Saposin C: neuronal effect and CNS delivery by liposomes.
Saposin C is one of four small lipid-binding proteins that derive from a single precursor protein, named prosaposin (PSAP). PSAP has several neuronal effects, including neurite outgrowth stimulation, neuron preservation, and nerve regeneration enhancement. A minimal domain required for PSAP's neurotrophic function is located in the amino-terminal half of saposin C. Genetic defects of the PSAP gene in humans and mice lead to a complex lysosomal storage disease. The skin fibroblasts from PSAP- and saposin C-deficient patients have a massive accumulation of multivesicular bodies (MVBs). Incorporation of exogenous saposin C-containing liposomes into the cultured PSAP-/- cells reduced the accumulated MVBs to normal levels. Internalized saposin C was localized to late endosomes and lysosomes. MVBs are crucial for maintaining the cellular homeostasis required for neuronal development and growth. PSAP-/- mice have a short life span (30 days) and central nervous system (CNS) neuronal degeneration. Similar to PSAP-/- fibroblasts, excessive MVBs accumulated in CNS neurons and brain tissues of PSAP-null mice. Cultured cortical and hippocampal neurons from PSAP-/- mice had poor survival and displayed a neurite degenerative pattern. Delivery of saposin C ex vivo into cultured neurons and in vivo into brain neuronal cells in mice across the blood-brain barrier was accomplished with intravenously administered dioleoylphosphatidylserine (DOPS) liposomes. These studies may yield a new therapeutic approach for neuron protection, preservation, and regeneration.


An Assessment of Comparative Medication Durability in Inflammatory Bowel Disease Patients With and Without Co-morbid Psoriasis, Rheumatoid Arthritis, and/or Enteropathic Arthritis.
Patients with inflammatory bowel disease (IBD) are at increased risk for many co-morbid diseases. However, little is known about durability of IBD medications in patients with co-morbid diseases. Determine medication durability in IBD patients with and without psoriasis, rheumatoid arthritis, and/or enteropathic arthropathy. All patients with at least three ICD-9 or 10 diagnoses for IBD were included in the cohort. The risk factors of interest were a co-morbid diagnosis of psoriasis (IBD-Ps), rheumatoid arthritis (IBD-RA), and/or enteropathic arthritis (IBD-EA). Medication durability was defined as days of medication use, calculated using order start and stop dates from the electronic medical record. Significant differences were tested using the Wilcoxon rank sum test for continuous variables and Fisher's exact test or Pearson's Chi-squared test, as appropriate, for categorical variables. Boxplots were constructed for graphical interpretation of results. In the psoriasis group, there were 481 patients with 831 medication exposures [131 IBS-Ps (16%), 700 IBD only (84%)]. The median days of medication use were numerically higher in the IBD-Ps group for all therapies [anti-TNF: 1109 vs 861 (p = 0.17); anti-IL-12/23: 984 vs 834 (p = 0.33); JAKi: 682 vs 230 (p = 0.13)], anti-TNF/IM: 370 vs 202 (p = 0.57), except anti-integrin therapy [214 vs 470 (p = 0.08)]. When restricting to UC only, patients with co-morbid again Ps had a significantly shorter duration on anti-integrin therapy (84 vs 456 days, p = 0.02). While not reaching statistical significance, there was a distinctly longer medication duration on JAKi therapy (910 vs 317, p = 0.10). When restricting to patients with CD only, no results reached statistical significance though there was a trend towards longer anti-TNF durability in CD-Ps (1340 vs 1000 days, p = 0.098). There were no differences in medication durability in IBD-RA or IBD-EA patients. Larger studies investigating medication durability of JAKi and anti-integrin therapy in IBD patients with psoriasis would be beneficial given noteworthy trends towards increased and decreased durability, respectively.


Window of opportunity for respiratory oscillometry: A review of recent research.
Oscillometry has been around for almost 70 years, but there are still many unknowns. The test is performed during tidal breathing and is therefore free from patient-dependent factors that could influence the results. The Forced Oscillation Technique (FOT), which requires minimal patient cooperation, is gaining ground, particularly with elderly patients and children. In pulmonology, it is a valuable tool for assessing obstructive conditions (with a distinction between central and peripheral obstruction) and restrictive disorders (intrapulmonary and extrapulmonary). Its sensitivity allows the assessment of bronchodilator and bronchoconstrictor responses. Different lung diseases show different patterns of changes in FOT, especially studied in asthma and chronic obstructive pulmonary disease. Because of these differences, many studies have analysed the usefulness of this technique in different areas of medicine. In this paper, the authors would like to present the basics of oscillometry with the areas of its most recent clinical applications.


Hepatic and cerebral pathology findings in children with fatal salicylate intoxication: further evidence for a causal relation between salicylate and Reye's syndrome.
Histology or necropsy records of 13 children with accidental or therapeutically induced salicylate intoxication were examined for the presence of hepatic and cerebral pathology findings characteristic of Reye's syndrome. Liver sections stained with haematoxylin and eosin showed intrahepatocytic microvesiculation (10 of 12 children) and absence of significant inflammation or necrosis (10 of 12 children). All 6 specimens of liver tissue stained with oil red O showed intrahepatocytic microvesicular fat with central hepatocytic nuclei distributed either diffusely throughout the lobule or more prominently in the lobular periphery. Liver tissue stained with the periodic-acid/Schiff method showed complete absence of stainable glycogen in 5 of 6 children. 9 of 12 children for whom information was available had cerebral oedema. It is concluded that the light-microscopy hepatic findings and the gross cerebral findings for the majority of these children with salicylate intoxication are the same as those for children with Reye's syndrome.


Transient fungemia and Candida arthritis due to Candida zeylanoides.
A 37 year old man developed transient fungemia caused by Candida zeylanoides following a kidney and pancreas transplant. For the next seven months the patient had signs and symptoms of right knee arthritis. Candida zeylanoides was finally identified as the aetiological agent. Treatment with intravenous amphotericin B was successful. To our knowledge this is the first report of Candida zeylanoides arthritis.


[Possibilities of detecting and differentiating central nervous effects of drugs in animal experiments with special consideration of behavioral-pharmacologic methods].
Animal experimental methods suitable for the assessment of actions of drugs of the central nervous system are described with special reference to behavioral actions. The value of those methods for the prediction of central nervous actions of drugs in man are discussed.


Nucleotide-sequence heterogeneity and sequence rearrangements in influenza virus cDNA.
Double-stranded cDNA has been synthesized from influenza virus RNA and cloned into derivatives of the bacteriophage M13 for sequence analysis. The characterization of over 200 clones has permitted an analysis both of nucleotide sequence heterogeneity and of clones containing unusual rearrangements of sequence. Heterogeneity, due to genetic variability in the RNA population and to in vitro synthetic errors, was detected at the low level of one nucleotide difference per 3 700 nucleotides. By contrast, gross sequence rearrangements were identified in eight clones. Inversions of sequence within the same cDNA molecule were the predominant type of rearrangement, and three mechanisms for producing such inversions are discussed. In addition, we observed rarer clones containing sequence from one RNA molecule joined to that from another molecule.


The structure of Cu(II) and Hg(II) complexes of bispyrenyl azine revisited.
Azine ligands show preference for the antiperiplanar conformation, but their 2:2 ligand-metal complexes can exhibit a central N4M2 core in the most stable chair arrangement, as in the case of the model lithium complex, with the ligand displaying a synclinal conformation that is not stable in the free ligand. According to DFT calculations, complexation of Cu2+ with bis(1-pyrenyl)azine (1) affords a C2-symmetric [1·Cu2+]2 species with a planar central N4Cu2 core exhibiting a weak cuprophilic interaction. The pendant pyrenyl substituents are brought close and parallel to each other, therefore accounting for the π-stacking that is responsible for excimer fluorescence. In case of Hg2+, complexation by the same ligand affords a C2-symmetric complex with an essentially linear N-Hg-C coordination environment at every metal center and without intermetallic interaction. T-Stacking interactions between pyrenyl groups explain the overall rigidity required for enhancement of fluorescence. Graphical abstract The structures of 2:2 complexes of Hg(II) and Cu(II) with bispyrenyl azine are reported.


The epidemiological profile of women with an interval cancer in the DOM screening programme.
Risk factors for breast cancer were compared in 107 women with interval breast cancer (cancers occurring within 2 years after a negative screen) and 258 women with breast cancer detected at 1st screening. All women (aged 40-67) were screened in the DOM project (the Utrecht programme for the early detection of breast cancer). Women with an interval cancer reported more often a history of benign breast disease (OR 4.66, 95% C.I. 2.08-10.41) and an artificial menopause (OR 4.07; 95% C.I. 1.74-9.55) than women with a screen detected cancer. Women with an interval cancer were taller than women with a screen detected cancer; this was seen most clearly in women with an artificial menopause (chi 2 for trend = 5.88; p = 0.02) and to a lesser extent in premenopausal women (chi 2 for trend = 1.70; p = 0.19). Premenopausal women with an interval cancer were heavier than women with a screen detected cancer (chi 2 for trend = 4.66; p = 0.03); whereas natural postmenopausal women with an interval cancer were leaner than women with a screen detected cancer (chi 2 for trend = 1.57; p = 0.21). All analyses were done while correcting for age and selected other risk factors for breast cancer. These results suggest that the epidemiological profile of pre- and post-menopausal women with an interval cancer differs from that of women with a screen detected cancer, which might imply a different natural history of these two types of breast tumours.


MR imaging of patients with localisation-related seizures: initial experience at 3.0T and relevance to the NICE guidelines.
The purpose of this study is to describe our initial experience of imaging adults with localisation-related epilepsy using MR imaging at 3.0T. We discuss the findings in the context of the recently released NICE guidelines that provide detailed advice on imaging people with epilepsy in the UK. 120 consecutive people over the age of 16 years with localisation-related epilepsy were referred for clinical MR examinations from a regional neuroscience centre in England. None of the people had had MR examinations prior to the present study. High resolution MR imaging was performed taking advantage of the high field strength and high performance gradients of the system. Two experienced neuroradiologists reported on the examinations independently and the presence and type of pathology was recorded. There was complete agreement between the two reporters in all 120 cases. The overall frequency of abnormalities shown by MR was 31/120 (26%) and the commonest abnormality shown was mesial temporal sclerosis found in 10/120 (8%). Tumours were shown in 4/120, all of which appeared low grade as judged by imaging criteria. Epilepsy is the commonest neurological condition and demands a significant resource in order to provide good care for sufferers. Recent guidelines published in the UK have suggested that the majority of people with epilepsy should receive brain MR as part of their routine assessment. Our work shows that using the most sophisticated MR imaging in a highly selected population there is a modest pick-up rate of brain abnormalities. If a widespread epilepsy-imaging programme is started the detection rate is likely to be much lower. Although MR is acknowledged to be a reliable way of detecting pathology in people with epilepsy there is a dearth of information studying the health economics of imaging epilepsy in relation to patient management and outcomes.


Formation of N-nitrosodimethylamine (NDMA) by ozonation of dyes and related compounds.
Formation of N-nitrosodimethylamine (NDMA) by ozonation of commercially available dyes and related compounds was investigated. Ozonation was conducted using a semi-batch type reactor, and ozone concentration in gas phase and the ozone gas flow were 10 mg L(-1) and 1.0 L min(-1), respectively. NDMA was formed by 15 min of ozonation of seven out of eight selected target compounds (0.05 mM) at pH 7. All the target compounds with N,N-dimethylamino functions were NDMA precursors in ozonation. The lowest and highest NDMA concentrations after ozonation of the target compounds were 13 ng L(-1) for N,N-dimethylformamide (DMF) and 1600 ng L(-1) for N,N-dimethyl-p-phenylenediamine (DMPD), respectively. NDMA concentrations after 15 min of ozonation of 0.05 mM methylene blue (MB) and DMPD increased with an increase in pH in its range of 6-8. The effects of coexisting compounds on NDMA concentrations after 15 min of ozonation of 0.05 mM MB and DMPD were examined at pH 7. NDMA concentrations after ozonation of MB and DMPD increased by the presence of 0.05 mM (0.7 mg L(-1) as N) nitrite (NO(2)(-)); 5000 ng L(-1) for MB and 4000 ng L(-1) for DMPD. NDMA concentration after MB ozonation decreased by the presence of 5mM tertiary butyl alcohol (TBA), a hydroxyl radical (HO.) scavenger, but that after DMPD ozonation was increased by the presence of TBA. NDMA concentrations after ozonation of MB and DMPD were not affected by the presence of 0.16 mM (5.3 mg L(-1)) hydrogen peroxide (H(2)O(2)). When 0.05 mM MB and DMPD were added to the Yodo and Tone river water samples, NDMA concentrations after 15 min of their ozonation at pH 7 increased compared with those in the case of addition to ultrapure water samples.


Validation of dynamic [18F]FE-PE2I PET for estimation of relative regional cerebral blood flow: a comparison with [15O]H2O PET.
Dopamine transporter (DAT) imaging is used in the diagnostic work-up in suspected parkinsonian syndromes and dementia with Lewy bodies but cannot differentiate between these syndromes, and an extra brain imaging examination of the regional cerebral blood flow (rCBF) or glucose metabolism is often needed for differential diagnosis. The requirement of two different imaging examinations is resource-consuming and inconvenient for the patients. Therefore, imaging of both cortical blood flow and DAT imaging with the same radiotracer would be more convenient and cost-effective. The aim of this study was to test whether relative regional cerebral blood flow (rCBFR) can be measured with the DAT-specific positron emission tomography (PET) tracer [18F]FE-PE2I (FE-PE2I), by validation with cerebral perfusion measured with [15O]H2O PET (H2O). The rCBFR was quantified by kinetic modeling for FE-PE2I (R1) and H2O (F). The R1 was calculated using the simplified reference tissue model, and F was calculated with a modified Koopman double-integration method. The linear relationship and intraclass correlation (ICC) between R1 and F were tested in image data derived from 29 patients with recent onset parkinsonism and 30 healthy controls. There was a strong linear correlation across all subjects between R1 and F in the frontal, parietal, temporal, cingulate and occipital cortex as well as in the striatum (r ≥ 0.731-0.905, p < 0.001) with a good-to-excellent ICC, ranging from 0.727 to 0.943 (p < 0.001). Our results suggest that FE-PE2I may be used as a proxy for cerebral perfusion, thus potentially serving as a radiotracer for assessment of both DAT availability and rCBFR in one single dynamic scan. This could be valuable in the differential diagnosis of parkinsonian syndromes. EUDRA-CT 2015-003045-26. Registered 23 October 2015 https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-003045-26.


The effect of cinnamaldehyde on the growth and the morphology of Candida albicans.
We examined the viability and morphology of Candida albicans under experimental conditions after treatment with varying concentrations of cinnamaldehyde, the major component of cassia (Cinnamomum cassia), using XTT assay, fluorescent microscopy, scanning electron microscopy, and thin-section electron microscopy. At 10 μg/ml level, cinnamaldehyde inhibited mycelial growth, but did not affect the growth of yeast cells, metabolic activity, cell shape, or the ultrastructure of the cells. At 40 μg/ml level, cinnamaldehyde showed fungicidal activity accompanied by alteration of the membrane and interior of Candida cells. These findings indicate that cinnamaldehyde has both fungistatic and fungicidal activities against C. albicans and affects the structure of the cells.


Understanding the Reshaping of Fluorinated Polyester Vitrimers by Kinetic and DFT Studies of the Transesterification Reaction.
Vitrimers are a third class of polymers gathering the mechanical properties and solvent resistance of 3D thermosets and the reprocessability of thermoplastics. This unique behaviour is due to the triggering of certain covalent exchange reactions that allow the network to rearrange upon application of a stimulus. The constitutive feature of vitrimers is the adoption of a glass-like viscosity during the rearrangement of the network, often due to an associative mechanism for the exchange reaction. Transesterification networks are one of the most studied type of vitrimers that usually require the incorporation of a catalyst, implying the associated drawbacks. Following up on a recent report on catalyst-free transesterification vitrimers in which the ester functions are particularly reactive thanks to the presence of fluorine atoms in α- or β-position, parallel DFT calculations and an experimental kinetic study on model molecules are presented in order to quantitatively assess the effect of neighbouring fluorinated groups on the transesterification reaction rate.


Modality-specific neural mechanisms of cognitive control in a Stroop-like task.
The successful resolution of ever-changing conflicting contexts requires efficient cognitive control. Previous studies have found similar neural patterns in conflict processing for different modalities using an event-related potential (ERP) approach and have concluded that cognitive control is supramodal. However, recent behavioral studies have found that conflict adaptation (a phenomenon with the reduction of congruency effect in the current trial after an incongruent trial as compared with a congruent trial) could not transfer across visual and auditory modalities and suggested that cognitive control is modality-specific, challenging the supramodal view. These discrepancies may have also arisen from methodological differences across studies. The current study examined the electroencephalographic profiles of a Stroop-like task to elucidate the modality-specific neural mechanisms of cognitive control. Participants were instructed to respond to a target always coming from the visual modality while disregarding the distractor coming from either the auditory or the visual modality. The results revealed significant congruency effects on both behavioral indices, i.e., reaction time and error rate, and ERP components, including the P3 and the conflict slow potential. Besides, the congruency effects on the amplitude of the P3 showed a negative correlation with reaction time, indicating an intrinsic link between these neural and behavioral indices. Furthermore, in the modality-repetition condition, conflict adaptation effects were significant on both reaction time and P3 amplitude, and the reaction time could be predicted by the P3 amplitude, while such effects were not observed in the modality-alternation condition. The time-frequency analysis also showed that conflict adaptation occurred in the modality-repetition condition, but not in the modality-alternation condition in low frequency bands, including the theta (4-8 Hz), alpha (8-12 Hz), and beta1 (12-20 Hz) bands. Taken together, our results revealed modality-specific patterns of the conflict adaptation effects on the P3 amplitude and oscillatory power (in theta, alpha, and beta1 bands), providing neural evidence for the modality specificity of cognitive control and expanding the boundaries of cognitive control.


Determination of volatile anesthetics isoflurane and enflurane in mouse brain tissues using gas chromatography-mass spectrometry.
A method for determination of the volatile anesthetics, isoflurane, and enflurane in mouse brain tissues using headspace gas chromatography-mass spectrometry (GC-MS) is described. Halothane was used as internal standard (I.S.). Brain samples were completely homogenized in ice-cold water and isoflurane, enflurane, and I.S. were extracted with headspace. One milliliter of headspace gas was injected onto the GC-MS and separation was achieved by using porous layer open tubular (PLOT) capillary column with a solid stationary phase (GSC). As a result, isoflurane, enflurane, and halothane were cleanly separated. The method demonstrated satisfactory recovery (72% and 76% for isoflurane and enflurane, respectively) and linear calibration ranges of 0.015-2.20 and 0.0152-3.94 microg/sample for isoflurane and enflurane, respectively. Reproducibility calculated as CV% was 3.3-3.9% for all intraday and interday determinations. The procedure was applied for quantitation of isoflurane and enflurane in about 300 mouse brain samples for genetic behavioral study. The method was achieved and shown to be effective.


Can acute abdominal CT prioritize patients with suspected diverticulitis for a subsequent clean colonic examination?
The aim of this study was to investigate whether patients with diverticulitis can be prioritized with higher urgency for a subsequent full colonic examination based upon the emergency abdominal CT scan performed at the time of presentation. All patients with a diagnosis of diverticulitis, hospitalized during 2006 and having a CT scan on admission and a subsequent 'clean colon' examination, were reviewed. The CT scan was reviewed by two independent and blinded senior radiologists (Radiologist A and Radiologist B) for signs inconsistent with diverticulitis and suggestive of malignancy. The patients were classified on the CT scan results into group 1 (normal findings, nontumour pathology or benign polyps < 1 cm) or group 2 (benign polyps ≥ 1 cm and cancer). Ninety-three patients (83 in group 1 and 10 in group 2) were reviewed. Radiologist A suggested high-priority colonic examination in 18% and 50% of patients in groups 1 and 2, respectively, and Radiologist B in 63% and 90% of patients, respectively. There was a statistically significant interobserver difference, and also lower accuracy of Radiologist B compared with Radiologist A in predicting a subsequent 'clean colon' examination. Use of an emergency acute CT scan at the time of diagnosis of diverticulitis to predict a clean colon examination for neoplasia is not reliable because there is a considerable degree of interobserver difference between radiologists.


Induction of natural killer cells and interferon during mouse hepatitis virus infection of resistant and susceptible inbred mouse strains.
Following infection by mouse hepatitis virus (JHM strain), an induction of natural killer (NK) cell activity was observed in C3H mice, which are considered to be sensitive to JHM virus infection. In contrast, mice of the resistant SJL strain did not show any increase of NK cell activity after JHM virus infection. However, infection of both SJL and C3H mice with mouse hepatitis virus type 3 (MHV3) resulted in an increase of NK level, comparable to that observed with the JHM virus infection in the C3H strain. No significant differences were observed in the NK cell activity of the peritoneal exudate or spleen cells of infected mice. Low levels of interferon were detected in serum or peritoneal exudate of C3H mice infected with JHM virus 18 or 24 hours before, but no detectable early interferon production was found. Also no interferon could be detected in the resistant SJL mice. After JHM virus infection, the number of peritoneal exudate cells (PEC) was increased significantly in C3H mice but not in SJL mice. Macrophages obtained from the C3H mice supported virus replication, whereas SJL macrophages did not. Our data suggest that NK cells do not play a role in the resistance of SJL mice against JHM virus infection but may participate in the defence mechanisms against this virus in C3H mice.


Basal ganglia: From the bench to the bed.
The basal ganglia (BG) encompass a set of archaic structures of the vertebrate brain that have evolved relatively little during the phylogenetic process. From an anatomic point of view, they are widely distributed throughout brain from the telencephalon to the mesencephalon. The fact that they have been preserved through evolution suggests that they may play a critical role in behavioral monitoring. Indeed, a line of evidence suggests that they are involved in the building of behavioral routines and habits that drive most of our activities in everyday life. In this article, we first examine the organization and physiology of the basal ganglia to explain their function in the control of behavior. Then, we show how disruption of the putamen, and to a lesser extent of the cerebellum, might lead to various dystonic syndromes that frequently arise during childhood.


Determination of doxycycline in chicken fat by liquid chromatography with UV detection and liquid chromatography-tandem mass spectrometry.
A sensitive analytical method for determination of doxycycline (DC) residues in chicken fat/fat and skin was developed. The extraction, in the presence of the internal standard (IS) minocycline (MINO), was carried out using solution of oxalic acid (pH 4.0) and ethyl acetate. The samples were cleaned up by solid phase extraction (SPE) procedure using, at first carboxylic acid and then polymeric Strata X cartridges. Chromatographic separation of DC by LC-UV was achieved on a Luna C8 analytical column and for LC-MS/MS analysis Luna C18 column was used. The presented procedures were evaluated according to the Commission Decision 2002/657/EC. Specificity, decision limit (CCα), detection capacity (CCβ), recovery (absolute and relative), precision (repeatability and reproducibility) were determined during validation process. The limit of detection (LOD) was 10μg/kg for LC-UV and 1μg/kg for LC-MS/MS method. The limit of quantitation (LOQ) was 15 and 2μg/kg for LC-UV and LC-MS/MS, respectively. The absolute recovery for the LC-UV and relative recovery for the LC-MS/MS method at 300μg/kg concentration level were 79%; 101% for fat and 82%; 99% for fat and skin, respectively. The developed liquid chromatography with ultraviolet detection (LC-UV) and liquid chromatography tandem mass spectrometry (LC-MS/MS) methods have been applied to quantitative determination of doxycycline (DC) in samples of chicken fat tissue obtained from animals treated with DC.


A multi-wavelength, laser-based optical spectroscopy device for breast density and breast cancer risk pre-screening.
Optical Breast Spectroscopy (OBS) has been shown to predict mammographic breast density, a strong breast cancer risk factor. OBS is a low-cost technique applicable at any age. OBS information may be useful for personalizing breast cancer screening programs based on risk to improve consensus on and adherence to screening guidelines. To facilitate the use of OBS in population-wide studies, a research prototype OBS device was modified to make it portable and cheaper and to require less operator interaction. Two major changes were made: (1) the broadband light source was replaced with a laser module with 13 individual wavelengths turned on sequentially, enabling the use of photodiode detectors instead of a spectrometer, and (2) the light sources and detectors were placed in fixed positions within 4 sizes of cup, eliminating the need for placement by the operator. Wavelengths were selected using data from two previous studies. The reduction in spectral content did not significantly reduce the ability to distinguish between different risk groups. Positions for the light sources and detectors were chosen based on Monte Carlo simulations to match the optically interrogated volumes of the original device. Two light sources and six detectors per cup were used in the final design.


A Pilot Study Examining the Use of Ultrasound to Measure Intravascular Volume Status in Agricultural Workers in a Field-Based Research Setting.
The aim of this pilot study was to explore if internal jugular vein (IJV) ultrasound studies on agricultural workers in a field-based research setting could assess volume status during a hydration intervention. We performed pre- and post-work shift IJV ultrasound images on 30 agricultural workers. The IJV collapsibility index values were <39% (euvolemic) or ≥39% (hypovolemic). Of the water group, 13% (2/15) had an IJV collapsibility index ≥39%, and this increased to 19% (3/16) by the end of the work shifts. The electrolyte group did not have any workers start the work shift with an IJV collapsibility index ≥39%; however, at the postshift assessment, 15% (2/13) were hypovolemic. Internal jugular vein ultrasounds may have the potential to be a useful tool to determine volume status in field-based research settings. Further investigation is needed to confirm these findings.


Valorizing cabbage (Brassica oleracea L. var. capitata) and capsicum (Capsicum annuum L.) wastes: in vitro health-promoting activities.
The capsicum seed core and cabbage outer leaves are common wastes generated in the vegetable processing industry. We explored the in vitro health-promoting activity of these waste products for valorization. Freeze-dried and pulverized cabbage wastes had a high bile acid binding capacity and the capsicum wastes inhibited glucose dialysis more effectively. Methanolic extracts prepared with conventional solvent extraction and ultrasound-assisted extraction were analyzed to determine their 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity, in vitro α-amylase inhibitory, in vitro lipase inhibitory, and prebiotic activity. Crude extracts of cabbage and capsicum wastes were screened using GC-MS analysis. The cabbage waste extracts showed high antioxidant activities but did not inhibit α-amylase. The capsicum waste extracts inhibited both lipase and α-amylase activities and supported the growth of the probiotic bacterium, Lactobacilli brevis. Volatile compounds of the vegetables consisted mainly of phenols and fatty acid esters. In all assays except the α-amylase inhibition assay, the extracts prepared with ultrasound-assisted solvent extraction showed higher activity than those prepared using the conventional method. The capsicum seed core and cabbage outer leaves are potential sources of phytochemicals and antioxidant fibers. Capsicum waste extract supported probiotic bacterial growth without a lag phase. These waste products may be processed into high-value functional ingredients.


Cell size regulation by the human TSC tumor suppressor proteins depends on PI3K and FKBP38.
TSC1 and TSC2 are responsible for the tumor suppressor gene syndrome tuberous sclerosis (TSC). Mammalian TSC genes have been shown to be involved in cell cycle regulation. Recently, in Drosophila, these data have been confirmed and TSC genes have further been demonstrated to affect cell size control. Here we provide supporting data for the fact that the latter function is conserved in mammals. Human TSC1 and TSC2 trigger mammalian cell size reduction and a dominant-negative TSC2 mutant induces increased size. These effects occur in all cell cycle phases, are dependent on the activity of the phosphoinositide-3-kinase and are abolished by co-overexpression of a dominant-negative Akt mutant. Two independent naturally occurring and disease-causing mutations within the TSC2 gene eliminate tuberin's capacity to affect cell size control, emphasizing the relevance of this function for the development of the disease. The same mutations have earlier been shown not to affect tuberin's antiproliferative capacity. That the consequences of modulated TSC gene expression on cell proliferation and on cell size can be assigned to separable functions is further supported by two findings: A mutation within the TSC1 gene, earlier shown to still harbor anti-proliferative effects, was found to eliminate the cell size regulating functions. An important mammalian cell size regulator, c-Myc, was found to inhibit tuberin's antiproliferative capacity, but to have no effects on tuberin-dependent cell size control. To obtain further mechanistical insights, microarray screens for genes involved in TSC1- or TSC2-mediated cell size effects were performed. Antisense experiments revealed that the so observed regulation of the FK506-binding protein, FKBP38, plays a role in TSC gene-dependent cell size regulation. These data provide new insights into mammalian cell size regulation and allow a better understanding of the function of human TSC genes.


Network Meta-analysis of Surgical Aortic Valve Replacement and Different Transcatheter Heart Valve Systems for Symptomatic Severe Aortic Stenosis.
Although different transcatheter heart valve (THV) systems have been introduced to overcome transcatheter aortic valve replacement (TAVR)-specific complications, head-to-head comparisons of these THV systems are scarce. The aim of this study was to compare different THV systems and surgical aortic valve replacement (SAVR) by conducting a network meta-analysis. PubMed and EMBASE were searched through November 2019 for studies comparing safety and efficacy of balloon-expandable valve (BEV), self-expanding valve (SEV), mechanically expandable valve (MEV), and SAVR for symptomatic severe aortic stenosis. End points in the short term at 30 days or discharge and the long term up to 2 years were assessed. We identified 11 randomized controlled trials with a total of 10,300 patients eligible for inclusion in our study. There were no significant differences in all-cause death among different THV systems and SAVR in both short and long terms. Disabling stroke was significantly lower with MEV vs BEV and SAVR (hazard ratios [HRs] 0.31 [95% confidence interval [CI] 0.12-0.77] and 0.33 [95% CI 0.14-0.76], respectively) in the long term. MEV was associated with an increased risk of new permanent pacemaker implantation compared with BEV, SEV, and SAVR (HRs 3.82 [95% CI 1.83-7.97], 1.85 [95% CI 1.02-3.36], and 5.23 [95% CI 2.61-10.47], respectively) in the long term. In patients with symptomatic severe aortic stenosis undergoing intervention, there were no significant differences in all-cause death among different THV systems and SAVR. MEV had low frequency of disabling stroke compared with BEV and SAVR, but an increased frequency of permanent pacemaker implantation compared with other interventions.


The progression rate of spinocerebellar ataxia type 3 varies with disease stage.
In polyglutamine (polyQ) diseases, the identification of modifiers and the construction of prediction model for progression facilitate genetic counseling, clinical management and therapeutic interventions. Data were derived from the longest longitudinal study, with 642 examinations by International Cooperative Ataxia Rating Scale (ICARS) from 82 SCA3 participants. Using different time scales of disease duration, we performed multiple different linear, quadratic and piece-wise linear growth models to fit the relationship between ICARS scores and duration. Models comparison was employed to determine the best-fitting model according to goodness-of-fit tests, and the analysis of variance among nested models. An acceleration was detected after 13 years of duration: ICARS scores progressed 2.445 (SE: 0.185) points/year before and 3.547 (SE: 0.312) points/year after this deadline. Piece-wise growth model fitted better to studied data than other two types of models. The length of expanded CAG repeat (CAGexp) in ATXN3 gene significantly influenced progression. Age at onset of gait ataxia (AOga), a proxy for aging process, was not an independent modifier but affected the correlation between CAGexp and progression. Additionally, gender had no significant effect on progression rate of ICARS. The piece-wise growth models were determined as the predictive models, and ICARS predictions from related models were available. We first confirmed that ICARS progressed as a nonlinear pattern and varied according to different stages in SCA3. In addition to ATXN3 CAGexp, AOga or aging process regulated the progression by interacting with CAGexp.


[Development of epidemiologic studies of multiple sclerosis].
The description of temporal trends of average, annual age-adjusted or crude multiple sclerosis mortality rates in Europe (1921-1984) was presented. The significance of long-run epidemiological surveys was discussed in the paper.


Development of high performance liquid chromatography methods with charged aerosol detection for the determination of lincomycin, spectinomycin and its impurities in pharmaceutical products.
Novel and simple liquid chromatography methods with charged aerosol detection (LC-CAD) for simultaneous quantitation of lincomycin and spectinomycin and its related substances have been developed and tested. This type of analysis is complicated due to the different chromatographic behavior of these two agents and the lack of chromophores in spectinomycin complex. CAD seems to be a promising alternative to overcome these difficulties. It shows a consistent inter-analyte response, independent of chemical structure of an analyte. It also enables the direct quantification of related substances for which no reference standards were available, with good accuracy and precision. Chromatographic separations were achieved using a C18 Hypersil(®) Gold column, with mobile phases consisting of water, acetonitrile and trifluoroacetic acid. All impurities were identified using time-of-flight mass spectrometry with electrospray ionization. The developed methods have been successfully used in the routine quality control analysis of pharmaceutical preparations.


Efficacy of intravitreal ceftazidime in acute postoperative endophthalmitis.
To assess the efficacy of intravitreal ceftazidime in acute postoperative endophthalmitis. Quasi experimental study. Department of Ophthalmology Unit I, Eye Hospital, Liaquat University of Medical and Health Sciences, Hyderabad, from November 2004 to November 2006. Twenty-one eyes of 21 patients of acute postoperative endophthalmitis were treated with intravitreal antibiotic ceftazidime. The inclusion criteria of the patients was the clinical diagnosis of acute postoperative endophthalmitis within 15 days of postoperative period with visual acuity better than or equal to hand movement close to face. After enrollment, vitreous tap was carried out in all cases followed by intravitreal ceftazidime injection. The outcome was measured in terms of clinical resolution of endophthalmitis and postresolution best corrected visual acuity. Mean of difference was tested by paired t-test. Nineteen eyes (90.5%) responded to intravitreal ceftazidime therapy alone, while an additional pars plana vitrectomy was required in one eye. Sixteen eyes (84%) retained a visual acuity of 6/60 or better at 3 months after the initiation of the therapy (p<0.001). Retinal detachment developed in one eye receiving intravitreal therapy. Ceftazidime was effective as intravitreal therapy for the management of acute postoperative endophthalmitis.


Contemporary Pharmacotherapy for Allergic Rhinitis and Chronic Rhinosinusitis.
Chronic rhinosinusitis (CRS) and allergic rhinitis (AR) are chronic conditions causing nasal inflammation. CRS is increasingly recognized as a chronic inflammatory process rather than a chronic infection. Although the primary initiating factors in CRS remain unclear, AR is driven by IgE-mediated hypersensitivity to environmental allergens. Understanding the underlying inflammatory pathways and disease endotypes are driving innovation toward novel pharmacotherapies targeting critical mediators implicated in CRS and AR, including IL-4, IL-13, IL-5, IgE, and epithelial initiators IL-33 and TSLP. Extensive investigations are needed to determine the role, timing, predictive prognostic factors and long-term safety and efficacy of these agents.


Effect of atrial fibrillation on mortality in SARS-CoV-2 patients: A propensity score-matched analysis of nationwide hospitalizations in the United States.
Atrial fibrillation (AF) is one of the most common arrhythmias encountered in patients with SARS-CoV-2 infection. There are racial disparities in the incidence of AF and COVID-19. Several studies have reported an association between AF and mortality. However, it remains to be determined if AF represents an independent risk factor for COVID-19-related mortality. A propensity score-matched (PSM) analysis was performed using data from the National Inpatient Sample to assess the risk of mortality among patients hospitalized with SARS-CoV-2 infection and incident AF from March 2020 through December 2020. AF was less common among patients who tested positive for SARS-CoV-2 as compared to those who tested negative (6.8% vs 7.4%, p < 0.001). White individuals with the virus had an increased incidence of AF but had lower mortality rates relative to Black and Hispanic patients. After PSM analysis, AF retained a significantly increased odds of mortality among patients with SARS-CoV-2 (OR: 1.35, CI: 1.29-1.41, p < 0.001). This PSM analysis shows that AF is an independent risk factor for inpatient mortality in those with SARS-CoV-2 infection and that White patients, while having a higher burden of SARS-CoV-2 and AF, demonstrate a significantly lower mortality rate as compared to their Black and Hispanic counterparts.


Clinical implication of radiologic complete remission on Crohn's Disease: Compared with endoscopic remission.
To determine the clinical implications of radiologic complete remission (CR) in Crohn's disease (CD) evaluated by computed tomography (CT) or magnetic resonance enterography (MRE) in comparison with endoscopic CR. Twenty-five CD patients who achieved endoscopic CR after medical treatment were retrospectively enrolled in this study. All patients underwent ileocolonoscopy, CT, or MRE at baseline, at the time of endoscopic CR, and during follow-up. Two radiologists assessed the mural and perienteric abnormalities on pre- and post-treatment CT or MRE in consensus. Patients were divided into radiologic CR and non-CR groups at the time of endoscopic CR. CD recurrence during subsequent follow-up periods was evaluated using clinical, laboratory, and CT/MRI findings. Statistical analysis was performed to assess whether there were significant differences in patient outcomes between the groups. At the time of endoscopic CR, nine patients (mean age, 36.6 years) showed normalization of all radiologic features and were designated as the radiologic CR group. However, 16 patients (mean age: 32.9 years) showed residual CT/MRE abnormalities, suggesting persistent active inflammation, and were designated as the radiologic non-CR group. During follow-up, there was a significant difference between the groups regarding clinical outcomes (deep CR, 8/9 vs 5/16, P = 0.011; CD recurrence, 1/9 vs 14/16, P < 0.001). The mean fecal calprotectin level was significantly lower in the radiologic CR group (287.5 ug/g) than in the non-CR group (652.4 ug/g) (P = 0.023). Radiologic CR can represent a better therapeutic endpoint in CD, showing superiority over endoscopic CR in predicting both clinical and biochemical outcomes.


Low-valent tungsten redox catalysis enables controlled isomerization and carbonylative functionalization of alkenes.
The controlled isomerization and functionalization of alkenes is a cornerstone achievement in organometallic catalysis that is now widely used throughout industry. In particular, the addition of CO and H2 to an alkene, also known as the oxo-process, is used in the production of linear aldehydes from crude alkene feedstocks. In these catalytic reactions, isomerization is governed by thermodynamics, giving rise to functionalization at the most stable alkylmetal species. Despite the ubiquitous industrial applications of tandem alkene isomerization/functionalization reactions, selective functionalization at internal positions has remained largely unexplored. Here we report that the simple W(0) precatalyst W(CO)6 catalyses the isomerization of alkenes to unactivated internal positions and subsequent hydrocarbonylation with CO. The six- to seven-coordinate geometry changes that are characteristic of the W(0)/W(II) redox cycle and the conformationally flexible directing group are key factors in allowing isomerization to take place over multiple positions and stop at a defined unactivated internal site that is primed for in situ functionalization.


Laboratory service relocation: experience and lessons learned from relocating a biosafety level-3 clinical mycobacteriology service to a new facility.
We recount our experiences of relocating an active mycobacteriology reference level service in Karachi, Pakistan, from an older accredited biosafety level-3 facility to a newly constructed and environmentally validated facility. The service relocation planning, execution, and verification stages are described in detail. Lessons learned from our experience include establishing a service transfer plan, including relevant service staff, obtaining their buy-in on the plan, arranging backup service facilities or liaisons for the execution phase, and ensuring viable backup arrangements for troubleshooting during the verification phase of services in the new facility. Careful planning and inclusion of all stakeholders are critical to avoid service interruptions. This narrative is expected to support other laboratorians, scientists, and clinicians providing laboratory services to large population sectors who are looking to move their services to a new location while continuing to offer said services in a proficient and reliable manner.


Pediatric unilateral below-elbow amputees: retrospective analysis of 34 patients given multiple prosthetic options.
Thirty-four unilateral below-elbow amputees from the Shriners Hospitals for Children/Twin Cities were retrospectively analyzed in long-term follow-up. All of these patients were provided with a variety of prosthetic options, including a "passive" cosmetic upper extremity device. Most of the patients were also fitted with conventional prostheses using a body-powered voluntary closing terminal device (97%) as well as myoelectric prostheses (82%). These patients were considered consistent prosthetic users by the clinic team. The average follow-up was 14 years, with many of the patients being followed up throughout their entire childhood. All patients were sent questionnaires, and the authors carried out patient interviews and chart review. Final analysis indicated that 15 patients (44%) selected a simple cosmetic "passive hand" as their prosthesis of choice. In long-term follow-up 14 patients (41%) continued as multiple users. Fourteen patients (41%) selected the conventional prosthesis using a voluntary closing terminal device as the prosthesis of choice. Only five patients (15%) selected the myoelectric device as their primary prosthesis. The authors conclude that successful unilateral pediatric amputees may choose multiple prostheses on the basis of function and that frequently the most functional prosthesis selected in the long term is the simplest in design. The authors believe strongly that unilateral pediatric amputees should be offered a variety of prosthetic options to help with normal activities of daily living.


A nomogram for predicting invasiveness of lung adenocarcinoma manifesting as pure ground-glass nodules: incorporating subjective CT signs and histogram parameters based on artificial intelligence.
To construct a nomogram based on subjective CT signs and artificial intelligence (AI) histogram parameters to identify invasiveness of lung adenocarcinoma presenting as pure ground-glass nodules (pGGNs) and to evaluate its diagnostic performance. 187 patients with 228 pGGNs confirmed by postoperative pathology were collected retrospectively and divided into pre-invasive group [atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS)] and invasive group [minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC)]. All pGGNs were randomly assigned to training cohort (n = 160) and validation cohort (n = 68). Nomogram was developed using subjective CT signs and AI-based histogram parameters by logistic regression analysis. The diagnostic performance was evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) curve. The nomogram was constructed with nodule shape, 3D mean diameter, maximum CT value, and skewness. It showed better discriminative power in differentiating invasive lesions from pre-invasive lesions with area under curve (AUC) of 0.849 (95% CI 0.790-0.909) in the training cohort and 0.831 (95% CI 0.729-0.934) in the validation cohort, which performed better than nodule shape (AUC 0.675, 95% CI 0.609-0.741), 3D mean diameter (AUC 0.762, 95% CI 0.688-0.835), maximum CT value (AUC 0.794, 95% CI 0.727-0.862), or skewness (AUC 0.594, 95% CI 0.506-0.682) alone in training cohort (for all, P < 0.05). For pulmonary pGGNs, the nomogram based on subjective CT signs and AI histogram parameters had a good predictive ability to discriminate invasive lung adenocarcinoma from pre-invasive lung adenocarcinoma, and it has the potential to improve diagnostic efficiency and to help the patient management.


Twin study of genetic and environmental influences on glucose tolerance and indices of insulin sensitivity and secretion.
Family and twin studies have reported different estimates of the relative contribution of genetic and environmental factors to the quantitative traits glucose tolerance, insulin secretion, and insulin sensitivity. Our aims were to estimate these relative influences in a large sample of twins from the population and to assess the effect of age. In this population-based, cross-sectional study we gave an oral glucose tolerance test to 317 women and 290 men who were same-sex healthy twin pairs between 18 to 67 years of age. The genetic, common environmental and individual environmental variance components for fasting and 120-min glucose and for fasting and 30-min insulin as well as the linear effects of age on these components were estimated by multivariate analysis (using the software FISHER). In women and men the heritability for fasting glucose was 12 and 38%, for 120-min glucose it was 38 and 43%, for fasting insulin it was 54 and 37%, and for 30-min insulin it was 57 and 47%, respectively. Under the assumption of no non-additive genetic effects (no intra- or inter-gene interaction) there was no strong evidence for common environmental effects, barring significant effects for fasting glucose in women. Heritability decreased with age for 120-min glucose in women and fasting insulin in men, whereas it increased for 120-min glucose in men. This study indicates a limited additive genetic influence on the result of an OGTT, possibly with sex-specific age effects, and generally little or no influence of the common environment. Accordingly, there is a considerable individual environmental variation.


A Retrospective Biopharmaceutical Analysis of >800 Approved Oral Drug Products: Are Drug Properties of Solid Dispersions and Lipid-Based Formulations Distinctive?
Increasing numbers of poorly water soluble drugs in development has intensified need for bio-enabling formulations including Lipid-Based Formulations (LBF) and Solid Dispersions (SD). Resultantly, a data-driven approach is required to increase formulation development efficiency. This review provides a retrospective analysis of molecular and biopharmaceutical properties of drugs commercialised as LBFs or SDs. A comprehensive stepwise statistical analysis of LBF and SD drug properties was conducted and compared to drugs not commercialised via either technology (Others), aiming to identify key predictors of successful formulation development. This review demonstrates LBF and SD drugs differ significantly in molecular weight, polar surface area, rotatable bonds and hydrogen bond acceptor count. Meanwhile, LBF and SD drugs display significantly different aqueous solubility, lipophilicity, size, molecular flexibility, hydrogen bonding capacity and rule-of-5 violations versus Others. LBF and SDs were 3 and 5 times more likely to display >1 rule-of-5 violation versus Others, over 55% of LBF drugs exceeded the reported melting point guide of <150 °C, while 24% of SD drugs contained >10 Hydrogen Bond Acceptors. Overall, by focusing on successfully commercialised drugs, this review provides improved understanding of links between drug properties and successful SD/LBF approaches, providing a framework for guiding pharmaceutical development on formulation approaches.


Data-driven adaptive GM(1,1) time series prediction model for thermal comfort.
In this paper, the future prediction of predicted mean vote (PMV) index of indoor environment is studied. PMV is the evaluation index used in this paper to represent the thermal comfort of human body. According to the literature, the main environmental factors affecting PMV index are temperature, humidity, black globe temperature, wind speed, average radiation temperature, and clothing surface temperature, and there is a complex nonlinear relationship between the six variables. Due to the coupling relationship between the six parameters, the PMV formula can be simplified under specific conditions, reducing the monitoring of variables that are difficult to observe. Then, the improved grey system prediction model GM(1,1) with optimized selection dimension is used to predict the future time of PMV. Due to the irregularity, uncertainty and fluctuation of PMV values in time series, based on the original GM(1,1) time series prediction, an adaptive GM(1,1) improved model is proposed, which can continuously change with time series and enhance its prediction accuracy. By contrast, the improved GM(1,1) model can be derived from the sliding window of the adaptive model through changes in the dataset and get better model grades. It lays a foundation for the future research on the predicted index of PMV, so as to set and control the air conditioning system in advance, to meet the intelligence of modern intelligent home and humanized function of sensing human comfort.


Does hybrid fixation prevent junctional disease after posterior fusion for degenerative lumbar disorders? A minimum 5-year follow-up study.
Medium- to long-term retrospective evaluation of clinical and radiographic outcome in the treatment of degenerative lumbar diseases with hybrid posterior fixation. Thirty patients were included with the mean age of 47.8 years (range 35 to 60 years). All patients underwent posterior lumbar instrumentation using hybrid fixation for lumbar stenosis with instability (13 cases), degenerative spondylolisthesis Meyerding grade I (6 cases), degenerative disc disease of one or more adjacent levels in six cases and mild lumbar degenerative scoliosis in five patients. Clinical outcomes were evaluated using Oswestry disability index (ODI), Roland and Morris disability questionnaire (RMDQ), and the visual analog scale (VAS) pain scores. All patients were assessed by preoperative, postoperative and follow-up standing plain radiographs and lateral X-rays with flexion and extension. Adjacent disc degeneration was also evaluated by magnetic resonance imaging (MRI) at follow-up. At a mean follow-up of 6.1 years, we observed on X-rays and/or MRI 3 cases of adjacent segment disease (10.0 %): two of them (6.6 %) presented symptoms and recurred a new surgery. The last patient (3.3 %) developed asymptomatic retrolisthesis of L3 not requiring revision surgery. The mean preoperative ODI score was 67.6, RMDQ score was 15.1, VAS back pain score was 9.5, and VAS leg pain score was 8.6. Postoperatively, these values improved to 28.1, 5.4, 3.1, and 2.9, respectively, and remained substantially unchanged at the final follow-up: (27.7, 5.2, 2.9, and 2.7, respectively). After 5-year follow-up, hybrid posterior lumbar fixation presented satisfying clinical outcomes in the treatment of degenerative disease.


Prognostic utility of the chest computed tomography severity score for the requirement of mechanical ventilation and mortality in hospitalized patients with COVID-19.
To correlate the chest computed tomography severity score (CT-SS) with the need for mechanical ventilation and mortality in hospitalized patients with COVID-19. The chest CT images of 224 inpatients with COVID-19, confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR), were retrospectively reviewed from April 1 to 25, 2020, in a tertiary health care center. We calculated the CT-SS (dividing each lung into 20 segments and assigning scores of 0, 1, and 2 due to opacification involving 0%, <50%, and ≥50% of each region for a global range of 0-40 points, including both lungs), and collected clinical data. The receiver operating characteristic curve and Youden Index analysis was performed to calculate the CT-SS threshold and accuracy for classification for risk of mortality or MV requirement. 136 men and 88 women were recruited, with an age range of 23-91 years and a mean of 50.17 years; 79 met the MV criteria, and 53 were nonsurvivors. The optimal threshold was >27.5 points for mortality (area under ROC curve >0.96), with a sensitivity of 93% and specificity of 87%, and >25.5 points for the need for MV (area under ROC curve >0.94), with a sensitivity of 90% and specificity of 89%. The Kaplan-Meier curves show a significant difference in mortality by the CT-SS threshold (Log Rank p < 0.001). In our cohort of hospitalized patients with COVID-19, the CT-SS accurately discriminates the need for MV and mortality risk. In conjunction with clinical status and laboratory data, the CT-SS may be a useful imaging tool that could be included in establishing a prognosis for this population.


Determinants of Cerebral Palsy in Pediatric Patients in Northern Ethiopia: A Hospital-Based Study.
Cerebral palsy is the most common neurologic disorder of childhood with lifelong implications in majority of patients. Knowledge of the determinants of cerebral palsy is important for accurate mobilization of resources in obstetric, perinatal, and infant care besides implementation of prevention systems. In Ethiopia, however, this knowledge gap exists as there are no published studies on determinants of cerebral palsy in the country. To assess the determinants of cerebral palsy in pediatric patients attending Ayder Comprehensive Specialized Referral Hospital between April 2019 and August 2019. An unmatched case-control study was conducted among 50 pediatric cerebral palsy patients and 100 controls, pediatric patients without cerebral palsy or other motor or central nervous system illnesses, attending Ayder Comprehensive Specialized Hospital, Mekelle, Ethiopia. The data were analyzed using SPSS version 27. Significant factors were operative vaginal delivery (AOR: 9.49, 95% CI: 1.31-68.88), central nervous system infections (AOR: 0.02, 95% CI: 0-0.58), neonatal admissions (AOR: 0.13, 95% CI: 0.03-0.61), and unknown maternal education status (AOR: 18.64, 95% CI: 2.15-161.73). Operative vaginal delivery, central nervous system infections in infancy, neonatal hospital admissions, and unknown maternal education status were found to be significant determinants for cerebral palsy. This knowledge aids focused hospital and regional health bureau development and implementation of prevention strategies for cerebral palsy, besides improvement of obstetric and neonatal healthcare services, and provides baseline data to the scientific community for further research.


Metabolism of prostaglandins E, A, and C in serum.
Three prostaglandin-metabolizing enzymes were detected in human serum. One enzyme was a dehydrase that converted prostaglandin E to prostaglandin A, the second was a prostaglandin A isomerase that converted prostaglandin A to prostaglandin C and the third was a prostaglandin C isomerase that converted prostaglandin C to prostaglandin B. All three were inactivated by sulfhydryl blocking agents. In human serum, only prostaglandin C isomerase had high activity, whereas the two other enzymes had very low activity. In rabbit serum both isomerases were very active, but dehydrase activity could not be detected. Prostaglandin C isomerase activity was also found in crystallized human serum albumin and rabbit serum albumin.


Rederived values of the eight coefficients of the Crohn's Disease Activity Index (CDAI).
A previous paper reported derivation of the Crohn's Disease Activity Index (CDAI) from data on 112 patients. We have now rederived the values of the eight coefficients of the CDAI using data from 1058 visits of patients enrolled in the National Cooperative Crohn's Disease Study and the Trial of Adjunctive Sulfasalazine in Crohn's Disease. The rederived coefficients are similar to the original ones. New and original index values calculated on the same data from patient visits correlated very highly. Because there is so little difference between the original and the rederived versions, continued use of the original version is suggested in order to maintain comparability of new studies employing this tool with those previously accomplished.


Influence of indomethacin amphoteric gel on gastric ulcerogenicity and absorption of indomethacin in rats.
Indomethacin is a potent and efficacious antiinflammatory agent. However, a limiting side effect is its ability to cause gastric ulceration. This study was designed to investigate the effects of an amphoteric gel on the gastric ulcerogenicity and pharmacokinetics of indomethacin. Oral administration (5 mg/kg) in a suspension and a gel formulation were compared to an intravenous (iv) formulation of indomethacin in rats. The iv formulation administered to rats produced large severe ulcers in some rats but not in others. In contrast, the oral suspension produced small ulcers in all rats. The difference in toxicities is attributed to a centrally mediated action as a result of high plasma levels of indomethacin following iv administration, compared to locally mediated action with the suspension, resulting from local high concentrations of indomethacin on the apical epithelial surface because of the presence of indomethacin crystals. Oral administration of the gel formulation did not result in any gastric ulceration and improved the bioavailability of indomethacin to 115.5%, compared with 68.2% for the suspension. The reduced gastrointestinal toxicity of indomethacin in the gel was attributed to the gel's ability to dissolve indomethacin, preventing the localized high concentration observed with the suspension and possibly providing a gastric protectant phospholipid. The gel formulation doubled the oral bioavailability and the tmax of indomethacin compared to the suspension but did not affect the half-life. The results indicate that the local irritant effect of indomethacin, in rats, can be reduced by appropriate formulation design and suggest that the ulcerogenicity index for indomethacin can be improved by the use of an amphoteric gel formulation.


Nanocomposite membrane and microbial community analysis for improved performance in microbial fuel cell.
To improve the performance of a microbial fuel cell (MFC), four variations of sulphonated silicon dioxide (S-SiO2) was incorporated into sulphonated poly ether ether ketone (SPEEK) membranes. S-SiO2 was characterized by scanning electron microscopy (SEM), fourier transform infra-red spectroscopy (FTIR) and X-ray diffraction (XRD) to confirm morphological, physical and chemical characteristics. The prepared membranes were incorporated into a fabricated tubular MFC of 300 mL holding capacity. Membrane characterizations such as water uptake, ion exchange capacity (IEC) and proton conductivity were determined. The highest maximum output of 154 ± 1.5 mW m-2 is produced by SPEEK +7.5 wt% S-SiO2 with an IEC of 1.82 ± 0.08 meq g-1 and an oxygen mass transfer coefficient of 1.42 × 10-6 cm s-1. Microbial community studies show the prevalence of novel microbial strains with the predominance of 3 distinct phyla, namely Betaproteobacteria, Gammaproteobacteria and Firmicutes. The results suggest that the prepared nanocomposite membrane proves to be an efficient and sustainable alternative for improving the performance of a MFC without abating the essential membrane characteristics.


Choosing the Right Therapy at the Right Time for Pediatric Inflammatory Bowel Disease: Does Sequence Matter.
Despite the enlarging therapeutic armamentarium, IBD is still plagued by a therapeutic ceiling. Precision medicine, with the selection of the "rights," may present a solution, and this review will discuss the critical process of pairing the right patient with right therapy at the right time. Firstly, the review will discuss the shift to and evidence behind early effective therapy. Then, it delves into promising future strategies of patient profiling to identify a patients' biological pathway(s) and prognosis. Finally, the review lays out practical considerations that drive treatment selection, particularly the impact of the therapeutic sequence.


Pancreatic steatosis: A frequent finding in a Chilean population.
Pancreatic steatosis is an incidental radiologic finding in asymptomatic patients, and its clinical importance is unclear. to study the prevalence of pancreatic steatosis (PS) in consecutive patients registered at our hospital, that underwent computed axial tomography (CAT) scanning of the abdomen and pelvis, excluding known pancreatic diseases. Secondary aim: to review the association of PS with the demographic and clinical data of the patients, as well as with hepatic steatosis (HS). An observational study was conducted on adult patients that had CAT scans of the abdomen and pelvis. a) tissue density was measured in Hounsfield units (HU) in five 1 cm2 areas of the pancreas, three areas of the spleen, and in segments VI and VII of the liver; b) fatty pancreas: a difference < -10 HU between the mean pancreas and mean spleen densities; and c) fatty liver: density < 40 HU. We registered the epidemiologic and laboratory data of the patients. The association of those factors with the presence of PS was analyzed using SPSS version 24.0 software, and statistical significance was set at a p < 0.05. Of the 203 patients, PS was found in 61 (30%). The patients with PS were significantly older and had a higher body mass index. We found no significant association with the rest of the parameters studied, nor with HS (55 patients). None of the patients had symptoms attributable to a disease of the exocrine pancreas. Fatty infiltration of the pancreas is a frequent finding in CAT scans, and its clinical importance is unclear. Aging of the population and the increase in obesity underline the need for future studies on PS.


Antibiotic administration within 1 hour for open lower extremity fractures is not associated with decreased risk of infection.
Open fractures have a high risk of infection with limited data correlating timing of prophylactic antibiotic administration and rate of subsequent infection. The Trauma Quality Improvement Program has established a standard of antibiotic administration within 1 hour of arrival, but there is a lack of adequately powered studies validating this quality metric. We hypothesize that open femur and/or tibia fracture patients undergoing orthopedic surgery have a decreased risk of infectious complications (osteomyelitis, deep and superficial surgical site infection) if antibiotics are administered within 1 hour of presentation compared with administration after 1 hour. The 2019 Trauma Quality Improvement Program was queried for adults with isolated (Abbreviated Injury Scale <1 for the head/face/spine/chest/abdomen/upper extremity) open femur and/or tibia fractures undergoing orthopedic surgery. Transfer patients were excluded. Patients receiving early antibiotics (EA) within 1 hour were compared with patients receiving delayed antibiotics (DA) greater than 1 hour from arrival. Of 3,367 patients identified, 2,400 (70.4%) received EA. Patients receiving EA had a higher rate of infections compared with DA (1.1% vs. 0.2%, p = 0.011). After adjusting for age, comorbidities, injury severity, nerve/vascular trauma to the lower extremity, washout of the femur/tibia performed in <6 hours, blood transfusion, and admission vitals, patients in the EA group had a similar associated risk of surgical site infection/osteomyelitis compared with the DA cohort ( p = 0.087). These results remained in subset analyses of patients with only femur, only tibia, and combined femur/tibia open fractures (all p > 0.05). In this large national analysis, approximately 70% of isolated open femur or tibia fracture patients undergoing surgery received antibiotics within 1 hour. After adjusting for known risk factors of infection, there was no association between timing of antibiotic administration and infection. Reconsideration of the quality metric of antibiotic administration within 1 hour for open fractures appears warranted. Therapeutic/Care Management; Level IV.


Detection of novel CYP11A1-derived secosteroids in the human epidermis and serum and pig adrenal gland.
To investigate whether novel pathways of vitamin D3 (D3) and 7-dehydrocholesterol (7DHC) metabolism initiated by CYP11A1 and previously characterized in vitro, occur in vivo, we analyzed samples of human serum and epidermis, and pig adrenals for the presence of intermediates and products of these pathways. We extracted human epidermis from 13 individuals and sera from 13 individuals and analyzed them by LC/qTOF-MS alongside the corresponding standards. Pig adrenal glands were also analyzed for these steroids and secosteroids. Epidermal, serum and adrenal samples showed the presence of D3 hydroxy-derivatives corresponding to 20(OH)D3, 22(OH)D3, 25(OH)D3, 1,25(OH)2D3, 20,22(OH)2D3, 20,23(OH)2D3, 20,24(OH)2D3, 20,25(OH)2D3, 20,26(OH)2D3, 1,20,23(OH)3D3 and 17,20,23(OH)3D3, plus 1,20(OH)2D3 which was detectable only in the epidermis. Serum concentrations of 20(OH)D3 and 22(OH)D3 were only 30- and 15-fold lower than 25(OH)D3, respectively, and at levels above those required for biological activity as measured in vitro. We also detected 1,20,24(OH)3D3, 1,20,25(OH)3D3 and 1,20,26(OH)3D3 in the adrenals. Products of CYP11A1 action on 7DHC, namely 22(OH)7DHC, 20,22(OH)27DHC and 7-dehydropregnenolone were also detected in serum, epidermis and the adrenal. Thus, we have detected novel CYP11A1-derived secosteroids in the skin, serum and adrenal gland and based on their concentrations and biological activity suggest that they act as hormones in vivo.


Selecting patients for exclusive permanent implant prostate brachytherapy: the experience of the Paris Institut Curie/Cochin Hospital/Necker Hospital group on 809 patients.
The aim of this study was to analyze overall and relapse-free survival in a cohort of 809 patients, 34% of whom corresponded to a higher-risk group than American Brachytherapy Society (ABS) criteria. Between January 1999 and September 2004, 809 patients were treated with permanent loose 125 iodine seed implantation (IsoSeed Bebig, Eckert and Ziegler) by the Paris Institut Curie, Cochin Hospital, and Necker Hospital group. Of these 809 patients, 533 (65.9%) corresponded exactly to ABS criteria. Two hundred and seventy-six patients (34.1%) had a prostate-specific antigen (PSA) level between 10 and 15, or a Gleason score of 7, or both (non-ABS group). Overall 5-year survival was 98%, with no difference between the ABS group and the non-ABS patient subgroups (p = 0.62).Five-year relapse-free survival was 97% in the ABS group; it was significantly lower (p = 0.001) in the non-ABS group but remained satisfactory at 94%. On subgroup analysis, the results appeared to be better for the subgroup of patients with PSA 10-15 than for the subgroup with a Gleason score of 7. Our results suggest that selected patients in the intermediate-risk group of localized prostate cancers can be safely proposed as recipients of permanent implant brachytherapy as monotherapy.


Bilateral retroesophageal course of the carotid arteries.
Many variations in the anatomy of the carotid artery are described in the literature. There are few case reports of hypoplasia or the retropharyngeal course of the internal carotid artery. We describe the unique case of a 72-year-old woman with bilateral complete retroesophageal common carotid arteries and concomitant hypoplasia of the right carotid system. Anatomical detection of such a variation is critical because the misidentification of a retroesophageal carotid artery carries the risk of potential injury during orotracheal intubation and oropharyngeal procedures.


Health care utilization and disability of migraine: the Ontario Health Survey.
To measure the prevalence of migraine, associated functional disabilities, use of medications and visits to physicians. 135,062 migraineurs in Ontario were estimated from the Ontario Health Survey (OHS). The population demographics, use of medications and visits to physicians were compared with these measures in individuals without migraine. The prevalence of migraine was estimated at 1.4% in Ontario. The migraineurs were heavy users of both prescription and non prescription drugs (98.0%). They were heavier users of pain relievers than the comparison group (91.2% versus 58.2%, p < 0.0000). According to the two-week disability reports, 11% of them were bedridden for an average of 1.6 days and 9.3% were restricted from normal activities for an average of 2.4 days because of migraine. Severe migraine headaches may result in a $31 million loss in productivity and $2 million in hospitalization costs. The findings of this study highlight both the medical and financial impact of migraine on the individual and the health care systems.


Visual and oculomotor function in optic chiasma-sectioned rabbits.
Anatomical and physiological findings indicate that the crossed optic fibres of the rabbit have a crucial role in binocular vision. In order to directly examine the visual functions of the uncrossed fibre system, a technique of sectioning the optic chiasma midsagitally was developed. Both normal and chiasma-sectioned rabbits were tested on a variety of visual discrimination tasks as well as such oculomotor control functions as the optokinetic and vestibulo-ocular reflexes. Following transection of all contralateral retinal projections, rabbits were found to retain the same visual capacity for detection of intensity and orientation differences as before the operation. There was, however, a complete loss of optokinetic reflexes and a 50% reduction of the vestibulo-ocular reflex both in the light and in the dark.


The effects of seed detectability and seed traits on hoarding preference of two rodent species.
Seed traits play an important role in affecting seed preference and hoarding behaviors of small rodents. Despite greatly affected by seed traits, seed detectability of competitors represents pilfering risks and may also modify seed hoarding preference of animals. However, whether seed traits and seed detectability show consistent effects on seed hoarding preference of animals remain largely unknown. Here, we explored how seed traits and seed detectability correlate with seed hoarding preference of Leopoldamys edwardsi and Apodemus chevrieri in a subtropical forest. Despite the effects of seed coat thickness and caloric value on hoarding preference of L. edwardsi, we detected no significant effects of other seed traits on hording preference of the 2 rodent species. There was no correlation between larder-hoarding preference and inter- or intra-specific seed detectability of L. edwardsi; however, seed detectability of L. edwardsi was negatively correlated with its own scatter-hoarding preference. Although scatter-hoarding preference of A. chevrieri was not correlated with inter- and intra-specific seed detectability, larder-hoarding preference of A. chevrieri was positively correlated with intra-specific seed detectability. Our study may provide evidence that intra-specific seed detectability rather than seed traits and inter-specific pilfering risks play an important role in modifying seed hoarding preference of rodents.


Clinical outcomes of stereotactic body radiotherapy for stage I non-small cell lung cancer using different doses depending on tumor size.
The treatment schedules for stereotactic body radiotherapy (SBRT) for lung cancer vary from institution to institution. Several reports have indicated that stage IB patients had worse outcomes than stage IA patients when the same dose was used. We evaluated the clinical outcomes of SBRT for stage I non-small cell lung cancer (NSCLC) treated with different doses depending on tumor diameter. Between February 2004 and November 2008, 124 patients with stage I NSCLC underwent SBRT. Total doses of 44, 48, and 52 Gy were administered for tumors with a longest diameter of less than 1.5 cm, 1.5-3 cm, and larger than 3 cm, respectively. All doses were given in 4 fractions. For all 124 patients, overall survival was 71%, cause-specific survival was 87%, progression-free survival was 60%, and local control was 80%, at 3 years. The 3-year overall survival was 79% for 85 stage IA patients treated with 48 Gy and 56% for 37 stage IB patients treated with 52 Gy (p = 0.05). At 3 years, cause-specific survival was 91% for the former group and 79% for the latter (p = 0.18), and progression-free survival was 62% versus 54% (p = 0.30). The 3-year local control rate was 81% versus 74% (p = 0.35). The cumulative incidence of grade 2 or 3 radiation pneumonitis was 11% in stage IA patients and 30% in stage IB patients (p = 0.02). There was no difference in local control between stage IA and IB tumors despite the difference in tumor size. The benefit of increasing the SBRT dose for larger tumors should be investigated further.


Long non-coding RNA MALAT1 targeting STING transcription promotes bronchopulmonary dysplasia through regulation of CREB.
Bronchopulmonary dysplasia (BPD) is a severe complication of preterm infants characterized by increased alveolarization and inflammation. Premature exposure to hyperoxia is believed to be a key contributor to the pathogenesis of BPD. No effective preventive or therapeutic agents have been created. Stimulator of interferon gene (STING) is associated with inflammation and apoptosis in various lung diseases. Long non-coding RNA MALAT1 has been reported to be involved in BPD. However, how MALAT1 regulates STING expression remains unknown. In this study, we assessed that STING and MALAT1 were up-regulated in the lung tissue from BPD neonates, hyperoxia-based rat models and lung epithelial cell lines. Then, using the flow cytometry and cell proliferation assay, we found that down-regulating of STING or MALAT1 inhibited the apoptosis and promoted the proliferation of hyperoxia-treated cells. Subsequently, qRT-PCR, Western blotting and dual-luciferase reporter assays showed that suppressing MALAT1 decreased the expression and promoter activity of STING. Moreover, transcription factor CREB showed its regulatory role in the transcription of STING via a chromatin immunoprecipitation. In conclusion, MALAT1 interacts with CREB to regulate STING transcription in BPD neonates. STING, CREB and MALAT1 may be promising therapeutic targets in the prevention and treatment of BPD.


Kinetic determination of sotalol by oxidation with sodium vanadate.
A kinetic method is described for the determination of sotalol. The method uses 0.033 M sodium vanadate to oxidize sotalol in 4 M sulphuric acid. The solution is heated at 90 degrees C and the absorbance is measured at 750 nm at a fixed time of 30 min. The concentration (c) of sotalol is calculated from the absorbance (A) by the equation: A = 0.04 + 0.0015625 c.


Stereoselective Synthesis of a Dipyridyl Transient Receptor Potential Vanilloid-3 (TRPV3) Antagonist.
An efficient asymmetric synthesis of dipyridyl TRPV3 antagonist 1 is reported. The four-step route involves two C-C bond-forming steps, a highly diastereoselective alkene hydration, and asymmetric ketone hydrosilylation in 97% ee.


Reproductive biology of the characid dourado Salminus franciscanus from the São Francisco River, Brasil.
The neotropical characid Salminus franciscanus is an economically valuable migratory fish whose populations have been drastically reduced in recent decades due to industrial and economic development in Brasil. To study its reproduction, a total of 283 adult specimens were captured in the Upper São Francisco River, downstream from the Três Marias dam, Minas Gerais, south-eastern Brasil, from August 2009 to July 2010. The gonadal maturity stages were determined from histological features of the gonads and gonadosomatic index (GSI). Gametogenesis was assessed by light and electron microscopy. For analysis of the oocyte's surface and fecundity, mature females were subjected to hormonal induction and oocyte stripping. Fish in resting (Stage 1) were common in all samplings, ripening/ripe and spawning (Stages 2 and 3) were predominant in October-November and December-January and post-spawning (Stage 4) occurred from December-January extending until April-May. The GSI followed the morphological changes of gonadal maturation, with a peak in October-November, when maximum GSI (7.08 in females and 3.46 in males) was achieved. From scanning electron microscopy, stripped oocytes showed a funnel-shaped micropyle and a simple oocyte surface arrangement, which is typical for non-adhesive eggs. Fecundity ranged from 160 to 440×10(3) oocytes per female and 129 to 175×10(3)oocytes/kg. The results of this study indicate that S. franciscanus reproduces in the Upper São Francisco River from October to January, exhibiting a total spawning pattern, non-adhesive eggs and high fecundity, providing support for aquaculture and conservation biology of this important neotropical characid fish.


Higher serum levels of vitamin D are associated with a reduced risk of diverticulitis.
Recent studies have shown geographic and seasonal variations in hospital admissions for diverticulitis. Because this variation parallels differences in ultraviolet light exposure, the most important contributor to vitamin D status, we examined the association of prediagnostic serum levels of vitamin D with diverticulitis. Among patients within the Partners Healthcare System who had blood drawn and serum levels of 25-hydroxyvitamin D (25-[OH]D) measured, from 1993 through 2012, we identified 9116 patients with uncomplicated diverticulosis and 922 patients who developed diverticulitis that required hospitalization. We used multivariate logistic regression to estimate relative risks and 95% confidence intervals to compare serum 25(OH)D levels between these groups. Patients with uncomplicated diverticulosis had significantly higher mean prediagnostic serum levels of 25(OH)D (29.1 ng/mL) than patients with diverticulitis who required hospitalization (25.3 ng/mL; P < .0001). Compared with patients in the lowest quintile of 25(OH)D, the multivariate-adjusted relative risk for diverticulitis hospitalization was 0.49 (95% confidence interval, 0.38-0.62; P for trend < .0001) among patients in the highest quintile of 25(OH)D level. Compared with patients with uncomplicated diverticulosis, the mean level of 25(OH)D was significantly lower for patients with acute diverticulitis without other sequelae (25.9 ng/mL; P < .0001; n = 594), for patients with diverticulitis with abscess (25.8 ng/mL; P = .0095; n = 124), for patients with diverticulitis requiring emergent laparotomy (22.7 ng/mL; P = .002; n = 65), and for patients with recurrent diverticulitis (23.5 ng/mL; P < .0001; n = 139). Among patients with diverticulosis, higher prediagnostic levels of 25(OH)D are associated significantly with a lower risk of diverticulitis. These data indicate that vitamin D deficiency could be involved in the pathogenesis of diverticulitis.


Removal of mercury by adsorption: a review.
Due to natural and production activities, mercury contamination has become one of the major environmental problems over the world. Mercury contamination is a serious threat to human health. Among the existing technologies available for mercury pollution control, the adsorption process can get excellent separation effects and has been further studied. This review is attempted to cover a wide range of adsorbents that were developed for the removal of mercury from the year 2011. Various adsorbents, including the latest adsorbents, are presented along with highlighting and discussing the key advancements on their preparation, modification technologies, and strategies. By comparing their adsorption capacities, it is evident from the literature survey that some adsorbents have shown excellent potential for the removal of mercury. However, there is still a need to develop novel, efficient adsorbents with low cost, high stability, and easy production and manufacture for practical utility.


New approaches to the concept of primary prevention of atherosclerosis.
Our understanding of the etiology of atherosclerosis and the mechanisms by which conventional cardiovascular risk factors cause disease is incomplete. Atherosclerosis may be regarded as a process of continuous injury and abnormal repair. The diagnosis and treatment of the disease should be targeted to the various stages of this process, from the early stages of vascular injury to the stabilization of the vulnerable plaque. Several novel concepts in atherosclerosis have been elucidated in the past two decades. Novel biomarkers and imaging techniques for early subclinical atherosclerotic lesions may facilitate earlier primary prevention. Future primary prevention of atherosclerosis should incorporate these novel concepts for creation of individualized risk profiles and therapies.


A daily multidisciplinary assessment of older adults undergoing elective colorectal cancer surgery is associated with reduced delirium and geriatric syndromes.
Comprehensive geriatric assessment (CGA) has shown to benefit older patients undergoing urological and orthopedic surgery. However, this approach has been scarcely assessed in patients elected for colorectal surgery. Retrospective cohort of patients aged ≥70 years admitted for elective colorectal cancer surgery to a single hospital between 2008 and 2012. Upon admission, patients were assigned to a usual care (UC) plan or a CGA-based care (GS) plan conducted by a multidisciplinary team, according to standard clinical criteria.Analyzed outcomes included the incidence of delirium and other geriatric syndromes during hospital stay, mortality, readmissions, andnumber of perioperative complications. The cohort included 310 patients, 203 assigned to the GS group and 107 to the UC group. Patients in the GS group had significantly lower Barthel and Lawton scores, higher prevalence of dementia and heart failure, and higher comorbidity burden. Fifty-four (17.5%) patientsexperienced delirium (23 [11.3%] and 31 [29.2%] in the GS and UC groups, respectively; p < .001), and 49 (15.8%) patient experienced other geriatric syndromes (21 [10.3%] and 28 [26.2%] in the GS and UC groups, respectively; p < .001). Serious complications were more frequent in the GS group: 154 (75.9%) vs 60 (56.1%) in the UC group; p < .001. No significant differences were observed between groups regarding readmissions, and in-hospital and post-discharge (1 year follow-up) mortality. Despite the poorer clinical condition of patients in the GS group, the CGA-based intervention resulted in a lower incidence of delirium and other geriatric syndromes compared with the UC group.


Author Correction: Mating of escaped domestic pigs with wild boar and possibility of their offspring migration after the Fukushima Daiichi Nuclear Power Plant accident.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Potentiometric behaviour of ion selective electrodes based on iron porphyrins: the influence of porphyrin substituents on the response properties and analytical determination of diclofenac in pharmaceutical formulations.
The potentiometric response characteristics of diclofenac selective electrodes based on Fe(III) tetraphenylporphyrin-chloride (Fe(III)TPP-Cl) and Fe(III) tetrakis(pentafluorophenyl)porphyrin-chloride (Fe(III)TPFPP-Cl) in different mediator solvents and ionic additives are compared. The sensitivity, working range, detection limit, response mechanism, and selectivity of the membrane sensor show a significant dependence on the type of carrier substituent and on the pH value of the sample solution. Studies performed with different amounts of cationic additive (tetra-n-octylammoniumbromide (TOABr)) and anionic additive (sodium tetraphenylborate (NaTPB)) in the membranes allowed the determination of the potentiometric mechanism of action of the used metalloporphyrins. For the analysis of real samples, Fe(III)TPFPP-Cl (type G), prepared in o-NPOE, incorporating 10 mol% of TOABr, was used. This potentiometric unit presented a linear response towards diclofenac concentrations between 10(-5) and 10(-2)mol l(-1) ( I=0.1 mol l(-1)) and slopes of about -59 mV dec(-1), exhibiting a response time of 10s in a buffered solution of ammonia-ammonium sulphate with pH 9.9. The potentiometric analysis of sodium diclofenac in pharmaceutical formulations was carried out by direct potentiometry and the obtained results were compared to those provided by HPLC, presenting relative errors inferior to 1.0%.


The assessment of adenoidal size by radiological means.
The purpose of this study was to evaluate the accuracy of radiology in the assessment of both adenoidal size and the size of the nasopharyngeal airway. There was a good correlation between the preoperative assessment of the size of the adenoid by radiology and the actual size of the adenoid removed at surgery. A method of estimating the size of the nasopharyngeal airway is described. There was a good inverse correlation between the size of the airway and the weight of the adenoid.


Alpha-1 antitrypsin phenotypes in demyelinating disease: an association between demyelinating disease and the allele PiM3.
Alpha-1 Antitrypsin, the major circulating protease inhibitor, has more than thirty alleles that can be identified by electrophoresis. In addition to its role as a protease inhibitor, alpha-1 antitrypsin may regulate the immune response. As there is evidence that both the inflammatory polyneuropathies and multiple sclerosis have an immune basis, and that genetic factors influence susceptibility, we have determined the alpha-1 antitrypsin phenotypes (protease inhibitor types) of 63 patients with Guillain-Barré syndrome, 52 patients with chronic inflammatory demyelinating polyneuropathy, and 178 patients with multiple sclerosis. In all 3 groups there was a significant increase in the proportion of patients with the protease inhibitor type M3 allele.


The Native Comic Book Project: native youth making comics and healthy decisions.
American Indians and Alaska Natives have traditionally used stories and drawings to positively influence the well-being of their communities. The objective of this study was to describe the development of a curriculum that trains Native youth leaders to plan, write, and design original comic books to enhance healthy decision making. Project staff developed the Native Comic Book Project by adapting Dr. Michael Bitz's Comic Book Project to incorporate Native comic book art, Native storytelling, and decision-making skills. After conducting five train-the-trainer sessions for Native youth, staff were invited by youth participants to implement the full curriculum as a pilot test at one tribal community site in the Pacific Northwest. Implementation was accompanied by surveys and weekly participant observations and was followed by an interactive meeting to assess youth engagement, determine project acceptability, and solicit suggestions for curriculum changes. Six youths aged 12 to 15 (average age = 14) participated in the Native Comic Book Project. Youth participants stated that they liked the project and gained knowledge of the harmful effects of commercial tobacco use but wanted better integration of comic book creation, decision making, and Native storytelling themes. Previous health-related comic book projects did not recruit youth as active producers of content. This curriculum shows promise as a culturally appropriate intervention to help Native youth adopt healthy decision-making skills and healthy behaviors by creating their own comic books.


Solitary Extraosseous Plasmacytoma of Submandibular Gland - Report of a Rare Case.
Plasmacytomas are tumors involving plasma cells that can be either osseous or extraosseous. Solitary extraosseous plasmacytomas are rarely found in the head and neck region. Various pathological, immuno-histochemistry, and radiological investigations must be done to distinguish it from multiple myeloma. A 41-year-old female presented with a progressively increasing mass in right submandibular region for 1 year. She also had complaints of dysphagia and dyspnea for 3 months. Histopathological examinations showed lymphoplasmacytic infiltrate and possibility of plasma cell neoplasm was suspected. On further investigations like immunohistochemistry, bone marrow biopsy, quantitative immunoglobulin, immunoelectrophoresis, and urine analysis, diagnosis of extraosseous plasmacytoma was made. Positron emission tomography-computed tomography (PET-CT) scan did not show any distant foci of the disease. The patient received definitive radiotherapy to the primary region and tolerated well. The patient is asymptomatic after 1 month of radiotherapy and is on regular follow-up. Extraosseous plasmacytoma of the submandibular region is very rare but radiosensitive tumor. Multiple myeloma must be ruled out prior to start of any treatment. Long term follow ups are required to comment on disease progression, dissemination, or recurrence.


Studies on the interaction of barbiturates with reactive oxygen radicals: implications regarding barbiturate protection against cerebral ischaemia.
Although the molecular basis of ischaemic damage of the brain is as yet unknown, it has been postulated that the uncontrolled production of reactive oxygenated species derived from molecular oxygen (including hydroxyl radicals, superoxide radicals and singlet oxygen) may play a major role in the production of such injury. The ability of various barbiturates to modify the nature and extent of membrane damage produced by various oxygen radicals generated under well-defined conditions in vitro has been directly examined using the human erythrocyte as model membrane system. Our results indicate that barbiturates are unlikely to exert their protective effects by directly scavenging singlet oxygen, superoxide or hydroxyl radicals. The highly lipophilic barbiturate thiopentone is capable of decreasing the susceptibility of membranes to oxidative degradation by a direct membrane action, a property shared by amphipathic membrane stabilizers such as propranolol. The barbiturates were found to stabilize the haeme moiety of haemoglobin preventing its conversion to methaemoglobin in the presence of hydrogen peroxide. It is postulated that a major aspect of barbiturate action in decreasing ischaemic injury to the brain may involve the stabilization of haeme-coordinated iron complexes, thereby preventing the participation of these ubiquitous substances in initiating and potentiating free radical-mediated processes which have been implicated in the production of such injury.


Auditory and visual evoked potentials in Huntington's disease.
Auditory and visual evoked potentials elicited by acoustic click (AEP) and checkerboard pattern flash (VEP) were recorded from 15 locations in 21 patients with Huntington's disease (HD) and 21 controls matched for age and sex. Peak latencies were approximately the same for both groups, except that AEP peak N100 appeared earlier in HDs. The main deviation in HDs consisted of generally reduced amplitude of VEP and AEP components; these deviations can be considered non-specific. Early VEP and AEP peaks contained no specific abnormalities comparable to those found in early somatosensory evoked potentials, as previously reported for the same subjects. VEP and AEP amplitudes were lower in medicated than in unmedicated HD patients, but amplitudes for both medicated and unmedicated HDs deviated from normal. Drugs may act to further diminish the already lower than normal amplitudes in HDs.


Nck-2 interacts with focal adhesion kinase and modulates cell motility.
Nck-2 is a ubiquitously expressed adaptor protein comprising primarily three N-terminal SH3 domains and one C-terminal SH2 domain. We report here that Nck-2 interacts with focal adhesion kinase (FAK), a cytoplasmic protein tyrosine kinase critically involved in the cellular control of motility. Using a mutational strategy, we have found that the formation of the Nck-2-FAK complex is mediated by interactions involving multiple SH2 and SH3 domains of Nck-2. The Nck-2 SH2 domain-mediated interaction with FAK is dependent on phosphorylation of Tyr397, a site that is involved in the regulation of cell motility. A fraction of Nck-2 co-localizes with FAK at cell periphery in spreading cells. Furthermore, overexpression of Nck-2 modestly decreased cell motility, whereas overexpression of a mutant form of Nck-2 containing the SH2 domain but lacking the SH3 domains significantly promoted cell motility. These results identify a novel interaction between Nck-2 and FAK and suggest a role of Nck-2 in the modulation of cell motility.