared with the control. This suggested the structure to be a viable and promising option for future photobioreactors.


Complete and Draft Genome Sequences of 52 Bacillus and Priestia Strains Isolated from West African Fermentations and 26 Reference Strains from a Public Culture Collection.
The whole genomes of 78 Bacillus and Priestia strains isolated from West African fermented foods (n = 52) or acquired from a public culture collection (n = 26) were sequenced using long-read sequencing and assembled into draft (n = 32) and complete (n = 46) genomes, allowing comparative genomics and taxonomic assignment of these strains with putative uses in fermented foods.


Separate verbal memory and naming deficits in attention deficit disorder and reading disability.
In this study, verbal memory and naming abilities were investigated in reading disabled (RD) and control children who were characterized according to the presence or absence of attention deficit disorder (ADD). Results indicate that deficits in learning and memory for recently acquired information occur as a function of ADD rather than RD while deficits in naming are specific to RD rather than ADD. We conclude that ADD is a major source of additional and separate cognitive morbidity in RD children.


Application of Behavioral Tests for Evaluation of an Experimental Model of Alzheimer's Disease in Female Rats.
Alzheimer's disease was modeled in female Wistar rats aged 4 months by stereotaxic bilateral injection of a synthetic peptide β-amyloid (Aβ1-42) into the hippocampus. Behavioral tests (open field, Y-maze, passive avoidance, and Morris water maze) revealed significant impairment of memory and spatial navigation 8 weeks after β-amyloid administration. At this term, the cognitive impairments typical of Alzheimer's disease are reproduced. The experimental model of Alzheimer's disease proposed by us can be used in preclinical studies of drugs for the treatment of this pathology.


PTHrP is a novel mediator for TGF-β-induced apoptosis.
Parathyroid hormone-related protein (PTHrP) is a polyhormone secretory protein that plays fundamental roles in the development and function of various tissues. Transforming growth factor (TGF)-β is an important tumor suppressor that induces cell cycle arrest and apoptosis. Increased PTHrP expression has been implicated in TGF-β-induced growth inhibition in human hepatocellular carcinoma cells. However, whether PTHrP is involved in TGF-β-induced apoptosis remains unknown. Using Hep3B and HuH-7, two human hepatocellular carcinoma cell lines, the current study examined the hypothesis that TGF-β-induced apoptosis is mediated by the induction of PTHrP expression. We found that (1) TGF-β induces PTHrP mRNA expression, protein expression and secretion in a time-dependent fashion; (2) knockdown of PTHrP gene expression or neutralization of secreted PTHrP isoforms blocks TGF-β-induced apoptosis; and (3) TGF-β-induced PTHrP expression is Smad3-dependent. Thus, we have identified PTHrP as a novel mediator for TGF-β-induced apoptosis in Hep3B cells. Our findings provide further insights into the mechanisms through which TGF-β conveys tumor suppression activity.


Kinetics of native and modified Bowman-Birk soya-bean trypsin inhibitor on growth and enzymes activities of the chick pancreas.
1. The Bowman-Birk soya-bean trypsin inhibitor (BBTI) begins to cause pancreatic enlargement and increased enzymic activity in the pancreas of chicks after a minimum of 7 d of feeding. 2. The active inhibitory site of BBTI against trypsin is the factor involved in the pancreatic enlargement and increase of pancreatic enzyme activity in chicks.


A case of Bartonella neuroretinitis with macular star diagnosed by clinical, epidemiological, serological, and molecular data: resolution after initiation of antimicrobial therapy.
The differential diagnosis of optic neuritis is broad and varied. We report the case of a 24-year-old Brazilian man who presented with five-week history of fever, malaise, myalgia, severe fatigue, tender right preauricular lymphadenopathy, and acute vision blurring associated with right optic disc swelling and exudates in a macular star pattern. His illness developed soon after an infestation of fleas broke out among his cats. Diagnosis of ocular bartonellosis was confirmed by serological and molecular analyses targeting amplification of Bartonella spp. htrA gene. Signs and symptoms only improved after initiation of antimicrobial therapy.


Investigations differentiating the mechanism of specific bradycardic agents from that of calcium channel blockers.
The effects of two "specific bradycardic agents", falipamil (AQ-A 39) and the alinidine-congener STH 2148 (2-[N-(cyclopropylmethyl)-N-(2,6-dibromophenyl)amino]-2-imidazolin e), on the spontaneous electrical discharge rate of intact guinea-pig sinus node preparations were investigated in comparison to that of the "calcium channel blocker" verapamil. Addition of falipamil (10 micrograms/ml) to a maximally rate lowering concentration of STH 2148 (30 micrograms/ml) exerted no further bradycardic effect. In contrast, verapamil (0.1 microgram/ml) added to either STH 2148 (30 micrograms/ml) or a maximally effective concentration of falipamil (30 micrograms/ml) resulted in a further, significant reduction of sinus rate. The results are compatible with the idea of a common mechanism of the two specific bradycardic agents, different from that of calcium channel blockers.


The members of M20D peptidase subfamily from Burkholderia cepacia, Deinococcus radiodurans and Staphylococcus aureus (HmrA) are carboxydipeptidases, primarily specific for Met-X dipeptides.
Three members of peptidase family M20D from Burkholderia cepacia (BcepM20D; Uniprot accession no. A0A0F7GQ23), Deinococcus radiodurans R1 (DradM20D; Uniprot accession no. Q9RTP6) and Staphylococcus aureus (HmrA; Uniprot accession no. Q99Q45) were characterized in terms of their preference for various substrates. The results thus reveal that all the enzymes including HmrA lack endopeptidase as well as aminopeptidase activities and possess strong carboxypeptidase activity. Further, the amidohydrolase activity exerted on other substrates like N-Acetyl-Amino acids, N-Carbobenzoxyl-Amino acids and Indole acetic acid (IAA)-Amino acids is due to the ability of these enzymes to accommodate different types of chemical groups other than the amino acid at the S1 pocket. Further, data on peptide hydrolysis strongly suggests that all the three enzymes are primarily carboxydipeptidases exhibiting highest catalytic efficiency (kcat/Km 5-36 × 10(5) M(-1) s(-1)) for Met-X substrates, where -X could be Ala/Gly/Ser/Tyr/Phe/Leu depending on the source organism. The supportive evidence for the substrate specificities was also provided with the molecular docking studies carried out using structure of SACOL0085 and homology modelled structure of BcepM20D. The preference for different substrates, their binding at active site of the enzyme and possible role of these enzymes in recycling of methionine are discussed in this study.


Bird communities across different levels of human settlement: A comparative analysis from two northern Amazonian ecoregions.
Urban ecosystems are increasingly dominating landscapes globally, so it is critical to understand the effects of human settlements on biodiversity. Bird communities are effective indicators because they are impacted by the size and expansion of human settlements, exemplified by changes in their habitat use, breeding and foraging behaviours, as well as patterns of richness and abundance. Existing studies on bird community responses to human settlements have mainly focused on single ecoregions and large cities, leaving a gap in comparative research on how differently sized human settlements affect bird communities across various ecoregions. To address this gap, we examine species richness, bird abundances and community composition in human settlements, which exhibit variable sizes, populations, landscape configurations, and overall intensity of settlement in two tropical ecoregions in Guyana, Amazonia: forest and savannah. In each ecoregion we explored how different groupings of urban tolerance in birds responded to human settlements of differing population size and building densities. Overall, we found significant differences in bird communities across the varying levels of human settlement intensity in both ecoregions, with greater differences in bird community composition in the forest ecoregion than the savannah region. In both ecoregions, species richness and abundance were highest at the medium level of settlement of human settlement. Our findings suggest that bird tolerance to human settlements varies based on ecoregion and site-level factors. In the savannah, built features may be benefitting birds from all urban tolerance levels, but they have a negative impact on less urban-tolerant species in the forest ecoregion. Our comparative analysis reveals for the first time that the impact of human settlements on avian communities in northern Amazonia varies among ecoregions, indicating that species evolved to live in a savannah may be more tolerant to human settlements than those more evolved to a forest system.


Comparison of the aqueous solubilization of practically insoluble niclosamide by polyamidoamine (PAMAM) dendrimers and cyclodextrins.
This study is the first report of the solubilization of niclosamide by cyclodextrin complexation or the interaction between the drug and polyamidoamine (PAMAM) dendrimers. Half generation dendrimers with more polar carboxylate surface functional groups did not increase the solubility of niclosamide. From the phase solubility studies, when the fold enhancement in solubility of niclosamide combined with full generation amine terminated PAMAM dendrimers was compared with that obtained when the drug was combined with beta- or hydroxypropyl-beta-cyclodextrin, the results showed that, except for G-0 dendrimer at pH 7, the solubility of niclosamide was significantly higher in the presence of the dendrimers. In addition, higher equilibrium stability constants and complexation efficiency showed that the dendrimers formed stronger more stable complexes than the CDs. However, the strong interaction between the amine surface functional groups and the niclosamide molecule complexes caused a decrease in dissolution rate compared to the CDs because the interaction retarded the release of the drug from the dendrimers. In addition to increasing the solubility, PAMAM dendrimers therefore also offer the possible for the controlled release of the drug from solid dosage forms.


The long-term consequences of repetitive head impacts: Chronic traumatic encephalopathy.
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts (RHI). Although described in boxers for almost a century, scientific and public interest in CTE grew tremendously following a report of postmortem evidence of CTE in the first former professional American football player in 2005. Neuropathologic diagnostic criteria for CTE have been defined, with abnormal perivascular deposition of hyperphosphorylated tau at the sulcal depths as the pathognomonic feature. CTE can currently only be diagnosed postmortem, but clinical research criteria for the in vivo diagnosis of CTE have been proposed. The clinical phenotype of CTE is still ill-defined and there are currently no validated biomarkers to support an in-life diagnosis of "Probable CTE." Many knowledge gaps remain regarding the neuropathologic and clinical make-up of CTE. An increased understanding of CTE is critical given the millions that could potentially be impacted by this disease. This chapter describes the state of the literature on CTE. The historical origins of CTE are first presented, followed by a comprehensive description of the neuropathologic and clinical features. The chapter concludes with discussion on future research directions, emphasizing the importance of diagnosing CTE during life to facilitate development of preventative and intervention strategies.