Geriatric depression and treatment with trazodone.
With the growing number of Americans over the age of 65 years, the high incidence of geriatric depression has become a major concern in the United States. Age-related circumstances--increased incidence of illness, bereavement, financial difficulties, and institutionalization--may contribute to an increased rate of depression in this age group. The signs and symptoms of depression in elderly patients are similar to those seen in younger individuals; therefore, standard Diagnostic and Statistic Manual III (DSM-III) criteria are reliable for making a diagnosis. However, symptoms such as insomnia, obsessional thought, and hypochondriasis may be relatively increased in the elderly patient; and the diagnosis of geriatric depression can be complicated by signs and symptoms of depression that may overlap with those of dementia. In the geriatric group, the mainstay of pharmacotherapy has been the reuptake antidepressant agents. Choice of antidepressant therapy is largely based on the side-effect profile. Thus, the fewer and less severe side effects associated with trazodone make it a suitable drug choice in these patients. Trazodone has been shown to demonstrate comparable efficacy to the other reuptake and monoamine oxidase inhibitors, but has the advantages of a low cardiovascular-risk profile, extremely low suicide toxicity, absence of anticholinergic side effects, and minimal effects on cognition.


Inattentive symptoms of ADHD are related to evening orientation.
Morningness is a stable characteristic of individuals, related to impulsivity and novelty seeking. The evening orientation is a risk factor for psychiatric conditions such as depression and personality disorders. The authors hypothesized that adults suspected of having ADHD are more evening oriented than adults without ADHD. Exploratory factor analyses were performed on the polychoric correlation matrices of the full Adult Self-Report Scale for ADHD (ASRS) and the Composite Scale of Morningness (CSM). As expected, two factors for the ASRS--Inattention and Impulsivity- Hyperactivity--and three factors for the CSM were retrieved. All three CSM factors correlated negatively with ASRS Inattention, none with ASRS Impulsivity-Hyperactivity. Inattention is more strongly related to eveningness than is Impulsivity-Hyperactivity, and therefore eveningness may constitute an endophenotype of the predominantly inattentive subtype of ADHD. These findings need to be replicated in a patient population with a standardized assessment of sleep quality.


[Intra-abdominal desmoplastic small round cell tumor. A case report].
Intra-abdominal desmoplastic small round cell tumor is an extremely rare and aggressive neoplasm that predominantly occurs in young adult men; it has an uncertain histogenesis, and predominant or exclusive intra-abdominal localisation without visceral origin involvement. This tumor is characterized by its distinct morphology and its multiphenotypic differentiation. We report a case of an intra-abdominal desmoplastic round cell tumor in a 24 years old woman. In the light of this case, the clinical morphological immunohistochemical and molecular of this rare desease are revewed.


Gastrointestinal Motility, Muscle Relaxation, Antipyretic and Acute Toxicity Screening of Amyrin Type Triterpenoid (Daturaolone) Isolated From Datura metel Linnaeus (Angel's Trumpet) Fruits.
Datura metel Linn is used traditionally for the treatment of various diseases including relaxation of smooth muscles, relief of fever, as well as gastrointestinal disorder. This study deals with the bio-guided isolation of an active, amyrin-type triterpenoid, namely 3-oxo-6-β-hydroxy-β-amyrin (daturaolone; 1), from the chloroform fraction of Datura metel L. (Angel's trumpet) fruits and its gastrointestinal motility, antipyretic, and muscle relaxation effects in animal models. The chemical structure of daturaolone (1) was elucidated by NMR spectroscopy and crystallography techniques. The chloroform fraction and daturaolone (1) were assessed for the GIT motility test. Data exhibited in charcoal meal GI transit test show that chloroform fraction and daturaolone (1) significantly reduce GIT motility and increased intestinal transit time, comparable to the standard (atropine), a muscarinic receptor blocking agent. Muscle relaxant potency of the extract and daturaolone (1) was assessed in various animal paradigms. In the inclined plane screening test, it produced a significant (P < 0.05) muscle relaxation potential in a dose-dependent manner after 30, 60, and 90 min. Likewise, the muscle relaxation potential of the extract and daturaolone (1) was strongly complemented by the chimney and traction test, representing a dominant effect after 60 min of sample administration. The chloroform fraction showed good antipyretic activity, and while daturaolone (1) exhibited significant activity at a higher dose, the maximum effect (84.64%) was at 20 mg/kg i.p. In acute toxicity screening test, the chloroform extract (100, 250, 500, and 1,000 mg/kg) and daturaolone (1) (5, 10, 20, and 50 mg/kg) were found safe. In conclusion, the chloroform extract and daturaolone (1) exhibited strong gastrointestinal motility, muscle relaxation, and antipyretic activity in different animal models and intestinally, was found safe at higher tested doses.


Halide ion effects on human Ether-à-go-go related gene potassium channel properties.
The human Ether-à-go-go related gene (hERG) potassium channel has been widely used to counter screen potential pharmaceuticals as a biomarker to predict clinical QT prolongation. Thus, higher throughput assays of hERG are valuable for early in vitro screening of drug candidates to minimize failure in later-stage drug development due to this potentially adverse cardiac risk. We have developed a novel method utilizing potassium fluoride to improve throughput of hERG counter screening with an automated patch clamp system, PatchXpress 7000A. In that method, ∼50% substitution of internal Cl(-) with F(-) greatly increases success rate without substantially altering the biophysical properties of the hERG channel or compromising data quality. However, effect of F(-) or other halide ions on hERG channel properties has not been studied in detail. In this study, we examined effects of complete replacement of Cl(-) in internal solution with halide ions, F(-), or Br(-). We found that (1) F(-) slightly shifts the voltage dependence of hERG channel activation to more positive voltages, while Br(-) shifts it to more negative voltages; (2) Br(-) shifts to more positive voltages both the inactivation-voltage relationship and the peak position of channel full activation of hERG; (3) F(-) slows hERG activation, while both F(-) and Br(-) make the channel close faster; (4) neither F(-) nor Br(-) have any effect on hERG inactivation kinetics. In conclusion, compared to Cl(-), F(-) has subtle effect on hERG activation, while Br(-) has distinct effects on certain, but not all biophysical properties of hERG channel.


The periosteum: its function reassessed.
A review of experimental work relating to the function of the periosteum, beginning with that of Macewen in 1912, is of special interest to clinicians. Macewen's failure to obtain new-bone formation following the subperiosteal removal of the radius was due to a technique that obliterated the space, an occurrence that is inevitable in total excision. The periosteum without an associated hematoma in contact with bone has no evident bone-forming properties. Except in avulsion fractures, the periosteum provides mechanical connection between the two bone fragments and is the vehicle for the revascularization of the contents of the periosteal tube. Loss of this continuity is one of the causes of fibrous union in avulsion fractures. In developing countries, delayed and unsatisfactory treatment of fractures provides valuable clinical information in the role of the periosteum. Destruction of the periosteum along with the bony shaft in extensive untreated osteomyelitis results in a missing segment of a major bone.


Malignant Rheumatic Heart Disease Presenting as Quadrivalvular Stenosis.
Rheumatic disease may involve the pulmonary valve, but is exceedingly rare. Simultaneous involvement of all four valves is more likely to be the result of combination of causes, such as congenital, rheumatic, infective or degenerative disease. A unitary cause for quadrivalvular involvement would be either rheumatic or myxomatous degeneration. A 16-year-old young boy presented with progressive exertional dyspnea for the past 3 years. On evaluation, he was in atrial fibrillation with congestive heart failure. On examination, evidence of stenosis of the mitral, aortic and tricuspid valves with a history of rheumatic fever in childhood was revealed. Transthoracic echocardiography showed the quadrivalvular involvement. Only few reports are available in the literature describing rheumatic quadrivalvar damage and that too in third and fourth decade. This is probably first to be reported in juvenile age group.


In situ hybridization of enzymes and their metal-organic framework analogues with enhanced activity and stability by biomimetic mineralisation.
By incorporating Cytochrome c (peroxidase, Cyt c) into a skeleton of its corresponding synthetic MOF analogue (peroxidase mimic, CuBDC), approximately 12-fold catalytic efficiency (kcat/KM) enhancement is observed compared to free Cyt c. Meanwhile, the shield endowed by CuBDC prevents encapsulated enzymes from deactivation by trypsin digestion, thermal treatment and long-term storage in vitro. This concept of combining enzymes and their MOF mimics with enhanced enzymatic activity and stability may provide new insights into the design of highly active, stable enzyme-MOF composite catalysts and holds promise for applications in biocatalysis, biosensing and drug delivery systems.


Widespread use of fluoroquinolones versus emerging resistance in pneumococci.
During the past decade, respiratory-tract pathogens have shown an increase in resistance to all classes of antimicrobial agents. Although the increasing prevalence of penicillin-resistant Streptococcus pneumoniae has resulted in an increased reliance on newer classes of agents, such as the fluoroquinolones, the broad use of these agents has contributed to increasing prevalence of strains with in vitro fluoroquinolone resistance, which are associated with treatment failures, nosocomial outbreaks, and patient fatalities. Strategies to limit this emerging dilemma and preserve the clinical utility of these agents are needed.


Passaged human chondrocytes accumulate extracellular matrix when induced by bovine chondrocytes.
A source of sufficient number of cells is a major limiting factor for cartilage tissue engineering. To circumvent this problem, we developed a co-culture method to induce redifferentiation in bovine articular chondrocytes, which had undergone dedifferentiation following serial passage in monolayer culture. In this study we determine whether human osteoarthritic (OA) and non-diseased passaged dedifferentiated chondrocytes will respond similarly. Human passaged chondrocytes were co-cultured for 4 weeks with primary bovine chondrocytes and their redifferentiation status was determined. Afterwards the cells were cultured either independently or in co-culture with cryopreserved passaged cells for functional analysis. The co-culture of passaged cells with primary chondrocytes resulted in reversion of their phenotype towards articular chondrocytes, as shown by increased gene expression of type II collagen and COMP, decreased type I collagen expression and extracellular matrix formation in vitro. Furthermore, this redifferentiation was stable, as those cells not only formed hyaline-like cartilage tissue when grown on their own but also they could induce redifferentiation of passaged chondrocytes in co-culture. These data suggest that it may be possible to use autologous chondrocytes obtained from osteoarthritic cartilage to form tissue suitable to use for cartilage repair.


The strand-biased mitochondrial DNA methylome and its regulation by DNMT3A.
How individual genes are regulated from a mitochondrial polycistronic transcript to have variable expression remains an enigma. Here, through bisulfite sequencing and strand-specific mapping, we show mitochondrial genomes in humans and other animals are strongly biased to light (L)-strand non-CpG methylation with conserved peak loci preferentially located at gene-gene boundaries, which was also independently validated by MeDIP and FspEI digestion. Such mtDNA methylation patterns are conserved across different species and developmental stages but display dynamic local or global changes during development and aging. Knockout of DNMT3A alone perturbed mtDNA regional methylation patterns, but not global levels, and altered mitochondrial gene expression, copy number, and oxygen respiration. Overexpression of DNMT3A strongly increased mtDNA methylation and strand bias. Overall, methylation at gene bodies and boundaries was negatively associated with mitochondrial transcript abundance and also polycistronic transcript processing. Furthermore, HPLC-MS confirmed the methylation signals on mitochondria DNA. Together, these data provide high-resolution mtDNA methylation maps that revealed a strand-specific non-CpG methylation, its dynamic regulation, and its impact on the polycistronic mitochondrial transcript processing.


Preparation of h-MoO3 and α-MoO3 nanocrystals: comparative study on photocatalytic degradation of methylene blue under visible light irradiation.
A detailed study on visible light photocatalytic degradation of methylene blue (MB) has been investigated in aqueous heterogeneous media containing hexagonal phase molybdenum oxide (h-MoO3) nanocrystals (NCs) which was identified as a new material for visible light driven photocatalysis. A simple and template-free solution based chemical precipitation method was employed to synthesize h-MoO3 NCs by reacting ammonium heptamolybdate tetrahydrate (AHM) with nitric acid. The formation and growth mechanism of h-MoO3 microstructures was explained. In addition, by annealing the h-MoO3 sample, the phase stability of hexagonal was retained up to 410 °C and showed an irreversible phase transition from hexagonal (h-MoO3) to highly stable orthorhombic phase (α-MoO3). Finally, the photocatalytic activities of h-MoO3 and α-MoO3 samples were evaluated using the degradation of MB, representing an organic pollutant of dye wastewater. The effects of various experimental parameters such as catalyst loading, initial dye concentration, light intensity, and operating temperature were analyzed for the degradation of MB. The results demonstrated that the efficiency of visible light assisted MB degradation using h-MoO3 NCs can be effectively enhanced by catalyst loading, light intensity, and operating temperature. However, the efficiency declined with the increase in initial dye concentration. Optimum conditions for higher photocatalytic performance were recognized as a catalyst loading of 100 mg L(-1), a dye concentration of 12 mg L(-1), a light intensity of 350 mW cm(-2), and an operating temperature of 45 °C.


Primary prevention: a simple, effective means of risk reduction.
Individuals without overt coronary heart disease (CHD) may nevertheless be at significant risk for future CHD events based on lipid and other risk factors. Recognition of this fact is reflected in the inclusion of measures of global risk in current CHD prevention guidelines. Given the fact that many patients in the primary prevention setting fail to achieve target lipid levels, simplicity of treatment can be considered to be of great importance. Drug treatment that can improve achievement of low-density lipoprotein cholesterol (LDL-C) targets and produce beneficial effects on other lipid risk factors at starting doses would be of considerable utility in this setting. A new statin, rosuvastatin, has been shown to produce greater reductions in LDL-C and to permit more patients to reach target levels than currently available statins, and has also demonstrated favorable effects on other lipid variables. Rosuvastatin may thus be a prime candidate for use in clinical practice to achieve the lipid goals recommended in guidelines for primary prevention of CHD.


Use of Alcalase in the production of bioactive peptides: A review.
This review aims to cover the uses of the commercially available protease Alcalase in the production of biologically active peptides since 2010. Immobilization of Alcalase has also been reviewed, as immobilization of the enzyme may improve the final reaction design enabling the use of more drastic conditions and the reuse of the biocatalyst. That way, this review presents the production, via Alcalase hydrolysis of different proteins, of peptides with antioxidant, angiotensin I-converting enzyme inhibitory, metal binding, antidiabetic, anti-inflammatory and antimicrobial activities (among other bioactivities) and peptides that improve the functional, sensory and nutritional properties of foods. Alcalase has proved to be among the most efficient proteases for this goal, using different protein sources, being especially interesting the use of the protein residues from food industry as feedstock, as this also solves nature pollution problems. Very interestingly, the bioactivities of the protein hydrolysates further improved when Alcalase is used in a combined way with other proteases both in a sequential way or in a simultaneous hydrolysis (something that could be related to the concept of combi-enzymes), as the combination of proteases with different selectivities and specificities enable the production of a larger amount of peptides and of a smaller size.


Data-Driven Polymer Model for Mechanistic Exploration of Diploid Genome Organization.
Chromosomes are positioned nonrandomly inside the nucleus to coordinate with their transcriptional activity. The molecular mechanisms that dictate the global genome organization and the nuclear localization of individual chromosomes are not fully understood. We introduce a polymer model to study the organization of the diploid human genome. It is data-driven because all parameters can be derived from Hi-C data; it is also a mechanistic model because the energy function is explicitly written out based on a few biologically motivated hypotheses. These two features distinguish the model from existing approaches and make it useful both for reconstructing genome structures and for exploring the principles of genome organization. We carried out extensive validations to show that simulated genome structures reproduce a wide variety of experimental measurements, including chromosome radial positions and spatial distances between homologous pairs. Detailed mechanistic investigations support the importance of both specific interchromosomal interactions and centromere clustering for chromosome positioning. We anticipate the polymer model, when combined with Hi-C experiments, to be a powerful tool for investigating large-scale rearrangements in genome structure upon cell differentiation and tumor progression.


Penta X syndrome: a case report with review of the literature.
We describe a 6 month-old girl with a 49, XX-XXX chromosome constitution. The patient had a characteristic round face, a low hairline, hypertelorism, epicanthus, a long philtrum, high-arched palate, short and webbed neck, small hands and feet, clinodactyly of the fifth fingers, overlapping toes, and separation between the first and the second toes. She also had atrial septal defect and patent ductus arteriosus complicated by myocarditis which exacerbated the course of her congestive heart failure. Psychomotor development was retarded with opisthotonoid posture, axial hypotonia, and with a borderline abnormal EEG. A densitometric, transmission analysis on X-linked polymorphic DNA-fragments of the Southern blots of the patient and the parents, using P20/MspI and pERT87-1/XmnI as probe/enzyme combinations, showed that the pentasomy X had resulted from 3 successive nondisjunctions at maternal meiosis. Clinical manifestations among 22 previously reported penta X syndrome patients are also reviewed.


Proteomic analysis of early-stage embryos: implications for egg quality in hapuku (Polyprion oxygeneios).
In order to develop biomarkers that may help predict the egg quality of captive hapuku (Polyprion oxygeneios) and provide potential avenues for its manipulation, the present study (1) sequenced the proteome of early-stage embryos using isobaric tag for relative and absolute quantification analysis, and (2) aimed to establish the predictive value of the abundance of identified proteins with regard to egg quality through regression analysis. Egg quality was determined for eight different egg batches by blastomere symmetry scores. In total, 121 proteins were identified and assigned to one of nine major groups according to their function/pathway. A mixed-effects model analysis revealed a decrease in relative protein abundance that correlated with (decreasing) egg quality in one major group (heat-shock proteins). No differences were found in the other protein groups. Linear regression analysis, performed for each identified protein separately, revealed seven proteins that showed a significant decrease in relative abundance with reduced blastomere symmetry: two correlates that have been named in other studies (vitellogenin, heat-shock protein-70) and a further five new candidate proteins (78 kDa glucose-regulated protein, elongation factor-2, GTP-binding nuclear protein Ran, iduronate 2-sulfatase and 6-phosphogluconate dehydrogenase). Notwithstanding issues associated with multiple statistical testing, we conclude that these proteins, and especially iduronate 2-sulfatase and the generic heat-shock protein group, could serve as biomarkers of egg quality in hapuku.


[Antibodies against hepatitis C virus. Experience with a second generation test].
A second generation recombinant immunoblot assay to detect antibodies against Hepatitis C virus (RIBA II, Ortho Diagnostic Systems) was applied to 30 serum samples repeatedly reactive to ELISA anti-HCV c100-3, 11 from hemodialysis patients, 11 from patients with chronic hepatitis and 8 from patients with cirrhosis. The assay detects individual antibodies directed to 4 antigenic components of the C virus, 2 antigens, c100 and 5-1-1 contained in the original ELISA assay and 2 new antigens, c33c and c22-3 the latter structural in nature. From the total of 30 samples, 23 (77%) were reactive, 4 (13%) indeterminate and 3 (10%) non reactive to the RIBA II assay. Much variation was observed regarding the response to each individual antigen. c22-3 was the most frequently reactive with the highest intensity. RIBA II assay confirmed a high percentage of the reactive results with the ELISA c-100-3, serum samples that were non reactive to RIBA showed a low optical density with ELISA. c22-3 was the most sensitive antigenic component.


Contraction-related factors affect the concentration of a kallidin-like peptide in rat muscle tissue.
In order to study the effects of the manipulation of various factors related to muscular activity on the concentration of kinins in muscular tissue, a microdialysis probe was implanted in the adductor muscle of the hindlimb in anaesthetized rats. After collection of baseline samples, the perfusion fluid was changed to a Ringer solution containing sodium lactate (10 or 20 mM), adenosine (50 or 100 microM) or a lower pH (7.0 or 6.6). Whereas perfusion with lactate did not have any significant effect on the concentration of kinins in the dialysate, the perfusion with a lower pH or with adenosine dose-dependently increased the kinin content in the samples. In a second microdialysis experiment, by using specific radioimmunoassays (RIA) for bradykinin and kallidin, we observed that about 70 % of the total kinins dialysed from rat muscle are a kallidin-like peptide. Also, the simultaneous perfusion with 100 microM caffeine totally abolished the increase in kinin levels induced by the perfusion at pH 6.6. In a third experiment, soleus muscles from rat were stimulated in vitro during 30 min in the presence or absence of 77 microM caffeine. Electrically stimulated contraction, but not the addition of 10 mU ml(-1) insulin, induced an increase in the concentration of the kallidin-like peptide in the buffer. This effect was totally prevented by the addition of the adenosine antagonist caffeine. These results show that a kallidin-like peptide is released from rat muscle, and that its production is enhanced by muscle activity. Furthermore, the increase in kinin peptides during muscle contraction may be mediated by an increase in adenosine levels.


Elastic Properties, Defect Thermodynamics, Electrochemical Window, Phase Stability, and Li(+) Mobility of Li3PS4: Insights from First-Principles Calculations.
The improved ionic conductivity (1.64 × 10(-4) S cm(-1) at room temperature) and excellent electrochemical stability of nanoporous β-Li3PS4 make it one of the promising candidates for rechargeable all-solid-state lithium-ion battery electrolytes. Here, elastic properties, defect thermodynamics, phase diagram, and Li(+) migration mechanism of Li3PS4 (both γ and β phases) are examined via the first-principles calculations. Results indicate that both γ- and β-Li3PS4 phases are ductile while γ-Li3PS4 is harder under volume change and shear stress than β-Li3PS4. The electrochemical window of Li3PS4 ranges from 0.6 to 3.7 V, and thus the experimentally excellent stability (>5 V) is proposed due to the passivation phenomenon. The dominant diffusion carrier type in Li3PS4 is identified over its electrochemical window. In γ-Li3PS4 the direct-hopping of Lii(+) along the [001] is energetically more favorable than other diffusion processes, whereas in β-Li3PS4 the knock-off diffusion of Lii(+) along the [010] has the lowest migration barrier. The ionic conductivity is evaluated from the concentration and the mobility calculations using the Nernst-Einstein relationship and compared with the available experimental results. According to our calculated results, the Li(+) prefers to transport along the [010] direction. It is suggested that the enhanced ionic conductivity in nanostructured β-Li3PS4 is due to the larger possibility of contiguous (010) planes provided by larger nanoporous β-Li3PS4 particles. By a series of motivated and closely linked calculations, we try to provide a portable method, by which researchers could gain insights into the physicochemical properties of solid electrolyte.


Accuracy of SCORTEN and ABCD-10 to predict mortality and the influence of renal function in Stevens-Johnson syndrome/toxic epidermal necrolysis.
Epidermal necrolysis (EN) compromises a spectrum of life-threatening dermatoses (Stevens-Johnson Syndrome [SJS], overlap syndrome and toxic epidermal necrolysis [TEN]). Currently, no active therapeutic regimen with unequivocal benefit exists for SJS/TEN. SCORTEN is the widely-used prognostic scale specific for SJS/TEN. Nevertheless, a new prognostic scale, the ABCD-10, has been recently proposed. In this context, acute renal failure (ARF) seems to be an important comorbidity that could influence prognosis in SJS/TEN patients more than it is assumed by these two scales. Our objectives were to compare the accuracy of the SCORTEN and ABCD-10 scales in predicting the mortality in SJS/TEN, and to investigate the influence of renal failure on prognosis. The prognostic results of 18 patients with EN treated in two referral centers between 2013 and 2018 are presented. SCORTEN, ABCD-10 and renal function values were retrospectively collected for all patients. Out of the 18 patients who were analyzed, nine (50%) received only supportive therapy, four were treated with etanercept 50 mg in a single dose (22.2%) and five with corticosteroids (27.8%). Five patients developed ARF. Predicted mortality was 3.48 for SCORTEN and 2.33 for ABCD-10. Eventually, four patients died (22.2%), all had ARF and none of them received active treatment. Despite study limitations and in the absence of active treatment of choice, SCORTEN behaved as a reliable predictor of mortality in patients with EN, outperforming the newer ABCD-10. ARF was an early event associated with a poor prognosis, which could represent a prognostic marker to consider in the future.


An indeterminate malignant soft-tissue tumour treated by exenteration.
PURPOSE. To present a case of malignant soft-tissue tumour, which has yet to be categorised despite review by an international panel of experts, and which was treated by exenteration. PATIENT & METHODS. A 15-year-old Caucasian girl presented with progressive, non-axial proptosis and diplopia. CT scan showed an extraconal mass in the supero-medial part of the orbit suggestive of a vascular neoplasm. After initial incisional biopsy, the pathology of the tumour was felt to be malignant but so unique that further tissue was required for classification/categorisation and that exenteration was the best way to proceed. RESULTS. Despite there being an adequate amount of tissue and opinions being sought from international experts, including the Children(1)s Soft Tissue Panel (of the United Kingdom), this tumour has yet to be categorised. Reports have suggested it to be anything from a malignant desmoplastic round-cell tumour or a synovial sarcoma to an epithelioid haemangioendothelioma, which is our current working diagnosis. CONCLUSION. This case is unique in that it has not been possible to classify the tumour. Categorisation is important in order to give a reasonably accurate prognosis to the patient. Exenteration was required to offer complete tumour excision and will hopefully prevent local recurrence and metastatic spread.


Perinatal exposure to morphine: reactive changes in the brain after 6-hydroxydopamine.
The effects of neonatal 6-hydroxydopamine treatment on the brain of control rats and of rats perinatally exposed to morphine were examined. Noradrenaline levels were increased in the pons-medulla, mesencephalon and caudate of 8-week-old control rats lesioned with neonatal 6-hydroxydopamine; perinatal morphine treatment prevented such an increase. In the caudate, there was a loss of dopamine and an increase of serotonin following the neurotoxic lesion; exposure to perinatal morphine prevented the serotonin increase. Brain expression of synapsin I mRNA was particularly abundant in cerebral cortex, hippocampus, dentate gyrus and olfactory bulb. In perinatal morphine-treated rats, the expression of synapsin I mRNA was significantly reduced; interestingly, the neonatal treatment with 6-hydroxydopamine normalized its expression. Therefore, brain-reactive neurochemical changes triggered by 6-hydroxydopamine were suppressed by perinatal morphine exposure whereas the association of morphine exposure and 6-hydroxydopamine lesion promoted the normal mRNA expression of the synaptic marker synapsin I.


Pulmonary mycobacteriosis caused by Mycobacterium peregrinum: A case report.
Mycobacterium peregrinum is a member of the group of rapidly growing nontuberculous mycobacteria. It mainly causes surgical site and catheter-related infections, while pulmonary infection is rare. We herein present a case of pulmonary infection caused by M peregrinum. A 62-year-old woman visited our hospital with dyspnea and was admitted for the treatment of pneumonia in July 2018. Chest computed tomography showed patchy opacities and consolidation in the bilateral lungs and a cavity in the right upper lobe, which persisted after the treatment of bacterial pneumonia 5 years ago. She was administered ceftriaxone and azithromycin. Consolidation in the bilateral lungs improved, whereas the cavity in the right upper lobe remained and the consolidation surrounding it gradually spread. On admission, the sputum acid-fast bacillus culture was positive, and M peregrinum was identified twice by mass spectrometry. The cavity and consolidation surrounding it were diagnosed as pulmonary mycobacteriosis caused by M peregrinum. Although we recommended treatment for mycobacteriosis, the patient refused it. The patient is regularly followed up; however, the cavity wall is thickening and shadows have become mildly enhanced over the course of 3 years. We herein present a rare case of pulmonary mycobacteriosis caused by M peregrinum and discuss the literature. Since limited information is currently available on pulmonary mycobacteriosis caused by M peregrinum, the accumulation of further case reports and the clarification of its clinical features are needed.


Conscious sedation for minor gynecologic surgery in the ambulatory patient. A pilot study.
A conscious sedation regimen consisting of alphaprodine, hydroxyzine, and methohexital together with intensive behavior modification was evaluated in an open pilot study for patients undergoing minor gynecologic surgery. This combination was found to result in hemodynamic stability, satisfactory patient compliance, and patient and surgeon acceptance. Patients were unable to recognize words taught to them just after drugs were administered.Electroencephalogram (EEG) changes seen in general anesthesia or deep sedation were not found in the EEG records of a subset of patients. These findings suggest that conscious sedation can provide adequate relief of pain and anxiety for minor gynecologic procedures when local anesthesia can achieve only partial pain relief.


Comparison Between M-Mode Ultrasonography and Fluoroscopy for Diaphragm Excursion Measurement in Patients With Acquired Brain Injury.
Patients with acquired brain injury show decreased pulmonary function and diaphragm excursion (DE), which can affect functional outcomes. This study aimed to compare ultrasonography (US) and fluoroscopy for DE assessment and to determine how the relationship between pulmonary function test results and DE differs according to the paralytic condition. From September 2017 to April 2018, we prospectively enrolled patients with acquired brain injury. The patients underwent a pulmonary function test, including the functional vital capacity, forced expiratory volume at 1 second, forced expiratory volume at 1 second-to-functional vital capacity ratio, peak cough flow, and respiratory muscle strength such as the maximal inspiratory pressure and maximal expiratory pressure. Diaphragm excursion was measured with M-mode US and fluoroscopy on admission. A partial correlation analysis was used to assess the correlation between US and fluoroscopy for DE assessment. During the study period, 50 patients with acquired brain injury were enrolled. After adjusting for age, sex, height, and weight, the correlation coefficients between US and fluoroscopy were 0.744 for the right side (P < .001) and 0.631 for the left side (P < .001). In a subgroup analysis for patients with hemiplegia, the correlation coefficients were 0.507 for the paretic side (P = .007) and 0.677 for the nonparetic side (P < .001). Diaphragm excursion in the nonparetic side was significantly correlated with the maximal inspiratory pressure, maximal expiratory pressure, and peak cough flow (P < .05). M-mode US can be an alternative method for DE measurement in patients with impaired locomotion function after acquired brain injury. Preserved function of the nonparetic side might affect pulmonary function after brain injury, which suggests the importance of prestroke respiratory function.


Mucosal and Systemic γδ+ T Cells Associated with Control of Simian Immunodeficiency Virus Infection.
γδ T cells act as a first line of defense against invading pathogens. However, despite their abundance in mucosal tissue, little information is available about their functionality in this compartment in the context of HIV/SIV infection. In this study, we evaluated the frequency, phenotype, and functionality of Vδ1 and Vδ2 T cells from blood, rectum, and the female reproductive tract (FRT) of rhesus macaques to determine whether these cells contribute to control of SIV infection. No alteration in the peripheral Vδ1/Vδ2 ratio in SIV-infected macaques was observed. However, CD8+ and CD4+CD8+ Vδ1 T cells were expanded along with upregulation of NKG2D, CD107, and granzyme B, suggesting cytotoxic function. In contrast, Vδ2 T cells showed a reduced ability to produce the inflammatory cytokine IFN-γ. In the FRT of SIV+ macaques, Vδ1 and Vδ2 showed comparable levels across vaginal, ectocervical, and endocervical tissues; however, endocervical Vδ2 T cells showed higher inflammatory profiles than the two other regions. No sex difference was seen in the rectal Vδ1/Vδ2 ratio. Several peripheral Vδ1 and/or Vδ2 T cell subpopulations expressing IFN-γ and/or NKG2D were positively correlated with decreased plasma viremia. Notably, Vδ2 CD8+ T cells of the endocervix were negatively correlated with chronic viremia. Overall, our results suggest that a robust Vδ1 and Vδ2 T cell response in blood and the FRT of SIV-infected macaques contribute to control of viremia.


Thermal acclimation of leaf dark respiration of beech seedlings experiencing summer drought in high and low light environments.
Little is known about how environmental factors shape the short- and long-term responses of leaf respiration to temperature under field conditions despite the importance of respiration for plant and stand carbon balances. Impacts of water availability and canopy cover on leaf dark respiration (R) and temperature sensitivity were assessed in beech (Fagus sylvatica L.) seedlings in a sub-Mediterranean population. We studied seedlings established within canopy gaps (39% global site factor; GSF) that were subject to either no watering (unwatered plants; UW) or regular watering (2-10% higher volumetric topsoil water content as summer progressed; W plants) and seedlings established beneath the adjacent understorey (12% GSF). Leaf R rose exponentially with diurnal increases in temperature; the same temperature sensitivity (Q(10): 2.2) was found for understorey and gap plants, irrespective of watering treatment. Respiration estimated at 25 degrees C (R(25)) was lower in the understorey than the gaps and was significantly lower in the unwatered than in the watered gap plants by the end of summer (0.65 versus 0.80 micromol m(-2) s(-1)). R(25) declined with increasing summer temperature in all plants; however, respiration estimated at the prevailing ambient temperature did not change through the summer. There were parallel declines in R(25) and concentrations of starch and soluble sugars with increasing summer temperature for gap plants. We conclude that seasonal shifts in temperature-response curves of beech leaf R occur in both low- and high-light environments; since leaf R decreased with increasing plant water deficit, such shifts are likely to be greater whenever plants experience summer drought compared to scenarios where plants experience high rainfall in summer.


[Curative limb saving operation (curative wide resection)].
The recent results of surgical treatment of soft tissue sarcomas have dramatically improved. The result of the group study of soft tissue sarcomas, which was supported by the Ministry of Health and Welfare (1962-1976) showed that the local recurrence rate was 50%, and the metastatic rate was 60%. In contrast with this result, the recent results of our curative wide resection showed the local recurrence rate of 10%, and the metastatic rate of 30%. These procedures are based on the clinico-pathological findings which we studied. Curative wide resection is a method of radical wide resection, similar to radical local resection (reported by Enneking) and radical local excision (reported by Stenar). Our procedures are the least aggressive of the three radical wide resections, but our results are the same as the other wide resection methods. To obtain good results with these procedures, accurate preoperative diagnosis and skillful surgery are necessary.


Eat a variety of healthful foods: old advice with new support.
Although dietary guidelines have long advised eating a variety of foods, most nutrition research has focused on specific nutrients and their relationships to health and disease. The recent failure of several randomized trials to confirm results of observational studies linking specific nutrients to disease outcomes, and a growing understanding of the beneficial phytochemicals in the natural food supply, has redirected attention to the complexity and importance of the foods themselves. Studies identifying associations between diet quality and mortality are beginning to quantify the importance of eating a variety of healthful foods and are helping to refine that advice.


Transdermal delivery of ketorolac tromethamine: permeation enhancement, device design, and pharmacokinetics in healthy humans.
Transdermal delivery of ketorolac tromethamine, a potent non-narcotic analgesic, through human skin in vitro and in vivo was investigated. In order to enhance and sustain the flux of ketorolac through human skin, various compositions of isopropyl alcohol (IPA), water, and isopropyl myristate (IPM) were evaluated. The solubility of ketorolac acid in an IPA/water binary vehicle mixture increased as the volume fraction of IPA increased from 0 to 90%. The solubility of ketorolac acid in an IPA/water/IPM (saturated) ternary vehicle mixture was practically the same as in the IPA/water binary vehicle mixture. The permeation of ketorolac acid through cadaver skin was evaluated using modified Franz diffusion cells. The skin flux increased as the IPA volume fraction was increased from 0 to 50% and then leveled off beyond 80% IPA loading. When IPM was added to the IPA/water binary vehicle mixture, a significant increase in the skin flux of ketorolac was observed. The skin flux decreased exponentially as the donor solution pH was raised from 3.5 to 7.0. The permeability of ketorolac through various membranes such as a microporous membrane and pressure-sensitive adhesive was evaluated. While a microporous membrane offered practically no diffusion resistance, the in vitro flux of ketorolac through cadaver skin decreased substantially upon lamination of pressure-sensitive adhesive onto a microporous membrane. Three liquid-reservoir type transdermal devices were fabricated using 6.5% ketorolac tromethamine gel, a microporous membrane, an adhesive membrane, and polyester backing film: TD-A (microporous membrane/acrylic adhesive), TD-B (microporous membrane/silicone adhesive), and TD-C (microporous membrane). The pharmacokinetics of ketorolac in 10 healthy humans following application of a transdermal device for 24 h was evaluated. The maximum plasma concentrations (Cmax) were 0.20, 0.18, and 0.82 microgram/mL for TD-A, TD-B, and TD-C, respectively. The total AUC values for the concentration-time curves were TD-C > TD-A > TD-B, and the terminal half-life ranged from 6.6 to 9.7 h.


Application of perineal ultrasound measurement and urodynamic study in the diagnosis and typing of stress urinary incontinence ultrasound and urodynamic study.
To explore the value of perineal ultrasound and urodynamic study in the clinical diagnosis with the morphological and functional changes and evaluation of clinical type in female patients with stress urinary incontinence (SUI). The records of 64 female patients with SUI were reviewed. Fifty females with urinary frequency but with no SUI symptoms served as controls. All of them underwent ultrasound and urodynamic measurement. P<0.05 was considered statistically significant. The maximum flow rate (Q max) was significantly higher in the patients than in the control group, but the maximal urethral pressure (MUP), maximal urethral closing pressure (MUCP) and functional urethral length (FUL) were significantly lower than in the control group. Ultrasound measurements showed that the rotation angle and movement of urethrovesical junction, funneling of bladder neck and posterior urethrovesical angle (PUVA) at rest and during straining were greater in patients than in the control group. Patients with higher abdominal leak point pressure (ALPP) had higher maximal urethral closing pressure (MUCP), greater rotation angle and movement of urethrovesical junction. Patients with higher MUCP had higher ALPP, greater rotation angle and movement of urethrovesical junction. The urodynamic study and perineal ultrasound have a great significance in the diagnosis and typing of SUI.


Testis-specific histone variants H2AL1/2 rapidly disappear from paternal heterochromatin after fertilization.
Before fertilization, the genome packaging of male and female gametes is very different. Indeed, whereas the female haploid genome is associated with histones in a somatic-like chromatin structure, most of the male genome is tightly bound to protamines. However, it has recently been demonstrated that the pericentric heterochromatin regions of the male genome are associated with specific H2A-like histone variants, named H2AL1 and H2AL2, suggesting a heterogeneous organization. The fate and role of the sex-specific genome packaging transmitted by germinal cells to the embryo are not well understood. The aim of the present study was to follow reprogramming of the parental genomes in early embryos after in vivo fertilization. We show here that two typical epigenetic markers, trimethylated lysine 9 of histone H3 (TriMethylH3K9) and acetylated H4, are asymmetrically distributed between the parental genomes in one-cell mouse embryos, confirming data from embryos obtained after intracytoplasmic sperm injection (ICSI) or in vitro fertilization (IVF). Indeed, whereas the maternal genome is highly enriched with trimethylH3K9, this mark is not detected in the paternal genome. On the contrary, histone H4 incorporated in the paternal genome is highly acetylated at an early stage, while in the maternal pronucleus, the level of acetylated H4 remains low in early one-cell embryos and becomes enriched at a later stage. Moreover, our results suggest a very quick disappearance of histone H2A variants H2AL1 and H2Al2 from the paternal pericentric heterochromatin regions after sperm-egg fusion.


Continuous-Variable Quantum Key Distribution Based on Heralded Hybrid Linear Amplifier with a Local Local Oscillator.
An improved continuous variable quantum key distribution (CVQKD) approach based on a heralded hybrid linear amplifier (HLA) is proposed in this study, which includes an ideal deterministic linear amplifier and a probabilistic noiseless linear amplifier. The CVQKD, which is based on an amplifier, enhances the signal-to-noise ratio and provides for fine control between high gain and strong noise reduction. We focus on the impact of two types of optical amplifiers on system performance: phase sensitive amplifiers (PSA) and phase insensitive amplifiers (PIA). The results indicate that employing amplifiers, local local oscillation-based CVQKD systems can enhance key rates and communication distances. In addition, the PIA-based CVQKD system has a broader application than the PSA-based system.


Intraoperative measurements to determine the extent of radical hysterectomy.
The extent of radical hysterectomy can be objectively measured and the measured extent of resection will correlate with morbidity. Observational. The extent of radical hysterectomy was determined by measurement of overall length and excised portions of the uterosacral and cardinal ligaments. Analysis of morbidity was performed on 120 patients. Univariate analysis was accomplished with correlation, t test, and chi(2) statistical methods, and regression models were used for multivariate analysis. In precisely defined terms, the patients in this study underwent modified radical hysterectomy. The extent of the resection had an independent relationship to blood loss, operative time, and duration of postoperative bladder drainage. The extent of resection was also directly related to persistent bladder and rectal dysfunction. This method for objectively measuring the extent of a radical hysterectomy is feasible. The extent of the procedure correlates with morbidity.


Improvisation as an adaptive strategy for occupational therapy practice.
ABSTRACT As health care environments become increasingly complex, practitioners must develop new adaptive skills to master practice. The idea of using theatrical improvisation (improv) in health care is relatively new. Occupational therapy students were taught a module of improvisational techniques as part of an academic seminar, learning improvisation rules, and enacting solutions to typical daily professional challenges. The purpose of this article is to recommend improvisational techniques as an adaptive skill to effectively blend art and science for occupational therapy practice in fast-paced and unpredictable health care environments.


Activated Carbon-Based System for the Disposal of Psychoactive Medications.
The misuse and improper disposal of psychoactive medications is a major safety and environmental concern. Hence, the proper disposal of these medications is critically important. A drug deactivation system which contains activated carbon offers a unique disposal method. In the present study, deactivation efficiency of this system was tested by using three model psychoactive drugs. HPLC validation was performed for each drug to ensure that the analytical method employed was suitable for its intended use. The method was found to be specific, accurate and precise for analyzing the drugs. The extent and rate of deactivation of the drugs was determined at several time points. After 28 days in the presence of activated carbon, the extent of leaching out of the drugs was evaluated. Deactivation started immediately after addition of the medications into the disposal pouches. Within 8 h, around 47%, 70% and 97% of diazepam, lorazepam and buprenorphine were adsorbed by the activated carbon, respectively. By the end of 28 days, over 99% of all drugs were deactivated. The desorption/leaching study showed that less than 1% of the active ingredients leached out from the activated carbon. Thus, this deactivation system can be successfully used for the disposal of psychoactive medications.


Atorvastatin decreases serum levels of advanced glycation endproducts (AGEs) in nonalcoholic steatohepatitis (NASH) patients with dyslipidemia: clinical usefulness of AGEs as a biomarker for the attenuation of NASH.
Advanced glycation endproducts (AGEs), final reaction products of protein with sugars, are known to contribute to various disorders, including diabetes, aspects of aging, and neurodegenerative diseases. Recently, we reported elevated levels of serum AGEs in patients with nonalcoholic steatohepatitis (NASH); further, we found that AGEs induced the generation of reactive oxygen species followed by the proliferation and activation of hepatic stellate cells, a major contributor to liver fibrosis. In this study, to explore the clinical usefulness of AGEs as a biomarker for the attenuation of NASH, we investigated whether the treatment of NASH with dyslipidemia could decrease serum levels of AGEs. This study included 43 patients with biopsy-proven NASH with dyslipidemia. Serum glyceraldehyde-derived AGE measurements and clinical laboratory tests were performed periodically during an open-label study of atorvastatin (10 mg daily) for 12 months. Standard weight-loss counseling was continued during the treatment period. Oral glucose tolerance tests and liver density assessment by computerized tomography were performed before and after treatment. Follow-up liver biopsy was performed in 22 patients. All 43 patients had dyslipidemia. The body mass indexes and serum glucose levels did not change during the treatment. After the treatment, NASH-related metabolic parameters were significantly improved. Serum glyceraldehyde-derived AGE levels were significantly decreased (10.4 +/- 3.8 and 2.5 +/- 1.1 IU/mL before and after treatment, respectively). The steatosis grade and nonalcoholic fatty liver disease (NAFLD) activity score were significantly improved. The present data demonstrated that atorvastatin decreased the serum levels of AGEs in NASH patients with dyslipidemia and suggest the usefulness of AGEs as a biomarker for the attenuation of NASH.


Near Point-of-Care HIV Viral Load: Targeted Testing at Large Facilities.
Point-of-care (POC) technologies in resource-limited settings can circumvent challenges of centralized laboratory testing, improving clinical management. However, higher device costs and uncertain indications for use have inhibited scaling up POC modalities. To address this gap, we investigated the feasibility and cost of targeted near-POC viral load (VL) testing in 2 large HIV clinics in Lilongwe, Malawi. VL testing using GeneXpert was targeted for patients suspected of treatment failure or returning to care after a previously elevated VL (>1000 copies/mL). Descriptive analysis of retrospective clinical and cost data is presented. Two thousand eight hundred thirteen near-POC VL tests were conducted. One thousand five hundred eleven (54%) tests were for patients for whom results and reason for the test were documented: 57% (794/1389) of tests were to confirm a previously high VL, and 33% (462/1389) were due to clinical indications. Sixty-one percent (926/1511) of patients had a high VL, of whom 78% (719/926) had a recorded clinical action: 77% (557/719) switched to second line antiretroviral therapy, and 15% (194/719) were referred for intensive adherence counseling. Eighty-two percent (567/687) of patients received a clinical action on the same day as testing. The "all-in" cost was $33.71 for a valid POC VL test, compared with an international benchmark for a centralized VL test of $28.62. Targeted, near-POC VL testing was feasible and consistently enabled prompt clinical action. The difference between the "all-in" cost of near-POC VL and centralized testing of $5.09 could be further reduced in an optimized national program by combining targeted near-POC testing and centralized testing.


Crystal structure of d(GCGAAAGCT) containing a parallel-stranded duplex with homo base pairs and an anti-parallel duplex with Watson-Crick base pairs.
A DNA fragment d(GCGAAAGCT), known to adopt a stable mini-hairpin structure in solution, has been crystallized in the space group I4(1)22 with the unit-cell dimensions a = b = 53.4 A and c = 54.0 A, and the crystal structure has been determined at 2.5 A resolution. The four nucleotide residues CGAA of the first half of the oligomer form a parallel duplex with another half through the homo base pairs, C2:C2+ (singly-protonated between the Watson- Crick sites), G3:G3 (between the minor groove sites), A4:A4 (between the major groove sites) and A5:A5 (between the Watson-Crick sites). The two strands remaining in the half of the parallel duplex are split away in different directions, and they pair in an anti-parallel B-form duplex with the second half extending from a neighboring parallel duplex, so that an infinite column is formed in a head-to-tail fashion along the c-axis. It seems that a hexa-ammine cobalt cation supports such a branched and bent conformation of the oligomer. One end of the parallel duplex is stacked on the corresponding end of the adjacent parallel duplex; between them, the guanine base of the first residue is stacked on the fourth ribose of another duplex.


Detection of human herpesvirus 8 in the skin of patients with pityriasis rosea.
Pityriasis rosea is an acute self-limiting dermatosis with clinical and epidemiological features that suggest viral involvement. The aim of this study was to investigate a possible association between pityriasis rosea and human herpesvirus 8 (HHV-8). Lesional skin tissue was obtained from 34 Kaposi's sarcoma-negative, immunocompetent patients with typical acute phase pityriasis rosea. Nested polymerase chain reaction with specific primer for HHV-8 DNA sequences was performed and all positive results were confirmed by sequencing. Seven out of 34 lesional skin specimens (20.5%) were found to be positive for the HHV-8 genome. All the positive samples were confirmed by DNA sequencing. We conclude that, in some cases, HHV-8 is implicated the pathogenesis of pityriasis rosea.


Stressing the development of small molecules targeting HSP90.
Inhibitors of the molecular chaperone HSP90 have been in clinical development as anticancer agents since 1999. Recent clinical studies, including the work of Saif and colleagues in this issue of Clinical Cancer Research, demonstrate that significant progress has been made in overcoming the obstacles preventing regulatory approval.


Unfocused effect on the measurement of ocular aberrations.
To evaluate the effect of unfocused measurement in the value of ocular aberrations. The present study was conducted at Siriraj Hospital, Mahidol University. Ocular aberrations of 20 eyes in 10 myopic patients (myopia less than -6.00 diopters (D) and astigmatism less than -2.00 diopters (D)) were analyzed by using Zywave aberrometer (Bausch and Lomb, USA). The measurements were done at the pupillary plane (focus) and 6 other different planes (unfocus); 5, 10 and 15 mm inside and outside pupillary plane respectively. The value of each measurement was analyzed to find the effect of unfocused measurement on ocular aberrations. The magnitude of error (root mean square, RMS) of the spherical component of refraction at 5, 10, 15 mm inside and outside the pupillary plane was 0.16, 0.44, 0.57 D and 0.21, 0.38, 1.35D respectively. The RMS of astigmatic component of refraction inside and outside the pupillary plane at the same distance was 0.19, 0.50, 0.80 and 0.18, 0.52, 1.55 D respectively. The RMS of higher order aberrations inside and outside the pupillary plane at the same distance was 0.05, 0.13, 0.15 and 0.06, 0.1, 0.1 microns respectively. There was more effect of outward unfocused measurement in the value of refraction (spherical and astigmatism) than inward unfocused measurement. Higher order aberration showed a similar error in both inward and outward defocus. The magnitude of error was 10 - 12% within 5 mm unfocused planes.


Long-term effect on the equine eye of an intravitreal device used for sustained release of cyclosporine A.
OBJECTIVE: To determine the long-term toxicity of an intravitreal device releasing continuous cyclosporinee A (CsA) in normal eyes of horses by evaluating clinical signs, electroretinography, and histopathology. Animals Studied Ten adult horses with normal ophthalmic examinations were used in this study Procedure(s) Four horses had one eye implanted with a CsA device, and six horses had the right eye implanted with a CsA-containing device (10 eyes with CsA in total) and the left eye (six eyes in total) with the device without drug (control). The implants were placed in the vitreous of the eyes through a sclerotomy 1 cm posterior to the limbus in the dorso-temporal quadrant of the eye. Scotopic electroretinograms were performed prior to implantation and at 1 week, and at 1, 3, 6, 9, and 12 months postimplantation. Two of the unilaterally implanted horses were euthanized at 1 weeks postimplantation, and two at 6 weeks postimplantation. Two of the bilaterally implanted horses were euthanized at 6 months, two at 9 months, and two at 12 months postimplantation. At euthanasia, the eyes were removed, aqueous and vitreous humor aspirated, and tissues fixed in 10% buffered formalin and processed for histopathology. CsA concentrations were measured by high pressure liquid chromatography in the aqueous and vitreous humors, and in peripheral blood. RESULTS: The devices were tolerated well in 14 of 16 eyes. There was minimal postoperative inflammation in most eyes, with a normal appearance within 7 days. In two eyes implanted with the CsA device, severe inflammation resulted in phthisis bulbi by 28 days. One of these eyes exhibited suspected bacterial endophthalmitis, and one had a sterile endophthalmitis and cataract presumably from trauma to the lens during implantation. In the other 14 eyes, no change was observed in the scotopic electroretinograms (ERG) from preoperative results, and no significant differences between the right (CsA) and left (control device) eyes were observed. CsA levels in the aqueous and vitreous humor, and peripheral blood were below the detection limit of the HPLC. Histologic findings revealed only a mild lymphoplasmacytic cellular infiltrate in the ciliary body and pars plana near the implantation site. CONCLUSIONS: The CsA devices were well tolerated with no long-term complications from the implants themselves. However, complications may occur from inadvertent implantation trauma or contamination during surgery. The long-term safety of the device may make it useful for delivery of CsA in the control of equine recurrent uveitis.


Differentiation of Dental Pulp Stem Cells on Gutta-Percha Scaffolds.
Advances in treatment of tooth injury have shown that tooth regeneration from the pulp was a viable alternative of root canal therapy. In this study, we demonstrated that Gutta-percha, nanocomposites primarily used for obturation of the canal, are not cytotoxic and can induce differentiation of dental pulp stem cells (DPSC) in the absence of soluble mediators. Flat scaffolds were obtained by spin coating Si wafers with three Gutta-percha compounds: GuttaCore™, ProTaper™, and Lexicon™. The images of annealed surfaces showed that the nanoparticles were encapsulated, forming surfaces with root mean square (RMS) roughness of 136⁻211 nm. Then, by culturing DPSC on these substrates we found that after some initial difficulty in adhesion, confluent tissues were formed after 21 days. Imaging of the polyisoprene (PI) surfaces showed that biomineral deposition only occurred when dexamethasone was present in the media. Spectra obtained from the minerals was consistent with that of hydroxyapatite (HA). In contrast, HA deposition was observed on all Gutta-percha scaffolds regardless of the presence or absence of dexamethasone, implying that surface roughness may be an enabling factor in the differentiation process. These results indicate that Gutta-percha nanocomposites may be good candidates for pulp regeneration therapy.


Prevalence of cognitive impairment and change in patients with breast cancer: A systematic review of longitudinal studies.
Patients with breast cancer face cognitive impairment that affects their quality of life; partially attributable to treatment. Our aim was to detail the prevalence and change of cognitive impairment during the course of treatment. We also investigated the effect of therapy (chemotherapy [CT]) vs. radiotherapy and/or endocrine therapy vs. healthy controls). This article reviews longitudinal cohort studies published to date in Medline and Embase that (i) assess cognition before and after therapy, (ii) report prevalence cognitive impairment or change, and (iii) use standardized and valid neuropsychological tests. We used the original authors' criteria for cognitive impairment. The title and abstract of 891 articles were screened, resulting in the identification of 90 potentially relevant articles while applying the eligibility criteria. After full-text examination, 17 studies were included. Prevalence of cognitive impairment range from 25% before therapy, through 24% after therapy to 21% at maximal 1-year follow-up (FU). Compared to their pretreatment cognitive functioning, 24% of patients decline after treatment and 24% at 1-year FU. Some studies also reported cognitive improvement showing that 15% and 31% of patients improve, respectively. In general, patients undergoing CT have a higher chance of cognitive impairment and decline than no-CT patients and healthy controls. This study shows that one out of four breast cancer patients shows cognitive impairment prior to treatment administration CT and a significant number of patients decline during the course of disease, suggesting that cognitive impairment is not exclusively related to CT and/or no-CT therapies. This study shows that assessment of cognitive functioning, ideally over time, is crucial and may help the implementation of personalized rehabilitation pathways.


[Renin and the heart].
The inhibition of renin-angiotensin system (RAS) has an effect beyond reducing blood pressure in the treatment of cardiovascular diseases; it also reduces mortality and morbidity. Although the classic RAS blockage is effective, due to blockage of negative feedback inhibition, it increases plasma renin activity and as a result generates a residual cardiovascular risk. Different from ACE-i and ARB treatments, aliskiren, a direct renin inhibitor, is the only pharmacologic agent that noticeably reduces the plasma renin activity, an independent cardiovascular risk factor. This creates a new option in RAS blockage. The efficacy and safety of aliskiren in the treatment of hypertension has been well established. The effect of aliskiren on cardiovascular mortality and morbidity is being researched. At this point there are many experimental and clinical studies to answer questions on this subject.


Butylated Hydroxytoluene Induced Resistance Against Botryosphaeria dothidea in Apple Fruit.
Apple ring rot caused by Botryosphaeria dothidea is an important disease in China, which leads to serious economic losses during storage. Plant activators are compounds that induce resistance against pathogen infection and are considered as a promising alternative strategy to traditional chemical treatment. In the present study, butylated hydroxytoluene (BHT), a potential plant activator, was evaluated for its induced resistance against B. dothidea in postharvest apple fruits. The physiological and molecular mechanisms involved in induced resistance were also explored. The results showed that BHT treatment could trigger strong resistance in apple fruits against B. dothidea, and the optimum concentration was 200 μmol L-1 by immersion of fruits. BHT treatment significantly increased the activities of four defensive enzymes and alleviated lipid peroxidation by increasing antioxidant enzyme activities. In addition, salicylic acid (SA) content was enhanced by BHT treatment as well as the expression of three SA biosynthesis-related genes (MdSID2, MdPAD4, and MdEDS1) and two defense genes (MdPR1 and MdPR5). Our results suggest that BHT-conferred resistance against B. dothidea might be mainly through increasing the activities of defense-related enzymes and activating SA signaling pathway, which may provide an alternative strategy to control apple ring rot in postharvest fruits.


Communication after laryngectomy: an assessment of quality of life.
The purpose of this study was to examine quality of life in laryngectomees using different methods of communication. A survey was mailed to all the living laryngectomees in Nova Scotia. Patients were asked to rate their ability to communicate in a number of common situations, to rate their difficulty with several communication problems, and to complete the EORTC QLQ-C30 quality-of-life assessment tool. Sixty-two patients responded (return rate of 84%); 57% were using electrolaryngeal speech, 19% esophageal speech, and 8.5% tracheoesophageal speech. These groups were comparable with respect to age, sex, first language, education level, and years since laryngectomy. There were very few differences between these groups in ability to communicate in social situations and no difference in overall quality of life as measured by these scales. The most commonly cited problem was difficulty being heard in a noisy environment. Despite the fact that tracheoesophageal speech is objectively most intelligible, there does not seem to be a measurable improvement in quality of life or ability to communicate in everyday situations over electrolaryngeal or esophageal speakers.


Effect of the Immobilization Strategy on the Efficiency and Recyclability of the Versatile Lipase from Ophiostoma piceae.
The recombinant lipase from Ophiostoma piceae OPEr has demonstrated to have catalytic properties superior to those of many commercial enzymes. Enzymatic crudes with OPEr were immobilized onto magnetite nanoparticles by hydrophobicity (SiMAG-Octyl) and by two procedures that involve covalent attachment of the protein (mCLEAs and AMNP-GA), giving three nanobiocatalysts with different specific activity in hydrolysis of p-nitrophenyl butyrate (pNPB) and good storage stability at 4 °C over a period of 4 months. Free OPEr and the different nanobiocatalysts were compared for the synthesis of butyl esters of volatile fatty acids C4 to C7 in reactions containing the same lipase activity. The esterification yields and the reaction rates obtained with AMNP-GA-OPEr were in general higher or similar to those observed for the free enzyme, the mCLEAs-OPEr, and the non-covalent preparation SiMAG-Octyl-OPEr. The time course of the esterification of the acids C4 to C6 catalyzed by AMNP-GA-OPEr was comparable. The synthesis of the C7 ester was slower but very efficient, admitting concentrations of heptanoic acid up to 1 M. The best 1-butanol: acid molar ratio was 2:1 for all the acids tested. Depending on the substrate, this covalent preparation of OPEr maintained 80-96% activity over 7 cycles, revealing its excellent properties, easy recovery and recycling, and its potential to catalyze the green synthesis of chemicals of industrial interest.


Growth and Aflatoxin Production by Aspergillus parasiticus in the Presence of Sodium Chloride.
Twenty-five milliliters of glucose-yeast-salt medium containing 0, 2, 4, 6, 8, or 10% NaCl was inoculated to contain, approximately 105 or 107 conidia of Aspergillus parasiticus NRRL 2999 and then incubated at 13 or 28°C. Amounts of aflatoxin produced were determined using Reversed-Phase High Performance Liquid Chromatography (HPLC). Increasing the concentration of NaCl reduced accumulation of aflatoxin and also induced a lag in growth of the culture. At 13°C, the mold produced small amounts of aflatoxin after an extended lag phase, and NaCl was markedly more inhibitory at 13 than at 28°C.


[The Spanish National Health System patient safety strategy, results for the period 2005-2007].
In 2005 the Spanish National Health System (SNHS) implemented a strategy aimed at improving patient safety in Spanish healthcare centres. Promote and develop knowledge of patient safety and a patient safety culture among health professionals and patients; design and implement adverse event information and reporting systems for learning purposes; introduce recommended safe practices in SNHS centres; promote patient safety research and public and patient involvement in patient safety policies. An Institutional Technical Committee was created with representatives from all the Spanish regions. All national organizations involved in healthcare quality and patient safety took part in the project. The strategy follows the WHO World Alliance for Patient Safety and Council of Europe recommendations. Budget allocated in the period 2005-2007: approximately EUR35 million. Around 5,000 health professionals were educated in PS concepts. Several studies were conducted on: adverse events in Hospitals and Primary Care, as well as studies to obtain information on health professionals' perceptions on safety, the use of medications and the situation regarding hospital-acquired infections. All the regions have introduced safe clinical practices related with the strategy. The strategy has been implemented in all the Spanish regions. Awareness was raised among health professionals and the public. A network of alliances has been set up with the regions, universities, schools, agencies and other organizations supporting the strategy.


Effects of kappa opioids in an assay of pain-depressed intracranial self-stimulation in rats.
Selective, centrally acting kappa opioid agonists produce antinociception in a wide range of preclinical assays, but these compounds perform poorly as analgesics in humans. This discrepancy may be related to the behavioral depressant effects of kappa agonists. Kappa antagonists do not typically produce antinociception, but they produce antidepressant-like effects in some preclinical assays. The objective of this study was to test the hypothesis that the kappa agonist U69,593 and the kappa antagonist norbinaltorphimine would produce pronociceptive and antinociceptive effects, respectively, in an assay of pain-depressed behavior. Effects of U69,593 (0.056-0.56 mg/kg), norbinaltorphimine (10-32 mg/kg), and morphine (3.2 mg/kg) were evaluated on the stimulation of a stretching response and the depression of intracranial self-stimulation (ICSS) of the medial forebrain bundle produced in rats by a common noxious stimulus (intraperitoneal administration of dilute lactic acid). U69,593 produced a dose-dependent blockade of acid-stimulated stretching but only exacerbated acid-induced depression of ICSS. Thus, U69,593 produced antinociception in the assay of pain-stimulated behavior but pronociceptive effects in the assay of pain-depressed behavior. Norbinaltorphimine did not alter acid-stimulated stretching or acid-induced depression of ICSS. The mu opioid agonist morphine blocked both acid-stimulated stretching and acid-induced depression of ICSS. These results support the hypothesis that prodepressant effects of kappa agonists may limit their clinical utility as analgesics. These results do not support the use of kappa antagonists to treat depressant effects of pain. These findings illustrate the potential value of using complementary assays of pain-stimulated and pain-depressed behaviors for preclinical evaluation of candidate analgesics.


[Microkeratome-assisted lamellar keratoplasty for recurrent corneal granular dystrophy after phototherapeutic keratectomy].
To evaluate the safety and efficacy of microkeratome-assisted lamellar keratoplasty (MLK) for the treatment of recurrent granular corneal dystrophy (GCD) after phototherapeutic keratectomy (PTK). We performed a prospective study of nine eyes (seven patients) with recurrent granular dystrophy after PTK. A microkeratome was used to cut partial-thickness sections through the anterior surface of the donor and host corneas. The donor disc was placed on the recipient bed with four or eight interrupted sutures. The stitches were removed between 4 and 6 weeks after surgery. Visual acuity (VA), corneal clarity, corneal thickness, and corneal topography were assessed before and at different time points after surgery. During a mean follow-up period of (18.9 +/- 4.1) months, all grafts were transparent without visible opacity at the interface, and no serious complications occurred. The VA was improved in all cases. seven eyes had best corrected visual acuity with spectacles of 20/40 or better, two eyes reached 20/25. At the last follow-up visit more than 12 months postoperatively, the mean corneal refractive power increased significantly by (2.34 +/- 0.93) D (P < 0.01), and the corneal astigmatism significantly decreased by (0.91 +/- 0.98) D (P < 0.05). The mean corneal thickness was (477.4 +/- 26.9) microm preoperatively and (507.8 +/- 23.4) microm at the last follow-up visit (P < 0.01). Our findings suggest that MLK for the treatment of recurrent GCD is a safe and easy-to-perform method for restoring VA.


Post-Operative Spinal Epidural Hematoma: Are We Discontinuing Aspirin Early Enough?
Retrospective cohort study. (1) To compare the risk of Spinal Epidural Hematoma (SEH) associated with specific pre-operative and post-operative anticoagulation (AC) and antiplatelet medications (APM). (2) To define the incidence of SEH and identify risk factors for SEH in our population. Thoracolumbar surgeries between October 2009 and March 2020 were collected. Patients who underwent incision and drainage of a symptomatic SEH were identified. AC and APM was recorded 14 days pre-operatively and post-operatively. Demographics and intra-operative factors were recorded. Relative risk with 95% confidence interval was used, with Bonferroni-corrected P-values <.05 used for significance. 9307 surgeries were identified. 177 (1.9%) patients returned to the OR within 30 days, 37 of whom (.39%) returned due to SEH. Seven patients were on either AC or APM pre-op, and sixteen post-op. Five were on aspirin pre-operatively (RR 3.2, 95% CI 1.25-8.22, P = .015). Risk was not increased in patients on multiple agents. No AC or APM demonstrated increased risk of hematoma post-operatively, despite trends toward significance with multiple agents. The use of a drain and complicated hypertension were associated with increased risk of SEH. Pre-operative aspirin is associated with increased risk of SEH, even when appropriately discontinued. Appropriately dosed post-operative anticoagulation does not increase the risk of SEH, though being on multiple agents trends toward statistical significance and should be better studied. Surgeons should be vigilant and carefully monitor patients on pre-operative antiplatelet medications for spinal epidural hematoma.


Cancer vaccines with emphasis on a viral oncolysate melanoma vaccine.
Biotherapy of malignant diseases has become the fourth treatment modality besides surgery, chemo- and radiotherapy. Whole cell melanoma vaccines with or without BCG and other adjuvants, purified ganglioside and shed antigens, recombinant viruses carrying tumor antigens, dendritic cells pulsed with antigenic peptides etc. are in clinical trials. Efficacious viral oncolysate vaccines induce the host to mount tumor-specific cytotoxic T-cell response and prevention of relapses is supported by clinical trials. The use of "polyvalent" whole cell vaccines vs. purified or genetically engineered single antigen vaccines is justified as i. only very few single tumor antigens are present in all tumors of a given histological type; and ii. antigen modulation occurs in tumors rendering them resistant to immune attack generated by vaccine against a single antigen. Thus polyvalent vaccines immunize against several antigens vs. against a selected antigen.


The undescended testis in adult life.
The management of the undescended testis in the adult patient presents problems in terms of locating the impalpable gonad, the risk of malignancy and prognosis with regard to fertility. CT scanning has been used to locate four intra-abdominal testes. The risk of malignancy has been assessed by determining the incidence of carcinoma in situ after orchiectomy or testicular biopsy in 90 patients (112 testes). Carcinoma in situ was found in 4 of 16 abdominal, 3 of 44 inguinal and none of 52 scrotal testes following orchiopexy in childhood. Seventy per cent of undescended testes in adult patients had no evidence of spermatogenesis. This fact, together with the risk of malignancy in those testes in which germ cells are present, suggests that orchiectomy should be performed in unilateral cases. Testicular biopsy is essential if an undescended testis is to be preserved for androgenic function.


Severe dapsone hypersensitivity syndrome.
Dapsone, a potent antiparasitic and anti-inflammatory compound, is mainly used in the treatment of leprosy and a variety of blistering skin diseases. It may cause a severe adverse drug reaction with multiorgan involvement known as dapsone hypersensitivity syndrome. We report the case of a 21-year-old female patient with dapsone hypersensitivity syndrome. The clinical presentation mimicked a viral exanthema.


[Skin manifestations of Fanconi anemia].
Fanconi's anemia is a rare autosomal recessive disorder associated with variable clinical manifestations. So far, eight complementation groups have been identified, and the genes of four of them have been cloned. Early-onset progressive bone marrow failure and a predisposition to malignancies, particularly acute myelogenous leukemia, liver tumors, and mucocutaneous squamous cell carcinomas, result in a poor prognosis. Additionally, almost all organs can be affected by this defect. Widespread areas of hyper- and hypopigmentation of the skin in a characteristic pattern and café-au-lait spots preceding the manifestation of panmyelopathy can aid early diagnosis. Here we report an 11-year-old boy with Fanconi's anemia presenting with typical cutaneous manifestations. We emphasize the important role of skin abnormalities of Fanconi's anemia as signs enabling early diagnosis. Moreover, we summarize clinical features, course, therapy, and new aspects of the molecular basis of Fanconi's anemia.


Fine mapping of a C-terminal linear epitope highly conserved among the major envelope glycoprotein E2 (gp51 to gp54) of different pestiviruses.
Envelope glycoprotein E2 (gp51 to gp54) is the major neutralizing antigen of pestiviruses, which include classical swine fever virus (CSFV), bovine viral diarrhoea virus (BVDV), and border disease virus (BVD). Previous studies carried out using a panel of monoclonal antibodies raised against CSFV strain Brescia have revealed the existence of four antigenic domains, A to D, of the E2 protein, all of which are located at the N-terminal half of the molecule. Here we report the detailed mapping, using three complementary techniques, of a novel linear epitope located at the C-terminal part of the molecule, which reacted with a monoclonal antibody (4-9D4) as well as polyclonal animal sera. This epitope is highly conserved in the three different members of pestiviruses and hence can be used as a genus-specific diagnosis tool. The observation that this epitope is not accessible on the native virus surface, together with its C-terminal location, supports a recently proposed structural model, indicating that the C-terminal part of E2 is membrane-bound while the N-terminal half of the molecule is exposed on the virus surface.


Total concentrations of dust in the air during farm work.
Total concentrations of dust in the air of work environments were measured on 20 Finnish farms during 1980-82. On 8 farms the main line of production was dairy farming, on 5 farms it was pig farming, on 4 farms poultry farming and on 3 farms grain production. Dust was measured by the gravimetric method according to the Finnish standard. Results were compared to the threshold limit value (TLV), which for inorganic dust is 10 mg/m3, and for organic dust 5 mg/m3. Mean concentrations of dust in the breathing zone exceeded the TLV for organic dust in all farm buildings, piggeries and poultry yards with coops having the highest mean concentrations, 12.6 mg/m3 and 12.8 mg/m3, respectively. Mean total concentrations of dust during seed dressing, harrowing, rolling and emptying the grain drier were 31.4, 14.0, 18.2 and 20.0 mg/m3, respectively. During sowing and haymaking, the total concentrations of dust were also high occasionally.


Self-assessed learning needs of oncology nurses caring for individuals with HIV-related disorders. A national survey.
A national survey of 10% of the members of the Oncology Nursing Society (ONS) was conducted to determine the knowledge and experience of oncology nurses caring for individuals with HIV-related disorders. This information was to serve as the framework for developing subsequent education and preparation of oncology nurses. A questionnaire containing 109 questions was mailed to 1,006 members of the ONS. Response rate was 70% (N = 693). Fifty-five of the 109 questions assessed clinical knowledge, experience, and care planning for adults. Additional questions elicited information about staff attitudes, problems in care delivery, priorities in nursing administration and research, and nurses' preferred methods of instruction. Results showed that oncology nurses are experienced in certain areas of importance to patients with AIDS but have educational and experiential deficits in the disease specifics associated with HIV-related disorders and in the nursing care of adults with multisystem involvement and in their treatment. Validity and reliability of this questionnaire were established (alpha = 0.93-0.97). Readers are encouraged to adapt this questionnaire to assess the learning needs of nurses in all specialty groups, and to develop appropriate educational programs to prepare nurses to provide care for this patient population.


Upregulation of KCNQ1OT1 promotes resistance to stereotactic body radiotherapy in lung adenocarcinoma by inducing ATG5/ATG12-mediated autophagy via miR-372-3p.
Stereotactic body radiotherapy (SBRT) has emerged as a standard treatment for non-small-cell lung cancer. However, its therapeutic advantages are limited with the development of SBRT resistance. The SBRT-resistant cell lines (A549/IR and H1975/IR) were established after exposure with hypofractionated irradiation. The differential lncRNAs were screened by microarray assay, then the expression was detected in LUAD tumor tissues and cell lines by qPCR. The influence on radiation response was assessed via in vitro and in vivo assays, and autophagy levels were evaluated by western blot and transmission electron microscopy. Bioinformatics prediction and rescue experiments were used to identify the pathways underlying SBRT resistance. High expression of KCNQ1OT1 was identified in LUAD SBRT-resistant cells and tissues, positively associated with a large tumor, advanced clinical stage, and a lower response rate to concurrent therapy. KCNQ1OT1 depletion significantly resensitized A549/IR and H1975/IR cells to radiation by inhibiting autophagy, which could be attenuated by miR-372-3p knockdown. Furthermore, autophagy-related 5 (ATG5) and autophagy-related 12 (ATG12) were confirmed as direct targets of miR-372-3p. Restoration of either ATG5 or ATG12 abrogated miR-372-3p-mediated autophagy inhibition and radiosensitivity. Our data describe that KCNQ1OT1 is responsible for SBRT resistance in LUAD through induction of ATG5- and ATG12-dependent autophagy via sponging miR-372-3p, which would be a potential strategy to enhance the antitumor effects of radiotherapy in LUAD.


Infrared study of the structure and composition of rabbit lens membranes: a comparative analysis of the lipids of the nucleus, cortex and epithelium.
Infrared spectra of the phospholipids extracted from the nuclear, cortical and epithelial regions of the rabbit lens membrane bilayers are examined for the first time. Major structural, conformational and compositional differences in the lens membrane are correlated at physiological temperature. Vibrational data distinguish two classes of the phospholipids present in the rabbit lens membranes. Sphingolipids with a sphingosine backbone are largely concentrated in the nucleus whereas phospholipids with a glycerol backbone (glycero-lipids) such as phosphatidylcholine and phosphatidylethanolamine are abundant in the cortical region of the lens. Nuclear lipids are more saturated by a factor of four over the lipids of the cortical region. Nuclear lipids also exhibit increased headgroup and interface hydration and stronger hydrogen bonding over cortical lipids which provide them additional structural stability needed for the clarity of the lens. The lipid composition of the epithelial membranes is structurally similar to that of the cortical region but the hydrocarbon chains are more saturated. Epithelial membranes are largely shielded from bilayer water indicating hydrophilic lipid-water interactions are not important for the stability of these membranes. These membranes exhibit much stronger lipid-lipid interactions, vital for many physical properties like membrane fluidity and permeability. The fiber cell membranes are stabilized by hydrogen bonding of the carbonyls of the interface region and by headgroup-specific lipid-water interactions, while epithelial membranes are stabilized primarily through hydrophobic lipid-lipid interactions. Data also exhibit two phase transitions around 16 and 35 degrees C corresponding to the melting of the hydrocarbon chains from two pools of the phospholipids i.e. glycero- and sphingophospholipids, respectively. The first transition is caused by disruption of the carbonyl hydrogen bonding and disordering of the acyl chains of the glycero-lipids, while second transition is driven mainly from the hydrogen bonding effects of the carbonyls of the sphingolipids followed by acyl/sphingosine chain disordering. Upon transition to the liquid-crystalline phase, a sizable amount of the fiber cell membranes are disordered (approximately 33%) due to increased conformational motion of the acyl chains resulting from a loss of extended CH2 trans segments. These chains of the fully hydrated lipids pack in an hexagonal or triclinic unit cell in rabbit lens membranes.


Response Surface Methodology and Artificial Neural Network Modelling of Membrane Rotating Biological Contactors for Wastewater Treatment.
Membrane fouling is a major hindrance to widespread wastewater treatment applications. This study optimizes operating parameters in membrane rotating biological contactors (MRBC) for maximized membrane fouling through Response Surface Methodology (RSM) and an Artificial Neural Network (ANN). MRBC is an integrated system, embracing membrane filtration and conventional rotating biological contactor in one individual bioreactor. The filtration performance was optimized by exploiting the three parameters of disk rotational speed, membrane-to-disk gap, and organic loading rate. The results showed that both the RSM and ANN models were in good agreement with the experimental data and the modelled equation. The overall R2 value was 0.9982 for the proposed network using ANN, higher than the RSM value (0.9762). The RSM model demonstrated the optimum operating parameter values of a 44 rpm disk rotational speed, a 1.07 membrane-to-disk gap, and a 10.2 g COD/m2 d organic loading rate. The optimization of process parameters can eliminate unnecessary steps and automate steps in the process to save time, reduce errors and avoid duplicate work. This work demonstrates the effective use of statistical modeling to enhance MRBC system performance to obtain a sustainable and energy-efficient treatment process to prevent human health and the environment.


Sequential changes of esophageal motility after endoscopic injection sclerotherapy or variceal ligation for esophageal variceal bleeding: a scintigraphic study.
Endoscopic injection sclerotherapy and variceal ligation are two popular endoscopic methods used to treat esophageal variceal hemorrhage. These two methods have not been compared with regard to esophageal dysfunction after treatment. This is a prospective investigation of esophageal dysmotility after endoscopic injection sclerotherapy and variceal ligation. Sequential changes of esophageal motility after endoscopic injection sclerotherapy (n = 25) and variceal ligation (n = 25) were investigated in 50 cirrhotic patients with recent variceal bleeding. Another 22 cirrhotics without esophageal varices were included as controls. Radionuclide esophageal transit tests were performed before initial endoscopic treatment, and 1 and 3 months after variceal eradication. The baseline esophageal transit time was longer in both the sclerotherapy (n = 25, 7.8 +/- 1.4 s) and ligation groups (n = 25, 8.2 +/- 1.8 s) than in controls (n = 22, 6.7 +/- 0.7 s, p < 0.005). The transit time was longer in patients with large varices than in those with small varices (8.3 +/- 1.7 vs. 7.2 +/- 0.7 s, p < 0.05). In the sclerotherapy group, the transit time was prolonged 1 month after variceal eradication, compared with its pretreatment state (n = 20, 7.6 +/- 1.5 vs. 10.0 +/- 2.2 s, p < 0.0001) but was shortened at 3 months compared with 1 month after variceal eradication (n = 12, 10.7 +/- 1.5 vs. 8.6 +/- 2.2 s, p < 0.05). Multiple regression analysis showed that the number of treatment sessions required to eradicate varices was the only significant factor associated with prolonged transit time (p < 0.05). In the ligation group, the transit time changed little at 1 month or 3 months after variceal eradication. Impairment of esophageal motility can be significant with endoscopic injection sclerotherapy but is reversible. However, endoscopic variceal ligation exerts no significant impact on esophageal motility.


Visible light communication based motion detection.
In this paper, a unique and novel visible light communication based motion detection is presented. The proposed motion detection is performed based on white light LEDs and an array of photodetectors from existing visible light communication (VLC) links, thus providing VLC with three functionalities of illumination, communication and motion detection. The motion is detected by observing the pattern created by intentional obstruction of the VLC link. Experimental and simulation results demonstrate the validity of the proposed VLC based motion detection technique. The VLC based motion detection can benefit smart devices control in VLC based smart home environments.


[Value of pulp recession in inveterate hook fingers. Techniques/indications].
The aim of this operation is to preserve the sensitivity whenever when a finger has to be amputated. We have reviewed 9 patients operated according to this technique, out of 14 patients for whom an amputation or a shortening arthrodesis was discussed. The results of pulp recession were most encouraging. The incision were located on both sides of the finger and distant from the ungueal matrix. The dorsal skin was elevated in the sub-periosteal plane. Resection of the necessary amount of 2nd phalanx to obtain an extended finger was performed. An osteosynthesis with pins is preferred for a duration of 6 weeks. This operation can be performed for very stiff finger, hooked fingers or dystrophic fingers with a good pulp. In extreme cases of shortening, the nail with its bed ar sacrificed, and the entire pulp is used to cover the distal stump. This principal of pulp recession has been used in two other cases in emergency surgery. The postoperative was marked by finger swelling and some pain of the distal sutured skin. Overall the results were satisfactory and patients were very satisfied to keep their finger, which would otherwise have been doomed.


Immune cell inhibition by SLAMF7 is mediated by a mechanism requiring src kinases, CD45, and SHIP-1 that is defective in multiple myeloma cells.
Signaling lymphocytic activation molecule F7 (SLAMF7) is a receptor present on immune cells, including natural killer (NK) cells. It is also expressed on multiple myeloma (MM) cells. This led to development of an anti-SLAMF7 antibody, elotuzumab, showing efficacy against MM. SLAMF7 mediates activating or inhibitory effects in NK cells, depending on whether cells express or do not express the adaptor EAT-2. Since MM cells lack EAT-2, we elucidated the inhibitory effectors of SLAMF7 in EAT-2-negative NK cells and tested whether these effectors were triggered in MM cells. SLAMF7-mediated inhibition in NK cells lacking EAT-2 was mediated by SH2 domain-containing inositol phosphatase 1 (SHIP-1), which was recruited via tyrosine 261 of SLAMF7. Coupling of SLAMF7 to SHIP-1 required Src kinases, which phosphorylated SLAMF7. Although MM cells lack EAT-2, elotuzumab did not induce inhibitory signals in these cells. This was at least partly due to a lack of CD45, a phosphatase required for Src kinase activation. A defect in SLAMF7 function was also observed in CD45-deficient NK cells. Hence, SLAMF7-triggered inhibition is mediated by a mechanism involving Src kinases, CD45, and SHIP-1 that is defective in MM cells. This defect might explain why elotuzumab eliminates MM cells by an indirect mechanism involving the activation of NK cells.


Potential of Nanoparticles as Permeation Enhancers and Targeted Delivery Options for Skin: Advantages and Disadvantages.
The topical route of administration has many advantages for the treatment of various skin disorders as well as cosmeceutical purposes. This route bypasses hepatic first-pass effect and systemic availability of many pharmaceuticals is limited to skin organelles such as hair follicles and so could avoid unwanted adverse reactions and increase the localized therapeutic effect. Despite such attributed advantages of the topical route, the most important challenge is skin barrier characteristics that should be overcome to obtain dermal or trans-dermal drug delivery. Different approaches have been recruited to overcome this barrier. In this review, different types of nanoparticles for skin permeation enhancement and targeted delivery to skin organelles are discussed. The potential mechanisms of each nanocarrier in permeation enhancement and dermal delivery are considered and finally, the most important advantages and disadvantages of each group are summarized.


Protein-protein interactions among ion channels regulate ion transport in the kidney.
Epithelial ion transport in various organs has long been known to be controlled by extracellular agonists acting via membrane receptors or by intracellular messengers. Evidence is mounting for regulation of transport by direct interaction among membrane proteins or between a membrane transport protein and membrane-attached proteins. The membrane protein CFTR (Cystic Fibrosis Transmembrane Regulator) is widely expressed along the length of the nephron, but its role as a chloride channel does not appear to be critical for renal handling of salt and water. It is well established that the inward rectifying K channels (ROMK = Kir 1.1) in the thick ascending limb of Henle and in principal cells of the collecting duct are inhibited by millimolar concentrations of cytosolic Mg-ATP. However, the mechanism of this inhibition has been an enigma. We propose that the ATP-Binding Cassette (ABC) protein CFTR is a cofactor for Kir 1.1 regulation. Indeed, Mg-ATP sensitivity of Kir 1.1 is completely absent in two different mouse models of cystic fibrosis. In addition, the open-closed state of CFTR appears to provide a molecular gating switch that prevents or facilitates the ATP sensing of Kir 1.1. Does Mg-ATP sensing by the CFTR- Kir 1.1 complex play a role in coupling metabolism to ion transport? Physiological intracellular ATP concentrations in tubule cells are in the millimolar range, a saturating concentration for the gating of Kir 1.1 by Mg-ATP. Therefore, Kir 1.1 channels would be closed and unable to contribute to regulation of potassium secretion unless some other process modulated the CFTR-dependent ATP-sensitivity of Kir 1.1. The third component of the metabolic sensor-effector complex for Kir 1.1 regulation is most likely the AMP-regulated serine-threonine kinase, AMP kinase (AMPK). Changing levels in AMP rather than in ATP constitute the metabolic signal "sensed" by tubule cells. Because AMPK inhibits CFTR by modulating CFTR channel gating, we propose that renal K secretion is physiologically regulated by tri-molecular interactions between Kir 1.1, CFTR and AMPK.