Wear characteristics of current aesthetic dental restorative CAD/CAM materials: two-body wear, gloss retention, roughness and Martens hardness.
This study determined the two-body wear and toothbrushing wear parameters, including gloss and roughness measurements and additionally Martens hardness, of nine aesthetic CAD/CAM materials, one direct resin-based nanocomposite plus that of human enamel as a control group. Two-body wear was investigated in a computer-controlled chewing simulator (1.2 million loadings, 49N at 1.7Hz; 3000 thermocycles 5/50°C). Each of the 11 groups consisted of 12 specimens and 12 enamel antagonists. Quantitative analysis of wear was carried out with a 3D-surface analyser. Gloss and roughness measurements were evaluated using a glossmeter and an inductive surface profilometer before and after abrasive toothbrushing of machine-polished specimens. Additionally Martens hardness was measured. Statistically significant differences were calculated with one-way ANOVA (analysis of variance). Statistically significant differences were found for two-body wear, gloss, surface roughness and hardness. Zirconium dioxide ceramics showed no material wear and low wear of the enamel antagonist. Two-body wear of CAD/CAM-silicate and -lithium disilicate ceramics, -hybrid ceramics and -nanocomposite as well as direct nanocomposite did not differ significantly from that of human enamel. Temporary polymers showed significantly higher material wear than permanent materials. Abrasive toothbrushing significantly reduced gloss and increased roughness of all materials except zirconium dioxide ceramics. Gloss retention was highest with zirconium dioxide ceramics, silicate ceramics, hybrid ceramics and nanocomposites. Temporary polymers showed least gloss retention. Martens hardness differed significantly among ceramics, between ceramics and composites, and between resin composites and acrylic block materials as well. All permanent aesthetic CAD/CAM block materials tested behave similarly or better with respect to two-body wear and toothbrushing wear than human enamel, which is not true for temporary polymer CAD/CAM block materials. Ceramics show the best gloss retention compared to hybrid ceramics, composites and acrylic polymers.


Generation of the VESPA response to rapid contrast fluctuations is dominated by striate cortex: evidence from retinotopic mapping.
The VESPA (visual-evoked spread spectrum analysis) method derives an impulse response function of the visual system from scalp electroencephalographic (EEG) data using the controlled modulation of some feature of a visual stimulus. Recent research using VESPA responses to modulations of stimulus contrast has provided new insights into both early visual attention mechanisms and the specificity of visual-processing deficits in schizophrenia. To allow a fuller interpretation of these and future findings, it is necessary to further characterize the VESPA in terms of its underlying cortical generators. To that end, we here examine spatio-temporal variations in the components of the VESPA as a function of stimulus location. We found that the first two VESPA components (C1/P1) each have a posterior dorsal midline focus and reverse in polarity across the horizontal meridian, consistent with retinotopic projections to calcarine cortex (V1) for the stimulus locations tested. Furthermore, the focal scalp topography of the VESPA was strikingly constant across the entire C1-P1 timeframe (50-120 ms) for each stimulus location, with negligible global scalp activity visible at the zero-crossing dividing the two. This indicates a common focal source underpinning both components, which was further supported by a significant correlation between C1 and P1 amplitudes across subjects (r=0.54; p<0.05). These results, along with factors implicit in the method of derivation of the contrast-VESPA, lead us to conclude that these responses are dominated by activity from striate cortex. We discuss the implications of this finding for previous and future research using the VESPA.


[Understanding and treatment strategy for disc displacement of temporomandibular disorders].
Understanding and treatment strategy for disc displacement of temporomandibular disorders (TMD) were discussed in the present review. It has been strongly recommended by the author that the treatment strategy for disc displacement, one subtype of TMD, should be mainly the reversible conservative treatment methods. The most important goal of treatment for disc displacement is to recover the mobility and function of the joint in order to improve the quality of the patient's life. Comprehensive assessments both from somatic and psychological aspects for each TMD patient are necessary, especially for the patients with chronic pain. Although the role of surgical operative treatments is very limited in the general treatment strategy for TMD, it is still important for a few patients who had definite diagnosis of intra-articular disorders, severe symptoms affecting the quality of patient's life and failed to response to the correct conservative treatments. It should be very careful to treat the TMD patients by surgical operation or irreversible occlusion treatments changing the natural denture of the patient, such as full mouth occlusional reconstruction and extensive adjustment of occlusion.


Normal pressure hydrocephalus as an unusual presentation of supratentorial extraventricular space-occupying processes: report on two cases.
Normal pressure hydrocephalus (NPH) is a clinical and radiographic syndrome characterized by ventriculomegaly, abnormal gait, urinary incontinence, and dementia. The condition may occur due to a variety of secondary causes but may be idiopathic in approximately 50% of patients. Secondary causes may include head injury, subarachnoid hemorrhage, meningitis, and central nervous system tumor. Here, we describe two extremely rare cases of supratentorial extraventricular space-occupying processes: meningioma and glioblastoma multiforme, which initially presented with NPH.


Pressure-induced protein unfolding in the ternary system AOT-octane-water is different from that in bulk water.
In a cellular environment, the presence of macromolecular cosolutes and membrane interfaces can influence the folding-unfolding behavior of proteins. Here we report on the pressure stability of alpha-chymotrypsin in the ternary system bis(2-ethylhexyl)sodium sulfosuccinate-octane-water using FTIR spectroscopy. The ternary system forms anionic reverse micelles which mimic cellular conditions. We find that inclusion of a single protein molecule in a reverse micelle does not alter its conformation. When pressurized in bulk water, alpha-chymotrypsin unfolds at 750 MPa into a partially unfolded structure. In contrast, in the ternary system, the same pressure increase induces a random coil-like unfolded state, which collapses into an amorphous aggregate during the decompression phase. It is suggested that the unfolding pathway is different in a cell-mimicking environment due to the combined effect of multiple factors, including confinement. A phase transition of the reverse micellar to the lamellar phase is thought to be essential to provide the conditions required for unfolding and aggregation, though the unfolding is not a direct result of the phase transition. Our observations therefore suggest that membranes may cause the formation of alternative conformations that are more susceptible to aggregation.


Platelet-Rich Plasma Composite Organohydrogel with Water-Locking and Anti-Freezing to Accelerate Wound Healing.
Hydrogels have gained impressive attention in biological medicine due to their excellent biosafety, softness, and varied functional components. However, conventional hydrogels have inherent defects, such as low tensile strength, weak water-locking, and poor anti-freezing. In tissue engineering, once the hydrogel loses water or freezes, it will harden the interaction interfaces and destroy the nascent granulation tissue. Herein, based on the design concept of "hard frame-soft penetration", a composite adhesive organohydrogel is fabricated by introducing bacterial cellulose and platelet-rich plasma (PRP) into a poly-N-(tris[hydroxymethyl]methyl)acrylamide (THMA)/N-acryloyl aspartic acid (AASP) hybrid gel network infiltrated with glycerol/water binary solvent. The resultant organohydrogels exhibit excellent antifreeze properties at low temperatures (-80 °C) and demonstrate stable long-term water retention (91%) in the open environment within 12 days and can adhere firmly to the tissues by the action of "hydrogen bond clusters". Additionally, the introduction of bacterial cellulose matrix endows the organohydrogel with high tensile strength similar to that of skin. In vivo, the PRP-loaded organohydrogel can release a variety of growth factors to accelerate the wound healing process through collagen deposition and angiogenesis. Altogether, this strategy will extend the life of the hydrogel in some harsh medical environments.


Group III and IV muscle afferents differentially affect the motor cortex and motoneurones in humans.
The influence of group III and IV muscle afferents on human motor pathways is poorly understood. We used experimental muscle pain to investigate their effects at cortical and spinal levels. In two studies, electromyographic (EMG) responses in elbow flexors and extensors to stimulation of the motor cortex (MEPs) and corticospinal tract (CMEPs) were evoked before, during, and after infusion of hypertonic saline into biceps brachii to evoke deep pain. In study 1, MEPs and CMEPs were evoked in relaxed muscles and during contractions to a constant elbow flexion force. In study 2, responses were evoked during elbow flexion and extension to a constant level of biceps or triceps brachii EMG, respectively. During pain, the size of CMEPs in relaxed biceps and triceps increased (by approximately 47% and approximately 56%, respectively; P < 0.05). MEPs did not change with pain, but relative to CMEPs, they decreased in biceps (by approximately 34%) and triceps (by approximately 43%; P < 0.05). During flexion with constant force, ongoing background EMG and MEPs decreased for biceps during pain (by approximately 14% and 15%; P < 0.05). During flexion with a constant EMG level, CMEPs in biceps and triceps increased during pain (by approximately 30% and approximately 26%, respectively; P < 0.05) and relative to CMEPs, MEPs decreased for both muscles (by approximately 20% and approximately 17%; P < 0.05). For extension, CMEPs in triceps increased during pain (by approximately 22%) whereas MEPs decreased (by approximately 15%; P < 0.05). Activity in group III and IV muscle afferents produced by hypertonic saline facilitates motoneurones innervating elbow flexor and extensor muscles but depresses motor cortical cells projecting to these muscles.


[Nocturia and benign prostatic hyperplasia].
Nocturia often occures in patients with benign prostata hyperplasia (BPH). The aim of the study was to investigate the frequency of nocturia in patients with BPH. Nocturia and other factors associated with it were also investigated. Forty patients with the confirmed diagnosis of BPH were studied. Transurethral and transvesical prostatectomy were performed in all the patients. Simptoms were evaluated with the International Prostete Sypmtom Score before, as well as three and six months after the surgery. All the results were compared with the control group. . There was no statistically significant difference between the patients before and after the surgery regarding nocturia. There was, howerer, a statistically significant difference between the operated patients and the control group regarding nocturia, as well as a statistically significant correlation between noctruia and the age of the patients in both the investigated and the control group. A correlation also existed between nocturia and the prostatic size. There was no statistically significant improvement in symptoms of nocturia after the surgery. It is necessary to be very careful in decision making in patients with nonabsolute indiction for surgery and isolated bothersome symptom of nocturia. Age of a patient should also be considered in the evaluation of favourable result of the surgery because of a significant correlation between noctura and the age of a patient.


Non-Close-Packed Particle Arrays Based on Anisotropic Red Blood Cell (RBC) like Particles via Stretching Deformation Method.
Non-close-packed (NCP) particle arrays have potential applications in many fields such as photonics and sensors. However, due to thermodynamic stability, it is still a challenge to produce NCP arrays by the traditional approach. Here, we demonstrated a facile method to fabricate hexagonal close-packed (HCP) arrays with different orientations from that of the Janus particles. After that, the HCP arrays can be easily tuned by stretching deformation of polyethylene film. By tuning the stretching elongations, NCP arrays with five Bravais lattice structures were obtained. Besides, to fabricate the complex structure, these arrays were used as templates to assemble binary particle arrays. Such tunable crystal lattice and binary self-assembly crystal can be useful for fabricating more flexible structures and more open systems.


Mosaic DNA imports with interspersions of recipient sequence after natural transformation of Helicobacter pylori.
Helicobacter pylori colonizes the gastric mucosa of half of the human population, causing gastritis, ulcers, and cancer. H. pylori is naturally competent for transformation by exogenous DNA, and recombination during mixed infections of one stomach with multiple H. pylori strains generates extensive allelic diversity. We developed an in vitro transformation protocol to study genomic imports after natural transformation of H. pylori. The mean length of imported fragments was dependent on the combination of donor and recipient strain and varied between 1294 bp and 3853 bp. In about 10% of recombinant clones, the imported fragments of donor DNA were interrupted by short interspersed sequences of the recipient (ISR) with a mean length of 82 bp. 18 candidate genes were inactivated in order to identify genes involved in the control of import length and generation of ISR. Inactivation of the antimutator glycosylase MutY increased the length of imports, but did not have a significant effect on ISR frequency. Overexpression of mutY strongly increased the frequency of ISR, indicating that MutY, while not indispensable for ISR formation, is part of at least one ISR-generating pathway. The formation of ISR in H. pylori increases allelic diversity, and contributes to the uniquely low linkage disequilibrium characteristic of this pathogen.


[CUTANEOUS METASTASIS OF UROTHERIAL CARCINOMA FOR WHICH MOHS PASTE WAS USEFUL: A CASE REPORT].
The patient was a 71-year-old man referred to our department because of asymptomatic gross hematuria. Detailed examination led to a diagnosis of bilateral ureteral cancer and prostate cancer. Total nephroureterectomy was performed for bilateral ureteral cancers on separate occasions, while prostate cancer was managed with hormone therapy. Because multiple bladder tumors were found by cystoscopy conducted after 3 months, total cystectomy was performed. Neither distant metastasis nor local recurrence had developed, 2 years later, when the patient visited our department again because of glans enlargement and received a diagnosis of penile cancer. Partial penectomy was performed, and a 1-cm indurated nodule was found in the skin of the hypogastric region during surgery and treated by simultaneous wedge-shaped excision. Histopathologically, the lesions were urothelial carcinomas. Multiple metastatic foci occurred in the skin postoperatively centering on the hypogastric region, growing rapidly and accompanied by bleeding and exudate causing a bad odor. Topical application of Mohs paste resulted in dramatic improvement of the pain and exudate, which thereby improved the patient's quality of life (QOL) to a level enabling discontinuation of narcotic drug therapy for cancer-related pain. Thereafter, hepatic metastasis was found and chemotherapy with gemcitabine and paclitaxel was administered. The patient did not respond to this chemotherapy and died of cancer 3 months later. Cutaneous metastasis of urothelial carcinoma, which is a very rare condition, is often managed with palliative therapy due to the lack of response to anticancer chemotherapy. In such cases, the use of Mohs paste appears to be of great value for maintaining the patient's QOL which otherwise might deteriorate markedly.


Adsorption-driven photocatalytic activity of mesoporous titanium dioxide.
Titanium dioxide with a mesoporous structure, when photoactivated in water, demonstrates an unprecedented photocatalytic activity, driven strongly by an adsorption degree of molecules onto the catalyst surface, which promotes a preferential conversion of a well-adsorbed molecule. This catalyzes a selective transformation of a well-adsorbed molecule into a less-adsorbed molecule, so-labeled "stick-and-leave" transformation, which promotes a direct hydroxylation of benzene to phenol, one of the most difficult synthetic reactions, with very high selectivity (>80%) and using water as a source of oxidant.


[Antimicrobial activity and constituents in rumput roman extract as a natural food preservative].
Rumput roman extract is used as a natural food preservative. Its antimicrobial activity and constituents were investigated as part of an ongoing study to evaluate its quality and safety as a food additive. The constituents were analyzed by GC/MS, and 5 major constituents were isolated and identified as capillin, capillene, caryophyllene oxide, alpha-curcumene and methyleugenol using NMR analysis. The antimicrobial activities against E. coli, S. cerevisiae and A. niger were measured by means of the halo test. Based on the results, we confirmed that capillin was the major active constituent. The concentrations of capillin and capillene were determined to 17.9 mg/mL and 36.1 mg/mL, respectively, from standard curves of authentic compounds on HPLC.


Use of antibiotics in hospitalized patients with COVID-19: evolving concepts in a highly dynamic antimicrobial stewardship scenario.
Excessive use of antibiotics has been frequently reported in hospitalized patients with COVID-19 worldwide, compared to the actual number of bacterial co-infections or super-infections. In this perspective, we discuss the current literature on the use of antibiotics and antimicrobial stewardship interventions in hospitalized patients with COVID-19. A search was conducted in PubMed up to March 2023. The COVID-19 pandemic has witnessed an excessive use of antibiotics in hospitals worldwide, especially before the advent of COVID-19 vaccination, although according to the most recent data there is still an important disproportion between the prevalence of antibiotic use and that of proven bacterial coinfection or superinfections. An important reduction in the prevalence of antibiotic use in COVID-19 patients reported in the literature, from 70-100% to 50-60%, has been observed after successful vaccination campaigns, likely related to the reduced median disease severity of hospitalized COVID-19 patients and some successful interventions of antimicrobial and diagnostic stewardship. However, the disproportion between antibiotic use and the prevalence of bacterial infections (4-6%) is still uncomfortable from an antimicrobial stewardship perspective and requires further attention.


Pathological changes in accessory sex organs of rams following experimental infection with Actinobacillus seminis.
To investigate and assess the susceptibility, lesions and route of dissemination in the accessory sex organs of young rams experimentally infected with Actinobacillus seminis. The accessory sex organs were obtained from 64 young rams. The test rams (n=52) were infected by instillation, drenching or injection of 2.3 x 10(9) cells/ml A. seminis organisms via nine different routes: intra-epididymal (1 ml), I/V (3 ml), intra-urethral (3 ml), intra-preputial (3 ml), ductus deferens (1 ml), I/M (3 ml), oral (10 ml), intranasal (3 ml), and intra-conjunctival (3 drops). All test rams were necropsied 1-44 days post-inoculation (p.i.). Control rams (n=12) were necropsied at 1-46 days p.i. Accessory sex organs were cultured for A. seminis, and thin tissue sections were collected and examined for histopathological changes. Vesicular adenitis was the most frequent lesion (21/52; 40%), followed by ampullitis, deferentitis, urethritis and bulbo-urethral adenitis (20/52 (38%), 16/52 (31%), 12/52 (23%), and 8/52 (15%), respectively). The prostate and prepuce were the least affected, and lesions occurred equally at 4% (2/52). Actinobacillus seminis was isolated from the accessory sex organs of 10 (19%) rams: from the vesicular glands (n=6), ductus deferens (n=3), ampullae (n=1), and prepuce (n=3). No lesions were seen in rams inoculated via the nasal and conjunctival routes. The pattern of involvement of both ascending and descending A. seminis infection of the genital tract is discussed. Involvement of the accessory sex organ of rams following all but the intranasal and intra-conjunctival routes of the nine routes of experimental inoculation tested helped to clarify the epidemiology, pathogenesis, and pathology of ovine genital actinobacillosis.


About the information depth of backscattered electron imaging.
The information depth of imaging with backscattered electrons in the scanning electron microscope was measured directly by comparison of a planar view of a steel sample with buried precipitates with an image of a section cut through precipitates by means of a Focused Ion Beam attachment. The information depth was determined across the electron energy range of units of keV and the results were compared with information depths calculated from two published equations and simulated using widely available Monte Carlo-based software. Recommendations are given for routine estimations of BSE information depths.


Variations in brachial plexus and the relationship of median nerve with the axillary artery: a case report.
Brachial Plexus innervates the upper limb. As it is the point of formation of many nerves, variations are common. Knowledge of these is important to anatomists, radiologists, anesthesiologists and surgeons. The presence of anatomical variations of the peripheral nervous system is often used to explain unexpected clinical signs and symptoms. On routine dissection of an embalmed 57 year old male cadaver, variations were found in the formation of divisions and cords of the Brachial Plexus of the right side. Some previously unreported findings observed were; direct branches to the muscles Pectoralis Minor and Latissimus dorsi from C6, innervation of deltoid by C6 and C7 roots and the origin of lateral pectoral nerve from the posterior division of upper trunk. The median nerve was present lateral to axillary artery. The left side brachial plexus was also inspected and found to have normal anatomy. The probable cause for such variations and their embryological basis is discussed in the paper. It is also concluded that although these variations may not have affected the functioning of upper limb in this individual, knowledge of such variations is essential in evaluation of unexplained sensory and motor loss after trauma and surgical interventions to the upper limb.


TMEM100 Modulates TGF-β Signaling Pathway to Inhibit Colorectal Cancer Progression.
This study investigated the functional mechanism of transmembrane protein 100 (TMEM100) as a tumor inhibitor gene in CRC cells and offered a reference for the treatment of CRC. The mRNA expression data of CRC were acquired from the TCGA database to mine differentially expressed mRNAs. The role of TMEM100 in the progression of CRC cells was evaluated by MTT, colony formation, scratch healing, and Transwell assays. The influence of TMEM100 on the TGF-β signaling pathway was detected by western blot. TMEM100 was markedly lowly expressed in CRC. CRC cell growth was significantly suppressed by overexpressing TMEM100 but noticeably facilitated by silencing TMEM100. Overexpression of TMEM100 inhibited the activation of the TGF-β signaling pathway, thus inhibiting malignant progression of CRC. TMEM100 is lowly expressed in CRC, which can suppress CRC cell growth by regulating the TGF-β signaling pathway.


Red blood cells prevent inhibition of hypoxic pulmonary vasoconstriction by nitrite in isolated, perfused rat lungs.
Nitrite reduction to nitric oxide (NO) may be potentiated by a nitrite reductase activity of deoxyHb and contribute to systemic hypoxic vasodilation. The effect of nitrite on the pulmonary circulation has not been well characterized. We explored the effect of nitrite on hypoxic pulmonary vasoconstriction (HPV) and the role of the red blood cell (RBC) in nitrite reduction and nitrite-mediated vasodilation. As to method, isolated rat lungs were perfused with buffer, or buffer with RBCs, and subjected to repeated hypoxic challenges, with or without nitrite. As a result, in buffer-perfused lungs, HPV was reduced at nitrite concentrations of 7 muM and above. Nitrite inhibition of HPV was prevented by excess free Hb and RBCs, suggesting that vasodilation was mediated by free NO. Nitrite-inhibition of HPV was not potentiated by mild acidosis (pH = 7.2) or xanthine oxidase activity. RBCs at 15% but not 1% hematocrit prevented inhibition of HPV by nitrite (maximum nitrite concentration of approximately 35 muM) independent of perfusate Po(2). Degradation of nitrite was accelerated by hypoxia in the presence of RBCs but not during buffer perfusion. In conclusion, low micromolar concentrations of nitrite inhibit HPV in buffer-perfused lungs and when RBC concentration is subphysiological. This effect is lost when RBC concentration approaches physiological levels, despite enhanced nitrite degradation in the presence of RBCs. These data suggest that, although deoxyHb may generate NO from nitrite, insufficient NO escapes the RBC to cause vasodilation in the pulmonary circulation under the dynamic conditions of blood flow through the lungs and that RBCs are net scavengers of NO.


Patient-reported outcomes and survival in multiple sclerosis: A 10-year retrospective cohort study using the Multiple Sclerosis Impact Scale-29.
There is increasing emphasis on using patient-reported outcomes (PROs) to complement traditional clinical outcomes in medical research, including in multiple sclerosis (MS). Research, particularly in oncology and heart failure, has shown that PROs can be prognostic of hard clinical endpoints such as survival time (time from study entry until death). However, unlike in oncology or cardiology, it is unknown whether PROs are associated with survival time in neurological diseases. The Multiple Sclerosis Impact Scale-29 (MSIS-29) is a PRO sensitive to short-term change in MS, with questions covering both physical and psychological quality of life. This study aimed to investigate whether MSIS-29 scores can be prognostic for survival time in MS, using a large observational cohort of people with MS. From 15 July 2004 onwards, MSIS-29 questionnaires were completed by people with MS registered with the MS Society Tissue Bank (n = 2,126, repeated 1 year later with n = 872 of the original respondents). By 2014, 264 participants (12.4%) had died. Higher baseline MSIS-29 physical (MSIS-29-PHYS) score was associated with reduced survival time (subgroup with highest scores versus subgroup with lowest scores: hazard ratio [HR] 5.7, 95% CI 3.1-10.5, p < 0.001). Higher baseline MSIS-29 psychological score was also associated with reduced survival time (subgroup with highest scores versus subgroup with lowest scores: HR 2.8, 95% CI 1.8-4.4, p < 0.001). In those with high baseline MSIS-29 scores, mortality risk was even greater if the MSIS-29 score worsened over 1 year (HR 2.3, 95% CI 1.2-4.4, p = 0.02). MSIS-29-PHYS scores were associated with survival time independent of age, sex, and patient-reported Expanded Disability Status Scale score in a Cox regression analysis (per 1-SD increase in MSIS-29-PHYS score: HR 1.8, 95% CI 1.1-2.9, p = 0.03). A limitation of the study is that this cohort had high baseline age and disability levels; the prognostic value of MSIS-29 for survival time at earlier disease stages requires further investigation. This study reports that PROs can be prognostic for hard clinical outcomes in neurological disease, and supports PROs as a meaningful clinical outcome for use in research and clinical settings.


Evaluation of alpine skiing and snowboarding injury in a northeastern state.
To demonstrate the injury patterns of Alpine skiing and snowboarding in a northeastern state and evaluate potential risk factors. The medical records of a single pediatric and adult Level I trauma center were evaluated from January 1, 1990, through December 31, 1995. All admissions with injuries caused by Alpine skiing or snowboarding were reviewed. Those patients arriving from two local ski resorts, all of whose injuries are referred to the institution for care, were separated out for consideration. Age, sex, type of injury, date of injury, Injury Severity Score, operations performed, and outcome (including mortality) were evaluated. In addition, resort utilization for the study period was obtained from the two resorts included in the evaluation. Mortality data was obtained from the Vermont office of the Chief Medical Examiner for the same time period. For the 6-year period of the study approximately 2,978,000 skier and snowboarder days were recorded at the study sites. Approximately 447,000 of those days were attributed to snowboarders (15%). In all, 279 patients were admitted for injuries (0.01%), 238 were related to Alpine skiing (incidence 0.01%) and 40 to snowboarding (incidence 0.01%). Snowboarders were statistically younger (20 years; range, 4-44 years) than skiers (29 years; range, 6-70 years) (p < 0.001) and had a significantly lower Injury Severity Score (15 in snowboarders vs. 27 in skiers, p < 0.03). Two female patients were injured snowboarding and 68 female patients were injured skiing. Eight percent of injured snowboarders and 16% of injured skiers sustained multiple injuries (p < 0.01). Injury patterns were significantly different. Upper extremity injuries were almost exclusively found in snowboarders (24% vs. 7%, p < 0.003), whereas cruciate ligament injuries occurred far more commonly in skiers (45% vs. 4%, p < 0.001 Lower extremity injuries in general were more common in skiers (78% vs. 38%, p < 0.001). Central nervous system injuries, including head and spine, were evenly distributed over the two groups, although the snowboarders with central nervous system injuries were younger. In addition, splenic injuries were more common in snowboarders (13% vs. 2%, p < 0.01). Snowboarding accidents were far more common in December, March, and April than other months. Fifty-one patients sustained abdominal or chest injuries and only two of these required operative intervention (two splenectomies). Other operative interventions were limited to extremity injuries, injuries of the spine, or placement of an intracranial pressure monitor. There were no fatalities recorded in this population, although over the 6.5 years, there were 25 deaths related to alpine skiing and one to snowboarding in the State (incidence 0.0000009 skier days). Victims tended to be male: 96% of the skiers and the one snowboarder. The predominant cause of death was blunt head trauma followed by blunt chest trauma. Helmets were not worn by those sustaining head injuries or fatalities. Spine injuries were recorded only in extremely young snowboarders and skiers out of control. Snowboarders and Alpine skiers are equally prone to injury. Snowboarding accidents are typically less severe and show significantly different injury patterns than skiing accidents. Abdominal and chest injuries in this population are generally amenable to nonoperative management. Prevention programs are best targeted at safe skiing and snowboarding practices, not skiing or snowboarding in poor conditions, use of helmets for skiers, and restraint of snowboard use in very young children.


Good Manufacturing Practice (GMP) Compliance for Phage Therapy Medicinal Products.
Facing the emergence of difficult-to-treat bacterial infections, the perspective of using bacteriophages has re-gained interest in many countries. In terms of pharmaceutical classification in EU and United States, phages are considered as anti-infectious medicinal products and biological products, given the intended use and their live nature. During the production steps, the compliance with the Good Manufacturing Practice (GMP) represents the gold-standard to ensure the quality, safety and efficacy of medicinal products, either investigational or approved. In practice, the implementation of GMP rules for phage therapy medicinal products benefits from the long history of vaccine development. Accordingly, a well-structured strategy can be defined for each medicinal product, taking into account the specified indication (i.e., the target bacteria species, the infected site, the route of administration, the product composition). Based on the experience of different phage therapy medicinal products from the recent years, the most important requirements to achieve and claim GMP grade are reviewed here, including for genetically modified phages. Like all new medicinal products, the manufacturing of investigational phages incorporates significant challenges. However, the use of GMP-certified phages provides the best guarantee for the rigorous assessment of quality, safety and efficacy during the clinical development of phage medicinal products, thus appears as a key component for the successful development of phage therapy approaches.


Transition-Metal-Catalyzed Addition of Organosulfur Compounds to Alkynes and Alkenes: Catalysis and Catalyst Poisons.
The addition of heteroatom compounds to alkynes and alkenes is an atom-efficient method of carbon-heteroatom bond formation and is widely used as a fundamental synthetic method for the construction of functional molecules. Nevertheless, examples of transition-metal-catalyzed addition reactions of group 16 heteroatom compounds to carbon-carbon unsaturated bonds have been limited due to the widespread belief that organic sulfur and selenium compounds are representative catalyst poisons. In recent decades, however, several seminal catalytic reactions of sulfur compounds have been developed, providing important insights into catalysis and poisons. Therefore, this paper focuses on the transition-metal-catalyzed addition of organosulfur compounds to alkynes and alkenes, gains comprehensive insights into the catalysis and catalyst poisons, and proposes concepts for the development of transition-metal-catalyzed reactions of group 16 heteroatom compounds.


Evaluation of the Level of Physical Activity and Muscle Strength of Quadriceps in Patients Hospitalized for E-COPD: A Longitudinal Study.
Physical inactivity and peripheral muscle dysfunction are considered two of the main contributors to hospitalizations due to exacerbation and, above all, predictors of mortality for these requirements in patients with COPD. Therefore, longitudinal studies are needed to determine the impact of exacerbations during hospitalization on these two factors, especially after three months of hospital discharge. The objectives of the present study were to assess the level of physical activity in daily life (PADL) and isometric muscle strength of the quadriceps in patients hospitalized for exacerbation of COPD and to verify changes after 3 months of hospital discharge. This is a longitudinal observational study that assessed the PADL level with an accelerometer, after 24 h of the hospitalization and the beginning of the drug treatment and assessed the quadriceps muscle strength with a manual dynamometer, after 72 h of hospitalization, in 32 patients with COPD (66 ± 7.61 years), in addition to repeating both assessments with 30 days of hospital discharge and after 3 months of follow-up. Cognition, dyspnea, general health, physical performance and lung function were assessed to characterize the sample. As main results, there was increase in active time (344 ± 260 - 447 ± 199 min; p = 0.04) and number of steps (4.241 ± 374 - 6.216 ± 400 steps; p = 0.02) after three months. In addition, inactive time showed significant reduction 30 days after hospital discharge (1.151 ± 249 - 1.065 ± 198 min; p = 0.02). The level of physical activity showed significant improvement due to the increase in active time and number of steps after three months of hospital discharge and to the reduction of inactive time 30 days after hospital discharge.


[Methods of determining conduction velocity along sensory fibers of peripheral nerves].
The results of determining the sensory conduction along the median nerve by the methods of Buchthal et al. and Gutmann are compared. Ten healthy subjects were examined using a serial myograph supplied by " Medicor ". The identical nature of the results obtained by both methods warranted the conclusion as to the high reliability of Gutmann's method. The authors describe the adequate operational regime of the frequency filters of the myograph as well as the technical procedures enabling the researcher to register low-amplitude action potentials of the peripheral nerve sensory fibers without an averager.


An overview of methods used to clarify pathogenesis mechanisms of Campylobacter jejuni.
Thermotolerant campylobacters are the most frequent cause of bacterial infection of the lower intestine worldwide. The mechanism of pathogenesis of Campylobacter jejuni comprises four main stages: adhesion to intestinal cells, colonization of the digestive tract, invasion of targeted cells, and toxin production. In response to the high number of cases of human campylobacteriosis, various virulence study models are available according to the virulence stage being analyzed. The aim of this review is to compare the different study models used to look at human disease. Molecular biology tools used to identify genes or proteins involved in virulence mechanisms are also summarized. Despite high cost and limited availability, animal models are frequently used to study digestive disease, in particular to analyze the colonization stage. Eukaryotic cell cultures have been developed because of fewer restrictions on their use and the lower cost of these cultures compared with animal models, and this ex vivo approach makes it possible to mimic the bacterial cell-host interactions observed in natural disease cases. Models are complemented by molecular biology tools, especially mutagenesis and DNA microarray methods to identify putative virulence genes or proteins and permit their characterization. No current model seems to be ideal for studying the complete range of C. jejuni virulence. However, the models available deal with different aspects of the complex pathogenic mechanisms particular to this bacterium.


Aspergillus coronary embolization causing acute myocardial infarction.
An increased frequency of disseminated aspergillosis has been observed in the last decade, mostly occurring in immunocompromised patients including the bone marrow transplant population. Cardiac involvement by Aspergillus remains rare. We report the clinical and postmortem findings of an unusual case of Aspergillus pancarditis in a 7-year-old bone marrow transplant patient with Aspergillus embolization to the coronary arteries leading to a massive acute myocardial infarction. This case suggests that myocardial injury secondary to disseminated aspergillosis should be included in the differential diagnosis of chest pain in the immunocompromised pediatric patient.


A Case Report of Cystic Pheochromocytoma.
BACKGROUND Pheochromocytoma is a rare catecholamine-producing tumor with an estimated incidence of less than 0.1% in the global population. We present a case of cystic pheochromocytoma that was diagnosed as an incidental finding. The patient presented with abdominal pain and had a history of hypertension. CASE REPORT A 64-year-old man with hypertension presented with a clinical history of intermittent abdominal pain for one year. He denied sweating, palpitations, headache or back pain. He was found to have an elevated blood pressure of 170/90 and no palpable abdominal mass. Contrast-enhanced computed tomography (CT) imaging of the abdomen and pelvis were performed that showed cystic mass measuring 9 cm in diameter arising from the left adrenal gland with contrast-enhancing mural nodules. Magnetic resonance imaging (MRI) confirmed the cystic nature of the mass. Laboratory analysis showed an elevated plasma normetanephrine (NMN) of 1,087 pg/ml and metanephrine (MN) of 372 pg/ml; 24-hour urine showed elevated levels of NMN and MN, 3,002 mg/24 h and 1,596 mg/24 h, respectively. Given the laboratory and radiologic findings, a diagnosis of cystic pheochromocytoma was made. After controlling blood pressure with the alpha-blocker, doxazosin, the patient was hydrated and scheduled for an elective adrenalectomy. The histopathology of the excised adrenal gland was consistent with a cystic pheochromocytoma. CONCLUSIONS Cystic pheochromocytoma is a very rare tumor that may present without symptoms. The clinical course of cystic pheochromocytoma is similar to that of solid pheochromocytoma. Early surgical intervention is recommended, following blood pressure control with an alpha-blocker, and adequate hydration.


Pharmacogenomics of drug transporters: a new approach to functional analysis of the genetic polymorphisms of ABCB1 (P-glycoprotein/MDR1).
In the 21st century, emerging genomic technologies (i.e., bioinformatics, functional genomics, and pharmacogenomics) are shifting the paradigm of drug discovery research and improving the strategy of medical care for patients. In order to realize the personalized medicine, it is critically important to understand molecular mechanisms underlying inter-individual differences in the drug response, namely, pharmacological effect vs. side effect. Evidence is now accumulating to strongly suggest that drug transporters are one of the determinant factors governing the pharmacokinetic profile of drugs. Effort has been made to identify genetic variation in drug transporter genes. In particular, genetic variations of the human ABCB1 (P-glycoprotein/MDR1) gene have been most extensively studied. Hitherto more than fifty single nucleotide polymorphisms (SNPs) and insertion/deletion polymorphisms in the ABCB1 gene have been reported. However, at the present time, information is still limited with respect to the actual effect of those genetic polymorphisms on the function of ABCB1. In this context, we have undertaken functional analyses of ABCB1 polymorphisms. To quantify the impact of genetic polymorphisms on the substrate specificity of ABCB1, we have developed a high-speed screening system and a new structure-activity relationship (SAR) analysis method. This review addresses functional aspects of the genetic polymorphism of ABCB1 and provides the standard method to evaluate the effect of polymorphisms on the function.


[Results after graded recession of inferior oblique muscle in strabismus sursoadductorius].
Introduction: Idiopathic strabismus sursoadductorius is characterized by an overaction of the inferior oblique (IO) muscle, with elevation of the eye in adduction. This can result in chronic headache, eye pain, diplopia and abnormal head posture. Aim: Presentation of clinical results after graded recession of inferior oblique overaction (IOOA) in strabismus sursoadductorius. Method: During a period of 6 years (2012-2017) we performed a dosed transposition of IO muscle in 53 patients in the Department of Ophthalmology of the Semmelweis University and analyzed the clinical results retrospectively. The mean age was 12.8, min-max: 2-51 years. The transposition of the muscle (8 mm, 10 mm or maximal) was performed because of IOOA and was planned depending on the vertical deviation (VD) in maximal adduction. In case of maximal transposition, the insertion of IO was placed under the lateral part of the lower rectus muscle. We evaluated the squint angle in five positions of gaze preoperatively and postoperative 1 week, 1 month and 3-6 months. We examined best corrected visual acuity, binocular vision and complications after surgery. Results: Postoperatively 25 patients had acceptable stereopsis (Titmus 5). Visual acuity remained stable after surgery in all cases. The VD measured in maximal adduction changed with a decrease of 7.5° when 8 mm transposition was performed, and changed with a decrease to 12°, when maximal recession was performed. The mean reduction of VD was 17.8 prism dioptres (PD) after 1 week (p<0.01), 20.5 PD after 1 month and remained stable during a follow-up of 3-6 months. Conclusion: Graded recession of inferior oblique muscle is a suitable proposed procedure in patients with marked strabismus sursoadductorius. The rates of functional under- or overcorrection or other complications are low. Orv Hetil. 2019; 160(27): 1064-1069.


New solid supports linking nucleoside scaffolds.
An easy and efficient strategy to obtain new nucleoside based solid supports in which the nucleoside moieties have been anchored to the solid support through the nucleobase is here proposed. A simple and efficient solid-phase synthesis of 5' and 3'-derivatized uridine analogues has so been developed, following methodologies well established in organic chemistry.


The comet assay: a heavenly method!
The contributions to this special issue of Mutagenesis have been selected to cover the main research areas served by the comet assay, namely genotoxicology, environmental toxicology, human biomonitoring and fundamental investigations into mechanisms of DNA damage and repair. Innovative methods are described, technical issues are explored, and guidelines are given for venturing into relatively new or unexploited areas of research. The popularity of the comet assay in a historical context is illustrated by a bibliometric survey.


Rapid oestrogenic regulation of social and nonsocial learning.
Much research on oestrogens has focused on their long-term action, exerting behavioural effects within hours to days through gene transcription. Oestrogens also affect behaviour on a much shorter time scale. These rapid effects are assumed to occur through cell signalling and can elicit a behavioural effect as early as 15 min after treatment. These effects on behaviour have primarily been explored through the action of oestradiol at three well-known oestrogen receptors (ERs): ERα, ERβ and the more recently described G protein-coupled ER1 (GPER1). The rapid effects of oestradiol and ER agonists have been tested on both social and nonsocial learning paradigms. Social learning refers to a paradigm in which an animal acquires information and modifies its behaviour based on observation of another animal, commonly studied using the social transmission of food preferences paradigm. When administered shortly before testing, oestradiol rapidly improves social learning on this task, although no ER agonist has definitive, comparable improving effects. Some evidence points to GPER1, whereas ERα impairs, and ERβ activation has no effect on social learning. Conversely, ERα and GPER1 play a larger role than ERβ in the rapid improving effect of oestrogens on nonsocial learning, including social and object recognition. In addition, when administered immediately post-acquisition, oestrogens also rapidly improve memory consolidation in a variety of learning paradigms: object recognition, object placement, inhibitory avoidance and the Morris water maze, indicating that oestradiol affects the consolidation of multiple types of memory. Evidence suggests that these improvements are the result of oestrogens acting in the dorsal hippocampus where selective activation of all three ERs shows rapid improving effects on spatial learning comparable to oestradiol. However, the hippocampus is not necessary for rapid oestradiol improvements on social recognition. Although acute treatment with oestradiol enhances learning and memory on various social and nonsocial learning paradigms, the specific ERs play different roles in each type of learning. Future research should aim to further determine the roles of ERs with respect to the enhancing effects of oestradiol on learning and memory, and also determine where in the brain oestradiol acts to affect social and nonsocial learning.


C NMR spectra of streptolydigin, tirandamycin, and related degradation products.
Absorptions of the 32 carbon atoms of streptolydigin, a 3-acyltetramic acid, have been assigned in its C NMR spectrum, as have the adsorptions of triandamycin and related degradation products. Methods employed in assigning the individual carbons include off-resonance decoupling, and comparison studies with appropriate model compounds.


Synthesis of novel polyhydroxylated pyrrolidine-triazole/-isoxazole hybrid molecules.
A straightforward synthesis of novel, 2-heterocyclyl polyhydroxylated pyrrolidines is described. Stereocontrolled additions of nucleophiles to cyclic nitrones generated the corresponding 2,3-trans adducts, allowing the synthesis of the corresponding pyrrolidines via key intermediates bearing an alkyne and a nitrile oxide. Three hybrid systems, including a pyrrolidine with two isoxazoles and one triazole, are efficiently prepared via 1,3-dipolar cycloaddition. Biological testing of the product alkaloids showed that subtle structural variations have drastic effects on their inhibitory activities against glucosidases.


Evaluation of ameliorative potential of selenium on carbendazim induced oxidative stress in male goats.
In the present investigation, ameliorative effect of selenium on carbendazim induced oral sub chronic toxicity in bucks was assessed by studying various indices of antioxidant defense system. Bucks were randomly divided into four groups of four animals each. Group I served as control, Group II was orally drenched carbendazim at the dose rate of 50mg/kg body weight for 90 consecutive days. Group III was orally administered selenium in the form of sodium selenite at the dose rate of 0.05mg/kg body weight for 90 consecutive days. Group IV was orally administered carbendazim along with selenium at the same dosages as Group II and III. Prolonged administration of carbendazim produced oxidative stress in goat bucks as evidenced by increase in lipid peroxidation and decline in total antioxidant capacity. The increase in the activity of antioxidant enzymes was not sufficient to prevent pesticide induced oxidative stress. Selenium supplementation provides some amelioration against this effect. Further study is needed to prove ameliorative potential of this antioxidant against carbendazim induced toxicity in goat bucks.


Therapeutics targeting innate immune/inflammatory responses through the interleukin-6/JAK/STAT signal transduction pathway in patients with cancer.
Over the last 15 years, there has been an evolution in the thinking of how tumors grow and disseminate: from the earlier work where it was considered that the intrinsic characteristics of the tumor largely determined the process to more recent work where local and systemic inflammatory responses play a key role in disease progression and survival in patients with cancer. Although the immune/inflammatory responses to cancer are complex, it is clear that targeting the host immune/inflammatory responses (in particular, innate/humoral responses) has considerable potential to improve outcomes in patients with a variety of common solid tumors. There are a wide variety of agents from the nonselective glucocorticoids to the selective Janus Activated Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) inhibitors that has considerable therapeutic potential. They may be considered to act through a main signal transduction mechanism, the interleukin-6/JAK/STAT pathway. This work heralds a new era in which it will be important not only to treat the tumor but also to treat the host, so called oncoimmunology.


Penetrability of ofloxacin into cultured epithelial cells and macrophages.
It is well known that the penetration of drugs into host cells is the minimal requirement to exhibit their efficacy against infections with intracellular bacteria. Thus the penetrability of new quinolones including ofloxacin, norfloxacin and ciprofloxacin was evaluated by comparing their intracellular and extracellular activities by the use of cell infection systems in vitro. It was evidenced that the new quinolones tested were penetrable into both epithelial cells and macrophages, however, ofloxacin was more penetrable than norfloxacin and ciprofloxacin into both types of cells which serve the nest for proliferation of intracellular bacteria.


Variation in Phenolic Profile, β-Carotene and Flavonoid Contents, Biological Activities of Two Tagetes Species from Pakistani Flora.
The objective of present study was to evaluate the variation in phenolic profile, β-carotene, flavonoid contents, antioxidant and antimicrobial properties of Tagetes erecta and Tagetes patula (T. erecta and T. patula) through different in vitro assays. Antioxidant activity was determined through 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and inhibition of linoleic acid peroxidation assays and antibacterial and antifungal activities studied using the disc diffusion and resazurin microtiter-plate assays against bacterial and fungal strains. Moreover, total phenolics (TP), total carotenoids (TC) and total flavonoids (TF) were also determined. Highest (TP 35.8 mg GAE/g) and TF (16.9 mg CE/g) contents were found in MeOH extract of T. patula. T. erecta extract showed higher TC contents (6.45 mg/g) than T. patula extract (6.32 mg/g). T. erecta exhibited the highest DPPH radical-scavenging activity (IC50 ) (5.73 μg/mL) and inhibition of linoleic acid peroxidation (80.1%). RP-HPLC revealed the presence of caffeic acid, sinapic acid and ferulic acid in Tagetes extracts, m-coumaric acid in T. erecta whereas chlorogenic acid in T. patula extract only. Both extracts possessed promising antimicrobial activity compared to the ciprofloxacin and flumequine (+ve controls) against Bacillus subtilis and Alternaria alternate. Both extract were rich source of polyphenols exhibiting excellent biological activities.


Reflections on designing and conducting long-term surgical studies.
Endodontic literature is replete with surgical success-failure studies. Efforts to compare them should be avoided because there are so many variables within each of these studies. Among these variables can be surgical technique, clinical ability, restorative materials, the use of pooled data, and interpretation of data. Many of these studies serve as an historical reference from which current-day evaluators can build and design studies that are more contemporary and relevant to modern endodontic surgery. If a study is to be considered valid, it should strive to examine a well-controlled population and use a reproducible and rigorous surgical protocol. It is often difficult for the reader to know how much credibility to place on a given study until he or she understands the criteria for the various types of success-failure studies.


[Cesarean section: current management of postoperative acute pain. Continuous and intermittent epidural analgesia with and without elastomeric infusion device].
To compare the analgesia quality obtained in the management of the acute pain in 50 puerperae post-cesarean section using one of the two therapeutic modalities. The results were evaluated using descriptive and inferential statistics. Controlled, systematized a clinical trial, carried out from January to June of 2001. REGIMES AND RESULTS: A) Continuous epidural analgesia. With fentanyl citrate plus bupivacaine using a low flow elastomerics infuser (Single day Baxter infuser) 85% referred mild pain in rest or activity; 3% or less in analogic scale visual (VAS) in the first 24 hours of postoperative. B) Intermittent epidural analgesia. With bupivacaine plus intravenous Ketorolaco; 59% of the cases referred mild pain, 32% moderate pain and 9% severe. Management of acute pain postcesarean section should be priority with continuous epidural analgesia using the infuser and concentrations of drugs referred in order to minimize the incidence and magnitude of acute postoperative pain.


Retrieving two-dimensional information of the subwavelength variation from far-field irradiance.
An eigenvalue-problem approach of blind deconvolution is developed to retrieve the information of two-dimensional subwavelength variation from far-field irradiance with an embedded-aperture configuration with three detectors. A reference signal has been implemented to determine the scaling issue, and hence it allows the exact order of magnitude of the retrieved signals to be estimated correctly. It is shown that the subwavelength variations of a two-dimensional aperture can be identified with a precision of better than a 1% error ratio.


Efficacy of ethylenediamine dihydriodide in the prevention of naturally occurring foot rot in cattle.
The efficacy of an ethylenediamine dihydriodide containing salt mixture was evaluated with regard to the prevention of naturally occurring foot rot in pastured cattle. Ninety-six cattle were assigned to the treatment group and 96 were assigned to the control group. The groups were allowed consumption of salt-mineral mixtures, ad libitum, that were identical, except with respect to iodine concentration. The control group's mixture contained 0.0025% iodine and the treatment group's mixture contained 0.125% iodine (0.156% ethylenediamine dihydriodide). The incidence of foot rot was measured, as was the severity of the lesions and accompanying lameness. The incidence of foot rot in the control group (20.8%) was significantly (P less than 0.05) greater than the incidence in the treatment group (8.3%). The severity of foot rot was greater (P = 0.024) in the control calves vs the treatment calves. Total serum iodine concentrations were measured in the 2 groups on days 0, 46, and 130 of the experiment. The serum iodine values of the treatment group on day 46 (46 +/- 19.8 g/dl) and day 130 (23 +/- 12.3 g/dl) were significantly different (P less than 0.01) than the serum iodine concentrations of the control animals and the pretreatment values (day 0) of both groups. Production was measured via calf weaning weights. There were no detectable differences between the 205-day adjusted weaning weights of the calves in the control group vs the calves in the treatment group. Clinical signs of iodism were not observed in the cattle involved in this study.


Establishing nucleosome architecture and stability at promoters: Roles of pioneer transcription factors and the RSC chromatin remodeler.
Improvements in deep sequencing, together with methods to rapidly deplete essential transcription factors (TFs) and chromatin remodelers, have recently led to a more detailed picture of promoter nucleosome architecture in yeast and its relationship to transcriptional regulation. These studies revealed that ∼40% of all budding yeast protein-coding genes possess a unique promoter structure, where we propose that an unusually unstable nucleosome forms immediately upstream of the transcription start site (TSS). This "fragile" nucleosome (FN) promoter architecture relies on the combined action of the essential RSC (Remodels Structure of Chromatin) nucleosome remodeler and pioneer transcription factors (PTFs). FNs are associated with genes whose expression is high, coupled to cell growth, and characterized by low cell-to-cell variability (noise), suggesting that they may promote these features. Recent studies in metazoans suggest that the presence of dynamic nucleosomes upstream of the TSS at highly expressed genes may be conserved throughout evolution.


Etomidate versus midazolam for procedural sedation in pediatric outpatients: a randomized controlled trial.
Midazolam is widely used for procedural sedation and analgesia. Etomidate has been studied mostly in adults. Our objective is to compare the efficacy of etomidate and midazolam for achieving procedural sedation and analgesia in children. A randomized, double-blind, emergency department and orthopedic clinic-based trial was carried out among patients aged 2 to 18 years with displaced extremity fractures. Patients were administered 1 microg/kg of fentanyl and either 0.2 mg/kg of etomidate or 0.1 mg/kg of midazolam. Adequate sedation was defined, for the purpose of this study, as a score of 4 or more on the Ramsay Sedation Scale. The primary outcome was induction and recovery time. The rates of adverse events, success of fracture reduction, and parent and physician satisfaction were also compared. From April to August 2004, 100 of 128 eligible patients were enrolled (age 8.7+/-3.7 years; 50% male patients). A higher proportion of patients attained adequate sedation among those who received etomidate: 46 of 50 (92%) versus 18 of 50 (36%) (delta 56%; 95% confidence interval [CI] 38% to 69%). Time taken for induction (hazard ratio 4.9; 95% CI 2.2 to 10.9) and time taken for recovery (hazard ratio 2.8; 95% CI 1.5 to 5.1) were lower among patients who received etomidate. The rates of adverse events were similar in both groups, except for myoclonus and pain at the injection site, which was more frequent in the etomidate group. Induction and recovery times are shorter with etomidate compared with midazolam. At the dosages used for procedural sedation and analgesia among children with displaced extremity fracture, etomidate has higher efficacy in comparison with midazolam.


Computer modeling with randomized-controlled trial data informs the development of person-centered aged care homes.
To answer questions on the essential components (services, operations and resources) of a person-centered aged care home (iHome) using computer simulation. iHome was developed with AnyLogic software using extant study data obtained from 60 Australian aged care homes, 900+ clients and 700+ aged care staff. Bayesian analysis of simulated trial data will determine the influence of different iHome characteristics on care service quality and client outcomes. Interim results: A person-centered aged care home (socio-cultural context) and care/lifestyle services (interactional environment) can produce positive outcomes for aged care clients (subjective experiences) in the simulated environment. Further testing will define essential characteristics of a person-centered care home.


Characterization of microparticle separation utilizing electrokinesis within an electrodeless dielectrophoresis chip.
This study demonstrated the feasibility of utilizing electrokinesis in an electrodeless dielectrophoresis chip to separate and concentrate microparticles such as biosamples. Numerical simulations and experimental observations were facilitated to investigate the phenomena of electrokinetics, i.e., electroosmosis, dielectrophoresis, and electrothermosis. Moreover, the proposed operating mode can be used to simultaneously convey microparticles through a microfluidic device by using electroosmotic flow, eliminating the need for an additional micropump. These results not only revealed that the directions of fluids could be controlled with a forward/backward electroosmotic flow but also categorized the optimum separating parameters for various microparticle sizes (0.5, 1.0 and 2.0 μm). Separation of microparticles can be achieved by tuning driving frequencies at a specific electric potential (90 Vpp·cm(-1)). Certainly, the device can be designed as a single automated device that carries out multiple functions such as transportation, separation, and detection for the realization of the envisioned Lab-on-a-Chip idea.


Validation of the Short Self-Regulation Questionnaire for Taiwanese College Students (TSSRQ).
While self-regulation has long been recognized as an important characteristic of an individual, instruments assessing the general aptitude of self-regulation remain limited especially in Asian countries. This study re-validated Carey et al.'s (2004) Short Self-Regulation Questionnaire based on a national sample of Taiwanese college students (N = 1,988). Item analysis, exploratory factor analysis, and confirmatory factor analysis (CFA) yielded 22 items in five internally consistent factors. Descriptive findings showed that, a lack of proactiveness and volitional control, and a decrease of self-regulation throughout the college span appeared to be an overarching problem among Taiwanese college students. Furthermore, male students achieved lower self-regulation scores than female ones, and students in Services and STEM-related majors are in the need of self-regulation enhancement. Due to the generic measurement of individual's self-regulation traits, the Taiwanese Short Self-regulation Questionnaire (TSSRQ) can be flexibly applied to various contexts and used to deal with different issues beyond learning such as college students' Internet or smartphone addiction. Through this study, we hope the validated TSSRQ can promote studies on self-regulation and associated antecedents and outcomes, in turn leveraging college students' life adjustment and well-being.


Post-vitrectomy cataract acceleration in phakic eyes: a review.
Vitrectomy is considered the standard therapy for the treatment of posterior segment disease; however, after a significant improvement of the visual acuity, there is a reduction in visual acuity due to cataract formation, which requires further surgery. Nuclear sclerotic cataract (NSC) is the most common type of cataract seen after vitrectomy. The pathogenesis of post-vitrectomy NSC is unclear; several hypotheses have been formulated without any conclusions. In order to correct post-vitrectomy NSC, phacoemulsification with intraocular lens implantation is performed. This surgery itself has some complications, such as longer surgical time and the increased risk of capsular rupture as compared to phacoemulsification done alone. In this review, different hypotheses proposed by different authors in their studies and possible measures that are known so far to prevent post-vitrectomy NSC are discussed along with its treatments and their complications. Moreover, we aim to describe the pathophysiology of the formation of post-vitrectomy NSC.


Sympathetic skin response: monitoring of CT-guided lumbar sympathetic blocks.
To prospectively evaluate accuracy of sympathetic skin response (SSR) for monitoring computed tomography (CT)-guided lumbar sympathetic blocks, with palpable temperature increase in the foot 30 minutes after injection serving as the reference standard. Institutional review board approval and written informed consent were obtained. Seventy individual lumbar sympathetic blocks were performed in 13 patients (six female, seven male; mean age, 45 years) with reflex sympathetic dystrophy of the foot. A 22-gauge needle was advanced to the sympathetic trunk at midlumbar level with CT fluoroscopic guidance, and 1 mL of iopamidol (200 mg of iodine per milliliter) and 5 mL of 0.5% bupivacaine were injected. SSR was monitored in both feet before and after bupivacaine injection. SSRs were activated with painless low-strength (5-20-mA) electrical stimuli. SSR ratio (SSR in the injected foot versus SSR in the contralateral foot) was calculated before injection and repeatedly at 1-minute intervals thereafter. Needle tip position and distribution of bupivacaine were measured on CT images. Receiver operating characteristic curves for SSR ratio were calculated until 7 minutes after injection. Logistic regression analyses adjusted for clustering were calculated for SSR ratio, injection parameters, needle tip position, and bupivacaine distribution. Thirty minutes after injection, 83% of procedures were considered clinically successful. An SSR cutoff ratio of 1:10 was used, and sensitivity, specificity, and accuracy of SSR for prediction of clinical success were 84%, 92%, and 86%, respectively, 4 minutes after injection and 95%, 92%, and 94%, respectively, 7 minutes after injection. Needle tip position (P = .19), medial and lateral borders of bupivacaine distribution (P = .11 and .056), and distance between bupivacaine distribution and the vertebral body (P = .41) were not significantly different between successful and unsuccessful injections. SSR can be used to correctly identify needle tip position in lumbar sympathetic blocks 6 and 7 minutes after injection.


Oral health-related quality of life determinants throughout adolescence: a cohort study in Brazil.
Oral health-related quality of life (OHRQoL) is a complex construct that reflects the interaction among well-being, socioeconomic, oral health status, and also contextual factors. This study aimed to verify the association between poorer socioeconomic background and oral health condition on OHRQoL throughout adolescence. A cohort study followed a random sample of 1134 participants aged 12 years in 2012 (T1), 770 adolescents with an average age of 14 years in 2014 (T2; retention rate, 67.9%), and 768 adolescents with an average age of 17.5 years in 2018 (T3; retention rate, 67.8%). OHRQoL was collected three times using the Brazilian short version of the Childhood Perception Questionnaire 11-14 (CPQ 11-14). At baseline, the adolescents were clinically assessed by dentists, and their demographic data, socioeconomic status, use of dental services, and toothache were evaluated. The mean income of the neighborhood was used as a proxy of contextual factors. This variable was obtained from an official municipal publication. Poisson multilevel regression analyses were performed using a hierarchical approach to assess the predictors of OHRQoL over time. Adolescents living in a neighborhood with low mean income, low household income, low education levels, girls, and nonwhite individuals reported poor OHRQoL. Clinical variables such as gingival bleeding and malocclusion were also associated with higher overall scores on CPQ11-14, indicating poor OHRQoL. Our results showed that the unfavorable contextual and individual socioeconomic environment, and oral disease negatively influenced OHRQoL during adolescence.


Evaluation of drug-related problems in older polypharmacy primary care patients.
Targeting older patients with predictive factors for drug-related problems (DRPs) could make clinical medication reviews more cost-effective. The aim of this study was to identify the number, type, and potential predictive factors for DRPs in older polypharmacy patients. Community pharmacists performed clinical medication reviews and documented DRPs, types of interventions, and their implementation in older patients. Three hundred eighty-eight medication reviews were analyzed, 964 DRPs (average 2.5 ± 1.9), and 1022 interventions (average 2.6 ± 2.0) were identified. The overall implementation rate of interventions was 70.1%, the highest was observed in interventions aiming to resolve the lack of therapy monitoring (86.8%). Patients with ≥12 medications had an increased risk of ≥5 DRPs (P < .001). Asthma was associated with lack of adherence (P = .002), lack of aspirin, statins, and proton pump inhibitors use with additional therapy needed (P = .002-.004). Predictive factors for drug interactions were antihypertensive medications and/or medications with narrow therapeutic index (P < .05). Lack of efficacy was associated with diabetes (P = .006). Nonsteroidal anti-inflammatory drugs were risk factors for inappropriate drug selection (P = .002). Lack of monitoring was associated with hypertension (P = .013), whereas benzodiazepines (P < .001) and aspirin (P = .021) were overused. Patients with asthma, hypertension, and diabetes and lack of statin, antithrombotic agent, and/or proton pump inhibitor use were associated with higher risks for DRPs.


Effect of trehalose on a phospholipid membrane under mechanical stress.
Explicit solvent molecular dynamics simulations were used to investigate at atomic resolution the effect of trehalose on a hydrated phospholipid bilayer under mechanical stress (stretching forces imposed in the form of negative lateral pressure). Simulations were performed in the absence or presence of trehalose at 325 K, and with different values for negative lateral pressure. In the concentration regime (2 molal) and range of lateral pressures (1 to -250 bar) investigated, trehalose was found to interact directly with the membrane, partially replacing water molecules in the formation of hydrogen bonds with the lipid headgroups. Similar to previous findings in the context of thermal stress, the number, degree of bridging, and reaching depth of these hydrogen bonds increased with the magnitude of perturbation. However, at the concentration considered, trehalose was not sufficient to preserve the integrity of the membrane structure and to prevent its extreme elongation (and possible disruption) under the effect of stretching forces.


Development of a novel bioactive glass suitable for osteosarcoma-related bone grafts.
In this study, zinc borate-based glasses with increasing gallium content (0, 2.5, 5, 10, and 15 wt % Ga) were synthesized and their effect on the viability and proliferation of preosteoblasts and osteosarcoma cancer cells were investigated. Methyl thiazolyl tetrazolium (MTT) cell viability assays using glass degradation extracts revealed that the extracts from glasses with lower Ga contents could enhance the viability of preosteoblasts, while extracts from the glass composition with 15 wt % Ga caused statistically significant reduction of their viability. MTT cell viability assays using the extracts and osteosarcoma cells showed that only extracts from the glass composition with 5 wt % Ga (G3) did not cause a statistically significant increase in the viability of cancer cells for all degradation periods (1 day, 7 days, and 28 days). G3 was selected as the most suitable composition for the osteosarcoma-related graft operations as it could improve the viability of preosteoblasts without increasing the viability of cancer cells. The viability of preosteoblasts and osteosarcoma cells in contact with the glass powders were also investigated using MTT assays. The results showed that the G3 powders could enhance the viability of preosteoblasts while decreasing the viability of osteosarcoma cells. Finally, live/dead assays revealed that suppression of proliferation appeared to be the mechanism causing the observed reductions in the viability of osteosarcoma cells exposed to G3 powders. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1186-1193, 2018.


Nanocapsules Containing Neem (Azadirachta Indica) Oil: Development, Characterization, And Toxicity Evaluation.
In this study, we prepared, characterized, and performed toxicity analyses of poly(ε-caprolactone) nanocapsules loaded with neem oil. Three formulations were prepared by the emulsion/solvent evaporation method. The nanocapsules showed a mean size distribution around 400 nm, with polydispersity below 0.2 and were stable for 120 days. Cytotoxicity and genotoxicity results showed an increase in toxicity of the oleic acid + neem formulations according to the amount of oleic acid used. The minimum inhibitory concentrations demonstrated that all the formulations containing neem oil were active. The nanocapsules containing neem oil did not affect the soil microbiota during 300 days of exposure compared to the control. Phytotoxicity studies indicated that NC_20 (200 mg of neem oil) did not affect the net photosynthesis and stomatal conductance of maize plants, whereas use of NC_10 (100:100 of neem:oleic acid) and NC_15 (150:50 of neem:oleic acid) led to negative effects on these physiological parameters. Hence, the use of oleic acid as a complement in the nanocapsules was not a good strategy, since the nanocapsules that only contained neem oil showed lower toxicity. These results demonstrate that evaluation of the toxicity of nanopesticides is essential for the development of environmentally friendly formulations intended for applications in agriculture.


Sickness behavior induced by cisplatin chemotherapy and radiotherapy in a murine head and neck cancer model is associated with altered mitochondrial gene expression.
The present study was undertaken to explore the possible mechanisms of the behavioral alterations that develop in response to cancer and to cancer therapy. For this purpose we used a syngeneic heterotopic mouse model of human papilloma virus (HPV)-related head and neck cancer in which cancer therapy is curative. Mice implanted or not with HPV+ tumor cells were exposed to sham treatment or a regimen of cisplatin and radiotherapy (chemoradiation). Sickness was measured by body weight loss and reduced food intake. Motivation was measured by burrowing, a highly prevalent species specific behavior. Tumor-bearing mice showed a gradual decrease in burrowing over time and increased brain and liver inflammatory cytokine mRNA expression by 28 days post tumor implantation. Chemoradiation administered to healthy mice resulted in a mild decrease in burrowing, body weight, and food intake. Chemoradiation in tumor-bearing mice decreased tumor growth and abrogated liver and brain inflammation, but failed to attenuate burrowing deficits. PCR array analysis of selected hypoxia and mitochondrial genes revealed that both the tumor and chemoradiation altered the expression of genes involved in mitochondrial energy metabolism within the liver and brain and increased expression of genes related to HIF-1α signaling within the brain. The most prominent changes in brain mitochondrial genes were noted in tumor-bearing mice treated with chemoradiation. These findings indicate that targeting mitochondrial dysfunction following cancer and cancer therapy may be a strategy for prevention of cancer-related symptoms.


Treatment of Tinea Pedis in Elderly Patients Using External Preparations.
Infection rate of tinea pedis is high in the elderly, wherein treatment by a dermatologist should be considered to prevent infecting their family members. About 90 percent of cases with tinea pedis is treated only using external preparations. In treating the elderly with tinea pedis using external preparation, we should take into consideration that the elderly have thinner and weaker skin compared to younger people. There are many kinds of dosage form (cream, ointments, lotion, spray, and so on) for external preparations to treat tinea pedis. Generally, liquid forms such as lotions and sprays cause stronger irritation compared to ointments and creams, thus, caution should be taken for side effects when applying them to the elderly. Contact dermatitis is the most frequent side effect of external preparations. Caution should also be taken for the type of additives used. The composition of the preparation should be checked when changing dosage forms, or when switching brand-name drugs to generic drugs. Since the adherence rate of external preparations is low, it is preferable to use those with strong antibacterial activity and only have to be applied once a day.


The clinical significance of plasmatic amyloid A{beta}-40 peptide levels in Alzheimer's disease patients treated with galantamine.
To date there are no conclusive reports on the usefulness of determining amyloid peptides in the serum of patients with Alzheimer's disease (AD). Only anecdotal works deal with the changes in the peptides produced by cholinesterase inhibitors. In this study, the authors investigated and studied the clinical significance of plasmatic Abeta-40 and Abeta-42 peptide levels in a series of 34 consecutive patients with AD. The baseline levels of the Abeta-40 peptide correlated negatively with the Mini Examen Cognoscitivo (Spanish version of the Mini-Mental test) score. Complete follow-up was possible in 22 patients. After 6 months of treatment with galantamine, the mean Abeta-40 peptide levels decreased from 31.86 to 24.22 pg/mL. The baseline levels of Abeta-40 were predictive of response to treatment in the Alzheimer's Disease Assessment Scale-Cognitive Subscale. The authors conclude that determining plasmatic Abeta-40 peptide levels could be useful in predicting and monitoring response to treatment in AD.


[The appearance of insecticide resistance in Blattella germanica in the German Democratic Republic].
A review is given on the situation of resistance in the German cockroach (Blattella germanica) to insecticides during the last 15 years in the GDR, and conclusions are drawn for the future. From 23 samples trapped in various localities and subsequently reared in the laboratory, susceptibilities were measured against lindane, pyrethrin + PBO, trichlorfon, dichlorvos, and propoxur, the most used insecticides against cockroaches in our country. Detection of resistance was done with discriminating doses and the degree of resistance was measured with the doses-mortality method in deposit tests. In no case we found any resistance to propoxur but, for the first time, strains with a low resistance to dichlorvos. There was a distinct increase in the resistance to lindane, trichlorfon and pyrethrins + PBO during the lost years. A strain selected with pyrethrins in the laboratory showed marked group resistance to all tested pyrethroids (permethrin, cyfluthrin, cypermethrin, tetramethrin, deltamethrin, bioresmethrin, bioallethrin), but no cross resistance to the other insecticides.


Immunosuppressive therapy in rheumatoid arthritis.
Immunosuppressive drugs are used since 1951 for the treatment of rheumatoid arthritis. The most extensive used ones are azathioprine, cyclophosphamide, chlorambucil and methotrexate. The efficacy of these immunosuppressive drugs is clinical proven. Nevertheless it is necessary to use these drugs in severe disease only that has failed to respond to less toxic agents. The number of severe side effects is higher and the consequences of this therapy concerning cancerogenity is not clear yet. The efficacy and side effects of these drugs are discussed and guidelines for using immunosuppressive drugs in the treatment of rheumatoid arthritis are given.


Ultrasound guided obturator versus sciatic nerve block in addition to continuous femoral nerve block for analgesia after total knee arthroplasty.
Both obturator and sciatic nerve block in combination with femoral nerve block (FNB) have been suggested to be useful in relieving pain after total knee arthroplasty (TKA), compared with FNB alone. We compared their efficacy in this retrospective study. For six consecutive months, patients undergoing unilateral TKA under general anesthesia with continuous FNB plus obturator nerve block (n = 8) or continuous FNB plus sciatic nerve block (n = 8) were investigated. Knee pain was assessed using visual analogue scale (VAS) on the day of surgery and on postoperative days one to three. In addition, we also investigated intraoperative and postoperative morphine consumption. VAS scores and total morphine consumption were not different between the two groups, although patients in the FNB plus sciatic nerve block group were administered less morphine during surgery. Sciatic nerve block with continuous FNB may be superior to obturator nerve block with continuous FNB for analgesia during surgery for TKA.


Prospective randomized comparison of minilaparoscopy and percutaneous liver biopsy: diagnosis of cirrhosis and complications.
Liver cirrhosis represents an advanced stage of hepatic fibrosis characterized by distortion of organ architecture and formation of regenerative nodules. Retrospective series reported percutaneous liver biopsy to miss cirrhosis in about 30%. The aim of this study was to prospectively compare diagnostic sensitivity regarding the detection of cirrhosis and the complication rates of percutaneous versus minilaparoscopic liver biopsy in chronic liver disease. Eight hundred fifty-seven patients were randomized to percutaneous (415) or to minilaparoscopic liver biopsy (442). Macroscopic liver evaluation was documented as normal, fibrosis, or cirrhosis. Liver specimens were assessed blindly according to the modified Ishak score. Demographic and clinical data of procedure groups were comparable. Histologic grading alone diagnosed cirrhosis in 22.3% (n=85) of liver specimens obtained by percutaneous route compared with 26.0% (n=98) obtained by minilaparoscopy (P=0.270). By combining macroscopy and histology, minilaparoscopic staging diagnosed a significantly higher rate of liver cirrhoses with 33.8% (n=127) compared with percutaneous route with 22.3% (n=85) (P=0.001). Analysis of minilaparoscopic data revealed that 33 of the 128 cirrhoses were diagnosed by inspection only, suggesting a 26% underestimation of cirrhosis by histology alone. Severe complications occurred in 1.0% (n=4) of percutaneous and in 0.2% (n=1) of minilaparoscopic procedures (P=0.025). Minilaparoscopic evaluation based upon the combined macroscopic and histologic assessment is more sensitive with regards to the detection of cirrhosis and has a comparable safety profile.


Fine-grained classification based on multi-scale pyramid convolution networks.
The large intra-class variance and small inter-class variance are the key factor affecting fine-grained image classification. Recently, some algorithms have been more accurate and efficient. However, these methods ignore the multi-scale information of the network, resulting in insufficient ability to capture subtle changes. To solve this problem, a weakly supervised fine-grained classification network based on multi-scale pyramid is proposed in this paper. It uses pyramid convolution kernel to replace ordinary convolution kernel in residual network, which can expand the receptive field of the convolution kernel and use complementary information of different scales. Meanwhile, the weakly supervised data augmentation network (WS-DAN) is used to prevent over fitting and improve the performance of the model. In addition, a new attention module, which includes spatial attention and channel attention, is introduced to pay more attention to the object part in the image. The comprehensive experiments are carried out on three public benchmarks. It shows that the proposed method can extract subtle feature and achieve classification effectively.


Calcium partitioning in human and bovine milk.
The partitioning of calcium in human milk was studied experimentally and compared with the distribution of calcium among the compartments of bovine milk. Care was taken to handle the milk samples to produce minimal disturbance of the milk fat globule membranes and the CO2 content. About 15% of the milk calcium was associated with casein in human milk; the remainder was in the aqueous phase. The equilibrium between ionized calcium and calcium complexes with smaller anions was examined. Ionized calcium varied between 2.3 and 4.0 mM across individuals (mean 3.0 +/- .1 mM) at 90 d of lactation. The remainder of the calcium in the aqueous phase was associated with citrate and phosphate. Changes in total calcium in human milk during lactogenesis and late lactation reflected changes in citrate and casein rather than alterations in ionized calcium.


Comparison of genotypes of Salmonella enterica serovar Enteritidis phage type 30 and 9c strains isolated during three outbreaks associated with raw almonds.
In 2000 to 2001, 2003 to 2004, and 2005 to 2006, three outbreaks of Salmonella enterica serovar Enteritidis were linked with the consumption of raw almonds. The S. Enteritidis strains from these outbreaks had rare phage types (PT), PT30 and PT9c. Clinical and environmental S. Enteritidis strains were subjected to pulsed-field gel electrophoresis (PFGE), multilocus variable-number tandem repeat analysis (MLVA), and DNA microarray-based comparative genomic indexing (CGI) to evaluate their genetic relatedness. All three methods differentiated these S. Enteritidis strains in a manner that correlated with PT. The CGI analysis confirmed that the majority of the differences between the S. Enteritidis PT9c and PT30 strains corresponded to bacteriophage-related genes present in the sequenced genomes of S. Enteritidis PT4 and S. enterica serovar Typhimurium LT2. However, PFGE, MLVA, and CGI failed to discriminate between S. Enteritidis PT30 strains related to outbreaks from unrelated clinical strains or between strains separated by up to 5 years. However, metabolic fingerprinting demonstrated that S. Enteritidis PT4, PT8, PT13a, and clinical PT30 strains metabolized L-aspartic acid, L-glutamic acid, L-proline, L-alanine, and D-alanine amino acids more efficiently than S. Enteritidis PT30 strains isolated from orchards. These data indicate that S. Enteritidis PT9c and 30 strains are highly related genetically and that PT30 orchard strains differ from clinical PT30 strains metabolically, possibly due to fitness adaptations.


Drinking water biofilms on copper and stainless steel exhibit specific molecular responses towards different disinfection regimes at waterworks.
Biofilms growing on copper and stainless steel substrata in natural drinking water were investigated. A modular pilot-scale distribution facility was installed at four waterworks using different raw waters and disinfection regimes. Three-month-old biofilms were analysed using molecular biology and microscopy methods. High total cell numbers, low counts of actively respiring cells and low numbers of cultivable bacteria indicated the high abundance of viable but not cultivable bacteria in the biofilms. The expression of the recA SOS responsive gene was detected and underlined the presence of transcriptionally active bacteria within the biofilms. This effect was most evident after UV disinfection, UV oxidation and UV disinfection with increased turbidity at waterworks compared to chemically treated and non-disinfected systems. Furthermore, live/dead staining techniques and environmental scanning electron microscopy imaging revealed the presence of living and intact bacteria in biofilms on copper substrata. Cluster analyses of DGGE profiles demonstrated differences in the composition of biofilms on copper and steel materials.


The nucleotide sequence of a major species of leucine tRNA from bovine liver.
Through the use of a variety of post-labeling techniques, the nucleotide sequence of a major species of leucine tRNA from bovine liver was determined to be pG-G-U-A-G-C-G-U-G-m-G-C-ac-C-G-A-G-C-G-G-D-C-psi-A-A-G-G-C-m-G-C-U-G-G-A-psim- U-I-A-G-m-G-C-psi-C-C-A-G-U-C-psi-C-psi-U-C-G-G-G-G-G-m-C-G-U-G-G-G-T-psi-C-G-m -A-A-U-C-C-C-A-C-C-G-C-U-G-C-C-A-C-C-AOH. A comparison of known sequences of leucine tRNAs shows a consistent set of features which clearly distinguish prokaryotic and eukaryotic leucine tRNAs from each other.


Survival of Patients with Hepatocellular Carcinoma in Renal Insufficiency: Prognostic Role of Albumin-Bilirubin Grade.
Renal insufficiency (RI) is commonly seen in patients with hepatocellular carcinoma (HCC). The prognostic role of albumin-bilirubin (ALBI) grade in this special setting is unclear. We aimed to investigate the role of ALBI grade associated with the impact of RI on HCC. A prospective cohort of 3690 HCC patients between 2002 and 2016 were retrospectively analyzed. The Kaplan-Meier method and multivariate Cox proportional hazards model were used to determine survival and independent prognostic predictors. Of all patients, RI was an independent predictor associated with decreased survival. In multivariate Cox analysis for patients with RI, α-fetoprotein level ≥20 ng/mL, tumor size >3 cm, vascular invasion, distant metastasis, presence of ascites, performance status 1-2, performance status 3-4, and ALBI grade 2 and grade 3 were independent predictors of decreased survival (all p < 0.05). In subgroup analysis of patients with RI undergoing curative and non-curative treatments, the ALBI grade remained a significant prognostic predictor associated with decreased survival (p < 0.001). In summary, HCC patients with RI have decreased survival compared to those without RI. The ALBI grade can discriminate the survival in patients with RI independent of treatment strategy and is a feasible prognostic tool in this special patient population.


Surface coat material associated with the cells of the developing lens vesicle in the chick embryo.
Ruthenium red (RR) and cetylpyridinium chloride (CPC) were used to demonstrate the distribution of cell surface coat material (SCM) on the free epithelial surface of the developing lens vesicle in stages 14-17 (50-64 hours) chick embryos. Observations were made by light microscopy and transmission. (TEM) and scanning (SEM) electron microscopy. A progressive increase in SCM is observed on cellular apices within the epithelium of the lens vesicle by means of RR staining, particularly at the margins of the aperture which are the sites of presumptive fusion. In contrast, a relatively thin layer of SCM persist on the adjacent surface ectoderm. Ruthenium red-positive SCM extends across the aperture of the lens vesicle prior to initial contact between the advancing epithelial surfaces. The presence of abundant SCM is interpreted as a possible significant prerequisite to invagination and to epithelial adhesion and fusion prior to detachment of the lens from surface ectoderm. When CPC is added to the fixative, a flocculent precipitate over the aperture of the lens vesicle and an associated band of modified surface ectoderm which extends ventrally from its lower margin are observed. The modified ectoderm and associated SCM likely represent a presumptive region of active coordinated cellular migration.


Vascular malformation and common keratinocytic nevus of the soft type: phacomatosis pigmentovascularis revisited.
Phacomatosis pigmentovascularis is a rare syndrome characterized by the coexistence of a pigmented nevus and a cutaneous vascular malformation. We report a 5-year-old boy with all the typical findings of phacomatosis pigmentovascularis type Ia. Although its existence according to the traditional classification has been questioned, this case represents a very rare association of a capillary vascular malformation and a common keratinocytic nevus of the soft type.


Suppressive effect of NMDA receptor antagonist MK-801 on nocturnal serotonin N-acetyltransferase activity in the rat pineal gland.
Treatment of rats at night with a non-competitive NMDA receptor antagonist MK-801 (0.025-1 mg/kg, i.p.) produced a dose-dependent decrease in the nocturnal activity of the pineal serotonin N-acetyltransferase (NAT), the rate limiting enzyme in melatonin biosynthesis. A maximal inhibition (by 67-75%) of the enzyme activity was observed after the drug doses of 0.1 mg/kg in female rats, and 1 mg/kg in male animals. The data suggest that the NMDA receptor-mediated glutamatergic neurotransmission is a step necessary for NAT induction (and melatonin biosynthesis) in the mammalian pineal gland.


Echocardiographic findings in mild and severe forms of sickle cell anemia.
M-mode echocardiographic findings were compared between sickle cell anemic and healthy children. Patients were composed of two groups; Group 1: mild group with no crises, no blood transfusions at the ages of 5.0 to 13.0, total of 12 children; Group 2: severe group, with frequent crises with requirement of blood transfusions at the ages of 3.0 to 13.0 years, total of 18 children. Control group was composed of 12 healthy children aged 5.0 to 13.0. When M-mode echocardiographic findings were compared, important findings were as follows: Mean left atrium dimension was increased both in the mild and severe groups (P < 0.001) compared with controls. This finding also supports the increase in the left ventricle end-diastolic dimension in both the severe and mild groups as compared with controls (P < 0.001). The increase in end-diastolic left ventricle dimension could be due to anemia present in the patients, but there was no difference between the two patient groups. Posterior left ventricle thickness and left ventricle mass was increased in both the mild and severe groups compared with controls (P < 0.001, P < 0.05), respectively. Left ventricular fractional shortening was more or less the same with controls. In spite of left ventricular volume load and dilatation, left ventricular contraction was good and systolic function was normal, and there was no correlation between the ECHO findings and hematological indices.


Heavy Metals in Spring and Bottled Drinking Waters of Sibylline Mountains National Park (Central Italy).
Heavy metal concentrations (cadmium, lead, and copper) in spring, tap, and bottled waters of the Sibylline Mountains National Park (central Italy) were investigated using square wave anodic stripping voltammetry from 2004 to 2011. The mean (±SD) concentrations detected (1.3 ± 0.4 ng L-1 cadmium, 14 ± 6 ng L-1 lead, and 0.16 ± 0.10 μg L-1 copper) were below the limits stipulated by Italian and European legislation for drinking and natural mineral water. In the three studied areas of the park (Mount Bove north, Mount Bove south, and springs of River Nera) with very few exceptions, both mineral waters bottled in the area and aqueduct waters from public fountains had approximately the same metal concentrations as did the spring waters from which they were derived. Conversely, substantially higher metal concentrations were found at some sites in private houses, which may be due to release of metals from old metal pipes. At the time of this study, waters of Sibylline Mountains National Park were of good quality, and no influence of the bottling process on heavy metal concentrations was found.


Quercetin regulates the inhibitory effect of monoclonal non-specific suppressor factor beta on tumor necrosis factor-alpha production in LPS-stimulated macrophages.
Monoclonal non-specific suppressor factor beta (MNSFbeta) is a member of the ubiquitin-like family that has been implicated in various biological functions. Previous studies have demonstrated that MNSFbeta regulates the ERK1/2-MAPK cascade in the macrophage cell line Raw 264.7. In this study, we found evidence that the flavonol quercetin regulates the effect of MNSFbeta on TNFalpha production in LPS-stimulated Raw264.7 cells. Quercetin inhibited MNSFbeta siRNA-mediated enhancement of both TNFalpha production and ERK1/2 phosphorylation in LPS-stimulated Raw264.7 cells. Quercetin decreased the expression of 33.5-kDa MNSFbeta adduct, which is important to the regulation of ERK1/2 activity, in unstimulated Raw264.7 cells. The various flavonoids tested, including other flavonols, did not affect the formation of this adduct. Collectively, MNSFbeta and quercetin might share a common pathway in regulating the ERK1/2 pathway in macrophages. This is the first report describing the involvement of flavonoids in the action of ubiquitin-like proteins.