Effect of different fluoride concentrations of experimental dentifrices on enamel erosion and abrasion.
It has been suggested that fluoride products are able to reduce erosive tooth wear. Thus, the purpose of this in vitro study was to evaluate the effect of dentifrices with different fluoride concentrations as well as of a low-fluoridated dentifrice supplemented with trimetaphosphate (TMP) on enamel erosion and abrasion. One hundred twenty bovine enamel blocks were assigned to the following experimental dentifrices: placebo, 1,100 microg F/g, 500 microg F/g plus 3% TMP and 5,000 microg F/g. The groups of enamel blocks were additionally subdivided into conditions of erosion (ERO) and of erosion plus abrasion (ERO + ABR). For 7 days, the blocks were subjected to erosive challenges (immersion in Sprite 4 times a day for 5 min each time) followed by a remineralizing period (immersion in artificial saliva between erosive challenges for 2 h). After each erosive challenge, the blocks were exposed to slurries of the dentifrices (10 ml/sample for 15 s). Sixty of the blocks were additionally abraded by brushing using an electric toothbrush (15 s). The alterations of the enamel were quantified using the Knoop hardness test and profilometry (measurements in micrometers). The data were analyzed using a 2-way ANOVA test followed by a Bonferroni correction (p < 0.05). In in vitro conditions, the 5,000 microg F/g and 500 microg F/g plus 3% TMP dentifrices had a greater protective effect when compared with the 1,100 microg F/g dentifrice, under both ERO and ERO + ABR conditions. The results suggest that dentifrices alone are not capable of completely inhibiting tooth wear.


Polycyclic aromatic hydrocarbons--catalysts for molecular hydrogen formation.
Polycyclic aromatic hydrocarbons (PAHs) have been shown to catalyse molecular hydrogen formation. The process occurs via atomic hydrogen addition reactions leading to the formation of super-hydrogenated PAH species, followed by molecular hydrogen forming abstraction reactions. Here, we combine quadrupole mass spectrometry data with kinetic simulations to follow the addition of deuterium atoms to the PAH molecule coronene. When exposed to sufficiently large D atom fluences, coronene is observed to be driven towards the completely deuterated state (C24D36) with the mass distribution peaking at 358 amu, just below the peak mass of 360 amu. Kinetic models reproduce the experimental observations for an abstraction cross-section of sigma(abs) = 0.01 angstroms2 per excess H/D atom, and addition cross-sections in the range of sigma(add) = 0.55-2.0 angstroms2 for all degrees of hydrogenation. These findings indicate that the cross-section for addition does not scale with the number of sites available for addition on the molecule, but rather has a fairly constant value over a large interval of super-hydrogenation levels.


A comprehensive characterization of longevity and culling reasons in Canadian Holstein cattle based on various systematic factors.
The decision of premature culling cows directly impacts the profitability of dairy farms. A comprehensive characterization of the primary causes of culling reasons would greatly improve both management and selection objectives in dairy cattle breeding programs. Therefore, this study aimed to analyze the temporal frequencies of 34 culling reasons in Canadian Holstein cows. After data editing and quality control, records from 3,096,872 cows culled from 9,683 herds spread across Canada were used for the analyses covering the periods from 1996 to 2020. Reproductive issues were the main culling reason accounting for 23.02%, followed by milk production (20.82%), health (20.39%), conformation problems (13.69%), economic factors (13.10%), accidents (5.67%), age-related causes (1.67%), and workability (1.63%). Nearly fifty-eight percent of cows were culled after 47 months of age. The observed frequencies of culling due to economic factors were lower than expected from 1996 to 2014 and higher than expected between 2015 and 2020. Reproduction issues had the highest culling frequencies during fall (24.54%), winter (24.02%), and spring (22.51%), while health issues were the most frequent (22.51%) culling reason in the summer season. Health issues (25.50%) and milk production (27.71%) were the most frequent culling reasons in the provinces of Quebec and Ontario, respectively. Reproductive issues showed the highest frequency across climates based on the Köppen climate classification, except for Csb (Dry-summer subtropical or Mediterranean climate) and Bsk (Middle latitude steppe climate), which correspond to small regions in Canada, where production was the most frequent culling reason (29.42% and 21.56%, respectively). Reproductive and milk performance issues were the two main culling reasons in most ecozones, except in Boreal Shield and Atlantic Marine, where health issues had the highest frequencies (25.12 and 23.75%, respectively). These results will contribute to improving management practices and selective decisions to reduce involuntary culling of Holstein cows.


The impact of Huntington's disease on family life.
By assessing a group of adults who grew up in a household with a parent affected by Huntington's disease (HD), the authors explored the hypothesis that HD causes major disruption in family life. High rates of family dysfunction were reported. Adverse parenting in the form of parental and maternal overcontrol and paternal abuse were endorsed for both the HD-positive and HD-negative parent. These results illustrate the impact on all members of a family coping with HD. They are particularly stark, given the overall psychological health of the sample, and suggest that there is an urgent need to use a family perspective when assessing the need for psychosocial intervention in HD.


Morphological and Phytochemical Diversity among Hypericum Species of the Mediterranean Basin.
The genus Hypericum L. (St. John's wort, Hypericaceae) includes more than 450 species that occur in temperature or tropical mountain regions of the world. Monographic work on the genus has resulted in the recognition and description of 36 taxonomic sections, delineated by specific combinations of morphological characteristics and biogeographic distribution. The Mediterranean Basin has been recognized as a hot spot of diversity for the genus Hypericum, and as such is a region in which many endemic species occur. Species belonging to sections distributed in this area of the world display considerable morphological and phytochemical diversity. Results of a cladistic analysis, based on 89 morphological characters that were considered phylogenetically informative, are given here. In addition, a brief overview of morphological characteristics and the distribution of pharmaceutically relevant secondary metabolites for species native to this region of the world are presented.


A new model for using quantitative urine testing as a diagnostic tool for oxycodone treatment and compliance.
We conducted a prospective, randomized, cross-sectional study to develop and validate a new model to predict oxycodone in urine that can be used to help evaluate whether patients are complying with their oxycodone dosing regimens. We studied 20 patients: eight black women, two white women, six black men, and four white men; ages 48 ± 10 years (mean ± SD); weight 97 ± 32 kg. Pain levels before treatment averaged 9.5 ± 0.9 out of 10. We prescribed oral oxycodone for each patient, tailoring the dosing regimen using clinical pharmacokinetics and measured the oxycodone concentration in each patient's urine 10 to 14 days after starting the dosing regimen. For each patient, we predicted oxycodone in their urine using our model, checked the actual concentration, and compared predicted with actual concentrations. For 18 of 20 patients (90%), actual results fell within ±10% of our model's prediction. One patient was 35% below the prediction; the other was 51% above. Our model accurately predicts oxycodone in urine (±10% for 90% of the patients). The model appears clinically useful for evaluating the results of a quantitative urine test, since it objectively discriminates between (1) a "normal" patient complying with their oxycodone dosing regimen, and (2) a patient who may require genetic testing to distinguish between unusual metabolism or abuse.


Percutaneous versus open pedicle screw instrumentation in treatment of thoracic and lumbar spine fractures: A systematic review and meta-analysis.
To assess the safety and efficacy of percutaneous short-segment pedicle instrumentation compared with conventionally open short-segment pedicle instrumentation and provide recommendations for using these procedures to treat thoracolumbar fractures. The Medline database, Cochrane database of Systematic Reviews, Cochrane Clinical Trial Register, and Embase were searched for articles published. The randomized controlled trials (RCTs) and non-RCTs that compared percutaneous short-segment pedicle instrumentation to open short-segment pedicle instrumentation and provided data on safety and clinical effects were included. Demographic characteristics, clinical outcomes, radiological outcomes, and adverse events were manually extracted from all of the selected studies. Methodological quality of included studies using Methodological Index for Non-Randomized Studies scale and Cochrane collaboration's tool for assessing the risk of bias by 2 reviewers independently. Nine studies encompassing 433 patients met the inclusion criteria. Subgroup meta-analyses were performed according to the study design. The pooled results showed there were significant differences between the 2 techniques in short- and long-term visual analog scale, intraoperative blood loss, operative time, postoperative draining loss, hospital stay, and incision size, although there were no significant differences in postoperative radiological outcomes, Oswestry Disability Index, hospitalization cost, intraoperative fluoroscopy time, and adverse events. Percutaneous short-segment pedicle instrumentation in cases with achieve satisfactory results, could replace in many cases extensive open surgery and not increased related complications. However, further high-quality RCTs are needed to assess the long-term outcome of patients between 2 techniques.


Bioluminescent Optogenetics 2.0: Harnessing Bioluminescence to Activate Photosensory Proteins In Vitro and In Vivo.
Bioluminescence - light emitted by a luciferase enzyme oxidizing a small molecule substrate, a luciferin - has been used in vitro and in vivo to activate light-gated ion channels and pumps in neurons. While this bioluminescent optogenetics (BL-OG) approach confers a chemogenetic component to optogenetic tools, it is not limited to use in neuroscience. Rather, bioluminescence can be harnessed to activate any photosensory protein, thus enabling the manipulation of a multitude of light-mediated functions in cells. A variety of luciferase-luciferin pairs can be matched with photosensory proteins requiring different wavelengths of light and light intensities. Depending on the specific application, efficient light delivery can be achieved by using luciferase-photoreceptor fusion proteins or by simple co-transfection. Photosensory proteins based on light-dependent dimerization or conformational changes can be driven by bioluminescence to effect cellular processes from protein localization, regulation of intracellular signaling pathways to transcription. The protocol below details the experimental execution of bioluminescence activation in cells and organisms and describes the results using bioluminescence-driven recombinases and transcription factors. The protocol provides investigators with the basic procedures for carrying out bioluminescent optogenetics in vitro and in vivo. The described approaches can be further extended and individualized to a multitude of different experimental paradigms.


Efficacy of relaxation techniques in hypertensive patients.
We examined 117 outpatients (20- to 45-year-old men) with mild essential hypertension before treatment, after the main treatment course (6 weeks), and at 12-month follow-up. The patients were randomized into two major groups: (a) a treatment group that received autogenic training (23 patients), biofeedback (24 patients), or breathing-relaxation training (23 patients) and (b) a control group that consisted of 24 patients who did not receive any intervention and 23 patients who were treated with a "psychological placebo." Clinical, psychological, and psychophysiological data from all patients who were offered relaxation therapy were analyzed. By the end of follow-up, and compared to the control group, the treatment group demonstrated a significant reduction in systolic and diastolic blood pressures, peripheral vascular resistance, and hypertensive response to emotional stress, and an improvement in psychological adaptation, quality of life, and capacity for work. Comparative analysis of the efficacy of different relaxation methods revealed that biofeedback and breathing-relaxation training resulted in the greatest reduction in blood pressure. The antihypertensive effect of relaxation therapy correlated positively with pretreatment blood pressure levels and negatively with the duration of illness and certain psychological features.


[Dark adaptation of patients with head and neck tumors].
20 patients with tumors of the head and neck region have a delayed dark adaption. The serum vitamin A levels in these patients are significantly diminished versus controls. Since disturbance of dark adaption does not occur before long during deficiency of vitamin A, it is assumed that the deficiency was existent long time before. With regard to the possible antineoplastic potency of vitamin A, this is considered a possibly important factor in tumor development and growth. The disturbed vitamin A metabolism is possibly due to a long lasting imbalanced diet.


Growth hormone inhibition of lipogenesis in sheep adipose tissue: requirement for gene transcription and polyamines.
The chronic inhibitory effect of growth hormone (GH) on lipogenesis in sheep adipose tissue explants was investigated in an in vitro tissue culture system. In the absence of other hormones, GH caused a decrease in the rate of lipogenesis after 6 h of culture. In contrast, when lipogenesis was stimulated by the presence of insulin plus dexamethasone, GH again decreased lipogenesis but after a lag of at least 12 h. Actinomycin D, an inhibitor of gene transcription, prevented the effect of GH on lipogenesis in both the absence and presence of insulin plus dexamethasone. Actinomycin D added to tissue previously incubated for 6 h in the presence of GH alone prevented further decline in lipogenesis over the next 5 h, suggesting that transcription of a short-lived mediator protein is required for the GH effect to occur. An increase in ornithine decarboxylase activity was detected in explants exposed to GH, reaching a peak after 12 h incubation; this was prevented by actinomycin D. Methylglyoxal bis-(guanylhydrazone), an inhibitor of polyamine biosynthesis, partially alleviated the effect of GH on lipogenesis; this was reversed by addition of spermidine. However, spermidine did not reverse the effects of actinomycin D, implicating a short-lived protein in addition to ornithine decarboxylase in the action of GH. In the absence of other hormones GH had no effect on either the expressed (initial) or total activity of acetyl-CoA carboxylase, but GH prevented the increase in both expressed and total activities of the enzyme induced by insulin plus dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)


Acid digestion of carbonates using break seal method for clumped isotope analysis.
Acid digestion of carbonates to release CO2 is a crucial and sensitive step in sample preparation for clumped isotope analysis. In addition to data reduction and instrumental artefacts, many other uncertainties in the clumped isotope analysis of carbonates arise from the method used for the preparation of CO2 . We describe here an in-house-designed reaction vessel that circumvents degassing and contamination problems commonly associated with the McCrea-type digestion protocols. We designed a leak-free break seal reaction vessel (made of Pyrex™) suitable for prolonged acid digestion at 25°C. Using this new vessel, several carbonate reference materials widely used in the clumped isotope community and other in-house laboratory standards were acid-digested and analysed for their δ13 C, δ18 O and Δ47 values with a dual inlet MAT 253 isotope ratio mass spectrometer following standard gas chromatography purification and data evaluation protocols. Long-term reproducibility in Δ47 determination was established using international references and in-house working standards as follows (mean and SE): Carrara-1 (0.395 ± 0.002‰, n = 43), Carrara-2 (0.441 ± 0.003‰, n = 22), OMC (0.587 ± 0.004‰, n = 16), NBS 19 (0.393 ± 0.005‰, n = 10), NBS 18 (0.473 ± 0.003‰, n = 5), ETH 1 (0.271 ± 0.005‰, n = 7), ETH 3 (0.698 ± 0.005‰, n = 3), MZ (0.715 ± 0.002‰, n = 3) and several others. A new method using a break seal tube was found to be efficient for the clumped isotope analysis of carbonates that require longer reaction time at 25°C. This method yields good precision in Δ47 analysis and was found to be suitable for acid digestions at any desired temperature.


Comparison of the C14 urea breath test and histopathology in the diagnosis of Helicobacter pylori in the elderly.
To compare the sensitivity and specificity of C[14] urea breath test with histopathological findings in biopsies obtained through endoscopy. In this cross-sectional study, conducted at the Medical Faculty Ankara University, Ankara, Turkey between January and October 2009, 100 patients aged 65 and above who fulfilled the criteria for inclusion were enrolled. Oesophago-gastroduodenoscopy was carried out on the patients after eight hours of fasting, using a Fujinon endoscope, by the same expert. C14 urea breath tests were carried out on all patients with a capsule containing 37 kBq(1micro Ci) C14 urea/citric acid. Evaluation of all data was carried out using SPSS 11.5. Categorical variables were compared through Pearson Chi squared or Fisher's exact test. P < 0.005 was taken as statistically significant. The average age of the patients was 71 +/- 5 years; 43 (43%) were male; and 57 (57%) were female. Helicobacter pylori positivity was found to be 35 (35%) in histopathological evaluation, and 36 (36%) in the C14 urea breath test. Of the 35 patients, 32 (91.4%) were found to be positive by the C14 urea breath test also. Of the 65 patients who were found to be negative on histopathology, 61 (93.8%) were also found to be Hp negative by the C14 urea breath test, and 4 (6.2%) were evaluated as false positive. A statistically significant correlation (p < 0.001) was found between histopathological and C14 urea breath test results. Compared with histopathology, the sensitivity of the urea breath test was 91.4%, and its specificity was 93.8%. A statistically significant (p < 0.001) relationship was found between histopathological results and the results of the C14 urea breath test. The sensitivity and specificity of the C[14] urea breath test in the group of elderly patients selected was high. The C14 urea breath test can be considered in the elderly group for diagnosis of Helicobacter pylori infection.


[Influence of mycobacterium on adaptive rearrangement in guinea pigs long exposed to polycystic aromatic hydrocarbon-containing agents].
Experiments on different groups of guinea pigs inoculated with Mycobacterium tuberculosis (MBT) and intact guinea pigs who received coal refining products and control ones indicated that long exposure to coal-tar resin enhanced mobilization of methionine from the liver with its accumulation in the lung and hematopoietic organs, increased the biosynthesis of arginine in the liver and its accumulation in the lung and hematopoietic organs. MBT drastically enhanced the exchange of the metabolites accumulated in the organs and prevented the formation of adaptive reactions to long-term exposure to polycyclic aromatic hydrocarbons at the level of membranous metabolism.


Effect of vaporization temperature on the diameter and chiral angle distributions of single-walled carbon nanotubes.
Pulsed laser vaporization synthesis of single-wall carbon nanotubes on Co/Ni and Rh/Pd catalysts was explored with respect to variations in the production temperature. The nanotube type populations were determined via photoluminescence, UV-Vis-NIR absorption and Raman spectroscopy. It was found that lowered production temperature leads to smaller nanotube diameters and exceptionally narrow (n, m) type distributions, with marked preference towards large chiral angles for both catalysts. Interestingly, larger nanotube diameters tend to be associated with larger chiral angles. These results demonstrate that PLV production technique can provide at least partial control over the nanotube (n, m) populations. In addition, these results have implications for the understanding the nanotube nucleation mechanism in the laser oven. SWCNT synthesized at lower temperatures appear quite attractive as a starting material for nanotube type separation experiments.


[Cystic fibrosis in a 70-year-old woman].
Cystic fibrosis is usually diagnosed in early childhood, and patients rarely live beyond the age of 40. We present a case of a 70-year-old woman, in whom cystic fibrosis was diagnosed with the rare mutation, R117C. Cystic fibrosis should therefore also be considered in older patients.


Effect of Secondary Alveolar Bone Grafting on the Maxillary Growth: Unilateral Versus Bilateral Cleft Lip and Palate Patients.
The purpose of this study was to investigate the effect of secondary alveolar bone grafting (SABG) on the maxillary growth in patients with unilateral (UCLP) and bilateral cleft lip and palate (BCLP). The samples consisted of 40 Korean boy cleft patients who had the similar initial skeletal characteristics and were treated with the identical treatment protocol. They were divided into UCLP group (N = 25; mean SABG age, 9.9 years; mean follow-up duration, 42.3 months) and BCLP group (N = 15; mean SABG age, 10.2 years; mean follow-up duration, 40.6 months). In the lateral cephalograms taken 1 month before (T1) and at least 2 years after SABG (T2), cephalometric variables were measured. At T1 stage, the 2 groups did not exhibit significant differences in the cephalometric variables except posterior maxillary height (P-HRP) (P < 0.05). At T2 stage, both groups exhibited the reduced sagittal growth (UCLP, ANB, P < 0.001; AB to facial plane angle (AB-FPA), P < 0.01; BCLP, A to N perpendicular, P < 0.05; ANB and AB-FPA, P < 0.001) and the undisturbed vertical growth (A-HRP and P-HRP, all P < 0.001) of the maxilla. During T1 to T2, BCLP group experienced more aggravation of Class III skeletal pattern than UCLP group (ΔAB-FPA, P < 0.05). There, however, were no differences in the amounts of changes in the maxillary vertical position and mandibular plane angulation between the 2 groups. Two-stage SABG procedure subgroup in patients with BCLP demonstrated a more retrusive maxilla compared with 1-stage SABG procedure subgroup (ΔSNA, P < 0.05). Patients with BCLP, especially who underwent 2-stage SABG procedure, might have a possibility of poor sagittal growth of the maxilla compared with patients having UCLP.


Region-specific permeability of the blood-brain barrier upon pericyte loss.
The blood-brain barrier (BBB) regulates differing needs of the various brain regions by controlling transport of blood-borne components from the neurovascular circulation into the brain parenchyma. The mechanisms underlying region-specific transport across the BBB are not completely understood. Previous work showed that pericytes are key regulators of BBB function. Here we investigated whether pericytes influence BBB permeability in a region-specific manner by analysing the regional permeability of the BBB in the pdgf-b ret/ret mouse model of pericyte depletion. We show that BBB permeability is heterogeneous in pdgf-b ret/ret mice, being significantly higher in the cortex, striatum and hippocampus compared to the interbrain and midbrain. However, we show that this regional heterogeneity in BBB permeability is not explained by local differences in pericyte coverage. Region-specific differences in permeability were not associated with disruption of tight junctions but may result from changes in transcytosis across brain endothelial cells. Our data show that certain brain regions are able to maintain low BBB permeability despite substantial pericyte loss and suggest that additional, locally-acting mechanisms may contribute to control of transport.


Antigen-binding activity and allergenicity of heterologous gamma-globulin absorbed from the rectum.
The molecular integrity of rectally absorbed antigens was studied in rats and mice. ABout 2% in the radioactivity of 125I-labelled horse gamma-globulin administered rectally reached the blood circulation. One fifth of this absorbed radioactivity (0.4%) reacted with anti-Fab antibody and about one eight (0.25%) of the original antigen-binding activity was maintained. The results indicated that a small but significant portion of the rectally administered proteins remained intact and retained the immunological function. Rectally-administered proteins induced IgE antibody responses in the rat and the mouse.


BeamLearning: An end-to-end deep learning approach for the angular localization of sound sources using raw multichannel acoustic pressure data.
Sound source localization using multichannel signal processing has been a subject of active research for decades. In recent years, the use of deep learning in audio signal processing has significantly improved the performances for machine hearing. This has motivated the scientific community to also develop machine learning strategies for source localization applications. This paper presents BeamLearning, a multiresolution deep learning approach that allows the encoding of relevant information contained in unprocessed time-domain acoustic signals captured by microphone arrays. The use of raw data aims at avoiding the simplifying hypothesis that most traditional model-based localization methods rely on. Benefits of its use are shown for real-time sound source two-dimensional localization tasks in reverberating and noisy environments. Since supervised machine learning approaches require large-sized, physically realistic, precisely labelled datasets, a fast graphics processing unit-based computation of room impulse responses was developed using fractional delays for image source models. A thorough analysis of the network representation and extensive performance tests are carried out using the BeamLearning network with synthetic and experimental datasets. Obtained results demonstrate that the BeamLearning approach significantly outperforms the wideband MUSIC and steered response power-phase transform methods in terms of localization accuracy and computational efficiency in the presence of heavy measurement noise and reverberation.


Determination of ammonia inhibition in fabric impregnated with antimicrobials.
A new method is described for determining the presence or absence of ammonia produced by urealytic microorganisms, using fabric which has been treated with an antimicrobial. Circular disks of fabric treated with various concentrations of an antimicrobial are placed in the bottoms of snap-on lid petri dishes. Nutrient medium containing urea, an indicator, and a dilution of an overnight culture of Proteus mirabilis is applied to the fabric disks. The lids are snapped on and the dishes are incubated at 37 degrees C. By examination of the fabric disks at regular intervals of time for a color change from white to red, one may determine whether the concentration of antimicrobial in the fabric is sufficient to inhibit the production of ammonia by a urealytic microorganism.


The aesthetic composite anterior single crown restoration.
Achieving natural aesthetics by harmoniously matching the shape and color of a single anterior crown is perhaps one of the greatest challenges in restorative dentistry. The clinician must often rely on the artistic skills of a laboratory technician who has no direct access to the patient. The shade selection process is, therefore, impaired, and the final result may be a restoration which does not emulate the aesthetics of the adjacent natural dentition. The learning objective of this article is to present an innovative technique which utilizes the qualities of high strength laboratory processing in association with the application of light curing and freehand bonding of composite resins. This combination allows the clinician to predictably achieve aesthetic results with single anterior crowns. The direct, indirect, and indirect/direct restorations are discussed, and the laboratory and clinical procedures are reviewed.


Jaboticabin and Related Polyphenols from Jaboticaba ( Myrciaria cauliflora) with Anti-inflammatory Activity for Chronic Obstructive Pulmonary Disease.
Myrciaria cauliflora (jaboticaba) is an edible fruit common in Brazil that has been used for treating respiratory diseases, including chronic tonsillitis and asthma. This study explores the distribution of an anti-inflammatory depside, jaboticabin, in different parts of the jaboticaba plant as well as major polyphenols from the wood of jaboticaba, some with biological activity similar to jaboticabin. The peel of the fruit was found to be the major source of jaboticabin. This is the first phytochemical study of the wood of M. cauliflora. The antioxidant-activity-guided fractionation strategy successfully identified 3,3'-dimethylellagic acid-4- O-sulfate from jaboticaba wood. This ellagic acid derivative, in a manner similar to jaboticabin, showed antiradical activity and inhibited the production of the chemokine interleukin-8 after treating the human small airway epithelial cells with cigarette smoke extract. The human intestinal Caco-2 cell studies demonstrated the jaboticabin transport in vitro. The polyphenols, jaboticabin and 3,3'-dimethyellagic acid-4- O-sulfate, from jaboticaba were both found to exhibit anti-inflammatory activities, thus suggesting the potential use of these compounds or even the fruits themselves for chronic obstructive pulmonary disease.


Cutaneous infections with community-acquired MRSA in aviators.
Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen of growing concern among community-based practices in medicine, particularly those in the military. The risk of colonization and infection by community-acquired MRSA (CA-MRSA) is significantly higher among military members than that of the general population. The unique environment of the deployed, military aviator (impaired hygiene practices, close contact in warm, space-limited cockpits, and shared life support equipment) may increase risks of colonization, infection, and transmission of CA-MRSA and hence warrants the clinical attention of the flight surgeon. Studies of molecular genetics indicate that isolates of CA-MRSA contain a unique mobile genetic element (SCCmec type IV), indicating that CA-MRSA evolved separately from nosocomially acquired MRSA. Skin infections involving CA-MRSA are unlike their nosocomial counterparts in that CA-MRSA infections are susceptible to multiple classes of antibiotics and, on average, are clinically more aggressive. Awareness of this pathogen and appropriate clinical intervention can lead to prompt resolution of the infection and reduce rates of CA-MRSA colonization.


Variations in Feulgen stainability of epithelial parenchymal cells extracted from paraffin-embedded salivary gland specimens.
The variations of Feulgen stainability of cells extracted from paraffin-embedded archival specimens for DNA assessment by means of image cytometry (ICM) were investigated in normal salivary gland parenchyma. The Feulgen stainability of the deparaffinized, rehydrated, and disaggregated preparations was found to exhibit variations of up to 300%, expressed by the mean of integrated optical density (IOD), when a routine procedure was applied to a first series of Cytospin preparations of disaggregated specimens. When measured in nondisaggregated tissue sections, only negligible variations were observed. After minimization of the mechanical strains to the cellular material in the Cytospin preparations in a second series, the variations in Feulgen stainability were found to be considerably lower. The findings indicate that the main reason for variations in the Feulgen stainability of extracted cells is, most likely, the disaggregation procedure itself. Factors such as initial treatment of the specimens, duration and kind of formalin fixation, and length of storage time periods seem to be of minor importance. Retrospective studies on paraffin-embedded specimens require a carefully controlled tissue type-adapted disaggregation procedure. In addition, we concluded that the interpretation of histograms, obtained by means of ICM DNA assessments in Cytospin preparations of archival material, requires a well-defined internal specific standard.


COPD exacerbations: causes, prevention, and treatment.
The mechanisms of chronic obstructive pulmonary disease exacerbation are complex. Respiratory viruses (in particular rhinovirus) and bacteria play a major role in the cause of these events. A distinct group of patients seems susceptible to frequent exacerbations, irrespective of disease severity, and this phenotype is stable over time. Many current therapeutic strategies help reduce exacerbation frequency. Further work is required to develop novel anti-inflammatory therapies for exacerbation prevention and treatment. This article focuses on the cause of chronic obstructive pulmonary disease exacerbations, and the current preventative and acute interventions available.


Epidemiology of proximal humeral fractures: a detailed survey of 711 patients in a metropolitan area.
Literature lacks data concerning several epidemiologic aspects of proximal humeral fractures (PHFs). This retrospective study included 711 consecutive patients (209 men, 502 women) who sustained a PHF in the last 3 years. Participants were divided into 2 groups, adults and children. Data regarding age, sex, date, and fracture side were collected. According to the mechanism of injury, we arbitrarily distinguished 7 subgroups. PHFs were classified according to the head-greater-lesser-shaft (HGLS)-Hertel classification and to the Salter-Harris classification using x-ray and computed tomography imaging. PHFs represent 5.03% of the overall fractures. The right side was involved in 389 patients (54.7%; P = .6). The mean age of male and female patients was 55.4 (standard deviation, 21.9) years and 67.0 (standard deviation, 16.1) years, respectively (P = .0001). Significant differences in the trauma mechanism between female patients (street/home low-energy trauma) and male patients (high-energy trauma) were found. A significant correlation between trauma mechanisms from 1 to 5 and fracture patterns H-G-L-S, HL-G-S, HGL-S, and HLS-G was observed. The occurrence of the same patterns significantly varied according to different age subgroups. Considering the pediatric population, a significant incidence of Salter-Harris 2 in both genders was found. No correlation was observed between the fracture patterns and the trauma mechanism. PHFs have a higher prevalence and incidence in females and in older age, respectively; they are more frequent in the winter months. In addition, male fractures are due to different traumatic events than those in females. A correlation between trauma and PHF pattern was evident only for adults. Some fracture patterns are correlated with different ranges of age in all patients.


De novo synthesis of amino acids during the maillard reaction: qTOF/ESI mass spectrometric evidence for the mechanism of Akabori transformation.
The transformation of α-amino acids into their hydroxymethyl derivatives during the Maillard reaction is an intriguing possibility for catalysis by metal salts in the presence of Strecker aldehydes; the process is commonly known as the Akabori reaction. The mechanism of this reaction was studied in the presence of glucose, using glycine copper complex and paraformaldehyde as Akabori model system in aqueous mixtures heated at 110 °C for 2 h and subsequently analyzed by qTOF/ESI/MS. Isotope-labeling studies of the various products identified have provided for the first time mass spectrometric evidence for the detailed mechanism of Akabori transformation, particularly the formation of Schiff base adducts prior to the final conversion into serine and hydroxymethyl-serine. Furthermore, the results have indicated that sugars do not interfere with such transformations and, on the contrary, the presence of glycine–copper complexes in the Maillard model systems can enhance the production of Maillard reaction intermediates.


High Rate, Long Lifespan LiV3 O8 Nanorods as a Cathode Material for Lithium-Ion Batteries.
LiV3 O8 nanorods with controlled size are successfully synthesized using a nonionic triblock surfactant Pluronic-F127 as the structure directing agent. X-ray diffraction, scanning electron microscopy, and transmission electron microscopy techniques are used to characterize the samples. It is observed that the nanorods with a length of 4-8 µm and diameter of 0.5-1.0 µm distribute uniformly. The resultant LiV3 O8 nanorods show much better performance as cathode materials in lithium-ion batteries than normal LiV3 O8 nanoparticles, which is associated with the their unique micro-nano-like structure that can not only facilitate fast lithium ion transport, but also withstand erosion from electrolytes. The high discharge capacity (292.0 mAh g-1 at 100 mA g-1 ), high rate capability (138.4 mAh g-1 at 6.4 A g-1 ), and long lifespan (capacity retention of 80.5% after 500 cycles) suggest the potential use of LiV3 O8 nanorods as alternative cathode materials for high-power and long-life lithium ion batteries. In particular, the synthetic strategy may open new routes toward the facile fabrication of nanostructured vanadium-based compounds for energy storage applications.


An Ex Vivo Vessel Injury Model to Study Remodeling.
Invasive coronary interventions can fail due to intimal hyperplasia and restenosis. Endothelial cell (EC) seeding to the vessel lumen, accelerating re-endothelialization, or local release of mTOR pathway inhibitors have helped reduce intimal hyperplasia after vessel injury. While animal models are powerful tools, they are complex and expensive, and not always reflective of human physiology. Therefore, we developed an in vitro 3D vascular model validating previous in vivo animal models and utilizing isolated human arteries to study vascular remodeling after injury. We utilized a bioreactor that enables the control of intramural pressure and shear stress in vessel conduits to investigate the vascular response in both rat and human arteries to intraluminal injury. Culturing rat aorta segments in vitro, we show that vigorous removal of luminal ECs results in vessel injury, causing medial proliferation by Day-4 and neointima formation, with the observation of SCA1+ cells (stem cell antigen-1) in the intima by Day-7, in the absence of flow. Conversely, when endothelial-denuded rat aortae and human umbilical arteries were subjected to arterial shear stress, pre-seeding with human umbilical ECs decreased the number and proliferation of smooth muscle cell (SMC) significantly in the media of both rat and human vessels. Our bioreactor system provides a novel platform for correlating ex vivo findings with vascular outcomes in vivo. The present in vitro human arterial injury model can be helpful in the study of EC-SMC interactions and vascular remodeling, by allowing for the separation of mechanical, cellular, and soluble factors.


Synthesis and pharmacological characterization of 1-phenyl-, 4-phenyl-, and 1-benzyl-1,2,3,4-tetrahydroisoquinolines as dopamine receptor ligands.
A series of 1-phenyl-, 4-phenyl-, and 1-benzyl-1,2,3,4-tetrahydroisoquinolines have been prepared as ring-contracted analogues of the prototypical D1 dopamine receptor antagonist SCH23390 [(R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H- 3-benzazepine]. The affinity and selectivity of these isoquinolines for D1 receptors was determined by three biochemical endpoints in membrane homogenates prepared from rat corpus striatum: the potency to complete for [3H]SCH23390 binding sites; the potency to compete for [3H]spiperone (a D2 receptor ligand) binding sites; and effects on dopamine-stimulated adenylate cyclase. Competitive binding measurements at D1 sites showed SCH23390 to possess the highest affinity, followed by 1-phenyl greater than 1-benzyl greater than 4-phenyl for the isoquinolines. These results were highly correlated with the ability of the test compounds to antagonize dopamine-stimulated adenylate cyclase (r = 0.98). None of the compounds alone stimulated cAMP formation at concentrations of 10 nM to 100 microM. D2 competition binding showed the 1-benzyl derivative to possess the highest affinity, followed by 4-phenyl greater than SCH23390 greater than 1-phenyl. The tertiary 1-phenyl derivative was more potent than the secondary 1-phenyl analogue in all assays. Interestingly, resolution and single-crystal X-ray analysis of the tertiary N-methyl-1-phenyltetrahydroisoquinoline showed the most active enantiomer to possess the S absolute configuration, in contrast to the benzazepine (R)-SCH23390.


Five-year outcome of 111 immediate nonfunctional single restorations.
Immediate loading is a surgical-prosthetic procedure extensively used in implant dentistry. Despite its frequent use, minimal data are available on the long-term clinical success rate of immediate functional loading (IFL) and immediate nonfunctional loading (INFL) of implants. The aim of this study was to evaluate the long-term survival and bone loss of immediate nonfunctional single implant restorations in a group of patients that were monitored for 5 years. One hundred and eleven patients (41.4% men) with a median age of 40 years were included in this study. A total of 111 implants were placed. All implants were placed with a minimum insertion torque of 25 Ncm. A temporary restoration was relined with acrylic resin, trimmed, polished, and cemented or screw-retained 1 to 2 hours later. Occlusal contact was avoided in centric and lateral excursions. After provisional crown delivery, a periapical radiograph was performed by means of a customized Rinn holder device. Data were analyzed by means of Kaplan-Meier and life-table algorithms. Stratification of implant survival was performed for the available variables of interest, and comparisons were analyzed using a log-rank test. Investigated parameters were time of implant placement, bone quality, implant site, implant diameter and length, and type of implant surface enhancement. The parameters for overall success rate were defined by bone resorption <1.5 mm after the first year of loading and <0.2 mm thereafter. During the 5-year follow-up period, a survival rate of 95.5% was observed. All failures occurred within 4 months of implant loading. There were statistically significant differences regarding healed vs post-extraction implant sites (100% and 92.5%, respectively, P = .05) and type of bone (D1 vs D4 yielded 100% and 95.5%, respectively, P <.05). No differences were detected for: (1) site (100% for mandible and 94.63% for maxilla, P =-.319); (2) implant diameter (survival rates of 97.26% for <4.5-mm diameter and 92.11% for >4.5mm diameter, P = .206); (3) implant lengths (survival rates of 96.97% for implants >13 mm and 94.87% for implants <13 mm, P =.624); and (4) type of implant surface enhancement (survival rates of 94.03% for 67 cases of grit-blasted and acid-etched surfaces and a failure rate of 4 out of 5, and 94.12% for 17 cases of hydroxyapatite (HA)-coated surfaces with only 1 failure). The success rate (defined as bone resorption >1.5 mm after the first year of loading and >0.2 mm thereafter) was 97.2%. Immediate nonocclusal loading of single implants is a reliable surgical-prosthetic procedure with a low rate of implant loss and a low quantity of peri-implant bone loss over time.


Ciprofloxacin liposomes as vesicular reservoirs for ocular delivery: formulation, optimization, and in vitro characterization.
Management of extraocular diseases is mainly limited by the inability to provide long-term drug delivery without avoiding the systemic drug exposure and/or affecting the intraocular structures and poor availability of drugs, which may be overcome by prolonging the contact time with the ocular system, for instance with liposomes. Development and optimization of reverse phase evaporation ciprofloxacin (CPF) HCl liposomes for ocular drug delivery was carried out using a 2(5) full factorial design based on five independent variables. The effects of the studied parameters on drug entrapment efficiency (EE), particle size, and percentage of drug released after 1 and 10 h were investigated. The results obtained pointed out that the molar concentration of cholesterol was the predominant factor that increased the EE% of the drug and the particle size responses. The percentage of drug released after 1 h was significantly controlled by the initial CPF concentration while that after 10 h was controlled by molar cholesterol concentration. The designed liposomes had average particle sizes that ranged from 2.5 to 7.23 microm. In addition, liposomes revealed a fast release during the first hour followed by a more gradual drug release during the 24-h period according to Higuchi diffusion model.


The role of intraspecific crop-weed hybridization in the evolution of weediness and invasiveness: Cultivated and weedy radish (Raphanus sativus) as a case study.
The phenotype of hybrids between a crop and its wild or weed counterpart is usually intermediate and maladapted compared to that of their parents; however, hybridization has sometimes been associated with increased fitness, potentially leading to enhanced weediness and invasiveness. Since the ecological context and maternal genetic effects may affect hybrid fitness, they could influence the evolutionary outcomes of hybridization. Here, we evaluated the performance of first-generation crop-weed hybrids of Raphanus sativus and their parents in two contrasting ecological conditions. Using experimental hybridization and outdoor common garden experiments, we assessed differences in time to flowering, survival to maturity, plant biomass, and reproductive components between bidirectional crop-weed hybrids and their parents in agrestal (wheat cultivation, fertilization, weeding) and ruderal (human-disturbed, uncultivated area) conditions over 2 years. Crop, weeds, and bidirectional hybrids overlapped at least partially during the flowering period, indicating a high probability of gene flow. Hybrids survived to maturity at rates at least as successful as their parents and had higher plant biomass and fecundity, which resulted in higher fitness compared to their parents in both environments, without any differences associated with the direction of the hybridization. Intraspecific crop-weed hybridization, regardless of the cross direction, has the potential to promote weediness in weedy R. sativus in agrestal and ruderal environments, increasing the chances for introgression of crop alleles into weed populations. This is the first report of intraspecific crop-weed hybridization in R. sativus.


Extracellular calcium dependence of contracture and modulation by serotonin in buccal muscle E1 of Aplysia.
Serotonin [5-hydroxytryptamine (5-HT)] enhances acetyl choline (ACh)-elicited contractures of Aplysia buccal muscles E1 and I5 . The possible role of external calcium in regulating the magnitude of ACh contracture in the presence and absence of 5-HT was investigated. Superfusion of E1 with zero calcium medium caused ACh contractures to fail within one to two minutes. Recovery of ACh contracture upon restoring normal medium occurred within two to four minutes. In the absence of 5-HT, ACh contracture decreased proportionally to external [Ca++] in the concentration range of 0-10 mM; however, the amount of enhancement of ACh contracture following 5-HT treatment did not decrease with external [Ca++] as long as [Ca++] was above a threshold concentration that varied from preparation to preparation. For most preparations, the enhancement of ACh contracture by 5-HT was dependent on the presence of external calcium during 5-HT treatment. Calcium influx into muscles E1 and I5 increased approximately two and a half fold in the presence of 10(-6) M 5-HT. A model in which 5-HT brings about calcium "loading" of an ACh releasable intracellular storage site is discussed.


Isolation of human corneal endothelial cell precursors and construction of cell sheets by precursors.
To review recently published experimental data on human corneal endothelium (CE) precursors. A sphere-forming assay was used for the isolation of human CE precursors from human donor corneas and cultured human CE. CE morphology derived from precursors was compared with that from cultured human CE. Human CE from donor corneas formed primary and secondary sphere colonies and expressed neural and mesenchymal proteins. The progeny of these colonies had a human-CE-like hexagonal shape and showed transport activity, suggesting that the isolated spheres were indeed precursors of human CE. Similar precursors were isolated from cultured human CE, which provided further evidence that the sphere-forming assay facilitates the mass production of human CE precursors. Cultured human CE obtained in this manner had a regular hexagonal morphology in contrast to passaged, cultured human CE. The sphere-forming assay may become a powerful tool for the regeneration of human CE by precursor injection and the construction of cultured CE sheets.


Bond-orientational order and Frank's constant in two-dimensional colloidal hard spheres.
Recently, the full phase behaviour of 2D colloidal hard spheres was experimentally established, and found to involve a first order liquid to hexatic transition and a continuous hexatic to crystal transition (Thorneywork et al 2017 Phys. Rev. Lett. 118 158001). Here, we expand upon this work by considering the behaviour of the bond-orientational correlation time and Frank's constant in the region of these phase transitions. We also consider the excess entropy, as calculated from the radial distribution functions, for a wide range of area fractions covering the liquid, hexatic and crystal phases. In all cases, the behaviour of these quantities further corroborates the previously reported melting scenario of 2D colloidal hard spheres.


Effects of feeding corn silage inoculated with microbial additives on the ruminal fermentation, microbial protein yield, and growth performance of lambs.
This study aimed to examine the effects of feeding corn silage inoculated without or with either Lactobacillus buchneri (LB) alone or a combination of LB and Lactobacillus plantarum (LBLP) on the apparent digestibility, ruminal fermentation, microbial protein synthesis, and growth performance of lambs. Thirty Santa Inês×Dorper crossbred intact males lambs weighing 20.4±3.8 kg were blocked by weight into 10 groups. Lambs in each group were randomly assigned to 1 of the following 3 dietary treatments: untreated (Control), LB, and LBLP silage. Lambs were fed experimental diets for 61 d. The apparent digestibility was indirectly estimated from indigestible NDF measured on d 57 to 59. Spot urine samples were collected from all animals on d 59 to estimate microbial protein synthesis. Lambs were slaughtered for carcass evaluation on d 61 when they weighed 32.4±5.2 kg. Six additional ruminally cannulated Santa Inês×Dorper crossbred wethers weighing 40.5±1.8 kg were used to examine dietary effects on ruminal fermentation. Average daily gain was increased when lambs were fed LBLP silage (P<0.05) but not LB silage. The LBLP silage had the highest (P<0.05) lactic acid concentration and both inoculated silages had greater acetic acid concentrations than the Control silage (P<0.05). Inoculation of corn silage increased intakes of DM, OM, CP, NDF, total carbohydrate (CHO), and GE by the lambs but decreased digestibility of DM, OM, CP, total and nonstructural carbohydrates, and concentration of GE and ME. (P<0.05). Nevertheless, lambs fed inoculated silages had greater microbial N supply than those on the Control treatment (P<0.05). The acetate to propionate ratio was lower in ruminal fluid of wethers in LBLP treatment than LB and Control treatment (P<0.05) and ruminal pH tended to be greater in LB lambs than in LBLP and Control wethers (P<0.10). Finally, the inoculation with both bacteria combined enhanced the silage fermentation. The intakes of DM, OM, CP, NDF, and GE were improved in the lambs fed corn silage inoculated with L. buchneri alone or combined with L. plantarum. The microbial N supply was enhanced in the lambs fed corn silage inoculated with L. buchneri. The inoculation of L. buchneri combined with L. plantarum reduced the acetate to propionate ratio in ruminal fluid and improved the ADG of lambs.


[Effects of cadmium stress on photosynthetic functions of strawberry].
With pot experiment, this paper studied the effects of cadmium stress on the leaf chlorophyll content, photosynthetic rate, stomatal conductance, transpiration rate, and intercellular CO2 concentration of strawberry. The results showed that cadmium reduced the chlorophyll content, and changed the chlorophyll a/b ratio. Cadmium reduced the photosynthetic rate and stomatal conductance, though they were increased by low concentration cadmium at the initial stage of cadmium stress. Cadmium also reduced the transpiration rate and intercellular CO2 concentration, but the decrement of intercellular CO2 concentration was relatively less.


Dynamic secondary structural changes in Ca²⁺-saturated calmodulin upon interaction with the antagonist, W-7.
Although the 3D structure of the Ca(2+)-bound CaM (Ca(2+)/CaM) complex with the antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7), has been resolved, the dynamic changes in Ca(2+)/CaM structure upon interaction with W-7 are still unknown. We investigated time- and temperature-dependent dynamic changes in Ca(2+)/CaM interaction with W-7 in physiological conditions using one- and two-dimensional Fourier-transformed infrared spectroscopy (2D-IR). We observed changes in the α-helix secondary structure of Ca(2+)/CaM when complexed with W-7 at a molar ratio of 1:2, but not at higher molar ratios (between 1:2 and 1:5). Kinetic studies revealed that, during the initial 125s at 25°C, Ca(2+)/CaM underwent formation of secondary coil and turn structures upon binding to W-7. Variations in temperature that induced significant changes in the structure of the Ca(2+)/CaM complex failed to do so when Ca(2+)/CaM was complexed with W-7. We concluded that W-7 induced stepwise conformational changes in Ca(2+)/CaM that resulted in a rigidification of the complex and its inability to interact with target proteins and/or polypeptides.


(18)F-labeled positron emission tomographic radiopharmaceuticals in oncology: an overview of radiochemistry and mechanisms of tumor localization.
Molecular imaging is the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in a living system. At present, positron emission tomography/computed tomography (PET/CT) is one the most rapidly growing areas of medical imaging, with many applications in the clinical management of patients with cancer. Although [(18)F]fluorodeoxyglucose (FDG)-PET/CT imaging provides high specificity and sensitivity in several kinds of cancer and has many applications, it is important to recognize that FDG is not a "specific" radiotracer for imaging malignant disease. Highly "tumor-specific" and "tumor cell signal-specific" PET radiopharmaceuticals are essential to meet the growing demand of radioisotope-based molecular imaging technology. In the last 15 years, many alternative PET tracers have been proposed and evaluated in preclinical and clinical studies to characterize the tumor biology more appropriately. The potential clinical utility of several (18)F-labeled radiotracers (eg, fluoride, FDOPA, FLT, FMISO, FES, and FCH) is being reviewed by several investigators in this issue. An overview of design and development of (18)F-labeled PET radiopharmaceuticals, radiochemistry, and mechanism(s) of tumor cell uptake and localization of radiotracers are presented here. The approval of clinical indications for FDG-PET in the year 2000 by the Food and Drug Administration, based on a review of literature, was a major breakthrough to the rapid incorporation of PET into nuclear medicine practice, particularly in oncology. Approval of a radiopharmaceutical typically involves submission of a "New Drug Application" by a manufacturer or a company clearly documenting 2 major aspects of the drug: (1) manufacturing of PET drug using current good manufacturing practices and (2) the safety and effectiveness of a drug with specific indications. The potential routine clinical utility of (18)F-labeled PET radiopharmaceuticals depends also on regulatory compliance in addition to documentation of potential safety and efficacy by various investigators.


B-cell epitope spreading is a critical step for the switch from C-protein-induced myocarditis to dilated cardiomyopathy.
Repeated inflammation in the heart is one of the initiation factors of dilated cardiomyopathy (DCM). In a previous study, we established a new animal model for DCM by immunization of rats with recombinant cardiac C-protein fragment 2 (CC2). The present study examined factors involved in the development of DCM. Analysis using overlapping peptides revealed that the major carditogenic epitope resides only in the residue 615-647 [CC2 peptide 12 (CC2P12)]. However, immunization with CC2P12 induced moderate inflammation without subsequent DCM. CDR3 spectratyping analysis of the T-cell repertoire demonstrated that Vbeta4-positive T cells were preferentially expanded in both CC2- and CC2P12-immunized rats. Although there was no significant difference in the T-cell characteristics, examinations of the B-cell epitope revealed that marked epitope spreading occurred in CC2-immunized but not CC2P12-immunized rats from 4 weeks after immunization. Consistent with this finding, immunization with CC2P12 and simultaneous transfer of anti-peptide antisera induced significantly more severe inflammation and fibrosis than CC2P12 immunization alone. However, the transfer of the antisera without CC2P12 immunization did not induce any pathology. These findings suggest that T-cell activation and B-cell epitope spreading in the CC2 molecule is a key step for the switch from myocarditis to the development of DCM.


Identification of novel small molecule inhibitors for solute carrier SGLT1; a computational exploration.
Diabetes results in substantial disabilities, diminished quality of life, and mortality that imposes a huge economic burden on societies and governments worldwide. Despite the absence of specific oral therapies at present, there exists an urgent requirement to develop a novel drug for the treatment of diabetes mellitus. The membrane protein sodium glucose co-transporters (SGLT1) present a captivating therapeutic target for diabetes, given its pivotal role in facilitating glucose absorption in the small intestine, offering immense promise for potential therapeutic intervention. In this connection, the present study is aimed at identifying potential inhibitors of SGLT1 from a small molecule database, including compounds from both natural as well as synthetic origins. A comprehensive approach was employed, by integrating homology modeling, ligand-based pharmacophore modeling, virtual screening, and molecular docking simulation. The process resulted in the identification of 16 new compounds, featuring similar attributes as observed for the documented actives. In a systematic screening procedure, five potential virtual hits were selected for simulation studies followed by subsequent binding free energy calculations, providing deeper insight into the time-dependent behavior of protein-ligand complexes in a dynamic state. In conclusion, our findings demonstrated that the identified compounds, particularly compounds 81 and 91, exhibit enhanced stability and favorable binding affinities with the target protein, marking them promising candidates for further investigations.Communicated by Ramaswamy H. Sarma.


Gram-negative bacteria in water distribution systems of hospitals.
A total of 67 samples of tap water were collected from faucets and showerheads in 6 hospitals located in the Lublin province (eastern Poland). The samples were examined for the presence and species composition of Legionella, Gram-negative bacteria belonging to family Enterobacteriaceae (GNB-E) and Gram-negative bacteria not belonging to family Enterobacteriaceae (GNB-NE), by filtering through cellulose filters and culture on respectively GVPC, EMB and tryptic soya agar media. On average, Legionella was isolated from 65.7% of the water samples taken in hospitals. Strains of the Legionella pneumophila types 2-14 predominated, forming 74.6% of total Legionella isolates. Legionella pneumophila type 1 strains constituted 13.5% of the total count, while other species of Legionella (referred to as Legionella spp.) formed 11.9% of the total. The concentrations of Legionella in positive water samples ranged from 3-350 cfu/100 ml. GNB-E were not found in the examined water samples. GNB-NE were isolated from 79.1% of the water samples taken in hospitals in the concentrations 11-300 cfu/100 ml. Species of the family Pseudomonadaceae predominated among GNB-NE strains isolated from the examined water samples, forming on average 71.5% of the total count. Altogether, 20 GNB-NE species were identified in the examined samples, out of which 12 were potentially pathogenic. In conclusion, Gram-negative flora of water samples taken in the examined hospitals complies with potable water sanitary standards by the lack of Enterobacteriaceae species, but creates a moderate health risk because of mediocre concentrations of Legionella and the presence of potentially pathogenic non-enterobacterial species.


[A case of neuroendocrine carcinoma of the duodenal papilla].
A 75-year-old man with a complaint of right hypochondrial pain consulted our hospital, and was diagnosed as having acute cholecystitis. We performed percutaneous transhepatic gallbladder drainage (PTGBD), and the cholecystitis resolved. However, obstructive jaundice occurred 2 weeks later. Thus, we performed an in-depth investigation and detected duodenal papilla cancer (cT3N1M0, Stage III). Pancreatoduodenectomy was performed. As postoperative histological diagnosis yielded positive and strongly positive immunostaining for synaptophysin and Ki-67, respectively, we diagnosed the patient as having neuroendocrine carcinoma (NEC) of the duodenal papilla. Three months after surgery, computed tomography (CT) scan showed multiple liver metastases and lymph node metastasis. Chemotherapy with carboplatin and etoposide was administered, but severe neutropenia developed, and therefore, the chemotherapy was discontinued. Subsequently, we decided on a policy of best supportive care (BSC). The patient died 11 months after surgery. NEC of the duodenal papilla is reported to be a rare and rapidly progressing disease and is associated with a very poor prognosis. Herein, we report a case of a patient in whom NEC of the duodenal papilla was resected.


Cytochrome P-450-dependent fatty acid hydroxylase system in Japanese house musk shrew, Suncus murinus.
The substrate specificity and other properties of a fatty acid hydroxylase system in liver microsomes of the Japanese house musk shrew, Suncus murinus, were examined. Shrew liver microsomes catalyzed the hydroxylation of various saturated fatty acids (C8-C18) to the corresponding omega- and (omega-1)-hydroxy derivatives. The relative activities of the hydroxylase with these substrates were as follows: C12 (100, actual conversion: 7.05 nmol/mg of microsomal protein/min), C10 (90), C14 (87), C16 (23), C8 (19), and C18 (11). The specific activity of the fatty acid hydroxylase in shrew liver was much higher than that in other species. The omega/omega-1-hydroxylation ratio decreased with increasing chain length of fatty acid substrates (C10-C18), but it was 0 for the C8 fatty acid. Both NADPH and O2 were required for hydroxylase activity, and NADH had little effect. The apparent Km value for laurate was 1.6 X 10(-5) M. The hydroxylase activity was 92% inhibited by CO at a CO-O2 ratio of 9. p-Chloromercuribenzoate (0.1 mM) inhibited hydroxylation by 94% whereas iodoacetate (0.1 mM) inhibited it by only 8%. SKF 525-A (1 mM) and menadione (0.01 mM), respectively, caused 41% and 29% inhibition of the activity. It is concluded that the hydroxylase catalyzing fatty acid hydroxylation in shrew liver microsomes is a typical cytochrome P-450-linked monooxygenase.


Model reference direct adaptive control of nonlinear plants using neural networks.
A learning scheme for multilayer feedforward neural networks used as direct adaptive controllers of nonlinear plants is suggested. This scheme is a supervised steepest descent one that does not require backpropagation of the error. Using a neural network controller trained with this method does not require the identification stage and this makes it superior to the other methodologies. Methods for using neural networks in plant control suggested in the literature are discussed and compared with the proposed system. The structure of the network and the training method used are explained. Simulations based on model reference control of some nonlinear plants show satisfactory performance.


Prevalence of HIV-associated cryptococcal meningitis and utility of microbiological determinants for its diagnosis in a tertiary care center.
Human immunodeficiency virus (HIV) infection continues to be the most important risk factor for the development of central nervous system (CNS) cryptococcosis, which in turn is an important contributor to morbidity and mortality in HIV-infected patients. Early diagnosis of such patients is the key to their therapeutic success. This study was undertaken to find out the prevalence of CNS cryptococcosis and to assess the role of microbiological parameters for its specific diagnosis in HIV-reactive hospitalized patients admitted with meningeal signs in a tertiary care setting. A total of 104 patients suspected to be suffering from meningitis/meningoencephalitis were subjected to cerebrospinal fluid (CSF) analysis (including India ink preparation, culture by conventional methods and Bactec MGIT 960 system, antigen detection) and tests for HIV antibodies by standard laboratory operating procedures. The prevalence of HIV infection in our study group was 12.5% (13/104), while the prevalence of cryptococcal CNS infection in HIV-reactive cohort was 46% (6/13). Additionally, 15.3% (2/13) of the patients from this cohort were positive for Mycobacterium tuberculosis. High prevalence of cryptococcal CNS infections in HIV-infected patients underscores the importance of precise and early microbiological diagnosis for better management of such patients.


Refractory Epilepsy-MRI, EEG and CT scan, a Correlative Clinical Study.
Refractory epilepsies (RE), as well as, the surgically correctable syndromes, are of great interest, since they affect the very young population of children and adolescents. The early diagnosis and treatment are very important in preventing the psychosocial disability. Therefore MRI and EEG are highly sensitive methods in the diagnosis and localization of epileptogenic focus, but also in pre-surgical evaluation of these patients. The aim of our study is to correlate the imaging findings of EEG, MRI and CT scan in refractory symptomatic epilepsies, and to determine their specificity in detecting the epileptogenic focus. The study was prospective with duration of over two years, open-labelled, and involved a group of 37 patients that had been evaluated and diagnosed as refractory epilepsy patients. In the evaluation the type and frequency of seizures were considered, together with the etiologic factors and their association, and finally the risk for developing refractory epilepsy was weighted. EEG and MRI findings and CT scan results were evaluated for their specificity and sensitivity in detecting the epileptogenic focus, and the correlation between them was analyzed. Regarding the type of seizures considered in our study, the patients with PCS (partial complex seizures) dominated, as opposed to those with generalized seizures (GS) (D=1.178, p < 0.05). Positive MRI findings were registered in 28 patients (75.7%). Most of them were patients with hippocampal sclerosis, 12 (42.8%), and also they were found to have the highest risk of developing refractory epilepsy (RE) (Odds ratio = 5.7), and the highest association between the etiologic factor and refractory epilepsy (p < 0.01). In detecting the epileptogenic focus, a significant difference was found (p < 0.01) between MRI and CT scan findings, especially in patients with hippocampal sclerosis and cerebral malformations. There was a strong correlation between the MRI findings and the etiologic factor (R = 1), and for CT scan and etiologic factor an R=0.75 correlation. There was a significant difference between imaging methods MRI/CT (p < 0.1), and CT/EEG (p < 0.05) in detecting the etiologic factor, and little difference was noticed between findings of EEG/MRI. Our study confirms that for an accurate diagnosis of refractory epilepsy in patients, a combination of neuroimaging and neurophysiologic methods is required. MRI showed to be highly sensitive in detecting the etiologic factor in RE patients, whereas EEG was sensitive in localization of the epileptogenic focus, with high correlation between these two methods. An early diagnosis of these patients is very important in having a better therapeutic response and prognosis for them.


The three-dimensional structure of a Tn5 transposase-related protein determined to 2.9-A resolution.
Transposon Tn5 employs a unique means of self-regulation by expressing a truncated version of the transposase enzyme that acts as an inhibitor. The inhibitor protein differs from the full-length transposase only by the absence of the first 55 N-terminal amino acid residues. It contains the catalytic active site of transposase and a C-terminal domain involved in protein-protein interactions. The three-dimensional structure of Tn5 inhibitor determined to 2.9-A resolution is reported here. A portion of the protein fold of the catalytic core domain is similar to the folds of human immunodeficiency virus-1 integrase, avian sarcoma virus integrase, and bacteriophage Mu transposase. The Tn5 inhibitor contains an insertion that extends the beta-sheet of the catalytic core from 5 to 9 strands. All three of the conserved residues that make up the "DDE" motif of the active site are visible in the structure. An arginine residue that is strictly conserved among the IS4 family of bacterial transposases is present at the center of the active site, suggesting a catalytic motif of "DDRE." A novel C-terminal domain forms a dimer interface across a crystallographic 2-fold axis. Although this dimer represents the structure of the inhibited complex, it provides insight into the structure of the synaptic complex.


[Thematic study of the narration of dreams of normal, and of schizophrenic and other psychotic subjects].
A thematic study according to Hall's and Van de Castle's method on the narrations of dreams by schizophrens and non schizophrens delirious patients attended to in a psychiatric hospital, compared with a group of control, all females. A report of the method and of the satistically significant results. A study of the sexual, benevolent and aggressive social interactions, of the authors of the acts, of the type of issues, of the intervention of chance and of the quality of emotions, as well, as of the diversity of the intervening people. Its is possible to distinguish the narrations of the normal people's dreams and of those of the patients. These tell less numerous dreams, which are shorter, less rich, heavier with aggressive events and painful sexuality and less provided with benevolence. Death is more frequent in them. Outside hostility is embodied by the father, unknown people or fate.


'It has to become true genetics': tumour genetics and the division of diagnostic labour in the clinic.
Tumour genetics is currently turning into a massive clinical approach. This paper is an enquiry into its practices as they expand beyond expert and experimental contexts and become routinised in clinical hospital settings. Studying a French university hospital, we unpack the content and everyday organization of diagnostic labour in this context. Exploring the sociotechnical frictions that arise in the process, we describe the ways in which they are collectively controlled, and stabilized through organizational fictions, that are instrumental in making tumour genetics doable in the hospital, at a large scale. We further show that the new role of external regulations in the production of clinical values for mutations has a strong impact on diagnostic work, making it possible to be performed locally without resorting to expert bioclinical collectives, and outside the professional jurisdiction of clinical geneticists. This division of labour appears as a necessary condition for the rise in clinical productivity required by a new function assigned to genetics: to guide the prescription of drugs for common diseases. This turn in the way genetics is embedded in the clinic calls for a thorough reassessment of its impacts on clinical discourses, practices and decisions.


The additional diagnostic value of motor nerve excitability testing in chronic axonal neuropathy.
To explore potential differences in motor nerve excitability testing (NET) variables at group levels between patients with a clinical diagnosis of polyneuropathy (PNP), which did not fulfil diagnostic criteria of conventional nerve conduction studies (NCS) and patients without polyneuropathy. Such differences could support a role for NET in increasing the diagnostic sensitivity of NCS in chronic axonal PNP. Motor NET was performed using the median nerve in patients with a clinical suspicion of PNP in addition to conventional NCS, skin biopsies, corneal confocal microscopy and structured clinical evaluation including scoring of neuropathy symptoms and signs. Of the 57 patients included, 32 had PNP, half of which had NCS, which fulfilled criteria for PNP (NCS+ PNP). There were no significant differences for any of the NET variables between PNP patients with non-diagnostic conventional NCS (NCS- PNP) and patients without PNP. Rheobase was increased, and Ted (undershoot) and subexcitability were decreased in NCS+ PNP. Sural amplitude, peroneal nerve F-wave latency and tibial nerve F-wave-latency were correlated with subexcitability, and tibial nerve motor amplitude was correlated with rheobase. NET was correlated with conventional NCS and no differences were found between NCS- PNP patients and patients without PNP. NET does not seem to offer any additional diagnostic value in chronic mixed etiology neuropathy.


UBE1C is upregulated and promotes neddylation of p53 in lung cancer.
NEDDylation is a type of protein post-translational modification that has high similarity to ubiquitination. UBE1C encodes NEDDylation E1 enzyme, locates at chromatin region 3p14.1 and shows high gene dosage amplification frequency in both Asian and Caucasian lung cancer patients. However, its NEDDylation substrates and roles in tumorigenesis remain elucidated. In this study, we aim to investigate the oncogenic role of UBE1C and its involvement in how NEDDylation regulates p53 in lung cancer. We found that UBE1C mRNA overexpression and DNA amplification in most of the lung cell lines and cancer patients. Patients with UBE1C overexpression showed poor prognosis. Moreover, we demonstrated that overexpression of UBE1C and NEDD8, a NEDDylation moiety, resulted in the p53 NEDDylation with inhibition of p53 acetylation at K373 residue. Importantly, UBE1C-mediated NEDDylation downregulated the transcriptional activity of p53 by inhibiting p53 ability to target promoter regions of its downstream transcription targets, consequently inhibiting the promoter activities and the expression of mRNA and protein of the p53 downstream genes including p21 and PTEN. In addition, UBE1C and NEDD8 overexpression promoted migration, invasion, and proliferation of lung cancer cells. Our findings suggest that UBE1C acts as an oncogene with prognostic potential and highlight a potential role of UBE1C-mediated NEDDylation in downregulation of p53 transcriptional activity in lung cancer.


Air exposure as a possible route for ESBL in pig farmers.
Livestock can carry extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, with blaCTX-M-1 being most prevalent. ESBL carriage in farmers is associated with ESBL carriage in animals, with direct animal-human contact considered as the dominant route of transmission. However, inhalation of stable air might represent another route of transmission. We, therefore, quantified presence of blaCTX-M group 1 genes (CTX-M-gr1) in dust and the association with CTX-M-gr1 carriage in pig farmers, family members and employees. We included 131 people living and/or working on 32 conventional Dutch pig production farms (farmers, family members and employees) during two sampling moments over a 12-month interval. Human stool samples, rectal swabs from 60 pigs per farm, and 2-5 dust samples collected using an electrostatic dust collector (EDC) (as a proxy for presence of viable CTX-M-gr1 carrying bacteria in air) were obtained per farm. Presence of ESBL-producing Escherichia Coli (E. coli) in stool samples and rectal swabs was determined by selective plating and CTX-M-gr1 was identified by PCR. Dust samples were analyzed directly by PCR for presence of CTX-M-gr1. Questionnaires were used to collect information on nature, intensity and duration of animal contact. Overall human prevalence of CTX-M-gr1 carriage was 3.6%. CTX-M-gr1 was detected in dust on 26% of the farms and in pigs on 35% of the farms, on at least one sampling moment. Human CTX-M-gr1 carriage and presence of CTX-M-gr1 in dust were associated univariately (OR=12.4, 95% CI=2.7-57.1). In multivariate analysis human CTX-M-gr1 carriage was associated with the number of working hours per week (OR=1.03, 95% CI=1.00-1.06), presence of CTX-M-gr1 carrying pigs on the farm (OR=7.4, 95% CI=1.1-49.7) and presence of CTX-M-gr1 in dust (OR=3.5, 95% CI=0.6-20.9). These results leave open the possibility of airborne CTX-M-gr1 transmission from animals to humans next to direct contact.


Prayer is part of holistic care.
How very sad that Sarah Kuteh was dismissed for telling a patient with cancer he would have a better chance of surviving an operation if he prayed ( see news ). We say similar things all the time in the United States. I have been a nurse for more than 20 years and have never heard anything so sad. Holistic care should include physical, social, psychological and spiritual care.


Fasting potentiates insulin-mediated glucose uptake in rested and prior-contracted rat skeletal muscle.
A single bout of exercise can potentiate the effect of insulin on skeletal muscle glucose uptake via activation of the AMPK-TBC1 domain family member 4 (TBC1D4) pathway, which suggests a positive correlation between AMPK activation and insulin sensitization. In addition, prolonged fasting in rodents is known to upregulate and thereby synergistically enhance the effect of exercise on muscle AMPK activation. Therefore, fasting may potentiate the insulin-sensitizing effect of exercise. In the present study, we mimicked exercise by in situ muscle contraction and evaluated the effect of a 36-h fast on muscle contraction-induced insulin sensitization. Male Wistar rats weighing 150-170 g were allocated to either a 36-h fasting or feeding group. The extensor digitorum longus (EDL) muscles were electrically contracted via the common peroneal nerve for 10 min followed by a 3-h recovery period. EDL muscles were dissected and incubated in the presence or absence of submaximal insulin. Our results demonstrated that acute muscle contraction and 36 h of fasting additively upregulated AMPK pathway activation. Insulin-stimulated muscle glucose uptake and site-specific TBC1D4 phosphorylation were enhanced by prior muscle contraction in 36-h-fasted rats, but not in fed rats. Moreover, enhanced insulin-induced muscle glucose uptake and Akt phosphorylation due to 36 h of fasting were associated with a decrease in tribbles homolog 3 (TRB3), a negative regulator of Akt activation. In conclusion, fasting and prior muscle contraction synergistically enhance insulin-stimulated TBC1D4 phosphorylation and glucose uptake, which is associated with augmented AMPK pathway activation in rodents.NEW & NOTEWORTHY In this study, we revealed that 36 h of fasting additively upregulated acute muscle contraction-induced AMPK pathway activation in rats. Besides, fasting and muscle contraction synergistically enhanced insulin-stimulated site-specific TBC1D4 phosphorylation and glucose uptake, which was associated with augmented AMPK pathway activation. These results contribute to understanding the regulation of muscle insulin sensitivity.


External fixation versus conversion to intramedullary nailing for definitive management of closed fractures of the femoral and tibial shaft.
External fixation for definitive therapy of closed diaphyseal femur and tibia fractures is the preferred method of treatment only in the pediatric population. In adult injuries, in particular open battle wounds, the timing of conversion of an external fixator to an intramedullary nail is determined by the condition of the soft tissues and the overall stability of the patient. In the tibia, conversion to an intramedullary nail is accomplished as expeditiously as possible. Early (< 2 weeks) conversion to an intramedullary implant may be accomplished safely. Increased infection rates have been documented when conversion is done after 2 weeks of external fixation. In the femur, conversion from external fixation to nailing is done as the patient's overall physical condition and soft tissues allow. Acute conversion to an intramedullary device in a single procedure is preferred in patients without evidence of pin-tract infection. Staged conversion to an intramedullary nail often requires a prolonged period of bed rest with skeletal traction to maintain fracture stability and patient comfort, with the attendant risks of pneumonia, decubiti, and thromboembolic events. Treatment of closed femoral and tibial diaphyseal fractures with external fixation, either definitively or as a bridge to intramedullary nailing, is a viable option in the patient with gross physiologic instability or an ipsilateral dysvascular limb. The decision to use definitive external fixation versus conversion to an intramedullary device should be made on a case-by-case basis. Additional prospective clinical studies are warranted to further delineate risks and benefits of these treatment modalities.


Possible Precise Measurement of Delbrück Scattering Using Polarized Photon Beams.
The advent of high-flux-polarized γ-ray sources makes possible the nearly isolated precise measurement of the vacuum contribution, Delbrück scattering, to the elastic scattering of these photons off nuclei. Because of the fact that the elastic scattering of the photons is a coherent summation of four processes and that up to now unpolarized sources have been used, the isolated measurement of Delbrück scattering has not been performed. We show that for the appropriate choice of scattering angles, photon polarization, and energies this scattering can be measured nearly independently of other scattering processes. This makes possible the precise measurement of the vacuum contribution to scattering and the possibility of the detection of new physics.


Mining Digital Traces of Facebook Activity for the Prediction of Individual Differences in Tendencies Toward Social Networks Use Disorder: A Machine Learning Approach.
More than three billion users are currently on one of Meta's online platforms with Facebook being still their most prominent social media service. It is well known that Facebook has designed a highly immersive social media service with the aim to prolong online time of its users, as this results in more digital footprints to be studied and monetized (via psychological targeting). In this context, it is debated if social media platforms can elicit addictive behaviors. In the present work, we demonstrate in N = 1,094 users that it is possible to predict from digital footprints of the Facebook users their self-reported addictive tendencies toward social media (R > 0.30) by applying machine-learning strategies. More specifically, we analyzed the predictive power of a set of models based on different sets of features extracted from digital traces, namely posting activity, language use, and page Likes. To maximize the predictive power of the models, we used an ensemble of linear and non-linear prediction algorithms. This work showed also sufficient accuracy rates (AUC above 0.70) in distinguishing between disordered and non-disordered social media users. In sum, individual differences in tendencies toward "social networks use disorder" can be inferred from digital traces left on the social media platform Facebook. Please note that the present work is limited by its cross-sectional design.


Parametric ultrasound imaging from backscatter coefficient measurements: image formation and interpretation.
A broadband method for measuring backscatter coefficients sigma b and other acoustic parameters is described. From the sigma b measurements, using a commercially-available imaging system, four high-resolution parametric ultrasound images are formed in a C-scan image plane. Scatterer size images are computed from the frequency dependence of sigma b and a correlation model function that describes the structure and elastic properties of the medium. Scattering strength images are computed from the absolute magnitude of sigma b. Chi-square images are generated to display how well the correlation model represents the interrogated medium. Integrated backscatter coefficient images are formed over the transducer bandwidth. All four images are generated simultaneously and compared with the corresponding B-mode image. Test samples with known physical properties were used to demonstrate experimentally that accurate parametric images are possible if an accurate correlation model is used. Local variations in attenuation, the center frequency and bandwidth of the transducer, and the distribution of scatterer sizes greatly influence the accuracy of estimates and the appearance of the image, thus demonstrating the importance of these factors in parametric image interpretation.


The effects of NAD+ precursor (nicotinic acid and nicotinamide) supplementation on weight loss and related hormones: a systematic review and meta-regression analysis of randomized controlled trials.
Despite the fact that obesity and overweight are serious major health problems worldwide, fighting against them is also considered a challenging issue. Several interventional studies have evaluated the potential weight-reduction effect of nicotinamide adenine dinucleotide (NAD+) precursor. In order to obtain a better viewpoint from them, this study aimed to comprehensively investigate the effects of NAD+ precursor supplementation on weight loss, adiponectin, and leptin. Scopus, PubMed/Medline, Web of Science, Cochrane, and Embase databases were searched using standard keywords to identify all controlled trials investigating the weight loss and related hormones effects of NAD+ precursor. Pooled weighted mean difference and 95% confidence intervals were achieved by random-effects model analysis for the best estimation of outcomes. Twenty two treatment arms with 5,144 participants' were included in this systematic review and meta-regression analysis. The pooled findings showed that NAD+ precursor supplementation has an effect on lowering BMI (weighted mean difference (WMD): -0.19 kg/m2, 95% confidence interval (CI): -0.29 to -0.09, p < 0.001) and increasing adiponectin (WMD: 1.59 μg/mL, 95% CI: 0.49 to 2.68, p = 0.004) in humans compared with control groups. However, no significant effect was observed on body weight and leptin. There was a significant relationship between doses of intervention with changes in BMI. In addition, subgroup analysis showed that BMI reduction was greater when receiving nicotinic acid (NA) supplementation than nicotinamide (NE) supplementation. NAD+ precursor had significant effects on weight management with the reduction of BMI and increasing adiponectin.


Confirmation of molecular weight of Aspergillus oryzae alpha-amylase using the low angle laser light scattering technique in combination with high pressure silica gel chromatography.
Molecular weight of Aspergillus oryzae alpha-amylase (Taka-amylase A) was estimated to be 51,000 +/- 500 by the combined use of high pressure silica gel (TSK-GEL G3000SW) chromatography and the low angle laser light scattering technique. The study was carried out partly to assess the performance of the combined technique, and results obtained indicate that it is highly promising as a method to determined protein molecular weight both accurately and quickly.


The impact of aging on human brain network target controllability.
Understanding how few distributed areas can steer large-scale brain activity is a fundamental question that has practical implications, which range from inducing specific patterns of behavior to counteracting disease. Recent endeavors based on network controllability provided fresh insights into the potential ability of single regions to influence whole brain dynamics through the underlying structural connectome. However, controlling the entire brain activity is often unfeasible and might not always be necessary. The question whether single areas can control specific target subsystems remains crucial, albeit still poorly explored. Furthermore, the structure of the brain network exhibits progressive changes across the lifespan, but little is known about the possible consequences in the controllability properties. To address these questions, we adopted a novel target controllability approach that quantifies the centrality of brain nodes in controlling specific target anatomo-functional systems. We then studied such target control centrality in human connectomes obtained from healthy individuals aged from 5 to 85. Main results showed that the sensorimotor system has a high influencing capacity, but it is difficult for other areas to influence it. Furthermore, we reported that target control centrality varies with age and that temporal-parietal regions, whose cortical thinning is crucial in dementia-related diseases, exhibit lower values in older people. By simulating targeted attacks, such as those occurring in focal stroke, we showed that the ipsilesional hemisphere is the most affected one regardless of the damaged area. Notably, such degradation in target control centrality was more evident in younger people, thus supporting early-vulnerability hypotheses after stroke.


[Treating patients suffering from dementia].
In the field of dementias, attention is focused on Alzheimer's disease (AD) and the hope of a treatment which could stop its evolution. Although research tracks exist, this goal is not yet reached. Moreover, all demented patients do not suffer from AD. Our commitment is to provide all patients with the best available treatments. First, cognitive disorders should be detected and investigated early. Behavioural disturbances should be properly managed. Analysis and diagnosis must precede non specific sedation. The primary goal of any therapeutic approach is the patient's quality of life.


[Effect of marathons on neuromuscular excitability; comparison of electromyographic and biochemical findings].
The aim of this paper is to study the neuromuscular excitability of a group of marathon runners and to see how it can be modified right after the marathon. Spontaneously appearing multiplets in EMG signal under ischaemia served as a test of the neuromuscular hyperexcitability. The percentage of positive tests is much higher than in the control population; as a rule, the effect of the marathon is to diminish the neuromuscular hyperexcitability. The concentrations of Ca, Mg and P in the plasma as well as the globular concentration of Mg have been determined several times, both before and after the marathon; no correlation has been found with the neuromuscular hyperexcitability.


Enhancement of paediatric oncology pharmacy practices in a low-middle-income country through teaching and training using the My Child Matters Grant.
The development of a successful oncology pharmacy system includes competency training, cost-efficient procurement, proper storage, preparation and administration of chemotherapy, and appropriate waste disposal. Low-middle-income countries such as Pakistan face several challenges within the realm of oncology pharmacy such as the unavailability of training programmes, resources and financial support, and inconsistencies in the safe handling of cytotoxic drugs. The Indus Hospital and Health Network (IHHN) is among the pioneers of oncology pharmacy practices in Pakistan, with a well-established Oncology Pharmacy Team and chemotherapy preparation in accordance with the United States Pharmacopeia 797 and 800 safety guidelines. The My Child Matters Grant was awarded by the Sanofi Espoir Foundation to the Department of Paediatric Hematology and Oncology at IHHN for holistic improvement in childhood cancer care through teaching, training and capacity building. Partnerships were formed with five public-sector paediatric oncology units nationwide. Initiatives were taken to improve oncology pharmacy practices including teaching and training courses, in-person assessment visits, and mentorship and liaison efforts. Despite prevailing challenges, promising improvements were noted at each centre. However, Pakistan needs to establish a national plan for childhood cancer with the creation of regional organisations for the training and monitoring of oncology pharmacists. Centralisation of pharmacy operations within hospitals is essential to maintain the availability, storage, preparation and administration standards of chemotherapy.


Incidence and characteristics of femoral deformities in the dysplastic hip.
Reorientation acetabular osteotomies can correct dysplastic deformities and provide marked improvement in hip function. Deformities of the proximal femur can produce suboptimal articulation or secondary impingement after acetabular reorientation, yet the incidence and characteristics of such deformities have not been well described. To describe the proximal femoral anatomy in patients with symptomatic acetabular dysplasia, we retrospectively analyzed the radiographs of 108 hips treated with periacetabular osteotomy. The radiographic findings were compared with those in 22 control hips. In the dysplastic group, 80 hips were in women and 28 in men, and the average age was 24.8 years. Of the 108 abnormal radiographs, 44% had coxa valga and 4% coxa vara. Seventy-two percent had an aspheric or deformed femoral head and the head-neck offset was insufficient in 75% of the hips. When compared with the control hips, dysplastic hips had differences in parameters of proximal femoral anatomy that we measured. These data demonstrate a high incidence of proximal femoral abnormalities associated with acetabular dysplasia. Identifying and treating these abnormalities may optimize joint congruency and minimize secondary impingement after acetabular reorientation. Level II, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.


Tumorigenicity, oncogene transfection, and radiosensitivity.
Reports that the incorporation of exogenous oncogenes confer radioresistance have excited interest and controversy. We investigate whether human cell lines transformed to a malignant phenotype by gamma-rays or by chemicals became radioresistant. Rodent intestinal epithelial cells immortalized by the HPV virus, human immortalized bronchoepithelial cells and their malignant counterparts transformed by alpha-particles, uroepithelial cells and their malignant counterparts transformed either by alpha-particles or methylcholanthrine-4, and osteosarcoma cells and their nonmalignant counterparts into which the Rb gene had been introduced were used. Dose response curves for all of these cell lines were obtained by exposure to cesium 137 gamma-rays at a dose-rate of 1.18 Gy/min. There was a dramatic increase in resistance to gamma-rays when H-ras was transfected into rodent intestinal epithelial cells. By contrast, in the case of the three human cell lines used, no consistent or significant change of radiosensitivity occurred when normal cells were transformed to a malignant state by alpha-particles or by a chemical carcinogen. Experiments involving the introduction of foreign oncogenes to cause tumorigenicity and accompanying radioresistance do not have direct relevance in human tumors. In a number of different instances, the conversion to malignancy by means that more closely reflect what happens in practice (i.e., by radiation or a chemical carcinogen) is not necessarily accompanied by an increased radioresistance to low doses of radiation.