Effect of Nutritionally Relevant Doses of Long-Chain N-3 Pufa on Lipid Status, Oxidative Stress and Inflammatory Markers in an Average Middle-Aged Serbian Population.
This study investigated the effects of a nutritionally relevant intake of eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids derived from oily fish or a fish oil supplement on selected cardiovascular risk factors in average middle-aged individuals. Thirty-three participants were randomized to receive salmon (oily fish) providing 274 mg EPA + 671 mg DHA/day or a commercial fish oil supplement providing 396 mg EPA + 250 mg DHA/day in a cross-over trial over an 8-week period separated by a 6-month washout period. Blood samples were collected before and after each intervention and lipids, inflammatory and oxidative stress parameters were determined. Plasma levels of EPA, DHA and total n-3 fatty acids significantly increased after both interventions. A decreasing trend in triglycerides was more pronounced with salmon than with the fish oil supplement, but the changes noticed were not significant. Although there were no relevant changes in inflammatory marker concentrations at the end of both interventions, significant negative correlations were noticed between total plasma n-3 fatty acids and soluble intercellular adhesion molecule and C-reactive protein throughout the whole intervention period (p<0.05). Among the oxidative stress parameters, intervention with salmon showed a prooxidative effect through a superoxide anion increase (p=0.025). A relevant positive correlation was also found between its concentration and total plasma n-3 fatty acids (p<0.05). Other oxidative stress markers were not significantly influenced by the dietary interventions applied. Following two sets of recommendations for n-3 fatty acids intake aimed at the general public had only a moderate effect on the selected cardiovascular risk factors in average healthy middle-aged subjects over a short-term period.


Local order around rare earth ions during the devitrification of oxyfluoride glasses.
Erbium L(3)-edge extended x-ray absorption fine structure (EXAFS) measurements were performed on rare earth doped fluorosilicate and fluoroborate glasses and glass ceramics. The well known nucleating effects of erbium ions for the crystallization of cubic lead fluoride (based on x-ray diffraction measurements) and the fact that the rare earth ions are present in the crystalline phase (as indicated by Er(3+) emission spectra) seem in contradiction with the present EXAFS analysis, which indicates a lack of medium range structural ordering around the Er(3+) ions and suggests that the lead fluoride crystallization does not occur in the nearest neighbor distance of the rare earth ion. Molecular dynamics simulations of the devitrification process of a lead fluoride glass doped with Er(3+) ions were performed, and results indicate that Er(3+) ions lower the devitrification temperature of PbF(2), in good agreement with the experimental results. The genuine role of Er(3+) ions in the devitrification process of PbF(2) has been investigated. Although Er(3+) ions could indeed act as seeds for crystallization, as experiments suggest, molecular dynamics simulation results corroborate the experimental EXAFS observation that the devitrification does not occur at its nearest neighbor distance.


Bartonella vinsonii subsp. berkhoffii endocarditis in a dog from Saskatchewan.
A dog referred for lameness was diagnosed with culture-negative endocarditis. Antibodies to Bartonella spp. were detected. Antibiotic treatment resulted in transient clinical improvement, but the dog developed cardiac failure and was euthanized. Bartonella vinsonii subsp. berkhoffii genotype IV was identified within the aortic heart valve lesions by PCR amplification and DNA sequencing.


Comparison of growth, biomass and nutrient distribution in five promising clones of Populus deltoides under an agrisilviculture system.
Variations in growth, above- and below-ground biomass and nutrient distribution were examined in five clones (G3, G48, 65/27, D121 and S7C1) of Populus deltoides grown under agrisilviculture system in sub-humid tropics of Central India. The monoclonal blocks were planted at 4x5 m in a randomized block design with three replications. Diameter at breast height (dbh) and tree height were consistently higher in clone 65/27 and lowest in clone S7C1. Mean annual increments (MAI) in dbh and height were 1.6 and 1.3 times higher in clone 65/27 compared to clone S7C1. Total biomass varied from 48.5 to 62.2 Mg ha(-1) in six-year-old clones. In rank order, the total biomass of clones was: 65/27>D121>G48>G3>S7C1. Stem wood accounted 60.4-68.9% to total biomass followed by coarse roots (12.2-18.9%), branches (12.3-15%), leaves (3.02-6.9%) and fine roots (1.5-2.7%). Root-shoot ratio ranged from 0.2 to 0.35. It was highest in clone G48 and lowest in clone S7C1. In six-year-old clones, total N ranged from 184.3 to 266.3 kg ha(-1), P from 16.8 to 31.1 kg ha(-1) and K from 81.9 to 128.7 kg ha(-1). Total N and P were highest in clone 65/27, while K in clone G48. Nutrients were lowest in clone S7C1. In general, maximum nutrients (N, P and K) were allocated to above-ground components (leaves>stem>branches) than below-ground components. Available N, P and K in the soil improved significantly after six years of planting. It was higher in 0-20 cm and decreased with soil depth. At 0-20 cm soil depth, N increased from 14.9% to 24.1%, P from 17.2% to 23.3% and K from 3.1% to 5.1% under different clones. The yield of both soybean and wheat reduced under poplar clones. Yield losses in soybean ranged from 10.1% to 33% and wheat from 15% to 30.3% under different clones. The management strategies for reducing tree-crop competition and nutrient export from the site under P. deltoides based agrisilviculture system for achieving sustainable production are discussed.


Influence of PEG Stoichiometry on Structure-Tuned Formation of Self-Assembled Submicron Nickel Particles.
Self-assembled submicron nickel particles were successfully synthesized via the one-step surfactant-assisted solvothermal method. The impact of surfactant and reducing agent stoichiometry is investigated in this manuscript. Different morphologies and structures of Ni particles, including flower-like nanoflakes, hydrangea-like structures, chain structures, sphere-like structures, and hollow structures were prepared through different processing conditions with two parameters such as temperature and time. Based on scanning electron microscopy (SEM), X-ray diffraction (XRD), thermal gravimetric analysis (TGA) and vibrating sample magnetometry (VSM), the submicron nickel particles show good saturation magnetization and excellent thermal stabilities with a possible growth mechanism for the variety of the structure-tuned formation. Importantly, the microwave absorption properties of the submicron nickel particles were studied. The lowest reflection loss of Ni-P₉/T200/H15 with a thin layer thickness of 1.7 mm can reach -42.6 dB at 17.3 GHz.


[Psychiatric morbidity and quality of life in Vitiligo: a case controlled study].
The aims of this study were to value the psychiatric morbidity and its influence on the quality of life of patients with vitiligo. It was a case-controlled study bearing on 60 outpatients with vitiligo examined in the department of Dermatology of the University Hospital of Monastir, compared to 60 controls matched according to age and sex, among outpatients with others dermatologic disorders as warts or superficial mycoses. The assessment consisted in the epidemiological and clinical evaluation, including these questionnaires: the Dermatology Life Quality Index (DLQI), the Montgomery and Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Appreciation Scale (HAMA). Mean scores of depression in the MADRS and anxiety in the HAMA were significantly more elevated in patients with vitiligo (p = 0.0005). Quality of life was significantly more altered in patients with vitiligo: DLQI mean score = 9.4 +/- 17.1 versus 2.5 +/- 1.0 among the controls (p < 0.0001). A positive correlation has been noted between the quality of life scores and the MADRS depression scores (p < 10(-10)) and the HAMA anxiety scores (p < 10(9)). The quality of life decrease in patients with vitiligo is especially related to the psychiatric comorbidity underlining the multidisciplinary therapeutic necessity including the psychotherapeutic approach.


Paneth cells: histochemical and morphometric study in control and Solanum glaucophyllum intoxicated rabbits.
The intestinal epithelium has a critical roll in host defence. One specialised cell type involved in this function is the Paneth cell, which secretes many substances with antimicrobial properties in response to different stimuli. Under pathological conditions, changes in the Paneth cell number, morphology and location as well as in granule number, morphology and composition have been reported. In the normal animal, 1,25-dihydroxyvitamin D3 participates in the maintenance of mineral homeostasis, immunomodulation and cell proliferation and differentiation. Solanum glaucophyllum, a calcinogenic plant containing high levels of 1,25-dihydroxyvitamin D3, is responsible for a condition known as enzootic calcinosis in ruminants, characterised by loss of body condition and mineralization of soft tissues. Using and established rabbit model, this study analyses the changes that rabbit Paneth cells undergo during intoxication with S. glaucophyllum. Male New Zealand white rabbits were experimentally intoxicated with S. glaucophyllum for 15 or 30 days. Lectin, immunohistochemical and morphometric studies were carried out on Paneth cells from samples of jejunum. SBA, DBA and WGA lectins bound to Paneth cells-granules in both normal and intoxicated rabbits, with more heterogenity in the labelling of granules from intoxicated rabbits. Paneth cells in both groups were immunonegative for lysosyme. A time and dose-dependent increase in the size and number of Paneth cells was found in both intoxicated groups. We suggest that the changes described in these cells may be directly or indirectly induced by S. glaucophyllum intoxication.


Effects of bromopride on the healing of left colonic anastomoses in rats with induced abdominal sepsis.
To evaluate the effects of bromopride on the healing of left colonic anastomoses in rats with induced abdominal sepsis. Forty rats were divided into two groups to receive either bromopride (experimental group- E) or saline (control group- C). Each group was divided into subgroups of ten animals each to be euthanized on third (E3 and C3) or seventh day (E7 and C7) after surgery. Sepsis was induced by cecal ligation and puncture. The rats underwent segmental left colon resection and end-to-end anastomosis. Adhesion formation, tensile strength and hydroxyproline concentration were assessed. Histomorphometry of collagen and histopathological analysis were also performed. On postoperative third day, anastomoses in bromopride-treated animals showed lower tensile strength (p=0.02) and greater reduction in hydroxyproline concentration (p=0.04) than in control animals. There was no statistical difference in these parameters on seventh day, and the remaining parameters were similar across subgroups. Collagen content was also similar across subgroups. In the presence of abdominal sepsis, the administration of bromopride was associated with decreased tensile strength and hydroxyproline concentration in left colonic anastomoses in rats three days after surgery.


Description and Early Results of the Kaiser Permanente Southern California COVID-19 Home Monitoring Program.
The Southern California region of Kaiser Permanente developed a COVID-19 Home Monitoring program as an alternative to hospital admission to decrease hospital bed days and mitigate the adverse effects of a surge. To date, more than 15,000 patients have been enrolled and approximately 10% of enrolled patients have been escalated to hospital care for timely treatment. Our objective is to describe our COVID-19 Home Monitoring program and present early results. We conducted an observational retrospective study of all patients enrolled in the COVID-19 Home Monitoring program between April 13, 2020 through February 12, 2021. Data analysis conducted includes patient demographics, enrollment, entry points, length of stay, mortality, additional treatment, utilization, adherence, satisfaction, and alert triggers. A total of 12,461 of 13,055 patients (95.5%) recovered and completed the program, 1387 patients (10.6%) were admitted to the hospital, and 20 patients (0.2%) died while they were being monitored at home. The mortality rate at 30 days from enrollment was 1.6%. Hospital length of stay for ambulatory patients receiving oxygen only was 5.4 days compared to 3.1 days for those ambulatory patients receiving oxygen, dexamethasone, and remdesivir. COVID-19 home monitoring appears to be safe and effective. Initial data suggest it can serve as an alternative to hospitalization, decreasing hospital length of stay when patients receive therapies in the ambulatory setting otherwise reserved for the hospital. Initial results of this Home Monitoring program appear to be promising, and a longer term prospective study is warranted.


Intrascrotal metastasis of renal cell carcinoma. Case reports and review of the literature.
In a series of 235 patients with testicular tumors 2 elderly patients (0.9%) had secondary testicular tumors: 1 from a renal cell carcinoma and 1 from an unclassified anaplastic neoplasm. The pathogenesis of intrascrotal metastases of renal carcinoma is demonstrated by angiography of the dilated spermatic vein. In a literature survey the incidence rate of secondary testicular tumors is found to range from 0.3 to 3.6%. 30 cases of intrascrotal secondaries of renal cell carcinoma have been identified in the literature.


Auto-balancing and robust interferometer designs for polarization entangled photon sources.
A new implementation of a Mach-Zehnder interferometer is presented. Aimed at facilitating coherent optical wavelength conversion, the interferometer utilizes a novel double displacement technique that eliminates dispersion induced phase discrepancies between its input and output arms. To demonstrate the design, the interferometer was incorporated into a source of polarization entangled photon pairs. The source produced on average 2-3 million photon pairs per second per mW of pump power, the pairs emitted being maximally entangled in the polarization degree of freedom with a fidelity of ≥98%_. The new interferometer implementation is simple and robust and promises to become a design benchmark for polarization entangled photon sources.


Pharyngeal flap and the internal carotid in velocardiofacial syndrome.
Internal carotid artery anomalies have been documented as a common clinical feature in velocardiofacial syndrome. There has been some controversy over the need for preoperative imaging procedures, such as magnetic resonance angiography, when planning pharyngeal surgery for correcting velopharyngeal insufficiency. The purpose of this article is to describe 20 patients with velocardiofacial syndrome who received comprehensive evaluation and underwent pharyngeal flap surgery within a 2-year period and to report the technique used for dissecting the flap and the surgical outcomes. Anomalies of the major neck vessels were present in all cases, but 5 of these 20 cases had particularly severe anomalies of the internal carotid arteries that placed the vessels directly deep within the donor site for the pharyngeal flap. Surgery was carried out successfully in all 20 cases using a modified approach after radiographic imaging was performed to locate the arteries. In the 5 cases with severe malpositioning of the internal carotid arteries, it was clear that the vessels could have been injured had their location not been identified and the surgical approach modified to avoid them.


An unusual tale of rat-bite fever endocarditis.
A 49-year-old man presented to our department with an acute history of right leg tenderness, rash, swelling and fever. CT of the chest, abdomen and pelvis and a transoesophageal echocardiogram confirmed the diagnosis of mitral valve infective endocarditis with distal splenic emboli. Positive blood cultures revealed the causative organism to be Streptobacillus moniliformis. The patient was treated with high-dose antibiotics and had mitral valve replacement surgery.


Fragments of beta-galactosidase from Escherichia coli. Fragmentation, purification, characterization and in vitro complementation.
Thermal fragmentation of the beta-galactosidase was studied in different buffer solutions and at different temperatures. Fragmentation of the subunits in small size polypeptides could be observed directly. The fragmentation proceeded in buffer solution, pH 7.0, at either 75 degrees C or 100 degrees C in the presence of sodium dodecyl sulfate. The elevated temperature appeared to accelerate this process. At 100 degrees C, pH 7.2, the fragmentation proceeded in the absence of sodium dodecyl sulfate, but in the presence of 8 M urea. Molecular weights, determined by sodium dodecyl sulfate disc gel electrophoresis were from 130,000 to about 20,000. Multiple bands were observed. After dissociation was complete at 37 degrees C, the fragments were purified by ion-exchange column chromatography. Of the five fragments thus obtained, four were homogeneous by disc-gel electrophoresis. Molecular weight of the homogeneous fragments were found to be near 25,000. The fifth comprised a mixture of four fragments having molecular weights from 29,000 to 72,000. Two of the fragments were active as the alpha-donor in in vitro complementation with mutant M15, which contains a deletion in the alpha-region of the z gene.


Therapy for specific problems: youth tobacco cessation.
Cigarette smoking is the leading cause of premature morbidity and mortality in the United States. The majority of children smoke their first cigarette in early adolescence, and many older teens have well-established dependence on nicotine. Efforts to promote and support smoking cessation among these youth smokers are critical. The available experimental studies of youth cessation interventions find that behavioral interventions increase the chances of youth smokers achieving successful cessation. Currently there is insufficient evidence for the effectiveness of pharmacological treatments with youth smokers. Many innovative studies have been compromised by challenges in recruiting sufficient numbers of youth, obtaining approval for waivers of parental consent, and high attrition in longitudinal studies. Key areas for future work include bridging the fields of adolescent development and treatment design, matching treatments to developmental trajectories of smoking behavior, better understanding treatment processes and treatment moderators, and building demand for evidence-based cessation treatments.


The impact of functional status on life expectancy in older persons.
Although life tables provide a basis for estimating remaining life by age, gender, and race, these tables do not consider clinical characteristics or functional status, which can lead to wide variations in remaining years. Inclusion of functional status may permit more precise prognostic estimates of life expectancy and proportion of time in various functional states. We used longitudinal data from the Established Populations for Epidemiologic Studies of the Elderly to determine transition probabilities between three functional states (independent in activities of daily living [ADL] and mobility, dependent in mobility but independent in ADL, and dependent in ADL) and death. These were used to estimate total life expectancy and life expectancy in each functional state. In general, the largest proportion of remaining life expectancy was spent in the persons' baseline functional status category. Persons younger than 80 years with dependencies, however, spend substantial proportions of their remaining years in a better functional status category, and mobility-disabled 70-year-old persons spend the greatest part of their life expectancy in the independent functional state. Functional status has a dramatic impact on life expectancy. For example, 75-year-old men and women without limitations have life expectancies 5 years longer than those with ADL limitation and more than 1 year longer than those limited in mobility. The life expectancy of an ADL-disabled 75-year-old is similar to that of an 85-year-old independent person; thus, the impact of the disability approximates being 10 years older with much more of the remaining life spent disabled. Both ADL and mobility disability result in diminished survival and more of that survival period spent in disabled states.


Fabricating High-Thermal-Conductivity, High-Strength, and High-Toughness Polylactic Acid-Based Blend Composites via Constructing Multioriented Microstructures.
The massive accumulation of plastic waste has caused a serious negative impact on the human living environment. Replacing traditional petroleum-based polymers with biobased and biodegradable poly(l-lactic acid) (PLLA) is considered an effective way to solve this problem. However, it is still a great challenge to manufacture PLLA-based composites with high thermal conductivity and excellent mechanical properties via tailoring the microstructures of the blend composites. In the present work, a melt extrusion-stretching method is utilized to fabricate biodegradable PLLA/poly(butylene adipate-co-butylene terephthalate)/carbon nanofiber (PLLA/PBAT/CNF) blend composites. It is found that the incorporation of the extensional flow field induces the formation of multioriented microstructures in the composites, including the oriented PLLA molecular chains, elongated PBAT dispersed phase, and oriented CNFs, which synergistically improve the thermal conductivity and mechanical properties of the blend composites. At a CNF content of 10 wt %, the in-plane thermal conductivity, tensile strength, and elongation at break of the blend composite reach 1.53 Wm-1 K-1, 66.8 MPa, and 56.5%, respectively, which increased by 31.9, 73.5, and 874.1% compared with those of the conventionally hot-compressed sample (1.16 Wm-1 K-1, 38.5 MPa, and 5.8%, respectively). The main mechanism for the improved thermal conductivity is that the multioriented structure promotes the formation of a CNF thermal conductive network in the composites. The strengthening mechanism is attributed to the orientation of both PLLA molecular chains and CNFs in the stretching direction, restricting the movement of PLLA molecular segments around CNFs, and the toughening mechanism is due to the transformation of PLLA molecular chains from low-energy gt conformers to high-energy gg conformers induced by extensional flow field. More interestingly, after the extrusion-stretched samples are annealed, the oriented PLLA molecular chains form oriented crystal structures such as extended-chain lamellae, common "Shish-kebabs," and hybrid Shish-kebabs, which further enhance the thermal conductivity and heat resistance of the samples. This work reveals the effects of the orientation of the matrix molecular chains and crystallites on the thermal conductivity and mechanical properties of composites and provides a new way to prepare high-performance PLLA-based composites with high thermal conductivity, excellent mechanical properties, and high heat resistance.


Generation of hepatocytes from cultured mouse embryonic stem cells.
Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of fertilized blastocysts in vitro. ES cells can be induced to undergo differentiation into potentially all cell types. The aim of this study is to examine the differentiating potential of mouse ES cells into hepatocytes in the presence of retinoic acid (RA), hepatocyte growth factor (HGF), and beta-nerve growth factor (beta-NGF). RA, HGF, and beta-NGF were added to the cell culture. Hepatocyte induction was confirmed morphologically, as well as biochemically, through immunohistochemical assays of alpha1-antitrypsin (alpha1-AT) and alfafetaprotein (AFP) expression and reverse-transcriptase polymerase chain reaction tests for the presence of albumin, transthyretin, glucose 6 phosphates, hepatic nuclear factor 4, and SAPK/ERK kinase-1 (SEK1) messenger RNA, produced only by functioning hepatocytes. Fifteen days after the addition of HGF and beta-NGF to the cell culture, many epithelioid cells were noticed. alpha1-AT, AFP, albumin, transthyretin, glucose 6 phosphates, hepatic nuclear factor 4, and SEK1 messenger RNA expression also was detected, indicating successful ES cell differentiation into functioning hepatocytes. However, in the presence of RA alone, only transthyretin messenger RNA was positive, whereas no other expression pertaining to functioning hepatocytes could be detected. In the presence of HGF and beta-NGF, mouse ES cells can differentiate into functioning hepatocytes, whereas RA function is limited.


Orthopedic pitfalls in the ED: radiographically occult hip fracture.
Acute hip fracture is among the most commonly encountered orthopedic injuries seen by the emergency physician. The majority of these fractures can be readily diagnosed on the basis of clinical findings and plain radiographs. When initial films are negative or equivocal, but a high clinical suspicion exists for a hip fracture, additional diagnostic studies need to be performed because significant morbidity can result from ambulation on an unrecognized fracture. The emergency physician needs to remain vigilant for this potential orthopedic pitfall. This review article examines the clinical presentation, diagnostic techniques, and management options applicable to the emergency practitioner.


Home care nurses' perceptions of control over cancer pain.
This qualitative study examined home care nurses' perceptions of control over cancer pain. Four major themes emerged: Being heard, feeling invisible in the pain management process; not knowing, a need for pain education; control through advocacy; and patient-related barriers to optimal pain management. This study documents the need for continued education in pain management and communication skills for home care nurses.


Skull osteology of Parvilacerta parva, a small-sized lacertid lizard from Asia Minor.
The skull of the poorly known Asia Minor lacertid lizard Parvilacerta parva is described. In comparison to other palaearctic lacertids, Parvilacerta parva displays several peculiar traits such as a large braincase, a short parietal table, closed post-temporal openings, reduced ossification, or a large lacrimal. Many features are related to the small size of Parvilacerta parva and are of apparently heterochronic nature, as they can also be found in certain ontogenetic stages of other lacertid species. Small size and heterochrony even seem to be factors involved in the less-developed sexual dimorphism of Parvilacerta parva. The described morphology is interpreted to be related to a life history strategy in r-selecting, semiarid environments.


Ablation of hippocampal neurogenesis in mice impairs the response to stress during the dark cycle.
The functional role of adult neurogenesis in the hippocampus remains the subject of intense speculation. One recent hypothesis is that adult-born neurons contribute to the endocrine and behavioural outputs of the stress response. Here we show a genetic model system to ablate neurogenesis by inducibly deleting Tbr2 gene function specifically in the hippocampus and corroborate our findings in a radiation-based model of neurogenesis deprivation. We found that mice with ablation of new neurons in the dentate gyrus exhibit reduced anxiety during the dark cycle. After restraint stress, corticosterone levels in neurogenesis-deficient mice decreased more quickly than controls and were more sensitive to suppression by dexamethasone. Furthermore, glucocorticoid receptor target genes and neuronal activity markers showed reduced expression after stress in neurogenesis-deficient mice. These findings suggest that newborn neurons in the hippocampus are involved in sensing and eliciting an appropriate response to stress.


CD40 ligand protects from TRAIL-induced apoptosis in follicular lymphomas through NF-kappaB activation and up-regulation of c-FLIP and Bcl-xL.
The TNF family member TRAIL is emerging as a promising cytotoxic molecule for antitumor therapy. However, its mechanism of action and the possible modulation of its effect by the microenvironment in follicular lymphomas (FL) remain unknown. We show here that TRAIL is cytotoxic only against FL B cells and not against normal B cells, and that DR4 is the main receptor involved in the initiation of the apoptotic cascade. However, the engagement of CD40 by its ligand, mainly expressed on a specific germinal center CD4(+) T cell subpopulation, counteracts TRAIL-induced apoptosis in FL B cells. CD40 induces a rapid RNA and protein up-regulation of c-FLIP and Bcl-x(L). The induction of these antiapoptotic molecules as well as the inhibition of TRAIL-induced apoptosis by CD40 is partially abolished when NF-kappaB activity is inhibited by a selective inhibitor, BAY 117085. Thus, the antiapoptotic signaling of CD40, which interferes with TRAIL-induced apoptosis in FL B cells, involves NF-kappaB-mediated induction of c-FLIP and Bcl-x(L) which can respectively interfere with caspase 8 activation or mitochondrial-mediated apoptosis. These findings suggest that a cotreatment with TRAIL and an inhibitor of NF-kappaB signaling or a blocking anti-CD40 Ab could be of great interest in FL therapy.


The links between the medical school of Padua and the Hellenic medical world.
Between the 15th and 19th centuries the University of Padua attracted a great number of Greek students, who wanted to study medicine. They came not only from Venetian dominions (where the percentage reaches 97% of the students in Italian universities) but also from Turkish-occupied territories of Greece. It is also characteristic that several professors of the School of Medicine and Philosophy of this famous University were Greeks. They were the following ten: giovanni Cottunio, Niccolò Calliachi, Giorgio Calafatti, Tomaso Catani, Simone Stratigo, Giovanni Zografo, Pietro Zografo, Marco Carburi, Pietro Antonio Bondioli, and Angelo Dalla Decima. It is also interesting that most physicians who distinguished themselves as leading personalities in the political and scientific life of Europe had studied at the University of Padua. Five names stand out from among the multitude: Alessandro Mavrocordato (politician and diplomat), Giovanni Capodistria (first governor of Greece), Lazzaro de Mordo (philosopher-physician), Giacomo Pilarino and Emmanuel Timoni (the two discoverers of the smallpox inoculation with pus extracted from a patient suffering from a slight attack of the disease). It is concluded that the close traditional relations between Greece and the Medical School of the Universitiy of Padua were at their strongest during the period from the 15th to the 19th centuries.


Binding of a venom Lys-49 phospholipase A(2) to LPS and suppression of its effects on mouse macrophages.
The Lys49-phospholipases A(2) (K49-PLAs) are abundant in many pit vipers' venom. They are highly basic myotoxins and capable of binding membranes but lack hydrolytic activity. Considerable attention has been directed to its antibacterial activity but the exact mechanisms remain unclear. We now evaluate the roles of a K49-PLA from Trimeresurus stejnegeri venom in antagonizing the effects of lipopolysaccharide (LPS) on mouse macrophages (RAW264.7 cells). The K49-PLA markedly reduced LPS-stimulated production of NO, MCP-1, RANTES, and iNOS. RT-PCR analysis also confirmed its suppression of LPS-induced transcription of these cellular proteins. Moreover, LPS-induced activation of NFkappaB was dramatically abolished, while phosphorylation and degradation of IkappaB were also inhibited. Other types of venom phospholipases tested did not show the same effects as K49-PLA. Finally, strong binding between K49-PLA and LPS with a dissociation constant at the order of 10nM was shown by microcalorimetry titration. These findings provide unprecedented evidence that a low dose of K49-PLA possesses potent anti-inflammatory and antibacterial properties, which raises the prospect of a new therapeutic approach against sepsis.


Factors influencing the degree of enhancement of prostate cancer on contrast-enhanced transrectal ultrasonography: correlation with biopsy and radical prostatectomy specimens.
This study was designed to identify factors that influenced the degree of enhancement of prostate cancer on contrast-enhanced transrectal ultrasonography (CETRUS). 139 patients suspected of prostate cancer were evaluated with CETRUS followed by systematic and targeted transrectal ultrasound-guided biopsies. The degree of enhancement of the lesions was objectively measured using peak intensity with time-intensity curve analysis software. Ultrasound findings were correlated with clinical characteristics as well as biopsy and radical prostatectomy findings. Prostate cancers were detected in 230 biopsy sites from 91 patients. The mean peak intensity value of prostate cancer was significantly higher than that of the benign lesions (9.82 ± 3.73 vs 7.51 ± 2.97; p<0.001), and the peak intensity value of the cancer foci varied across the prostate. The mixed model analysis revealed that the location and Gleason score of tumour foci were the influencing factors of the peak intensity value, and the former had a stronger influence upon peak intensity than the latter (p=0.000 and 0.040, respectively). However, age, prostate volume or serum prostate-specific antigen of the patient had no significant influence on the peak intensity value (p>0.05). Furthermore, the peak intensity value of tumours larger than 5 mm diameter was significantly higher than tumours of 5 mm or smaller diameter (9.28 ± 2.46 vs 6.69 ± 2.65; p<0.001). The prostate cancer lesions with a higher Gleason score and larger tumour size which were located in the lateral peripheral zone (PZ) were more likely to show a marked enhancement. Lesions with lower peak intensity that are located in the medial PZ should also be treated as suspicious.


The reduction in leaf area precedes that in photosynthesis under potassium deficiency: the importance of leaf anatomy.
Synergistic improvement in leaf photosynthetic area and rate is essential for enhancing crop yield. However, reduction in leaf area occurs earlier than that in the photosynthetic rate under potassium (K) deficiency stress. The photosynthetic capacity and anatomical characteristics of oilseed rape (Brassica napus) leaves in different growth stages under different K levels were observed to clarify the mechanism regulating this process. Increased mesophyll cell size and palisade tissue thickness, in K-deficient leaves triggered significant enlargement of mesophyll cell area per transverse section width (S/W), in turn inhibiting leaf expansion. However, there was only a minor difference in chloroplast morphology, likely because of K redistribution from vacuole to chloroplast. As K stress increased, decreased mesophyll surface exposed to intercellular space and chloroplast density induced longer distances between neighbouring chloroplasts (Dchl-chl ) and decreased the chloroplast surface area exposed to intercellular space (Sc /S); conversely this induced a greater limitation imposed by the cytosol on CO2 transport, further reducing the photosynthetic rate. Changes in S/W associated with mesophyll cell morphology occurred earlier than changes in Sc /S and Dchl-chl , inducing a decrease in leaf area before photosynthetic rate reduction. Adequate K nutrition simultaneously increases photosynthetic area and rate, thus enhancing crop yield.


Environmental properties of long chain alcohols. Part 1: Physicochemical, environmental fate and acute aquatic toxicity properties.
This paper summarises the physicochemical, biodegradation and acute aquatic ecotoxicity properties of long chain aliphatic alcohols. Properties of pure compounds are shown to follow somewhat predictable trends, which are amenable to estimation by quantitative structure-activity relationships ((Q)SARs). This allows predictions of data relating to human and environmental safety profiles and patterns. These alcohols have been shown to be rapidly degradable under standard conditions up to C(18). Furthermore, evidence suggests that longer chain lengths are also rapidly biodegradable. While logK(ow) values suggest possible bioaccumulation potential, available data suggest that these substances are not as bioaccumulative as estimations would predict. For acute aquatic toxicity, solubility limits the possibility of effects being appropriately observed and become increasingly challenging above C(12). Further, a model has been developed for multi-component mixtures which give an excellent account of aquatic ecotoxicity allowing for the prediction of acute effects of un-tested mixtures.


The presence of Interleukin-13 in nasal lavage may be a predictor of nasal polyposis in pediatric patients with cystic fibrosis.
Sinonasal disease is a common feature of cystic fibrosis (CF) and can cause significant morbidity in these patients. Our objective was to determine if CF individuals with concomitant nasal polyposis (NP) express a unique profile of inflammation and if so, whether these inflammatory cytokine mediators have predictive value in identifying these individuals for prompt management by an Otolaryngologist. Nasal lavage samples and clinical outcomes of disease severity were obtained from thirty-eight pediatric CF individuals. Participants were subdivided based on the presence or absence of NP. Nasal lavage samples were analyzed on a panel of seventeen cytokine targets using a Bio-Plex Luminex assay. A Perl Permutation test with correction for multiple hypotheses was performed to identify uniquely expressed cytokines between CF individuals with NP (CFwNP) and those without (CFsNP). Thirty-five patients were included in the analysis. Cytokines IL-13 and GM-CSF were uniquely expressed in the CFwNP group when compared to the CFsNP group. Logistic regression analysis demonstrated a significant association of IL-13 with NP. In children diagnosed with CF, the level of IL-13 in nasal lavage samples could potentially serve as a non-invasive clinical tool in predicting NP in this population, and a target for future immunotherapy.


Point-of-care genetic profiling and/or platelet function testing in acute coronary syndrome.
Our aim was to demonstrate that the sequential use of the Verigene® rapid CYP2C19 test for genetic profiling and the VerifyNowTM bedside test for platelet function measurement in ACS patients may optimise P2Y12 inhibition. "Rapid" (CYP2C19*1/*1 or CYP2C19*17 carriers, n=211) and "slow" metabolisers (CYP2C19*2 carriers, n=58) were first put on clopidogrel and prasugrel for ≥ 2 weeks, respectively. Patients with low platelet reactivity (PRU<30) on prasugrel or high platelet reactivity (>208 PRU) on clopidogrel were then switched to clopidogrel and prasugrel, respectively. Our objectives were (i) to demonstrate that the proportion of "rapid" metabolisers on 75 mg of clopidogrel within 30-208 (PRU) of P2Y12 inhibition is non-inferior to "slow" metabolisers on prasugrel 10 mg and (ii) to evaluate the same end-point after switching drugs. The proportion of "rapid" and "slow" metabolisers within 30-208 PRU of P2Y12 inhibition was 71% and 56.9%, respectively, an absolute difference of +14.1% (95% CI, -0.05% to 28.28%) with a non-inferiority margin greater than the predefined margin of -10%. Among patients out of target, all but one "slow" metabolisers displayed low-on prasugrel platelet reactivity while the majority of "rapid" metabolisers (68%) displayed high-on clopidogrel platelet reactivity. After switching, the proportion of patients within 30-208 PRU of P2Y12 inhibition was 83.6% and 79.3% in "rapid" and "slow" metabolisers, respectively (+4.3%, 95% CI -7.3% to 15.9%). In conclusion, this study demonstrates a loose relationship between genotype and platelet function phenotype approaches but that they are complementary to select prasugrel or clopidogrel MD in stented ACS patients.


Regulation of SIRT1 and Its Roles in Inflammation.
The silent information regulator sirtuin 1 (SIRT1) protein, a highly conserved NAD+-dependent deacetylase belonging to the sirtuin family, is a post-translational regulator that plays a role in modulating inflammation. SIRT1 affects multiple biological processes by deacetylating a variety of proteins including histones and non-histone proteins. Recent studies have revealed intimate links between SIRT1 and inflammation, while alterations to SIRT1 expression and activity have been linked to inflammatory diseases. In this review, we summarize the mechanisms that regulate SIRT1 expression, including upstream activators and suppressors that operate on the transcriptional and post-transcriptional levels. We also summarize factors that influence SIRT1 activity including the NAD+/NADH ratio, SIRT1 binding partners, and post-translational modifications. Furthermore, we underscore the role of SIRT1 in the development of inflammation by commenting on the proteins that are targeted for deacetylation by SIRT1. Finally, we highlight the potential for SIRT1-based therapeutics for inflammatory diseases.


Mouse rods signal through gap junctions with cones.
Rod and cone photoreceptors are coupled by gap junctions (GJs), relatively large channels able to mediate both electrical and molecular communication. Despite their critical location in our visual system and evidence that they are dynamically gated for dark/light adaptation, the full impact that rod-cone GJs can have on cone function is not known. We recorded the photovoltage of mouse cones and found that the initial level of rod input increased spontaneously after obtaining intracellular access. This process allowed us to explore the underlying coupling capacity to rods, revealing that fully coupled cones acquire a striking rod-like phenotype. Calcium, a candidate mediator of the coupling process, does not appear to be involved on the cone side of the junctional channels. Our findings show that the anatomical substrate is adequate for rod-cone coupling to play an important role in vision and, possibly, in biochemical signaling among photoreceptors. DOI: http://dx.doi.org/10.7554/eLife.01386.001.


[Study on dosage rules of Aconitum herbs in oral prescriptions based on efficacy-toxicity relation].
Based on the relation of efficacy and toxicity, this study mined the dosage rules and characteristics of Aconitum herbs in oral prescriptions from 48 traditional ancient books from Eastern Han dynasty to Qing dynasty, to provide the basis for strengthening the clinical risk pharmacovigilance. In the 48 traditional ancient books, 4 521 prescriptions with clear daily oral dosage were included to establish a database. SPSS 20.0 software was used for statistics and analysis of the daily dosage characteristics with different kinds of herbs, indications, dose forms, processing, use in special population, and other aspects. The results showed that 67% prescriptions contained Aconitum carmichaeli(Fuzi), and 90% of them was less than 14.87 g·d⁻¹; The dosage of A. carmichaeli(Chuanwu) and A. kusnezoffii(Caowu) were less than 3.14 g·d⁻¹. In the prescriptions for treating typhoid, epidemic, edema and phlegm, the dosage of Aconitum was larger. There dosage in the decoction and vinum was significantly higher than that in the pill and powder. With the dynastic evolution, the dosage of Aconitum herbal medicines prescriptions and the application percentage of superposition drug also had decreased. For the special populations that with different metabolism process, such as old people, children, pregnant and lactating women, the application of Aconitum was not only with relatively small ratio, but also with lower dose. Therefore, based on the data-mining of ancient books, the dosage of Aconitum should not exceed the limit prescribed by the current China Pharmacopoeia, and also should be strictly controlled by considering various factors, which will ensure the balance of efficacy and toxicity.


Stroke-induced progenitor cell proliferation in adult spontaneously hypertensive rat brain: effect of exogenous IGF-1 and GDNF.
Progenitor cells in the dentate gyrus of hippocampus (DG) and the subventricular zone of lateral ventricles (SVZ) generate new neurons throughout the life of mammals. Cerebral ischemia increases this basal progenitor cell proliferation. The present study evaluated the time frame of proliferation, length of survival and the phenotypes of the new cells formed after transient middle cerebral artery occlusion (MCAO) in adult spontaneously hypertensive rats. Compared to sham controls, ischemic rats showed a significantly higher number of newly proliferated cells (as defined by BrdU immunostaining) in both the DG (by fourfold, p < 0.05) and the SVZ (by twofold, p < 0.05). DG showed increased proliferation only in the first week of reperfusion and 49% of the cells formed in this period survived to the end of third week. Whereas, SVZ showed a continuous proliferation up to 3 weeks after MCAO, but the cells formed survived for less than a week. In both DG and SVZ, at the end of the first week of reperfusion, majority of the BrdU-positive (BrdU+) cells were immature neurons (DCX positive). In the DG, 28% of the cells formed in the first week after MCAO mature into neurons (NeuN positive). The ischemic cortex and striatum showed several BrdU+ cells which were ED-1 positive microglia/macrophages. At 1 week of reperfusion, MCAO-induced progenitor cell proliferation in the ipsilateral DG was significantly increased by i.c.v. infusion of IGF-1 (by 127 +/- 14%, p < 0.05) and GDNF (by 91 +/- 5%, p < 0.05), compared to vehicle. In the growth factor treated rats subjected to transient MCAO, several BrdU+ cells formed in the first week survived up to the third week.


Activation of Muscarinic M1 Acetylcholine Receptors Induces Long-Term Potentiation in the Hippocampus.
Muscarinic M1 acetylcholine receptors (M1Rs) are highly expressed in the hippocampus, and their inhibition or ablation disrupts the encoding of spatial memory. It has been hypothesized that the principal mechanism by which M1Rs influence spatial memory is by the regulation of hippocampal synaptic plasticity. Here, we use a combination of recently developed, well characterized, selective M1R agonists and M1R knock-out mice to define the roles of M1Rs in the regulation of hippocampal neuronal and synaptic function. We confirm that M1R activation increases input resistance and depolarizes hippocampal CA1 pyramidal neurons and show that this profoundly increases excitatory postsynaptic potential-spike coupling. Consistent with a critical role for M1Rs in synaptic plasticity, we now show that M1R activation produces a robust potentiation of glutamatergic synaptic transmission onto CA1 pyramidal neurons that has all the hallmarks of long-term potentiation (LTP): The potentiation requires NMDA receptor activity and bi-directionally occludes with synaptically induced LTP. Thus, we describe synergistic mechanisms by which acetylcholine acting through M1Rs excites CA1 pyramidal neurons and induces LTP, to profoundly increase activation of CA1 pyramidal neurons. These features are predicted to make a major contribution to the pro-cognitive effects of cholinergic transmission in rodents and humans.


The surgical treatment of cholelithiasis in cats: a study of nine cases.
Nine cats that had surgical treatment for obstructive cholelithiasis were reviewed to evaluate clinical signs, diagnostic test results, and outcome after surgery. Common clinical signs included progressive vomiting (9/9), dehydration (9/9), anorexia (6/9), icterus (5/9), and lethargy (4/9). Five cats had a cholecystectomy performed, one cat had a cholecystotomy, and three cats had a biliary diversion procedure. Four of the cats that had a cholecystectomy had no recurrence of vomiting or anorexia. The majority of cats (7/9) had multiple choleliths, which were radiopaque and most commonly composed of calcium carbonate. Seven cats were diagnosed with cholangiohepatitis, and four of these cats did not need long-term medical therapy. Most cats (7/9) survived long term postsurgery (mean, 21 months; median, 24 months) without additional medical therapy, while the two cats with concurrent hepatic lipidosis died. Cholecystectomy appeared to have low morbidity with good clinical success.


R-Spondin 1 (RSPO1) Increases Mouse Intestinal Organoid Unit Size and Survival in vitro and Improves Tissue-Engineered Small Intestine Formation in vivo.
Introduction: Cell therapy and tissue engineering has recently emerged as a new option for short bowel syndrome (SBS) treatment, generating tissue engineered small intestine (TESI) from organoid units (OU) and biodegradable scaffolds. The recombinant human R-Spondin 1 (rhRSPO1) protein may be a key player in this process due to its mitogenic activity in intestinal stem cells. Objective: Aiming at optimizing the TESI formation process and advancing this technology closer to the clinic, we evaluated the effects of rhRSPO1 protein on OU culture and TESI formation. Methods: Intestinal OU were isolated from C57BL/6 mice and cultured in Matrigel in the presence or absence of recombinant human rhRSPO1. Throughout the culture, OU growth and survival rates were evaluated, and cells were harvested on day 3. OU were seeded onto biodegradable scaffolds, in the presence or absence of 5 μg of rhRSPO1 and implanted into the omentum of NOD/SCID mice in order to generate TESI. The explants were harvested after 30 days, weighed, fixed in formalin and embedded in paraffin for histological analysis and immunofluorescence for different cell markers. Results: After 3 days, rhRSPO1-treated OU attained a larger size, when compared to the control group, becoming 5.7 times larger on day 6. Increased survival was observed from the second day in culture, with a 2-fold increase in OU survival between days 3 and 6. A 4.8-fold increase of non-phosphorylated β-catenin and increased relative expression of Lgr5 mRNA in the rhRSPO1-treated group confirms activation of the canonical Wnt pathway and suggests maintenance of the OU stem cell niche and associated stemness. After 30 days of in vivo maturation, rhRSPO1-treated TESI presented a larger mass than constructs treated with saline, developing a more mature intestinal epithelium with well-formed villi and crypts. In addition, the efficiency of OU-loaded rhRSPO1-treated scaffolds significantly increased, forming TESI in 100% of the samples (N = 8), of which 40% presented maximum degree of development, as compared to 66.6% in the control group (N = 9). Conclusion: rhRSPO1 treatment improves the culture of mouse intestinal OU, increasing its size and survival in vitro, and TESI formation in vivo, increasing its mass, degree of development and engraftment.


Head-to-head comparison of BNP and IL-6 as markers of clinical and experimental heart failure: Superiority of BNP.
Activation of BNP and IL-6 are hallmarks of left ventricular (LV) dysfunction and congestive heart failure (CHF). To assess the relative activation of BNP and IL-6 in clinical and experimental heart failure, we performed a human study in which plasma N-terminal proBNP (NT-proBNP) and IL-6 were measured in a large group of patients in the chronic phase after myocardial infarction (MI) and an animal study in which LV gene expression of BNP and IL-6 was assessed in rapid ventricular pacing-induced heart failure. In the human study, NT-proBNP and IL-6 were measured by non-extracted, enzyme-linked immunoassay in 845 subjects (n=468 outpatients after MI, MONICA MI register Augsburg; and 377 siblings without MI, control). NT-proBNP (295+/-23pg/mL vs. CTRL 84+/-8, P<0.05) and IL-6 (2.7+/-0.1pg/mL vs. CTRL 2.1+/-0.1, P<0.05) were both elevated in subjects with MI. These increases were particularly pronounced in the presence of concomitant CHF (both P<0.01 vs. CTRL) and LV dysfunction (EF<45%, both P<0.05 vs. CTRL). However, NT-proBNP was significantly correlated with several cardiac structural and functional parameters (EF, LVMI, history of MI, CHF symptoms; all P<0.05) upon regression analysis whereas IL-6 was only correlated with history of MI (P<0.001). Accordingly, MI subjects with symptomatic LV dysfunction were detected by NT-proBNP with a greater sensitivity, specificity, and ROC-area (85%, 88%, and 0.87, respectively) as compared to IL-6 (69%, 53%, and 0.67, respectively). In the animal study, IL-6 and BNP expression were both significantly elevated in CHF (both P<0.05) but with a much greater absolute activation of BNP. In addition, BNP mRNA expression displayed a stronger inverse correlation with LV function (r=-0.74; P<0.001) than IL-6 (r=-0.53; P=0.001) and was a markedly more sensitive and specific molecular marker of LV dysfunction (sensitivity 91%, specificity 100%, ROC-area 0.94) than IL-6 (sensitivity 74%, specificity 83%, ROC-area 0.87). Our animal study provides evidence that IL-6 expression is activated in heart failure but to a significantly lesser degree than that of BNP. Both the stronger expression of BNP and the better correlation with LV function provide the molecular basis for a diagnostic superiority of NT-proBNP in clinical LV dysfunction and heart failure.


Metagenome-wide association study revealed disease-specific landscape of the gut microbiome of systemic lupus erythematosus in Japanese.
Alteration of the gut microbiome has been linked to the pathogenesis of systemic lupus erythematosus (SLE). However, a comprehensive view of the gut microbiome in SLE and its interaction with the host remains to be revealed. This study aimed to reveal SLE-associated changes in the gut microbiome and its interaction with the host by a comprehensive metagenome-wide association study (MWAS) followed by integrative analysis. We performed a MWAS of SLE based on shotgun sequencing of the gut microbial DNA from Japanese individuals (Ncase=47, Ncontrol=203). We integrated the result of the MWAS with the genome-wide association study (GWAS) data and plasma metabolite data. Via species level phylogenetic analysis, we identified and validated increases of Streptococcus intermedius and Streptococcus anginosus in the patients with SLE. Microbial gene analysis revealed increases of Streptococcus-derived genes including one involved in redox reaction. Additionally, microbial pathways related to sulfur metabolism and flagella assembly were altered in the patients with SLE. We identified an overlap in the enriched biological pathways between the metagenome and the germline genome by comparing the result of the MWAS and the GWAS of SLE (ie, MWAS-GWAS interaction). α-diversity and β-diversity analyses provided evidence of dysbiosis in the metagenome of the patients with SLE. Microbiome-metabolome association analysis identified positive dosage correlation of acylcarnitine with Streptococcus intermedius, an SLE-associated taxon. Our MWAS followed by integrative analysis revealed SLE-associated changes in the gut microbiome and its interaction with the host, which contribute to our understanding of the relationship between the microbiome and SLE.


Identification of 4438 novel lincRNAs involved in mouse pre-implantation embryonic development.
Long intergenic non-coding RNAs (lincRNAs) as a key group of non-coding RNAs have gained substantial attention. Though lincRNAs have been systematically explored in various mouse tissues and cell lines, large-scale identification of lincRNAs in mouse pre-implantation embryonic development (PED) process has not be documented previously. Therefore, it is important to identify and characterize novel lincRNAs that may be involved in PED. In this paper, we performed transcriptome assembly based on published single-cell RNA-seq data during mouse PED and identified 4,438 putative lincRNAs. Combining these with Ensembl lincRNAs, we established a reference catalog of 5,808 transcribed lincRNAs in PED. We then systematically analyzed the lincRNAs in this reference catalog and revealed that the identified novel PED lincRNAs are generally comparable with known Ensembl lincRNAs in genomic aspects. In addition, the global expression patterns can be separated by zygote first cleavage division in clustering analysis and we further identified and analyzed differentially expressed lincRNAs involved in this process. The expression of lincRNAs involved in the process is negatively correlated with promoter methylation in trend. The identified lincRNAs involved in zygote first cleavage division could have important roles in mouse early embryonic development and need further functional studies. Altogether, a novel reference catalog of mouse PED lincRNAs is provided and characterized, which would be a valuable resource for further functional analyses and may help elucidate the pre-implantation regulatory mechanism.


In Vitro Effect of 30 nm Silver Nanoparticles on Adipogenic Differentiation of Human Mesenchymal Stem Cells.
With the combined use of silver nanoparticles (Ag NPs) and human bone marrow derived mesenchymal stem cells (hMSCs) in bone tissue engineering, more knowledge of the effects of Ag NPs on hMSCs is required. Up to date, researches mainly focused on the cytotoxicity and genotoxicity of Ag NPs, only few studies discussed their influence on the differentiation of stem cells, especially adipogenic differentiation. In the present study, we investigated the in vitro uptake of 30 nm PVP-coated Ag NPs in hMSCs and their effects on cell viability, cell morphology and adipogenic differentiation of hMSCs. HMSCs were exposed to Ag NPs at concentrations of 25 and 50 μg/mL for 24 hours and at concentrations of 5 and 10 μg/mL throughout the whole differentiation period. Results of cell viability showed that Ag NPs caused time- and dose-dependent toxicity in hMSCs. Transmission electron microscopy (TEM) confirmed the uptake of Ag NPs into cytoplasm of hMSCs. No influence on cell morphology was observed. The 30 nm sized Ag NPs had no effects on adiponectin secretion, lipid droplet formation and the expression of adipogenic marker genes. It is concluded that under our experimental conditions, 30 nm PVP-coated Ag NPs do not influence the adipogenic differentiation of hMSCs in vitro. The present results provide a reference for the usage of 30 nm Ag NPs in the presence of hMSCs in bone tissue engineering.


The usefulness of the brainstem auditory evoked potential in the early diagnosis of cranial nerve neuropathy associated with diabetes mellitus.
An evaluation of the extent and mechanism of damage of the central nervous system in diabetes mellitus is of high value in current neurological research. Electrophysiological abnormalities are frequently present is completely asymatomatic diabetes mellitus (DM) patients. Limited data is available in the use of brainstem auditory evoked potential (BAEP) in DM. Is to evaluate the efficacy of BAEP as a method useful in the diagnosis of subclinical damage of the central nervous system in DM. 67 diabetes and 32 healthy controls - age and sex matched - were chosen. The diabetes were of type I and II and more than or less than 10 years duration. The BAEP was elicited by using auditory stimulus by using Dantec Evomatic 4000 evoked potential machine. The latency of component response recored as waves I, III and V, interpeak latency (IPLs) I - III, I - V, III - V and amplitude of waves V. The difference was highly significant in the increased latency of waves I, III and V, interpeak latency (IPLs) I - III, I - V, III - V and amplitude of waves V of each type of diabetes as compared to control. Comparison of the type and duration of diabetes between each other showed no significant difference. BAEP recording can represent an objective, clinically useful and non invasive procedure to stress the early impairment both of the auditory nerve and of brainstem function.


Analysis and refactoring of the A-74528 biosynthetic pathway.
A-74528 is a C30 polyketide natural product that functions as an inhibitor of 2',5'-oligoadenylate phosphodiesterase (2'-PDE), a key regulatory enzyme of the interferon pathway. Modulation of 2'-PDE represents a unique therapeutic approach for regulating viral infections. The gene cluster responsible for biosynthesis of A-74528 yields minute amounts of this natural product together with considerably larger quantities of a structurally dissimilar C30 cytotoxic agent, fredericamycin. Through construction and analysis of a series of knockout mutants, we identified the genes necessary for A-74528 biosynthesis. Remarkably, the formation of six stereocenters and the regiospecific formation of six rings in A-74528 appear to be catalyzed by only two tailoring enzymes, a cyclase and an oxygenase, in addition to the core polyketide synthase. The inferred pathway was genetically refactored in a heterologous host, Streptomyces coelicolor CH999, to produce 3 mg/L A-74528 in the absence of fredericamycin.


Clinical implications of glycoproteomics for Acinetobacter baumannii.
The opportunistic human pathogen Acinetobacter baumannii persists in the healthcare setting because of its ability to survive exposure to various antimicrobial and sterilization agents. A. baumannii's ability to cause multiple infection types complicates diagnosis and treatment. Rapid detection of A. baumannii infections would likely improve treatment outcomes. Recently published Acinetobacter glycoproteomic data show the prevalence of O-linked glycoproteins, suggesting the possibility for an O-glycan-based detection technology. O-glycan biosynthesis is required for protein glycosylation and capsular polysaccharide production in A. baumannii. Recent publications demonstrate key roles for protein glycosylation and capsular polysaccharide in the pathogenicity of A. baumannii. Targeted antimicrobial development against O-glycan biosynthesis may produce new effective treatment options for A. baumannii infections. Here, we discuss how the data gathered through Acinetobacter glycoproteomics can be used to develop technologies for rapid diagnosis and reveal potential antimicrobial targets. In addition, we consider the efficacy of glycoconjugate vaccine development against A. baumannii.


Modified trapeziectomy with ligament reconstruction tendon interposition for the treatment of advanced thumb carpometacarpal arthritis: A case report.
Thumb carpometacarpal (CMC) arthritis is a common disease. Various procedures have been described for the treatment of advanced thumb CMC arthritis. This essay shows a CMC arthritis case treated by modified trapeziectomy with ligament reconstruction tendon interposition (LRTI). A 53-year-old Chinese female complained of pain and swelling at the base of the left thumb for 10 years. Visual analog scale (VAS) for thumb was 7 points, Disabilities of Arm, Shoulder and Hand (DASH) score was 51 points, and Kapandji score was 6 points before surgery. Preoperative range of motion (ROM) for radial abduction and volar abduction were 63°and 62°, respectively. Grip power was 15.3 kg and key-pinch power was 1.8 kg before operation. Preoperative waist flexion power was 20.9 kg. Hand x-ray showed left thumb CMC arthritis in Eaton stage III and the height of the trapezial space was 10 mm. She was diagnosed with left thumb CMC arthritis (Eaton III stage). The patient underwent modified trapeziectomy with LRTI. After exposing and removing trapezium, and a hole from the dorsal base to the center of the articular surface was drilled. Then we cut the whole flexor carpi radialis and divided it into 2 halves. Afterward, we passed one-half through the hole and tied it to the other part and sutured them. The rest tendon was then tied continuously and sutured. Then we rolled it up into the space where previous trapezium was located. Two years after operation, pain and swelling relieved and no recurrence of the clinical symptoms occurred. VAS, DASH, and Kapandji score were 2, 22, 7 points, respectively. ROM for radial abduction and volar abduction were 79° and 78°, respectively. Furthermore, grip power was 22.7 kg and key-pinch power was 3.8 kg. Waist flexion power was 20.0 kg. Hand x-ray showed that the height of the trapezial space was 9.8 mm. Modified trapeziectomy with LRTI in treatment of advanced thumb CMC arthritis had a satisfactory efficacy. This new procedure not only prevents thumb sinking, but also provides enough support for thumb.


[Effect of airway pressure and Trendelenburg position on the cross-sectional area of the internal jugular vein in anesthetized patients].
Several maneuvers such as, Trendelenburg position or breath holding, are proposed to increase success rate and decrease complications during internal jugular vein cannulation. We investigated the relationship between the cross-sectional area of the right internal jugular vein (RIJV) and several maneuvers in anesthetized patients. We studied 18 adult patients (10 males, 8 females) undergoing RIJV cannulation after anesthetic induction and endotracheal intubation. We measured cross-sectional area of the RIJV at the level of the cricoid cartilage using ultrasound imaging and standardized by dividing it with body weight. Measurements were taken at supine position (S), supine plus 20 cmH2O breath hold (SH), 10 degrees Trendelenburg position (T-position) (T), and 10 degrees T-position plus 20 cmH2O breath hold (TH). We also measured blood volume (BV) with pulse dye-densitometry. The standardized cross-sectional areas of the RIJV during S, SH, T and TH maneuvers were 1.92 +/- 1.5, 2.82 +/- 1.8, 2.71 +/- 1.5, 3.51 +/- 1.6 mm2 x kg(-1), respectively. Every maneuver increased significantly the cross-sectional area compared to that of supine position (P < 0.05). The effects of the maneuvers tended to be larger when the BV was smaller. Breath holding at 20 cmH2O and 10 degrees T-position showed almost the same dilatation effects on RIJV (164%, 159%). Simultaneous performance of the both maneuvers was most effective (222%) in dilating cross-sectional area of RIJV in anesthetized patients.


DNA single strand breaks in peripheral lymphocytes associated with urinary thiodiglycolic acid levels in polyvinyl chloride workers.
The association between vinyl chloride monomer (VCM) exposure and DNA damage has been established. However, the relationship between individual exposure and DNA single strand breaks was limited. Since environmental monitoring may not reflect the actual exposure, a useful marker of exposure is needed to assess the individual exposure. In our previous study, we have found a high correlation between air VCM level and urinary thiodiglycolic acid (TdGA) at the commencement of the next shift. Here, we further used comet assay to evaluate the relationship between urinary TdGA levels and DNA single strand breaks in polyvinyl chloride monomer (PVC) workers. Urinary TdGA levels (n=26) at the commencement of the following shift were analyzed. Ten of the 26 workers also had personal air sampling for air VCM exposure. Questionnaires were administered to obtain epidemiological information including detailed history of occupation and lifestyles. Workers experiencing air VCM level greater than 5 ppm had higher tail moment and tail intensity (%) than those experiencing VCM exposure between 1 and 5, or <1 ppm, respectively (P < 0.05). The results also revealed that level of DNA single strand breaks, including tail moment and tail intensity, were increased with urinary TdGA level. The dose-response relationship of urinary TdGA level and DNA single strand breaks was particularly significant among the workers with 4 mg/g Cr of urinary TdGA level, which is equivalent to 5 ppm air VCM level. We concluded that air VCM exposure greater than 5 ppm could induce DNA damage. Further sensitive assay should be developed for the diction of DNA damage when air VCM exposure below 5 ppm.


Regio- and Enantioselective Photodimerization within the Confined Space of a Homochiral Ruthenium/Palladium Heterometallic Coordination Cage.
The photoinduced regio- and enantioselective coupling of naphthols and derivatives thereof is achieved in the confined chiral coordination space of a RuII metalloligand based cage. The racemic or enantiopure cages encapsulate naphthol guests, which then undergo a regiospecific 1,4-coupling, rather than the normal 1,1-coupling, to form 4-(2-hydroxy-1-naphthyl)-1,2-napthoquinones; moderate stereochemical control is achieved with homochiral cages. The photoreactions proceed under both aerobic and anaerobic conditions but through distinct pathways that nevertheless involve the same radical intermediates. This unusual dimerization constitutes a very rare example of asymmetric induction in biaryl coupling by making use of coordination cages with dual functionality-photoredox reactivity and stereoselectivity.


Late-onset delusional depression: a distinct clinical entity?
A comparison of the prevalence of delusions was made between early-onset (less than age 60) and late-onset (greater than or equal to age 60) primary endogenous depressives. Depressives with onset after age 60 had delusions more frequently than those with earlier onset. Fourteen of 16 late-onset depressives but only 5 of 18 earlier onset patients were delusional (p less than .005). Within the early onset group, those with delusions tended to be older at index episode than those without delusions (.05 less than p less than .10). This correlation between age of onset of depression and the tendency to be delusional is of heuristic and possibly pathogenetic interest.


Guillain-Barre Syndrome Associated With COVID-19 Infection: A Case Report With Review of Literature.
COVID-19 has become a pandemic. It affects multiple systems of the body including the nervous system. It invades the nervous systems through multiple routes - either olfactory tract, bloodstream (by binding to endothelial receptors) or via ACE-2 receptors in the brain. We report a case of Guillain-Barré syndrome (GBS) variant (acute motor axonal neuropathy (AMAN type)) associated with COVID-19 infection with positive polymerase chain reaction (PCR) test for COVID-19 and positive contact history with infected family member. GBS and its variants like AMAN can occur due to COVID-19 infection through its immune-mediated effects. Diagnosis of GBS should depend on the clinical and supportive criteria. The treatment should be started early to prevent progression and disease co-morbidities.


Radiomics and radiogenomics for precision radiotherapy.
Imaging plays an important role in the diagnosis and staging of cancer, as well as in radiation treatment planning and evaluation of therapeutic response. Recently, there has been significant interest in extracting quantitative information from clinical standard-of-care images, i.e. radiomics, in order to provide a more comprehensive characterization of image phenotypes of the tumor. A number of studies have demonstrated that a deeper radiomic analysis can reveal novel image features that could provide useful diagnostic, prognostic or predictive information, improving upon currently used imaging metrics such as tumor size and volume. Furthermore, these imaging-derived phenotypes can be linked with genomic data, i.e. radiogenomics, in order to understand their biological underpinnings or further improve the prediction accuracy of clinical outcomes. In this article, we will provide an overview of radiomics and radiogenomics, including their rationale, technical and clinical aspects. We will also present some examples of the current results and some emerging paradigms in radiomics and radiogenomics for clinical oncology, with a focus on potential applications in radiotherapy. Finally, we will highlight the challenges in the field and suggest possible future directions in radiomics to maximize its potential impact on precision radiotherapy.


Systemic treatment of hepatocellular carcinoma: Past, present and future.
Hepatocellular carcinoma (HCC) is a common neoplasia which represents the second leading cause of cancer related death. Most cases occur in developing countries, but its incidence is rising in Western countries due to hepatitis C. Although hepatitis therapies have evolved and the HCC screening has increased in several areas, 40% present with advanced disease which is only amenable for palliative systemic treatment. HCC continues posing a challenge, in part due to the inherent chemoresistance of this neoplasia, the pharmacologic challenges due to an ill liver, difficulty in assessing radiological responses accurately, etc. Traditional chemotherapy have shown some responses without clear survival benefit, however, sorafenib demonstrated advantages in survival in advanced HCC when liver function is kept and recently immunotherapy seems to be a promising approach for some patients. This article will briefly expose the most relevant systemic treatment modalities to offer a general view from the past to the future.


Controlling the polarization dependence of the complex transmission spectrum using the Brewster effect in metafilms.
We propose a method for controlling the polarization dependence of the complex transmission spectrum using the Brewster effect in a two-dimensional array of meta-atoms with finite thickness, which we refer to as a metafilm. We show that the complex transmission spectra of the orthogonal linear polarization components can be controlled independently without reflection by stacking multiple metafilms that exhibit only an electric dipole resonance. As a proof-of-concept numerical demonstration, we design several broadband waveplates with high transmission efficiency based on simple design principles. The proposed method would enable us to easily design anisotropic metamaterials with various complex transmission spectra.


Exploring Patients' Experience with Clinicians Who Recognize Their Unmet Palliative Needs: An Inpatient Study.
Background: Given the national shortage of palliative care specialists relative to the need for their services, engaging nonspecialists is important to ensure patients with serious illness have an opportunity to share their goals and values with their providers. Hospital medicine clinicians are well positioned to conduct these conversations given they care for many medically complex patients. Yet, little is known about the patient experience of inpatient goals and values conversations led by hospitalist teams. Objective: To assess patients' experience and perception of the quality of goals and values conversations. Design/Setting/Participation: Single center, tertiary care, nonrandomized, two group cohort trial of patients hospitalized on general medical inpatient units staffed by hospital medicine clinicians previously trained to conduct serious illness conversations. Intervention: An automated screening tool was used to identify patients at increased risk for unmet palliative needs. The multidisciplinary team was informed of the screen's results on the intervention units but not on the control units. Intervention unit clinicians were asked to consider talking with patients about their goals and values. Results: One hundred thirty patients participated in the study. The intervention patients reported improved quality of communication and fewer anxiety and depression symptoms compared with the control patients. Hospice utilization in addition to emergency department visits and hospital readmissions did not differ between the two groups. Conclusion: This study suggests that informing the care team regarding their patients' potential unmet palliative care needs is associated with patients reporting improved experience of their care without adverse effects on their mood.


Fatal Folic Acid Toxicity in Humans.
Folic acid is B-9 vitamin. Folic acid is prescribed commonly for pregnant women to prevent neural tube defects in the fetus, patients under chemotherapy, pernicious anemia and to reduce the risk of stroke and cardiovascular disease. Acute or chronic ingestion of a large dose of folic acid generally manifests as neurological complications, which are reversible. In this present case, a 23-year-old pregnant woman committed suicide by consuming folic acid tablets and succumbed to death within 36 h. Postmortem toxicological analysis detected folic acid in viscera. Death following acute consumption of folic acid is rare and has been not reported in the literature, to the best of our knowledge.


Platelets at the Vessel Wall in Non-Thrombotic Disease.
Platelets are small, anucleate entities that bud from megakaryocytes in the bone marrow. Among circulating cells, platelets are the most abundant cell, traditionally involved in regulating the balance between thrombosis (the terminal event of platelet activation) and hemostasis (a protective response to tissue injury). Although platelets lack the precise cellular control offered by nucleate cells, they are in fact very dynamic cells, enriched in preformed RNA that allows them the capability of de novo protein synthesis which alters the platelet phenotype and responses in physiological and pathological events. Antiplatelet medications have significantly reduced the morbidity and mortality for patients afflicted with thrombotic diseases, including stroke and myocardial infarction. However, it has become apparent in the last few years that platelets play a critical role beyond thrombosis and hemostasis. For example, platelet-derived proteins by constitutive and regulated exocytosis can be found in the plasma and may educate distant tissue including blood vessels. First, platelets are enriched in inflammatory and anti-inflammatory molecules that may regulate vascular remodeling. Second, platelet-derived microparticles released into the circulation can be acquired by vascular endothelial cells through the process of endocytosis. Third, platelets are highly enriched in mitochondria that may contribute to the local reactive oxygen species pool and remodel phospholipids in the plasma membrane of blood vessels. Lastly, platelets are enriched in proteins and phosphoproteins which can be secreted independent of stimulation by surface receptor agonists in conditions of disturbed blood flow. This so-called biomechanical platelet activation occurs in regions of pathologically narrowed (atherosclerotic) or dilated (aneurysmal) vessels. Emerging evidence suggests platelets may regulate the process of angiogenesis and blood flow to tumors as well as education of distant organs for the purposes of allograft health following transplantation. This review will illustrate the potential of platelets to remodel blood vessels in various diseases with a focus on the aforementioned mechanisms.


Seasons and ALS time of death.
Respiratory complications are the main cause of death in amyotrophic lateral sclerosis (ALS). Season-associated-death risk was not addressed before. To assess month/season-associated death risk in ALS. We included all patients followed in our unit who died before 1 January 2016, excluding those with uncertain information. A χ2 test assessed differences between months/seasons. A two-step cluster analysis explored the significant survival independent factors. Values of p < 0.05 or p < 0.01 (multiple comparisons) were considered significant. From 778 patients, 543 had died at censor date. Absolute death number was 46,46,37,47,38,50,41,43,41,48,40,66, for each month from January to December. No significant difference existed when considering all months and seasons globally (p > 0.05). Significant differences were found comparing December (highest rate, 12.2%) with March, May, July, August, September, November (p < 0.05). Deaths were higher in winter than in spring (p = 0.031), but similar between winter and summer (p = 0.16), and winter and autumn (p = 0.087). Bulbar-onset patients had a relatively increased death rate in summer, while spinal-onset patients died more frequently in winter. Death risk factors are probably dehydration for patients with dysphagia during summer and respiratory infections for patients with weak cough during winter. Flu vaccination, better ventilatory/cough assistance in winter and hydration in summer are recommended.


Tumor size is a determinant of stage distribution in t1 non-small cell lung cancer.
Despite renewed interest in early detection of lung cancer, the relationship between tumor size and survival remains controversial. The objective of this study was to evaluate the relationship between size and stage in patients with T1 (< or = 3.0 cm) non-small cell lung cancer (NSCLC). A retrospective review of a lung cancer database from 1995 to 2003 identified 503 patients with completely resected invasive NSCLC with tumors < or = 3 cm. All clinical and pathologic characteristics were recorded. Univariate associations between nodal status and other prognostic factors were explored by chi2 and t tests. The independent effect of tumor size > 2 cm vs < or = 2 cm on the risk of nodal disease was analyzed using a logistic regression model. Of the 503 patients, 324 patients (64.4%) had stage IA disease, 52 patients (10.3%) had stage IB disease, 37 patients (7.4%) had stage IIA disease, 15 patients (3%) had stage IIB disease, 43 patients (8.6%) had stage IIIA disease, 24 patients (4.8%) had stage IIIB disease, and 8 patients (1.6%) had stage IV disease. One hundred patients (19.9%) had nodal metastases. The mean (+/- SD) tumor size of cases without nodal disease was 1.90 +/- 0.67 cm, compared to 2.18 +/- 0.69 cm for node-positive tumors (p = 0.0003; 95% confidence interval [CI] for mean difference, 0.13 to 0.43). Forty-eight of 308 patients (15.6%) with smaller carcinomas (< or = 2.0 cm) compared to 52 of 195 patients (26.7%) with carcinomas > 2.0 cm had nodal metastases (p = 0.002). Exploratory multivariate analysis revealed that only tumor size (< or = 2.0 cm [referent] vs > 2.0 cm) affected nodal status and thus stage (adjusted odds ratio, 2.0; 95% CI, 1.3 to 3.1; p = 0.002). Primary invasive NSCLC > 2.0 cm was twice as likely to have nodal metastases than carcinomas < or = 2.0 cm. Our results suggest that in lung cancer smaller lesions may represent earlier stage disease. These results also suggest the need for further subclassification by tumor size within the current International Union Against Cancer/American Joint Committee on Cancer stage I, with tumors < 2 cm in size contained in a separate substage. This refinement may help to better clarify which patients might benefit from novel adjuvant or neoadjuvant therapeutic interventions.


Developing the building blocks to elucidate the impact of the urban exposome on cardiometabolic-pulmonary disease: The EU EXPANSE project.
By 2030, more than 80% of Europe's population will live in an urban environment. The urban exposome, consisting of factors such as where we live and work, where and what we eat, our social network, and what chemical and physical hazards we are exposed to, provides important targets to improve population health. The EXPANSE (EXposome Powered tools for healthy living in urbAN SEttings) project will study the impact of the urban exposome on the major contributors to Europe's burden of disease: Cardio-Metabolic and Pulmonary Disease. EXPANSE will address one of the most pertinent questions for urban planners, policy makers, and European citizens: "How to maximize one's health in a modern urban environment?" EXPANSE will take the next step in exposome research by (1) bringing together exposome and health data of more than 55 million adult Europeans and OMICS information for more than 2 million Europeans; (2) perform personalized exposome assessment for 5,000 individuals in five urban regions; (3) applying ultra-high-resolution mass-spectrometry to screen for chemicals in 10,000 blood samples; (4) evaluating the evolution of the exposome and health through the life course; and (5) evaluating the impact of changes in the urban exposome on the burden of cardiometabolic and pulmonary disease. EXPANSE will translate its insights and innovations into research and dissemination tools that will be openly accessible via the EXPANSE toolbox. By applying innovative ethics-by-design throughout the project, the social and ethical acceptability of these tools will be safeguarded. EXPANSE is part of the European Human Exposome Network.


Accelerated somatic mutation calling for whole-genome and whole-exome sequencing data from heterogenous tumor samples.
Accurate detection of somatic mutations in DNA sequencing data is a fundamental prerequisite for cancer research. Previous analytical challenge was overcome by consensus mutation calling from four to five popular callers. This, however, increases the already nontrivial computing time from individual callers. Here, we launch MuSE2.0, powered by multi-step parallelization and efficient memory allocation, to resolve the computing time bottleneck. MuSE2.0 speeds up 50 times than MuSE1.0 and 8-80 times than other popular callers. Our benchmark study suggests combining MuSE2.0 and the recently expedited Strelka2 can achieve high efficiency and accuracy in analyzing large cancer genomic datasets.


Chronic stress effects and their reversibility on the Fallopian tubes and uterus in rats.
The durational effects of chronic stress on the Fallopian tubes and uterus were studied by exposing rats to stressors in the form of restraint (1h) and forced swimming (15min) daily for 4, 8 or 12 weeks. One group of stressed rats from each time period was then maintained without exposure to stressors for a further 4 weeks to assess their ability to recover from stress. All time periods of stress exposure resulted in decreased weight of the body and Fallopian tubes; however, the relative weight of the uterus and serum concentrations of oestradiol and insulin increased significantly. The antioxidant potential was decreased with increased malondialdehyde concentrations in the Fallopian tubes following all durations of exposure and after 4 and 8 weeks of stress exposure in the uterus. Interestingly, rats stressed for 12 weeks showed an increase in serum testosterone concentration and antioxidant enzyme activities with a decrease in malondialdehyde concentration in the uterus. The antioxidant enzyme activities and malondialdehyde concentration in the Fallopian tubes of all recovery group rats were similar to stressed rats. However, in the uterus these parameters were similar to controls in recovery group rats after 4 weeks or 8 weeks of exposure, but after 12 weeks of stress exposure these parameters did not return to control levels following the recovery period. These results reveal, for the first time, that chronic stress elicits an irreversible decrease in antioxidant defence in the Fallopian tubes irrespective of exposure duration, whereas the uterus develops reversible oxidative stress under short-term exposure but increased antioxidant potential with endometrial proliferation following long-term exposure.


Fatal hepatitis B reactivation in a patient with islet cell tumor on octreotide and sirolimus.
Reactivation of hepatitis B viral infection (HBVr) is a known risk in cancer patients with a history of chronic hepatitis B infection receiving cytotoxic or immunosuppressive therapies. Patients with hematologic malignancies or those who have received stem cell transplantation seem to be most at risk but reactivation has been reported with various malignancies. Reactivation can present as asymptomatic liver function test abnormalities (LFTs), with symptoms of abdominal pain, encephalopathy, or as fulminant hepatitis and liver failure. Here we report the first case of a patient with islet cell tumor on octreotide and sirolimus who developed hepatitis B reactivation with fulminant liver failure and death.


Inference of Vohradský's models of genetic networks by solving two-dimensional function optimization problems.
The inference of a genetic network is a problem in which mutual interactions among genes are inferred from time-series of gene expression levels. While a number of models have been proposed to describe genetic networks, this study focuses on a mathematical model proposed by Vohradský. Because of its advantageous features, several researchers have proposed the inference methods based on Vohradský's model. When trying to analyze large-scale networks consisting of dozens of genes, however, these methods must solve high-dimensional non-linear function optimization problems. In order to resolve the difficulty of estimating the parameters of the Vohradský's model, this study proposes a new method that defines the problem as several two-dimensional function optimization problems. Through numerical experiments on artificial genetic network inference problems, we showed that, although the computation time of the proposed method is not the shortest, the method has the ability to estimate parameters of Vohradský's models more effectively with sufficiently short computation times. This study then applied the proposed method to an actual inference problem of the bacterial SOS DNA repair system, and succeeded in finding several reasonable regulations.


Renal morphologic lesions reminiscent of diabetic nephropathy.
Nodular, intercapillary glomerulosclerotic lesions resembling Kimmelstiel-Wilson nodules commonly observed in diabetic nephropathy can also be seen in patients without any clinical history or evidence of diabetes. To discuss the pathobiology of lesions reminiscent of diabetes nephropathy, including light-chain deposition disease, amyloidosis, immunotactoid nephropathy, the membranoproliferative form of glomerulonephritis, and idiopathic nodular glomerulosclerosis, and how to differentiate them from diabetic nephropathy. Published literature and authors' personal experience. The well-formed, intercapillary, nodular mesangial lesions, along with thickened glomerular basement membranes and tubular basement membranes, and hyaline arteriolosclerosis are virtually pathognomic of diabetic nephropathy. However, the pathologist must exclude lesions reminiscent of diabetic nephropathy by performing special stains on histologic sections, immunofluorescence, and electron microscopic studies.


Two Cases of Excessive Internet Use with Comorbid Family Relationship Problems.
Although the internet is used effectively and beneficially in every aspect of life, several users have been experiencing some problems due to excessive and uncontrolled use. While the term "internet addiction" still remains controversial, disturbed family relationships are considered to be a diagnostic criterion. The use of the internet, even in non-excessive levels, is associated with disturbance in family and social life. As considering from systemic point of view; while family relationships may be disturbed with internet addiction, people who have problems with their family relationships also may use internet excessively. This case report is composed of both the cases with excessive internet usage and those who had problems in complying with the changes in their family systems following the decrease in duration of internet usage during the treatment process.


Abnormal distance of the extralaryngeal bifurcation point of the recurrent laryngeal nerve from the cricothyroid joint.
The extralaryngeal bifurcation point of the recurrent laryngeal nerve (RLN) is typically located in a mean distance of 0-2 cm from the cricothyroid joint (CTJ). In the presented case though, the left RLN was unexpectedly identified bifurcating in a mean distance of 7 cm from the left CTJ in a young woman with multinodular goiter during total thyroidectomy. The RLN was carefully exposed throughout its course for the avoidance of iatrogenic injury of the nerval structure. The operation was uneventful. The present manuscript aims to highlight a scarce anatomic variation and its implications for thyroidectomy. Rare anatomic variations of the RLN such as the presented one encumber thyroid surgery and represent a severe risk factor of RLN injury. Meticulous operative technique combined with surgeons' perpetual awareness concerning this peculiar anatomical aberration leads to an injury-free thyroid surgery.


Prevalence and characteristics of pain in persons with terminal-stage AIDS.
A retrospective chart review was undertaken to collect and report data on the prevalence and characteristics of pain in persons with terminal-stage AIDS. A convenience sample consisting of 50 patient charts at a residential AIDS hospice was utilized. Data were collected from the McCaffery Initial Pain Assessment Tool (IPAT) (1983) which was completed at the time of each hospice admission. The IPAT is composed of 10 sections that collectively describe the patient's pain experience. Demographic and AIDS-related pathology data were also collected. Data were analysed using descriptive statistics to examine the incidence and characteristics of pain. Pain was experienced by a majority of the subjects in the sample. Pain levels for 'present pain', 'worst pain gets', 'best pain gets' and 'acceptable level of pain' are reported. Characteristics of pain including location, causal factors and verbal descriptors are reported. Implications for nursing practice and suggestions for further research are discussed.


Clinical and Imaging Correlations of Generalized Hypersynchronous Alpha Activity in Human EEG Recordings, During Alertness.
In a considerable percentage of individuals with a detectable alpha rhythm in their EEG, bursts of generalized hypersynchronous alpha activity (GHSAA) may occur, during alertness. The aim of this study was to examine whether appearance of GHSAA, which probably generates from transcortical circuitry, shows any correlation with demographic characteristics, underlying normal or abnormal pathophysiology, or substances in use. The authors retrospectively reviewed 441 EEG recordings performed in their laboratory during a 1-year period for presence of GHSAA, concomitantly collecting data that concerned symptoms, diagnosis, imaging, medication, and demographics. Recordings in mental states other than alertness were excluded from the sample. Generalized hypersynchronous alpha activity was found in 22.95% of the study population. Its occurrence was diminished in male gender (P < 0.001), older age (Kendall tau, 0.16; P < 0.0001), and disorders involving structural abnormalities like brain lesions or neurodegeneration (P < 0.02). Dementia, Parkinson disease, and psychoses showed individually a trend towards lower GHSAA presence. In the sample, the presence of GHSAA was commonly observed in the cohort of patients without abnormalities in their neuroimaging studies. Generalized hypersynchronous alpha activity is a finding of youth and requires a properly functioning cerebral cortex in order to emerge. Female preponderance may signify underlying trangender differences in alpha rhythm generators. These preliminary results indicate that the significance of GHSAA alterations deserves more thorough evaluation in larger groups of patients suffering from a variety of different neuropsychiatric disorders.


Intracranial lipoma of the Sylvian region.
The incidental autopsy finding of an intracranial lipoma in the left Sylvian region is reported. This is a rare location for an uncommon lesion. A recent theory on its pathogenesis as a congenital lesion is presented and current methods of diagnosis and treatment are discussed.


Metal-on-metal bearing wear with different swing phase loads.
There is currently much discussion about the most clinically relevant testing methods for evaluating total hip replacements. This study examined the effect of different swing phase loads, including microseparation, on the wear, friction, and wear particles of metal-on-metal (MOM) hip replacements. MOM hip replacements were tested for 5 million cycles with the use of a hip simulator; prostheses were tested with a low (100-N) and ISO (280-N) swing phase load, and under microseparation conditions. Increasing the swing phase load from 100 to 280 N in the same hip simulator increased the wear of the MOM hip replacements by over tenfold. Introducing microseparation into the gait cycle increased wear further, and stripe wear was observed on the femoral heads, accompanied by corresponding rim damage on the acetabular cups. No significant difference in wear particle size was observed between wear particles produced by low load and microseparation hip simulator conditions. Introducing microseparation into the hip simulator gait cycle increased the wear of MOM prostheses. Joint laxity and separation may lead to increased wear rates of MOM prostheses in vivo. Additionally elevated positive swing phase loads may also increase wear. Variable swing phase load conditions in vivo may contribute to variations in clinical wear rates.


Learning Progressions: An Empirically Grounded, Learner-Centered Framework to Guide Biology Instruction.
Vision and Change challenged biology instructors to develop evidence-based instructional approaches that were grounded in the core concepts and competencies of biology. This call for reform provides an opportunity for new educational tools to be incorporated into biology education. In this essay, we advocate for learning progressions as one such educational tool. First, we address what learning progressions are and how they leverage research from the cognitive and learning sciences to inform instructional practices. Next, we use a published learning progression about carbon cycling to illustrate how learning progressions describe the maturation of student thinking about a key topic. Then, we discuss how learning progressions can inform undergraduate biology instruction, citing three particular learning progressions that could guide instruction about a number of key topics taught in introductory biology courses. Finally, we describe some challenges associated with learning progressions in undergraduate biology and some recommendations for how to address these challenges.