Unilateral hallucinations and other psychotic symptoms due to otosclerosis.
We report the case of a 35-year-old man suffering from otosclerosis and unilateral auditory hallucinations as well as other psychotic symptoms that disappeared completely after surgery for otosclerosis. The patient experienced a change of his acoustic sensations: the tinnitus was transformed into music, and 4 months later the music changed into commenting and imperative voices. However, on both occasions the transformation from one form to another occurred during an alcohol withdrawal syndrome characterized mainly by vivid visual hallucinations. Some theoretical considerations on hallucinatory predisposition, development of hallucinations, and psychological factors determining psychotic symptoms will be discussed.


Influence of the linac design on intensity-modulated radiotherapy of head-and-neck plans.
In this study, we quantify the impact of linac/MLC design parameters on IMRT treatment plans. The investigated parameters were leaf width in the MLC, leaf transmission, related to the thickness of the leaves, and penumbra related primarily to the source size. Seven head-and-neck patients with stage T1-T3N0-N2cM0 oropharyngeal cancer were studied. For each patient nine plans were made with a different set of linac/MLC parameters. The plans were optimized in Pinnacle(3) v7.6c and PLATO RTS v2.6.4, ITP v1.1.8. A hypothetical ideal linac/MLC was introduced to investigate the influence of one parameter at a time without interaction of other parameters. When any of the three parameters was increased from the ideal set-up values (leaf width 2.5 mm, transmission 0%, penumbra 3 mm), the mean dose to the parotid glands increased, given the same tumour coverage. The largest increase was found for increasing leaf transmission. The investigation showed that by changing more than one parameter of the ideal linac/MLC set-up, the increase in the mean dose was smaller than the sum of dose increments for each parameter separately. As a reference to clinical practice, we also optimized the plans of the seven patients with the clinically used Elekta SLi 15, equipped with a standard MLC with a leaf width of 10 mm. As compared to the ideal linac, this resulted in an increase of the average dose to the parotid glands of 5.8 Gy.


Cytological diagnostic features of late breast implant seromas: From reactive to anaplastic large cell lymphoma.
Late breast implant seroma may be the presentation of a breast implant-associated anaplastic large cell lymphoma (BI-ALCL), which claims for a prompt recognition. However, BI-ALCL diagnosis on fine-needle aspiration (FNA) might be challenging for pathologists lacking experience with peri-implant breast effusions. Sixty-seven late breast implant seromas collected by FNA from 50 patients were evaluated by Papanicolaou smear stain and immunocytochemistry on cell blocks. A diagnostic algorithm based on the cellular composition, cell morphology and percentage of CD30+ cells was developed. Histological evaluation of the corresponding peri-prosthetic capsules was also performed. Most of the effusions (91% of the samples) were classified as reactive and 9% as BI-ALCL. In the BI-ALCL cases, medium-to-large atypical cells expressing CD30 represented more than 70% of the cellularity, whereas in in the reactive effusions CD30+ elements were extremely rare (<5%) and consisted of non-atypical elements. The reactive effusions were categorized into three patterns: i) acute infiltrate with prominent neutrophilic component (33% of the samples); ii) mixed infiltrate characterized by a variable number of neutrophils, lymphocytes and macrophages (30% of the samples); iii) chronic infiltrate composed predominantly of T lymphocytes or macrophages with only sporadic granulocytes (37% of the samples). The inflammatory cytological patterns were consistent with the histology of the corresponding capsules. Our results indicate that cytological analysis of late breast implant effusions, supported by the knowledge of the heterogeneous cytomorphological spectrum of late seromas, is a valuable approach for the early recognition of BI-ALCL.


Copper Phosphide Nanostructures Covalently Modified Ti3 C2 Tx for Fast Lithium-Ion Storage by Enhanced Kinetics and Pesudocapacitance.
2D layer Ti3 C2 Tx material attracts enormous attention in lithium ion energy storage field owing to the unique surface chemistry properties, but the material still suffers from restacking issue and the restriction on capacity. Herein, copper phosphide (Cu3 P) nanostructures@Ti3 C2 Tx composites are prepared by the in situ generation of Cu-BDC precursor in the bulk material followed with phosphorization. The uniformly distributed copper phosphide nanostructures effectively expand the interlayer spacing promoting the structural stability, and achieves the effective connection with the bulk material accelerating the diffusion and migration of lithium ions. The electrochemical activity of Cu3 P also provides more lithium ion active sites for lithium storage. The X-ray photoelectron spectroscopy (XPS) analysis verifies that Ti─O─P bond with strong covalency allows the upper shift of maximum valence band and Fermi level, stimulating the charge transportation between Cu3 P and the bulk Ti3 C2 Tx for better electrode kinetics. 3Cu3 P@Ti3 C2 Tx exhibits excellent rate performance of 165.4 mAh g-1 at 3000 mA g-1 and the assembled 3Cu3 P@Ti3 C2 Tx //AC Lithium-ion hybrid capacitorsLIC exhibits superior energy density of 93.0 Wh kg-1 at the power density of 2367.3 W kg-1 . The results suggest that the interfacial modification of Ti3 C2 Tx with transition metal phosphides will be advantageous to its high energy density application in lithium-ion storage.


[Augmentation of NK activity in peripheral blood lymphocytes of cancer patients by intermittent GE-132 administration].
The natural killer (NK) activity of peripheral blood lymphocytes from 18 cancer patients was studied prior to and after multiple administration of organo-germanium compound (Ge-132). In successive oral administration of Ge-132 at a dose of 1000 mg/day for 10 days, NK-activity of patients was augmented at 3 days, but by 10 days, depression of NK activity was observed in all cases. In intermittent oral administration of Ge-132, however, more than half of the patients with augmented NK activity at day 3 maintained the high activity level at day 10. This result suggests the superiority of intermittent administration of Ge-132 for clinical use.


The capacity of duckweed to treat wastewater: ecological considerations for a sound design.
Duckweed species are promising macrophytes for use in sustainable wastewater treatment due to their rapid growth, ease of harvest, and feed potential as a protein source. This paper reviews growth rates of different duckweed species on wastewater and ammonia toxicity to duckweed and summarizes insights into the mechanism of organic matter and nutrient removal. Results were gained from laboratory experiments in small, shallow, duckweed-covered semicontinuous batch systems. Growth rates on different types of wastewater vary considerably among different species. Ammonia is toxic for duckweed in both the ionized and un-ionized forms. Duckweed, however, can be used to treat wastewater containing very high total ammonia concentrations as long as certain pH levels are not exceeded. The degradation of organic material is enhanced by duckweed through both additional oxygen supply and additional surface for bacterial growth. The duckweed mat with attached bacteria and algae is, independent of the loading rates, responsible for three-quarters of the total nitrogen (N) and phosphorus (P) loss in very shallow systems. Based on our results we suggest that full-scale pilot plants with duckweed should be shallower than the range encountered in the literature. A harvesting schedule that allows doubling times of 2 to 3.5 d, maintenance of a full coverage, and plug flow conditions are recommended.


Interferon and 2',5'-oligo(A) synthetase activities in serum and blood mononuclear leukocytes of cattle after injection of bovine interferon-alpha 1.
Cell extracts that were prepared from blood mononuclear leukocytes from 66 samples obtained from 6 clinically normal calves contained mean 2',5'-oligoadenylate (2',5'-oligo[A]) synthetase activity sufficient to synthesize 186 +/- 82 pmol of 2',5'-oligo(A)/h/10(6) cells. Calves had no measurable serum interferon (IFN) activity. Five calves were given IM injections of 10(4), 10(5), 5 x 10(5), 10(6), and 10(7) U of bovine IFN-alpha 1/kg of body weight at 2-week intervals. Five dosing sequences were used with a 5 x 5 Latin square design so that each calf received each dose once. Activity of 2',5'-oligo(A) synthetase increased at 24 hours in response to all dosages of IFN and then declined following first-order kinetics, with an apparent half-life (t1/2) of 2.1 +/- 0.5 days. The area under the concentration-time curve for 2',5'-oligo(A) synthetase increased with dose of IFN more rapidly than did peak response. Serum IFN that was measured at 1-day intervals following administration of IFN was consistently measurable only at dosages above 10(6) U of IFN/kg. The t1/2 for circulating IFN was 12.4 +/- 1.0 hours. Over all dosages, increases in 2',5'-oligo(A) synthetase activity were measurable for 3.5 days longer than were increases in IFN following IM injection of IFN. None of the calves developed detectable anti-IFN antibodies.


Comparison of cyanopeptolin genes in Planktothrix, Microcystis, and Anabaena strains: evidence for independent evolution within each genus.
The major cyclic peptide cyanopeptolin 1138, produced by Planktothrix strain NIVA CYA 116, was characterized and shown to be structurally very close to the earlier-characterized oscillapeptin E. A cyanopeptolin gene cluster likely to encode the corresponding peptide synthetase was sequenced from the same strain. The 30-kb oci gene cluster contains two novel domains previously not detected in nonribosomal peptide synthetase gene clusters (a putative glyceric acid-activating domain and a sulfotransferase domain), in addition to seven nonribosomal peptide synthetase modules. Unlike in two previously described cyanopeptolin gene clusters from Anabaena and Microcystis, a halogenase gene is not present. The three cyanopeptolin gene clusters show similar gene and domain arrangements, while the binding pocket signatures deduced from the adenylation domain sequences and the additional tailoring domains vary. This suggests loss and gain of tailoring domains within each genus, after the diversification of the three clades, as major events leading to the present diversity. The ABC transporter genes associated with the cyanopeptolin gene clusters form a monophyletic clade and accordingly are likely to have evolved as part of the functional unit. Phylogenetic analyses of adenylation and condensation domains, including domains from cyanopeptolins and microcystins, show a closer similarity between the Planktothrix and Microcystis cyanopeptolin domains than between these and the Anabaena domain. No clear evidence of recombination between cyanopeptolins and microcystins could be detected. There were no strong indications of horizontal gene transfer of cyanopeptolin gene sequences across the three genera, supporting independent evolution within each genus.


Embracing Their Prey at That Dark Hour: Common Cuttlefish (Sepia officinalis) Can Hunt in Nighttime Light Conditions.
Cuttlefish are highly efficient predators, which strongly rely on their anterior binocular visual field for hunting and prey capture. Their complex eyes possess adaptations for low light conditions. Recently, it was discovered that they display camouflaging behavior at night, perhaps to avoid detection by predators, or to increase their nighttime hunting success. This raises the question whether cuttlefish are capable of foraging during nighttime. In the present study, prey capture of the common cuttlefish (Sepia officinalis) was filmed with a high-speed video camera in different light conditions. Experiments were performed in daylight and with near-infrared light sources in two simulated nightlight conditions, as well as in darkness. The body of the common cuttlefish maintained a velocity of less than 0.1 m/s during prey capture, while the tentacles during the seizing phase reached velocities of up to 2.5 m/s and accelerations reached more than 450 m/s2 for single individuals. There was no significant difference between the day and nighttime trials, respectively. In complete darkness, the common cuttlefish was unable to catch any prey. Our results show that the common cuttlefish are capable of catching prey during day- and nighttime light conditions. The common cuttlefish employ similar sensory motor systems and prey capturing techniques during both day- and nighttime conditions.


Antibody-mediated versus nontargeted delivery in a human small cell lung carcinoma model.
The uptake of macromolecular agents in tumor cells (LX-1, human small cell lung carcinoma) and in corresponding tumor xenografts was compared in a parallel study utilizing a long-circulating biocompatible graft copolymer, MPEGs-PL-DTPA [Bogdanov, A., Jr., et al. (1995) Adv. Drug Delivery Rev. 16, 335-348; Bogdanov, A., Jr., et al. (1996) Bioconjugate Chem. 7, 144-149] and a tumor-specific chimeric monoclonal antibody, BR96 [Hellstrom, I., et al. (1990) Cancer Res. 50, 2183-2190; Garrigues, J., et al. (1993) Am. J. Pathol. 142, 607-622]. Covalent grafted conjugates of methoxy-(polyethylene glycol)succinate and polylysine and BR96 were modified with DTPA, biotinyl, or rhodamine-X-residues. Using radionuclide and fluorescent labeled derivatives of the copolymer and the antibody, we established that (1) the copolymer does not associate with the plasma membrane in N-ethylmaleimide-treated cells and is slowly internalized by live cells at 37 degrees C; (2) the antibody binds rapidly to the surface of LX-1 cells and shows active internalization in vesicles with a subsequent slow decrease in the cell-associated antibody concentration; (3) LX-1 cells bear more than 1 million BR96 binding sites/cell (with an apparent Kd of 4.5 x 10[-7] M); and (4) intravesicular fluorescence intensity in LX-1 cells was linearly dependent on copolymer concentration, suggesting fluid phase endocytosis. Tumor localization by nuclear imaging, biodistribution, microdistribution by histology, and determination of tumor cell fraction uptake was performed in LX-1 tumor xenografts. In vivo study showed that MPEGs-PL-DTPA progressively accumulates in the tumor, yielding from 2.8+/-1.5% injected dose per gram of tissue (ID/g) at 24 h to 5.2+/-1.7% ID/g of tissue at 48 h. The antibody accumulation peaked at 24 h (6.0+/-3.2% ID/g) and decreased thereafter. We determined that at 24 h 43.9+/-11.29% of the polymer accumulated in the tumor was associated with tumor cell fraction with the remainder of the accumulated dose localized in the interstitium. Accumulation of the biotinylated graft copolymer and the antibody in LX-1 xenografts and their uptake in cells were confirmed by histology using avidin-peroxidase staining. Our study demonstrates that, although BR96 is highly specific in vitro, tumoral drug delivery in vivo can be equally high with long-circulating graft copolymers because of slow extravasation at the tumor site.


Developmental ability of oocytes retrieved from Meishan neonatal ovarian tissue grafted into nude mice.
Ovarian xenografting makes it possible to obtain oocytes with fertilization ability from immature pigs of Western breeds. In this study, we applied these methods to the Meishan, an indigenous Chinese pig breed, and investigated the developmental competence of oocytes grown in their neonatal tissue after grafting into nude mice. First, mice harboring neonatal ovarian tissue were infused with follicle stimulating hormone (FSH) (62.5 U/ml) for 13 days starting at 10, 30, and 60 days after vaginal opening (D10-, D30-, and D60-FSH groups, respectively). Development of antral follicles and their oocytes was most enhanced in the D60-FSH group. For the next step, we examined the in vitro maturation ability of the oocytes recovered from host mice after infusion with FSH at a dose of 62.5 U/ml or 125 U/ml (FSH-62.5 or -125 group) for 13 days starting at 60 days after vaginal opening. Many more oocytes with maturation ability were obtained from the FSH-125 group. The FSH-125 mature oocytes were fertilized in vitro, as shown by formation of male and female pronuclei, but did not reach the blastocyst stage. These results indicate that Meishan neonatal ovaries are able to produce oocytes with fertilization ability after being grafted into nude mice.


Car Transfer and Wheelchair Loading Techniques in Independent Drivers with Paraplegia.
Car transfers and wheelchair (WC) loading are crucial for independent community participation in persons with complete paraplegia from spinal cord injury, but are complex, physically demanding, and known to provoke shoulder pain. This study aimed to describe techniques and factors influencing car transfer and WC loading for individuals with paraplegia driving their own vehicles and using their personal WCs. Sedans were the most common vehicle driven (59%). Just over half (52%) of drivers place their right leg only into the vehicle prior to transfer. Overall, the leading hand was most frequently placed on the driver's seat (66%) prior to transfer and the trailing hand was most often place on the WC seat (48%). Vehicle height influenced leading hand placement but not leg placement such that drivers of higher profile vehicles were more likely to place their hand on the driver's seat than those who drove sedans. Body lift time was negatively correlated with level of injury and age and positively correlated with vehicle height and shoulder abduction strength. Drivers who transferred with their leading hand on the steering wheel had significantly higher levels of shoulder pain than those who placed their hand on the driver's seat or overhead. The majority of participants used both hands (62%) to load their WC frame, and overall, most loaded their frame into the back (62%) vs. the front seat. Sedan drivers were more likely to load their frame into the front seat than drivers of higher profile vehicles (53 vs. 17%). Average time to load the WC frame (10.7 s) was 20% of the total WC loading time and was not related to shoulder strength, frame weight, or demographic characteristics. Those who loaded their WC frame into the back seat had significantly weaker right shoulder internal rotators. Understanding car transfers and WC loading in independent drivers is crucial to prevent shoulder pain and injury and preserve community participation.


Catalytic properties of Al13TM4 complex intermetallics: influence of the transition metal and the surface orientation on butadiene hydrogenation.
Complex intermetallic compounds such as transition metal (TM) aluminides are promising alternatives to expensive Pd-based catalysts, in particular for the semi-hydrogenation of alkynes or alkadienes. Here, we compare the gas-phase butadiene hydrogenation performances of o-Al13Co4(100), m-Al13Fe4(010) and m-Al13Ru4(010) surfaces, whose bulk terminated structural models exhibit similar cluster-like arrangements. Moreover, the effect of the surface orientation is assessed through a comparison between o-Al13Co4(100) and o-Al13Co4(010). As a result, the following room-temperature activity order is determined: Al13Co4(100) < Al13Co4(010) < Al13Ru4(010) < Al13Fe4(010). Moreover, Al13Co4(010) is found to be the most active surface at 110°C, and even more selective to butene (100%) than previously investigated Al13Fe4(010). DFT calculations show that the activity and selectivity results can be rationalized through the determination of butadiene and butene adsorption energies; in contrast, hydrogen adsorption energies do not scale with the catalytic activities. Moreover, the calculation of projected densities of states provides an insight into the Al13TM4 surface electronic structure. Isolating the TM active centers within the Al matrix induces a narrowing of the TM d-band, which leads to the high catalytic performances of Al13TM4 compounds.


Severe viral gastroenteritis in children after suboptimal rotavirus immunization in Taiwan.
The study aimed to investigate the molecular epidemiology of severe viral gastroenteritis (AGE) in children in Taiwan after the implementation of the rotavirus vaccine in the private sector. Fecal samples from hospitalized children with severe AGE from April 2004 to March 2011 were examined by reverse transcription-polymerase chain reaction or polymerase chain reaction to identify enteric viral pathogens. The study period was divided to prevaccine (before September 2006) and postvaccine (after October 2006) periods. The prevalence of enteric viruses between the 2 periods was analyzed. The disease burdens of rotavirus- and norovirus-associated diseases were assessed according to vaccine implementation status and were adjusted for age. A total of 755 stool samples were collected from hospitalized patients with AGE; enteric viruses were identified in 586 patients (77.6%), including 44 with concomitant bacterial infection. Viral enteric infection by rotavirus, norovirus, astrovirus, sapovirus, enteric adenovirus, multiple viruses and bacterial coinfections were found in 216 (28.6%), 128 (17.0%), 24 (3.2%), 6 (0.8%), 69 (9.1 %), 99 (13.1%) and 44 (5.8%) patients, respectively. A significant increase of norovirus infection was found in the postvaccine period (P < 0.001); on the other hand, rotavirus infection in infants has been reduced substainally (P = 0.056) and the annual peak of rotavirus infection has gradually become less prominent, with a significant decline of coinfection of rotavirus with other pathogens. Suboptimal use of rotavirus vaccines in the private sector caused a slow but modest impact on severe rotavirus AGE, whereas norovirus infection became more common.


Induced deficits in speed perception by transcranial magnetic stimulation of human cortical areas V5/MT+ and V3A.
In this report, we evaluate the role of visual areas responsive to motion in the human brain in the perception of stimulus speed. We first identified and localized V1, V3A, and V5/MT+ in individual participants on the basis of blood oxygenation level-dependent responses obtained in retinotopic mapping experiments and responses to moving gratings. Repetitive transcranial magnetic stimulation (rTMS) was then used to disrupt the normal functioning of the previously localized visual areas in each participant. During the rTMS application, participants were required to perform delayed discrimination of the speed of drifting or spatial frequency of static gratings. The application of rTMS to areas V5/MT and V3A induced a subjective slowing of visual stimuli and (often) caused increases in speed discrimination thresholds. Deficits in spatial frequency discrimination were not observed for applications of rTMS to V3A or V5/MT+. The induced deficits in speed perception were also specific to the cortical site of TMS delivery. The application of TMS to regions of the cortex adjacent to V5/MT and V3A, as well as to area V1, produced no deficits in speed perception. These results suggest that, in addition to area V5/MT+, V3A plays an important role in a cortical network that underpins the perception of stimulus speed in the human brain.


The effects of blood conditioning films on the antimicrobial and retention properties of zirconium-nitride silver surfaces.
External bone fixation devices provide support and rehabilitation for severely damaged/broken bones, however, this invasive procedure is prone to infection. Zirconium nitride/silver (Ti-ZrN/Ag) coatings were characterised for surface topography, chemical composition, physicochemistry and antimicrobial efficacy (against Staphylococcus aureus and Staphylococcus epidermidis), in the presence of a blood conditioning film. The conditioning film altered the width of the microtopography of the surfaces however, the depth of the features remained relatively constant. The conditioning film also altered the coatings from hydrophobic to hydrophilic/partially hydrophilic surfaces. Following the MATH assay, the presence of a conditioning film reduced affinity towards the hydrocarbons for both microorganisms. The addition of a blood conditioning film reduced the antimicrobial efficacy of the Ti-ZrN/Ag coatings but also reduced the number of retained bacteria. This study suggests that the presence of a pre-defined blood conditioning film may result in surfaces with anti-adhesive properties, potentially leading to a reduction in bacterial retention. This, combined with the antimicrobial efficacy of the coatings, could reduce the risk of infection on biomaterial surfaces.


Electrical remodeling of the ventricular myocardium in myocarditis: studies of rat experimental autoimmune myocarditis.
The purpose of this study was to evaluate the electrical remodeling of the ventricular myocardium in the experimental autoimmune myocarditis (EAM) model in Lewis rats. EAM was induced by immunization with cardiac myosin. During the active myocarditis phase, the effective refractory period (ERP), the duration of the monophasic action potential (MAPD) was extracted from the left ventricular free wall, and the mRNA levels of Kv1.4, 4.2, 4.3 and L type Ca2+ channel were determined by RNase protection assays. The inducibility of ventricular arrhythmia was higher in EAM rats than in the control rat, and the direct relationship between the coupling intervals of the premature stimulus and the ventricular arrhythmia in EAM rats. The ERP was prolonged in EAM rats compared with the control group. The MAPDs determined as 20% and 90% repolarization time, were both longer in EAM rats than in the controls. The level of expression of Kv4.2 mRNA was reduced in EAM rats in comparison with the controls, whereas those of Kv1.4, 4.3 and the L type Ca2+ channel were unchanged. Ventricular vulnerability was higher in EAM rats than in the control rats, and some of the ventricular arrhythmias observed in the EAM group seemed to be based on triggered activity. The level of expression of Kv4.2 mRNA was significantly reduced, and this change was compatible with prolongation of the action potential duration.


[B Cell Activating Transcription Factor Regulates Acute Airway Inflammation in Asthmatic Mice].
To investigate the regulatory effect of B cell activating transcription factor (BATF) on acute airway inflammation and its association with retinoic acid orphan nuclear receptors gammat (RORyt) in asthmatic mice. 24 female BALB/c mice were randomly and equally divided into three groups (n 8): normal saline (NS) treated, asthma (AS) control and dexamethasone (DEX) treated. AS mice were sensitized and challenged with OVA to establish murine asthma model. Histological changes in lung tissues of the mice were observed by HE staining. Numbers of white blood cell (WBC), polymorphonuclear leukocyte (PMN) and eosinophils (EOS) in the bronchoalveolar lavage fluid (BALF) of the mice were counted. The concentration of interleukin-17 (IL-17) in BALF was measured by ELISA. Quantitative real-time PCR (RT-PCR) was performed to assess the mRNA expressions of BATF, IL-17 and RORγt in the lung tissues. The HE staining showed a higher level of inflammatory cell infiltration around the bronchi of AS mice compared with those treated with NS, predominantly in the forms of EOS, PMN and lymphocytes. The AS and DEX treated mice had higher levels of EOS, PMN, WBC and mRNA expressions of BATF, IL-17 and RORγt in BALF than those treated with NS (P < 0.05). DEX reduced the levels of EOS, PMN, WBC and IL-17 in BALF significantly (P < 0.05). The mRNA expression of BATF in lung tissues of mice was positively correlated with the expression of IL-17, RORγt and the counts of WBC,EOS and PMN in BALF (P < 0.05). Asthmatic mice have increased expressions of BATF, IL-17 and RORγt in bronchial and lung tissues. BATF can, through regulating the secretion of Th17 cells, readjust the airway inflammatory. The regulatory function may take effect through synergy with RORγt .


Whole-Exome Sequencing Solved over 2-Decade Kidney Disease Enigma.
Chronic kidney disease of unknown etiology (CKDu) has been a problem in renal practice as indefinite diagnosis may lead to inappropriate management. Here, we report a 54-year-old father diagnosed with CKDu at 33 years old and his 8-year-old son with steroid-resistant nephrotic syndrome. Using whole-exome sequencing, both were found to be heterozygous for c.737G>A (p.Arg246Gln) in LMX1B. The diagnosis of LMX1B-associated nephropathy has led to changes in the treatment plan with appropriate genetic counseling. The previously reported cases with this particular mutation were also reviewed. Most children with LMX1B-associated nephropathy had nonnephrotic proteinuria with normal renal function. Interestingly, our pediatric case presented with steroid-resistant nephrotic syndrome at 8 years old and progressed to ESRD requiring peritoneal dialysis at the age of 15 years. Our report emphasized the need of genetic testing in CKDu for definite diagnosis leading to precise management.


Anterior-posterior thigh diameter measured by two-dimensional sonography: indicator of fetal age at 18 to 28 weeks gestation ?
Little published research exists in the area of fetal thigh biometry, specifically in the use of the anteriorposterior fetal thigh diameter (APTD). A continuing review of existing practices needs to be coupled with evaluation of alternate or additional methodology. This study evaluated the usefulness and direct correlation of a simple, new method of predicting fetal age by measurement of the anterior-posterior thigh diameter (APTD) in a normal 18-to 28 week pregnancies using two-dimensional sonography. This was a quantitative prospective study of 55 patients in the High Level General Hospital, Alberta, Canada. Anterior-posterior thigh diameters (APTD) were sonographically measured and the normal range for each week of pregnancy was determined five times for reliability. Significant correlation was found between (APTD) and fetal age from simple line regression analysis, with >99.9% confidence intervals at each week from 18 to 28 weeks gestation. There was a correlation of 1 mm APTD per 1 week of fetal age. The standard error of estimation was very low at (0.08664) in edition (r>0.9993) and (p < than 0.0001). The residual scatter plots confirmed the APTD validity. APTD is a reliable and valid method for assessing fetal age in a normal pregnancy and may be particularly useful when other parameters are unable accurately to predict fetal age. An accurate linear measurement of multiple fetal parameters allows a more complete profile of fetal growth and estimated date of delivery (EDD). APTD may also be useful in identifying fetal growth problems. All of the values of fetal age lie directly on the "best-fit" regression line. Since the coefficient of determination (Rsq) is very high, this model is very effective.


Codon-substitution models for detecting molecular adaptation at individual sites along specific lineages.
The nonsynonymous (amino acid-altering) to synonymous (silent) substitution rate ratio (omega = d(N)/d(S)) provides a measure of natural selection at the protein level, with omega = 1, >1, and <1, indicating neutral evolution, purifying selection, and positive selection, respectively. Previous studies that used this measure to detect positive selection have often taken an approach of pairwise comparison, estimating substitution rates by averaging over all sites in the protein. As most amino acids in a functional protein are under structural and functional constraints and adaptive evolution probably affects only a few sites at a few time points, this approach of averaging rates over sites and over time has little power. Previously, we developed codon-based substitution models that allow the omega ratio to vary either among lineages or among sites. In this paper we extend previous models to allow the omega ratio to vary both among sites and among lineages and implement the new models in the likelihood framework. These models may be useful for identifying positive selection along prespecified lineages that affects only a few sites in the protein. We apply those branch-site models as well as previous branch- and site-specific models to three data sets: the lysozyme genes from primates, the tumor suppressor BRCA1 genes from primates, and the phytochrome (PHY) gene family in angiosperms. Positive selection is detected in the lysozyme and BRCA genes by both the new and the old models. However, only the new models detected positive selection acting on lineages after gene duplication in the PHY gene family. Additional tests on several data sets suggest that the new models may be useful in detecting positive selection after gene duplication in gene family evolution.


[Investigation of transcriptional regulation of Oct4 (POU5F1) gene with distal enhancer].
Investigations of transcriptional regulation of Oct4 gene in mouse embryonic stem cells have revealed an important cis-element--the distal enhancer (DE). DE consists of two functionally significant elements--DEa and DEb. Both elements are necessary to complete the DE-mediated expression of Oct4 gene in pluripotent cells. The most likely candidates for the binding site DEb are Oct4 itself in complex with Sox2 protein. It remains unclear which transcriptional proteins bind to the DEa site and what is the mechanism of the co-operation between the DEa and the DEb. Through the use of using the EMSA and chromatographic fractionation of proteins from extracts of mouse embryonic stem cells and mouse tissues, were isolated proteins specifically interacting with the sequence DEa Oct4 gene.


Regulation of inflammation and immunity in sepsis by E3 ligases.
Sepsis is a life-threatening organ dysfunction caused by an abnormal infection-induced immune response. Despite significant advances in supportive care, sepsis remains a considerable therapeutic challenge and is the leading cause of death in the intensive care unit (ICU). Sepsis is characterized by initial hyper-inflammation and late immunosuppression. Therefore, immune-modulatory therapies have great potential for novel sepsis therapies. Ubiquitination is an essential post-translational protein modification, which has been known to be intimately involved in innate and adaptive immune responses. Several E3 ubiquitin ligases have been implicated in innate immune signaling and T-cell activation and differentiation. In this article, we review the current literature and discuss the role of E3 ligases in the regulation of immune response and their effects on the course of sepsis to provide insights into the prevention and therapy for sepsis.


Molecular cloning, expression, and characterization of chicken IFN -lambda.
Interferons (IFN) provide a critical first line of defense against viral infection in vertebrates. Moreover, IFN-lambda, a recently identified group of mammalian IFN, has demonstrated antiviral potential in the treatment of mammalian viruses. With the growing concern over such diseases as avian influenza (AI), there is a pressing need for new antiviral strategies to manage problem viruses in poultry. Furthermore, the use of immune molecules, such as IFN-lambda, provides an attractive option for treating poultry by augmenting the host response to virus. With this in mind, we report here the first cloning, expression, and analysis of biologic activity of chicken IFN-lambda (ChIFN-lambda). We compared the similarity of ChIFN-lambda to those identified in other species and demonstrate that ChIFN-lambda has antiviral properties similar to those of human IFN-lambda (HuIFN-lambda). Our results demonstrate that in the chicken, as in human, the antiviral activity demonstrated by ChIFN-lambda supports its inclusion in therapeutic strategies directed against viral infections.


Ogilvie Syndrome, Bradycardia, and Neostigmine.
Acute colonic pseudo-obstruction (ACPO), known as Ogilvie Syndrome, is an acute dilation of the colon in the absence of an underlying mechanical or anatomic cause. Neostigmine treatment is indicated following failed conservative management of ACPO, however neostigmine has its contraindications. This is a report of a unique case of a patient with a past medical history of symptomatic first degree heart block with a permanent pacemaker who received a bolus dosage of neostigmine treatment for ACPO in an ICU setting.


Retraction.
Retraction: "The role of HOTAIR-induced downregulation of microRNA-126 and interleukin-13 in the development of bronchial hyperresponsiveness in neonates," by Dong-Mei Wu, Zi-Hui Zheng, Shan Wang, Xin Wen, Xin-Rui Han, Yong-Jian Wang, Min Shen, Shao-Hua Fan, Zi-Feng Zhang, Qun Shan, Meng-Qiu Li, Bin Hu, Yuan-Lin Zheng, Gui-Quan Chen, Jun Lu, J Cell Physiol. 2019; 16400-16411: The above article, published online on 21 February 2019 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/full/10.1002/jcp.28309), has been retracted by agreement between the journal's Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed after Gui-Quan Chen stated to be listed as a coauthor despite qualification for contributorship was not fulfilled. An investigation revealed several flaws and inconsistencies between results presented and experimental methods described were found, and so the editors consider the conclusions of this article to be invalid. The authors were not available for a final confirmation of the retraction.


Prevalence of metabolic syndrome among the adult population in western China and the association with socioeconomic and individual factors: four cross-sectional studies.
This study explored the prevalence of and individual influencing factors for metabolic syndrome (MS) as well as associated socioeconomic factors and regional aggregation. Four cross-sectional surveys were analysed for trends in MS and associations with socioeconomic and individual factors through multilevel logistic regression analyses. The risk associated with nutrient intake was also assessed through a dietary survey in 2015. From 2010 to 2018, 8-15 counties/districts of West China were included. A total of 28 274 adults were included in the prevalence analysis. A total of 23 708 adults were used to analyse the related factors. The overall prevalence of MS ranged from 21.4% to 27.8% over the 8 years, remaining basically stable within the 95% CI. Our study found that the urbanisation rate and hospital beds per 1000 people were positively associated with MS, and the number of doctors in healthcare institutions per 1000 persons was negatively associated with MS. The ORs for females, people with college education and higher and unmarried or single people were 1.49, 0.67 and 0.51, respectively (p<0.05). The ORs of people who smoked at least 20 cigarettes/day, ate more than 100 g of red meat/day, consumed fruit or vegetable juice and drank carbonated soft drinks less than weekly were 1.10, 1.16, 1.19-1.27 and 0.81-0.84, respectively. The ORs rose with increasing sedentary time and decreased with higher physical activity. The high burden of MS, unreasonable proportions of energy and micronutrient intake and low percentage of high levels of physical activity were the major challenges to public health in western China. Improving the human resources component of medical services, such as the number of doctors, increasing the availability of public sports facilities and E-health tools and improving individual dietary quality and education might help prevent MS.


You known who and what's her name: the woman's role in sex therapy.
As sex therapy becomes an established mode of treatment, the original Masters and Johnson model of cotherapy is its most common form. The complex issues in the relationship between cotherapists who are doing sex therapy have not received adequate attention. Differences in status, experience, and training combine with aspects of the personal relationship between therapists to make cotherapy a substantial problem. Whether the cotherapists are married, otherwise involved in a personal relationship, or even when they are a physician and his nurse or two independent therapists, the sexual content of their work inevitably raises issues that need to be resolved. These issues include erotic fantsies and power struggles between the therapists that can affect the outcome of treatment.


Positioning blinatumomab in the frontline of adult B-cell acute lymphoblastic leukemia treatment.
Blinatumomab is a bispecific T cell engager that has shown efficacy in relapsed/refractory Philadelphia chromosome (Ph)-positive and Ph-negative acute lymphoblastic leukemia (ALL). Considering its favorable safety and activity in advanced ALL, blinatumomab as a targeted immunotherapy is fast gaining a frontline position in the ALL treatment paradigm. There have been multiple completed and ongoing studies showing significant promise with improved response rates and survival outcomes and decreased treatment toxicity and need for multi-agent chemotherapy regimens. The early use of blinatumomab has established success in Ph-negative and Ph-positive B-ALL, and this has extended to older adults with ALL who have historically had substantially inferior outcomes compared to their pediatric and young adult counterparts. Herein we will review the current data describing the early use of blinatumomab in newly diagnosed adults with B-cell ALL and future directions.


Laser-driven shock waves studied by x-ray radiography.
Multimegabar laser-driven shock waves are unique tools for studying matter under extreme conditions. Accurate characterization of shocked matter is for instance necessary for measurements of equation of state data or opacities. This paper reports experiments performed at the LULI facility on the diagnosis of shock waves, using x-ray-absorption radiography. Radiographs are analyzed using standard Abel inversion. In addition, synthetic radiographs, which also take into account the finite size of the x-ray source, are generated using density maps produced by hydrodynamic simulations. Reported data refer to both plane cylindrical targets and hemispherical targets. Evolution and deformation of the shock front could be followed using hydrodynamic simulations.


Clinical Features and Diagnostic Considerations in Psoriatic Arthritis.
Psoriatic arthritis is an inflammatory musculoskeletal disease affecting almost a third of patients with psoriasis. Clinical presentations are complex and varied and include peripheral arthritis, axial disease, dactylitis, and enthesitis, as well as skin and nail manifestations. We lack diagnostic biomarkers, but specific clinical and imaging features distinguish psoriatic arthritis from other forms of arthritis such as rheumatoid arthritis, gout, osteoarthritis, and other forms of spondyloarthritis.


Implementation of the Sono-Heat-Exchanger in the Extra Virgin Olive Oil Extraction Process: End-User Validation and Analytical Evaluation.
The use of innovative systems, such as the heat exchanger, for production of extra virgin olive oil should allow maintenance of the same quality of those oils derived from traditional processes, and presents specific advantages. The performance of this system was evaluated by (i) determining the parameters directly measurable by the olive millers (i.e., end-user validation based on the production yields when the plant is located in different processing lines) and (ii) assessing the product quality through estimation of the content of phenolic and volatile compounds. The phenols were determined by High Performance Liquid Chromatography with Diode Array Detector (HPLC-DAD) before and after acidic hydrolysis while the volatile fraction was studied by Head-Space Solid-Phase-Micro-Extraction Gas-Chromatography with Mass Detector (HS-SPME-GC-MS). The use of the sono-heat-exchanger presents several advantages: it is a flexible machine, able to interface with all devices of the world's leading manufacturers of the Extra Virgin Olive Oil (EVOO) extraction plant, and it guarantees shorter processing times and energy savings. Our results also pointed out its capability to increase the oil yields up to 5.5%, particularly when it extracts oil from unripe fruits, which in traditional processes yield oils with higher phenolic contents, but with lower oil yields. Overall, the quality of virgin olive oils was maintained, avoiding decreases of phenolic content or detrimental effects on the sensory characteristics.


Changes of AM fungal abundance along environmental gradients in the arid and semi-arid grasslands of northern China.
Arbuscular mycorrhizal (AM) fungi are ubiquitous symbionts of higher plants in terrestrial ecosystems, while the occurrence of the AM symbiosis is influenced by a complex set of abiotic and biotic factors. To reveal the regional distribution pattern of AM fungi as driven by multiple environmental factors, and to understand the ecological importance of AM fungi in natural ecosystems, we conducted a field investigation on AM fungal abundance along environmental gradients in the arid and semi-arid grasslands of northern China. In addition to plant parameters recorded in situ, soil samples were collected, and soil chemo-physical and biological parameters were measured in the lab. Statistical analyses were performed to reveal the relative contribution of climatic, edaphic and vegetation factors to AM fungal abundance, especially for extraradical hyphal length density (HLD) in the soil. The results indicated that HLD were positively correlated with mean annual temperature (MAT), soil clay content and soil pH, but negatively correlated with both soil organic carbon (SOC) and soil available N. The multiple regressions and structural equation model showed that MAT was the key positive contributor and soil fertility was the key negative contributor to HLD. Furthermore, both the intraradical AM colonization (IMC) and relative abundance of AM fungi, which was quantified by real-time PCR assay, tended to decrease along the increasing SOC content. With regard to the obvious negative correlation between MAT and SOC in the research area, the positive correlation between MAT and HLD implied that AM fungi could potentially mitigate soil carbon losses especially in infertile soils under global warming. However, direct evidence from long-term experiments is still expected to support the AM fungal contribution to soil carbon pools.


Effect of Anticoagulant Administration on the Mortality of Hospitalized Patients With COVID-19: An Updated Systematic Review and Meta-Analysis.
Background: Anticoagulation is generally used in hospitalized patients with coronavirus disease 2019 (COVID-19) as thromboprophylaxis. However, results from different studies comparing the effect of anticoagulation on the mortality of COVID-19 patients with non-anticoagulation are inconclusive. Methods: Our systematic review included observational trials if they studied anticoagulant therapy in hospitalized patients with COVID-19 for mortality or bleeding events. Dichotomous variables from individual studies were pooled by risk ratio (RR) and their 95% confidence interval (95% CI) using the random-effects model. Grading of Recommendations Assessment, Development and Evaluation was used to assess the quality of evidence. Results: A total of 11 observational studies enrolling 20,748 hospitalized COVID-19 patients overall were included. A pooled meta-analysis of these studies showed that anticoagulation therapy, compared with non-anticoagulation therapy, was associated with lower mortality risk (RR 0.70, 95% CI 0.52-0.93, p = 0.01). The evidence of benefit was stronger among critically ill COVID-19 patients in the intensive care units (RR 0.59, 95% CI 0.43-0.83, p = 0.002). Additionally, severe bleeding events were not associated with the administration of anticoagulants (RR 0.93, 95% CI 0.71-1.23, p = 0.63). Conclusion: Among patients with COVID-19 admitted to hospital, the administration of anticoagulants was associated with a decreased mortality without increasing the incidence of bleeding events.


Black-Si as a Photoelectrode.
The fabrication and characterization of photoanodes based on black-Si (b-Si) are presented using a photoelectrochemical cell in NaOH solution. B-Si was fabricated by maskless dry plasma etching and was conformally coated by tens-of-nm of TiO2 using atomic layer deposition (ALD) with a top layer of CoO x cocatalyst deposited by pulsed laser deposition (PLD). Low reflectivity R < 5 % of b-Si over the entire visible and near-IR ( λ < 2   μ m) spectral range was favorable for the better absorption of light, while an increased surface area facilitated larger current densities. The photoelectrochemical performance of the heterostructured b-Si photoanode is discussed in terms of the n-n junction between b-Si and TiO2.


Restriction fragment length polymorphism (RFLP) of exon 2 of the MhcBibi-DRB3 gene in American bison (Bison bison).
Polymerase chain reaction (PCR) primers specific to exon 2 of the bovine lymphocyte antigen (BoLA)-DRB3 gene were successfully used to amplify the equivalent region in 469 American bison (Bison bison). In domestic cattle, alleles of DRB3 are assigned through a restriction fragment length polymorphism (RFLP) analysis of the patterns of fragment lengths observed after digestion with the restriction enzymes RsaI, BstYI and HaeIII. In bison, using the same procedure, the observed RFLP patterns provided evidence for the strong conservation of restriction sites previously reported in cattle.


Deubiquitinating enzyme 4 facilitates chemoresistance in glioblastoma by inhibiting P53 activity.
Glioblastoma is a malignant primary brain tumor with poor prognosis with a median survival of only 12-15 months. The high mortality rate of this disease is mainly due to the chemoresistance resulting from various reasons. Ubiquitin-specific protease 4 (USP4) has recently been found to be elevated in various types of cancer through regulating P53 activity. However, whether USP4 is responsible for chemoresistance in glioblastoma is not clear. In the present study, the expression of USP4 in glioblastoma tissues and cell lines, as well as its association with temozolomide (TMZ) chemoresistance was analyzed. The results demonstrated that USP4 was significantly upregulated in glioblastoma tissues and cell lines at the mRNA and protein levels. Notably, USP4 knockdown alone did not affect glioblastoma cell viability; however, when USP4 knockdown cells were treated with TMZ, the cell viability was decreased significantly. In addition, the results revealed that cleaved poly(ADP-ribose) polymerase level increased when USP4 was knocked down in glioblastoma cells treated with TMZ. It was also observed that P53 was increased in U251 and U87 cells with USP4 knockdown. Following treatment with a P53 specific inhibitor, the results suggested that USP4 mediated chemoresistance through inhibiting apoptosis in a P53-dependent manner. In conclusion, the data revealed the critical role of USP4 in TMZ resistance in glioblastoma and provided new insight for future drug development for the treatment of this disease.


Chronic Kidney Disease (CKD): An Observational Study of Etiology, Severity and Burden of Comorbidities.
To study the etiology and burden of comorbidities across stages of chronic kidney disease (CKD). Children, 2-16 y of age with CKD Stages II- IV were recruited over 12 mo. The etiology, clinical presentation and severity of complications were studied. Among 78 children [Stage II (n = 21), Stage III (n = 26), Stage IV (n = 31)], congenital anomalies of the kidney and urinary tract (CAKUT) was the commonest etiology and 28 were newly diagnosed in Stage III /IV. High prevalence of comorbidities was observed with growth retardation (65%), hypertension (59%), hyperphosphatemia (32%), vitamin D deficiency (92%), dyslipidemia (64%), left ventricular hypertrophy (45%) and hyperparathyroidism (56%). While most comorbidities correlated with the estimated glomerular filtration rate and severity of CKD, hypertension, vitamin D deficiency and cardiovascular morbidity were prevalent even in early stages. CAKUT was the commonest cause of CKD. Late detection and high prevalence of comorbidities even in early stages of CKD were observed.


Effect of laser photocoagulation on the retinal vessel diameter in branch and macular vein occlusion.
To investigate the response of retinal vessel diameters to photocoagulation treatment and their role for the success of laser treatment in patients with retinal vein occlusion. The study included 14 patients with branch vein occlusion or macular vein occlusion. The ophthalmologic examination included best-corrected visual acuity, biomicroscopy, fundus photography, and fluorescein angiography. Retinal vessel diameters were quantified before and after laser photocoagulation using a retinal vessel analyzer. Retinal vessel diameters. In cases manifesting macular vein occlusions, no significant change of the vessel diameter in any vessel was observed during the follow-up period. In the group with branch vein occlusion, all vessels tended to constrict after the laser photocoagulation. The effect of laser treatment on retinal vessel diameters was significant for superotemporal (P =.045, analysis of variance [ANOVA]) and inferotemporal branch veins (P =.03, ANOVA). Vasoconstriction was more pronounced in the occluded branch veins (P =.009, ANOVA) compared with the nonaffected veins (P =.12; ANOVA). The change of visual acuity after 3 months was correlated with the change of vessel diameter 3 months after laser treatment for occluded venular branches (r = 0.78, P =.02, linear regression). There was no correlation between the number of laser burns and the change of vessel diameters in the affected veins in this period (r = 0.12, P =.75, linear regression). Our results show that retinal photocoagulation in patients with branch vein occlusion has a vasoconstrictive effect on occluded veins. The correlation between the change in visual acuity and the change in vessel diameter indicates that branch vein constriction after photocoagulation may be an early indicator of the success of laser treatment.


Uremic frost: a harbinger of impending renal failure.
Uremic frost is a striking cutaneous finding seen in patients with severe kidney disease. Familiarity with this condition can be a life-saving signal to initiate urgent dialysis. Uremic frost generally occurs at blood urea nitrogen levels of approximately 200 mg/dl, although it may arise with less severe uremia. Recently confirmed urea transporters in the skin may play a role in the development of uremic frost. Alternatively, damage to the cutaneous microvasculature and pilosebaceous units, as seen in chronic kidney disease, could account for the high levels of urea deposited outside the skin. The treatment of uremic frost is largely aimed at correcting the underlying cause of uremia and the other life-threatening conditions associated with renal failure.


Regulation of alternative splicing in the generation of isoforms of the mouse Ly-5 (CD45) glycoprotein.
Alternative splicing generates various Ly-5 glycoprotein isoforms of the cell surface that typify different cell lineages and stages of hematopoietic differentiation in the mouse; exons 4-6 are incorporated to generate a B-cell isoform (B220) and excluded from a T-cell isoform (T200), the other coding exons (3 and 7-33) being shared. As a first step to understanding the mechanisms regulating Ly-5 alternative splicing, and thus determining Ly-5 isoforms, a minigene representing exons 3-7 was transfected into Ly-5-expressor T cells and B cells and into nonexpressor L cells for comparison of splicing patterns. We conclude that all the information required for faithful splice-site selection according to cell type is contained within the resulting pre-mRNA. The splicing pattern manifested by nonexpressor L cells may represent a default and nonregulated type. We postulate trans-acting factor(s) to account for the selection of appropriate exons, and we provide support for this interpretation from analysis of fused hybrid T-B cells, which exhibited B-cell specific Ly-5 transcripts. Splicing patterns were well conserved despite substantial disruption of constructs. However, extensive deletion analyses suggested that cis sequences flanking and within exon 6 affect the exclusion of that exon in T cells.


Drosophila UBE3A regulates satiety signaling through the Piezo mechanosensitive ion channel.
Angelman syndrome (AS) is a rare neurogenetic disorder characterized by developmental delays, speech impairments, ataxic movements, and in some cases, hyperphagic feeding behavior. Loss of function mutations, loss of expression from the maternal allele or absence of maternal UBE3A result in AS. Recent studies have established a connection between UBE3A and the mechanosensitive ion channel PIEZO2, suggesting the potential role of UBE3A in the regulation of PIEZO channels. In this study, we investigated the role of Drosophila UBE3A (Dube3a) in Piezo associated hyperphagic feeding behavior. We developed a novel assay using green fluorescent protein (GFP) expressing yeast to quantify gut distention in flies with Piezo and Dube3a mutations. We confirmed that Dube3a15b loss of function flies displayed gut distention to almost identical levels as PiezoKO flies. Further analysis using deficiency (Df) lines encompassing the Dube3a locus provided proof for a role of Dube3a in satiety signaling. We also investigated endogenous Piezo expression across the fly midgut and tracheal system. Piezo protein could be detected in both neurons and trachea of the midgut. Overexpression of Dube3a driven by the Piezo promoter resulted in distinct tracheal remodeling within the midgut. These findings suggest that Dube3a plays a key role in the regulation of Piezo and that subsequent dysregulation of these ion channels may explain the hyperphagic behavior observed in 32% of cases of AS. Further investigation will be needed to identify the intermediate protein(s) interacting between the Dube3a ubiquitin ligase and Piezo channels, as Piezo does not appear to be a direct ubiquitin substrate for UBE3A in mice and humans.


ON EVOLUTION UNDER SEXUAL AND VIABILITY SELECTION: A TWO-LOCUS DIPLOID MODEL.
A two-locus diploid model of sexual selection is presented in which the two loci govern, respectively, a trait limited in expression in one sex (generally male) and the mating preferences of the other sex (generally female). The viability of a male depends on its genotype at the trait locus. In contrast, all females are equally viable and all individuals are equally fertile with respect to the two loci. Near fixation at both loci, evolution at the mating locus is neutral and hence a new mating preference allele will increase only through random genetic drift or through a correlated response to the increase of a new advantageous trait allele. If, however, a polymorphism is already maintained at the trait locus through overdominance in fitness then the increase of a rare preference allele depends only on the recombination rate between the loci and not on the new preference scheme.


Vertebrate Reproduction.
Vertebrate reproduction requires a myriad of precisely orchestrated events-in particular, the maternal production of oocytes, the paternal production of sperm, successful fertilization, and initiation of early embryonic cell divisions. These processes are governed by a host of signaling pathways. Protein kinase and phosphatase signaling pathways involving Mos, CDK1, RSK, and PP2A regulate meiosis during maturation of the oocyte. Steroid signals-specifically testosterone-regulate spermatogenesis, as does signaling by G-protein-coupled hormone receptors. Finally, calcium signaling is essential for both sperm motility and fertilization. Altogether, this signaling symphony ensures the production of viable offspring, offering a chance of genetic immortality.


Understanding the basis of parasite strain-restricted immunity to Theileria parva.
Infection with Theileria parva is asymptomatic in African buffalo but results in severe disease in cattle. Currently, vaccination relies on infection and treatment, using a mixture of three parasite isolates to overcome the strain specificity of immunity. Genotypic analyses of field populations of T. parva indicate a panmictic population structure, reflecting frequent sexual recombination. Profound immunodominance of protective CD8 T cell responses, together with polymorphism of the target antigens and frequent genetic recombination, contribute to the strain-restricted immunity. The dominant CD8 target antigens are highly polymorphic, but the live vaccine appears to contain limited diversity. A model to explain the ability of the vaccine to confer immunity against highly diverse field parasite challenge is discussed. Parasites in cattle exhibit much more limited antigenic diversity than parasites in buffalo, consistent with other evidence that the cattle-maintained population represents a subset of T. parva recently adapted to cattle.


Evaluation of a fixed-dose combination of benazepril and pimobendan in dogs with congestive heart failure: a randomized non-inferiority clinical trial.
A fixed-dose combination tablet of benazepril and pimobendan (Fortekor Plus; Elanco Animal Health) was tested in dogs with congestive heart failure (CHF) caused by myxomatous mitral valve disease (MMVD) in a three-arm, masked, randomized, non-inferiority clinical trial in Japan. The test group (n = 34) received Fortekor Plus twice daily. Two control groups received registered formulations of benazepril (Fortekor; Elanco Animal Health) and pimobendan (Vetmedin; Boehringer Ingelheim Vetmedica) with administration of Vetmedin twice daily and Fortekor twice (Control I, n = 14) or once (Control II, n = 19) daily. Diuretics were used in 22 dogs (32.8%). Global clinical scores decreased significantly from baseline in all groups; there were no significant differences between groups, and non-inferiority of Fortekor Plus compared to Control I, Control II, and combined Control I + II groups was demonstrated. There were no significant differences between groups for relevant clinical chemistry and hematology variables or frequency of all adverse events. Frequency of emesis was significantly (p = 0.0042) lower in the Fortekor Plus (8.8%) group than in the Control I + II (39.4%) group. In conclusion, Fortekor Plus had non-inferior efficacy and was associated with significantly less emesis compared to Fortekor and Vetmedin in dogs with CHF caused by MMVD.


Effects of dextran molecular weight on red blood cell aggregation.
The reversible aggregation of human red blood cells (RBC) by proteins or polymers continues to be of biologic and biophysical interest, yet the mechanistic details governing the process are still being explored. Although a depletion model with osmotic attractive forces due to polymer depletion near the RBC surface has been proposed for aggregation by the neutral polyglucose dextran, its applicability at high molecular mass has not been established. In this study, RBC aggregation was measured over a wide range of dextran molecular mass (70 kDa to 28 MDa) at concentrations <or=2 g/dL. Our results indicate that aggregation does not monotonically increase with polymer size; instead, it demonstrates an optimum dextran molecular mass around 200-500 kDa. We used a model for depletion-mediated RBC aggregation to calculate the expected depletion energies. This model was found to be consistent with the experimental results and thus provides new insight into polymer-RBC interactions.


A Broadly Applicable Method for Characterizing the Slope of the Electrically Evoked Compound Action Potential Amplitude Growth Function.
Amplitudes of electrically evoked compound action potentials (eCAPs) as a function of the stimulation level constitute the eCAP amplitude growth function (AGF). The slope of the eCAP AGF (i.e., rate of growth of eCAP amplitude as a function of stimulation level), recorded from subjects with cochlear implants (CIs), has been widely used as an indicator of survival of cochlear nerve fibers. However, substantial variation in the approach used to calculate the slope of the eCAP AGF makes it difficult to compare results across studies. In this study, we developed an improved slope-fitting method by addressing the limitations of previously used approaches and ensuring its application for the estimation of the maximum slopes of the eCAP AGFs recorded in both animal models and human listeners with various etiologies. The new eCAP AGF fitting method was designed based on sliding window linear regression. Slopes of the eCAP AGF estimated using this new fitting method were calculated and compared with those estimated using four other fitting methods reported in the literature. These four methods were nonlinear regression with a sigmoid function, linear regression, gradient calculation, and boxcar smoothing. The comparison was based on the fitting results of 72 eCAP AGFs recorded from 18 acutely implanted guinea pigs, 46 eCAP AGFs recorded from 23 chronically implanted guinea pigs, and 2094 eCAP AGFs recorded from 200 human CI users from 4 patient populations. The effect of the choice of input units of the eCAP AGF (linear versus logarithmic) on fitting results was also evaluated. The slope of the eCAP AGF was significantly influenced by the slope-fitting method and by the choice of input units. Overall, slopes estimated using all five fitting methods reflected known patterns of neural survival in human patient populations and were significantly correlated with speech perception scores. However, slopes estimated using the newly developed method showed the highest correlation with spiral ganglion neuron density among all five fitting methods for animal models. In addition, this new method could reliably and accurately estimate the slope for 4 human patient populations, while the performance of the other methods was highly influenced by the morphology of the eCAP AGF. The novel slope-fitting method presented in this study addressed the limitations of the other methods reported in the literature and successfully characterized the slope of the eCAP AGF for various animal models and CI patient populations. This method may be useful for researchers in conducting scientific studies and for clinicians in providing clinical care for CI users.


Inflammatory cell infiltration and survival in squamous cell carcinoma of the vulva.
The prognostic significance of tumour infiltration by inflammatory cells in squamous cell carcinoma of the vulva was examined in a cohort of 34 patients surviving without recurrence for at least 5 years after radical surgery, and a comparative cohort of 35 patients who died of their diseases. Overall, heavy inflammatory infiltration correlated with a good prognosis and light infiltration with a poor one, independent of other indices such as differentiation, tumour size and nodal status. IgA-containing cell infiltration also correlated with a good prognosis but the presence of IgA-containing cells did not alone account for all the inflammation in the good prognosis group. An immunological response to the tumour may be influencing prognosis. At a practical level, the extent of inflammation appears, at least in this material, to be as useful a prognostic index as many more conventional ones.


Immunohistological identification of interleukin-1 activated chondrocytes.
Interleukin-1 activated chondrocytes have been identified in pig articular cartilage by immunolocalisation using a polyclonal antiserum recognising cytokine induced surface epitopes. Although chondrocytes with membrane staining were noted in all zones of the cartilage, only a proportion of the cells were positive within the range of antiserum dilution used (1:100-1:2000). Maximum staining was found after four days' treatment of cultured cartilage with pig IL-1 alpha, though weak staining was just detectable after treatment for one day at high antiserum concentration. Immunoreactivity was also shown in cartilage which had been cultured with human recombinant IL-1 alpha.


Serotonin and neuroplasticity - Links between molecular, functional and structural pathophysiology in depression.
Serotonin modulates neuroplasticity, especially during early life, and dysfunctions in both systems likewise contribute to pathophysiology of depression. Recent findings demonstrate that serotonin reuptake inhibitors trigger reactivation of juvenile-like neuroplasticity. How these findings translate to clinical antidepressant treatment in major depressive disorder remains unclear. With this review, we link preclinical with clinical work on serotonin and neuroplasticity to bring two pathophysiologic models in clinical depression closer together. Dysfunctional developmental plasticity impacts on later-life cognitive and emotional functions, changes of synaptic serotonin levels and receptor levels are coupled with altered synaptic plasticity and neurogenesis. Structural magnetic resonance imaging in patients reveals disease-state-specific reductions of gray matter, a marker of neuroplasticity, and reversibility upon selective serotonin reuptake inhibitor treatment. Translational evidence from magnetic resonance imaging in animals support that reduced densities and sizes of neurons and reduced hippocampal volumes in depressive patients could be attributable to changes of serotonergic neuroplasticity. Since ketamine, physical exercise or learning enhance neuroplasticity, combinatory paradigms with selective serotonin reuptake inhibitors could enhance clinical treatment of depression.


Enabling Extreme Low-Temperature (≤ -100 °C) Battery Cycling with Niobium Tungsten Oxides Electrode and Tailored Electrolytes.
The degradation of current Li-ion batteries (LIBs) hinders their use in electronic devices, electric vehicles, and other applications at low temperatures, particularly in extreme environments like the polar regions and outer space. This study presents a pseudocapacitive-type niobium tungsten oxides (NbWO) electrode material combined with tailored electrolytes, enabling extreme low-temperature battery cycling for the first time. The synthesized NbWO material exhibits analogous structural properties to previous studies. Its homogenous atom distribution can further facilitate Li+ diffusion, while its pseudocapacitive Li+ storage mechanism enables faster Li+ reactions. Notably, the NbWO electrode material exhibits remarkable battery performance even at -60 and -100 °C, showcasing capacities of ≈90 and ≈75 mAh g-1 , respectively. The electrolytes, which have demonstrated favorable Li+ transport attributes at low temperatures in the earlier investigations, now enable extreme low-temperature battery operations, a feat not achievable with either NbWO or the electrolytes independently. Moreover, the outcomes extend to -120 °C and encompass a pouch-type cell configuration at -100 °C, albeit with reduced performance. This study highlights the potential of NbWO for developing batteries for their use in extremely frigid environments.


Pediatric catheter interventions: a year in review 2004-2005.
The fields of pediatric and congenital cardiac interventions continue to expand at a rapid pace. The last few years have witnessed a tremendous explosion in procedures such as the transcatheter closure of secundum atrial septal defects, patent foramen ovale, patent ductus arteriosus, stent placement for pulmonary artery stenosis, and coarctation of the aorta. The purpose of this review is to highlight important publications in the last year and the direction the field is taking. Research data over the last year has concentrated on six main themes: (a) mid-to-long-term data for device closure of atrial septal defects, the incidence of late cardiac erosions, thrombus formation and heart block; (b) the transcatheter closure of muscular ventricular septal defects; (c) the transcatheter closure of perimembranous ventricular septal defects; (d) the placement of bioprosthetic valves in the pulmonary and aortic positions; (e) the 'hybrid' approach that combines surgical and interventional techniques in the management of various congenital cardiac defects; and (f) fetal interventions. This review outlines the key data presented in the literature involving interventional cardiology for pediatric and congenital cardiac defects over the last year. It illustrates that in close collaboration with industry, together with bioengineers and cardiothoracic surgeons, adult cardiac interventionists and perinatologists should continue to expand the role of pediatric catheter interventions. Fetal interventions have the potential to alter the natural history of abnormal cardiac development.


Diagnostic Importance of Platelet in Patients with Acute Coronary Syndrome Admitted in Mymensingh Medical College Hospital.
This cross sectional descriptive study was carried out in the Department of Cardiology, Mymensingh Medical College Hospital from July 2015 to December 2015, included 50 patients admitted with acute coronary syndrome diagnosed on the basis of history, typical anginal type of chest pain, characteristic electrocardiographic changes and increased cardiac biomarkers. Platelet count (PC), Mean platelet volume (MPV) and platelet distribution width (PDW) were measured using automated hematological analyzer and compared them with 50 age and sex matched healthy controls. All platelet parameter indices - platelet count (PC), mean platelet volume (MPV) & platelet distribution width (PDW) - were significantly raised in patients with ACS. In patients with ACS the mean values of platelet count, MPV & PDW were 352.2×10⁹/L), 13.9fL & 15.6fL, respectively; while in normal healthy control the mean values of these indices were 256.2×10⁹/L), 8.1fL & 10.5fL, respectively. Statistically significant difference in mean values of these indices was found (p value <0.05). Larger platelets are haemostatically more active and are a risk factor for developing coronary thrombosis and subsequent acute coronary events (myocardial infarction and unstable angina). Patients with larger platelets can easily be identified during routine hematological analysis and could possibly benefit from preventive treatment.


Optimization of Electrochemical Treatment Process Conditions for Distillery Effluent Using Response Surface Methodology.
Distillery industry is recognized as one of the most polluting industries in India with a large amount of annual effluent production. In this present study, the optimization of electrochemical treatment process variables was reported to treat the color and COD of distillery spent wash using Ti/Pt as an anode in a batch mode. Process variables such as pH, current density, electrolysis time, and electrolyte dose were selected as operation variables and chemical oxygen demand (COD) and color removal efficiency were considered as response variable for optimization using response surface methodology. Indirect electrochemical-oxidation process variables were optimized using Box-Behnken response surface design (BBD). The results showed that electrochemical treatment process effectively removed the COD (89.5%) and color (95.1%) of the distillery industry spent wash under the optimum conditions: pH of 4.12, current density of 25.02 mA/cm(2), electrolysis time of 103.27 min, and electrolyte (NaCl) concentration of 1.67 g/L, respectively.


Localized kinking during deployment of a flow redirection lumen device (FRED) could be due to excessive pushing.
The safety and efficacy analysis of flow redirection lumen device (FRED) demonstrated the excellent safety profile of FREDs for aneurysm treatment. We describe the first case in which FRED deployment for a paraclinoid aneurysm resulted in in-stent stenosis, necessitating balloon angioplasty, and an additional stent. A 50-year-old woman had a left paraclinoid aneurysm with a maximum diameter of 6.1 mm. We planned FRED deployment. We experienced in-stent stenosis just after the deployment of a FRED. Devices such as guidewires and catheters could not cross the lesion through the FRED because of an obstruction in the FRED. Balloon angioplasty and subsequent stenting resolved thrombosis and kinking. FRED has potential for kinking locally. Surgeons should consider this possibility when treating cerebral aneurysm using FRED. Cone-beam computed tomography after deployment of FRED may be useful for evaluating the stent shape.


Dual-parameter model for prediction of type I diabetes mellitus.
The recent cloning and recombinant expression of novel islet autoantigens [glutamic acid decarboxylase (GAD) 65 and islet-cell autoantibody 512 (ICA512)] has made possible the determination of whether the quantitative expression of autoantibodies to these molecules is correlated with age of diabetes onset and rate of progression to diabetes, similar to insulin autoantibodies (IAAs). We measured autoantibodies reacting with GAD65 (GAD65AA), ICA512 (ICA512AA), and insulin in patients who recently had received a diagnosis of diabetes and in first-degree relatives prospectively identified and then followed because of the expression of high titers of ICA. Levels of IAAs (but not GAD65AA or ICA512AA) correlated inversely with age at diagnosis of diabetes and directly with time to diabetes onset among the ICA-positive relatives. In multiple linear regression models, the level of IAAs remained a significant predictor of the time to diabetes after allowing for first-phase insulin secretion. The unique and dramatic association of IAAs with progression to diabetes suggests that IAAs contribute directly to disease pathogenesis or that levels of IAAs are influenced uniquely by the process, leading--at different rates in different prediabetic individuals--to type I diabetes. In addition, the linear regression model described (involving two variables, first-phase insulin secretion and levels of IAAs) aids in the prediction of time to diabetes among ICA-positive relatives.


Identification of opuC as a chill-activated and osmotically activated carnitine transporter in Listeria monocytogenes.
The food-borne pathogen Listeria monocytogenes is notable for its ability to grow under osmotic stress and at low temperatures. It is known to accumulate the compatible solutes glycine betaine and carnitine from the medium in response to osmotic or chill stress, and this accumulation confers tolerance to these stresses. Two permeases that transport glycine betaine have been identified, both of which are activated by hyperosmotic stress and one of which is activated by low temperature. An osmotically activated transporter for carnitine, OpuC, has also been identified. We have isolated a Tn917-LTV3 insertional mutant that could not be rescued from hyperosmotic stress by exogenous carnitine. The mutant, LTS4a, grew indistinguishably from a control strain (DP-L1044) in the absence of stress or in the absence of carnitine, but DP-L1044 grew substantially faster under osmotic or chill stress in the presence of carnitine. LTS4a was found to be strongly impaired in KCl-activated as well as chill-activated carnitine transport. 13C nuclear magnetic resonance spectroscopy of perchloric acid extracts showed that accumulation of carnitine by LTS4a was negligible under all conditions tested. Direct sequencing of LTS4a genomic DNA with a primer based on Tn917-LTV3 yielded a 487-bp sequence, which allowed us to determine that the opuC operon had been interrupted by the transposon. It can be concluded that opuC encodes a carnitine transporter that can be activated by either hyperosmotic stress or chill and that the transport system plays a significant role in the tolerance of L. monocytogenes to both forms of environmental stress.


Microfluidic assistant beat-frequency interferometer based on a single-hole-infiltrated dual-mode microstructured optical fiber.
A microfluidic assistant beat-frequency interferometer based on a single-hole-infiltrated dual-mode microstructured optical fiber (DM-MOF) is proposed and demonstrated. The interferometer is constructed by inserting a piece of fluid-filled DM-MOF into two sections of single-mode fiber with slight core-offset. The mode-mismatch induced interferences with high-frequency dips and low-frequency envelope are observed in the transmission spectrum. Theoretical and experimental investigations reveal that the beat-frequency spectrum works from the interferences between LP(01) core mode and the components of LP(11) core mode with close but different frequencies. The deliberately infiltrated liquid rod in the air hole located at the second ring near the core of the DM-MOF enhances the sensitivity of the envelope to temperature or axial force. However, it shows little impact on the high-frequency dips. The distinguishing sensitivities of -959.22 pm/°C (-70.59 pm/°C) and 24.26 nm/N (-3.14 nm/N) for the envelope (dips) are simultaneously achieved in experiment, allowing for dual parameter measurement in such a compact structure.


Fast simulation and design of the fiber probe with a fiber-based pupil filter for optical coherence tomography using the eigenmode expansion approach.
Fiber probes for optical coherence tomography (OCT) recently employ a short section of step-index multimode fiber (SIMMF) to generate output beams with extended depth of focus (DOF). As the focusing region of the output beam is generally close to the probe end, it is not feasible to adopt the methods for bulk-optics with spatial pupil filters to the fiber probes with fiber-based filters. On the other hand, the applicable method of the beam propagation method (BPM) to the fiber probes is computationally inefficient to perform parameter scan and exhaustive search optimization. In this paper, we propose the method which analyzes the non-Gaussian beams from the fiber probes with fiber-based filters using the eigenmode expansion (EME) method. Furthermore, we confirm the power of this method in designing fiber-based filters with increased DOF gain and uniformly focusing by introducing more and higher-order fiber modes. These results using the EME method are in good agreement with that by the BPM, while the latter takes 1-2 orders more computation time. With higher-order fiber modes involved, a novel probe design with increased DOF gain and suppressed sidelobe is proposed. Our findings reveal that the fiber probes based on SIMMFs are able to achieve about four times DOF gain at maximum with uniformly focusing under acceptable modal dispersion. The EME method enables fast and accurate simulation of fiber probes based on SIMMFs, which is important in the design of high-performance fiber-based micro-imaging systems for biomedical applications.


Feasibility, comprehensibility and acceptability of the VISION-Cog, a novel tool to assess cognitive impairment in visually impaired older adults: a cross-sectional pilot study in Singapore.
We pilot-tested the VISually Independent test battery Of NeuroCOGnition (VISION-Cog) to determine its feasibility, comprehensibility and acceptability in evaluating cognitive impairment (CI) in visually impaired older Asian adults. The VISION-Cog was iteratively fine-tuned through pilot studies and expert-panel discussion. In the first pilot study (Stage 1), we recruited 15 visually impaired and cognitively normal participants aged ≥60 years to examine the pilot VISION-Cog's feasibility (length of time to administer), comprehensibility (clarity of instructions) and acceptability (participant burden). We then presented the pilot results to the expert panel (Stage 2) who decided via agreement on a revised version of the VISION-Cog. Subsequently, we conducted a second pilot study (Stage 3) on another four participants to ascertain improvement in feasibility, comprehensibility and acceptability of the revised version. Singapore Eye Research Institute. Nineteen Asian adults aged ≥60 years with visual impairment (defined as near visual acuity worse than N8) were recruited. Revised VISION-Cog. The VISION-Cog was deemed feasible, taking approximately 60 min to complete on average. All participants agreed that the test instructions were clear, and the battery did not cause undue discomfort or frustration. The data collector rated all tests as very user-friendly (score of 5/5). Minor modifications to the pilot VISION-Cog were suggested by the panel to improve its safety, clarity of instructions and content validity, which were incorporated and iteratively tested in the second pilot study until no further issues emerged. Using an iterative mixed-methods process, we have developed a feasible, comprehensible and acceptable 5-domain and 9-item visually independent VISION-Cog test battery suitable to assist CI diagnosis in older adults with visual impairment. We will assess its diagnostic potential against clinician-based assessment of CI in subsequent phases.


The critical interval in dolphin echolocation: what is it?
A backward masking function relating target detection to masker delay was generated for a bottlenosed dolphin in an active echolocation target detection task. The masker was triggered by each outgoing echolocation click and could be temporally adjusted from coincidence with the target echo to delays of 700 microseconds. The animal reported target condition using a go/no-go response procedure. A modified method of constants was used to present the four masking delay intervals. Results indicated that 700- and 500-microseconds delays had little effect on target detection. However, as the delay was reduced to 100 microseconds, detection dropped to chance performance. The calculated 70% detection threshold corresponded to a delay of 265 microseconds. The results are discussed in support of the view that time separation pitch (TSP) may be an analytic mechanism used by the dolphin to discern various within-echo target attributes rather than an analytic mechanism for determining target range.


Neuropsychological tests in the elderly: methods and sample characteristics of a GRECC study.
This report describes the methods and sample characteristics of a neuropsychological study of the elderly conducted by the Geriatric Research, Education and Clinical Center of the Department of Veterans Affairs Medical Center in Minneapolis, Minnesota. The goal of the study was to provide normative data, internal consistency and 1-year reliability estimates, and validated methods of estimating expected performance level. Thirty-one cognitive measures and a demographic questionnaire were administered to an age-, education-, and gender-stratified sample ( N = 349) and a validation sample (N = 70). After 1 year, 104 of the participants were retested. Relative to published, nationally based normative data, the stratified sample showed performance levels that ranged from average to high average across the five tests examined.


Highly efficient degradation of pharmaceutical sludge by catalytic wet oxidation using CuO-CeO2/γ-Al2O3 as a catalyst.
Pharmaceutical sludge is considered as a hazardous material with high treatment and disposal costs. In the present study, the catalytic wet oxidation (CWO) of pharmaceutical sludge by CuO-CeO2/γ-Al2O3 as the catalyst was investigated. The catalyst was prepared by traditional wet impregnation. The catalyst was characterized using X-ray Powder Diffraction (XRD) and Scanning Electron Microscopy (SEM). CWO was performed in an experimental batch reactor. Several parameters that could affect the catalytic degradation efficiency, including catalyst dose, temperature, time, oxygen pressure and pH, were investigated. Under optimum conditions, the highest removal rate of volatile suspended solids (VSS) was 87.3% and was achieved at 260°C for 60 min with an oxygen pressure of 1.0 MPa and 10 g/L of catalyst. At the same time, the chemical oxygen demand (COD) removal rate reached as high as 72.6%. This work implies that catalytic wet oxidation is a promising method for the highly efficient degradation of pharmaceutical sludge.


Variations in consenting practice for laparoscopic cholecystectomy.
To compare the variations in consenting practice amongst trainees and consultant surgeons for laparoscopic cholecystectomy with specific reference to the documentation of significant risks of surgery. A proforma was devised which included significant and/or commonly recognised complications of laparoscopic cholecystectomy. This was then cross-referenced with the consent forms for the 80 patients included in the study and the documented risks explained in each case were noted. The results showed that there is considerable variation between the three grades of clinicians involved in obtaining a patient's consent for laparoscopic cholecystectomy. There was a clear difference in emphasis of the significant complications depending on the seniority of the consenter. Over 80% of the consents in this study were still being obtained by junior staff. More often than not, patients are not provided with consistent information to make an informed choice. We suggest that a preprinted consent form will provide a more uniform approach to consenting practice for laparoscopic cholecystectomy.


Novel Approaches to Analyze Immunoglobulin Repertoires.
Analysis of immunoglobulin (Ig) repertoires aims to comprehend Ig diversity with the goal of predicting humoral immune responses in the context of infection, vaccination, autoimmunity, and malignancies. The first next-generation sequencing (NGS) analyses of bulk B cell populations dramatically advanced sampling depth over previous low-throughput single-cell-based protocols, albeit at the expense of accuracy and loss of chain-pairing information. In recent years the field has substantially differentiated, with bulk analyses becoming more accurate while single-cell approaches have gained in throughput. Additionally, new platforms striving to combine high throughput and chain pairing have been developed as well as various computational tools for analysis. Here we review the developments of the past 4-5 years and discuss the open challenges.


[Imaging of nasopharyngeal diseases].
This article gives an overview about the main nasopharyngeal pathologies and incidental findings, which a radiologist could be confronted with in daily practice. These include nasopharyngeal cysts, lymphoid hyperplasia, juvenile angiofibroma, carcinomas and non-Hodgkin lymphoma. Typical radiological findings, possibilities for making a specific diagnosis, differential diagnosis and description of the spread of a neoplasm are the central points. Investigation techniques and clinical signs are briefly summarized.


Malaria in Children.
Malaria is a leading cause of morbidity and mortality in endemic areas, leading to an estimated 438,000 deaths in 2015. Malaria is also an important health threat to travelers to endemic countries and should be considered in evaluation of any traveler returning from a malaria-endemic area who develops fever. Considering the diagnosis of malaria in patients with potential exposure is critical. Prompt provision of effective treatment limits the complications of malaria and can be life-saving. Understanding Plasmodium species variation, epidemiology, and drug-resistance patterns in the geographic area where infection was acquired is important for determining treatment choices.


A double blind, placebo-controlled randomized comparative study on the efficacy of phytosterol-enriched and conventional saw palmetto oil in mitigating benign prostate hyperplasia and androgen deficiency.
The present clinical trial was conducted to evaluate the efficacy and tolerability of a standardized saw palmetto oil containing 3% β-sitosterol in the treatment of benign prostate hyperplasia (BPH) and androgen deficiency. Subjects aged 40-65 years with symptomatic BPH were randomized to 12-week double-blind treatment with 500 mg doses of β-sitosterol enriched saw palmetto oil, conventional saw palmetto oil and placebo orally in the form of capsules (n = 33 in each group). BPH severity was determined using the International Prostate Symptom Score (IPSS), uroflowmetry, serum measurement of prostate specific antigen (PSA), testosterone and 5α-reductase. During the trial, the androgen deficiency was evaluated using Aging Male Symptoms (AMS) scale, the Androgen Deficiency in the Aging Male (ADAM) questionnaire, serum levels of free testosterone. Subjects treated with β-sitosterol enriched saw palmetto oil showed significant decrease in IPSS, AMS and ADAM scores along with reduced postvoiding residual volume (p < 0.001), PSA (p < 0.01) and 5α-reductase from baseline to end of 12-week treatment as compared to placebo. There was also a significant increment in the maximum and average urine flow rate (p < 0.001), and serum free testosterone level of subjects treated with enriched saw palmetto oil as compared to placebo. This study demonstrates the efficacy of β-sitosterol enriched saw palmetto oil superior to conventional oil thus extending the scope of effective BPH and androgen deficiency treatment with improved quality of life through the intake of functional ingredients. CTRI/2018/12/016724 dated 19/12/2018 prospectively registered. URL: http://ctri.nic.in/Clinicaltrials/advsearch.php.


Molecular Characterization of a Recombinant Isolate of Tomato Leaf Curl New Delhi Virus Associated with Severe Outbreaks in Zucchini Squash in Southern Italy.
The molecular characterization of a tomato leaf curl New Delhi virus (ToLCNDV) isolate, denoted ToLCNDV-Le, is reported. The virus was associated with severe and recurrent outbreaks in protected crops of zucchini squash grown in the Province of Lecce (Apulia, southern Italy). The fully sequenced genome of ToLCNDV-Le consists of two genomic components named DNA-A and DNA-B of 2738 and 2683 nt in size, respectively. Like other ToLCNDV isolates, ToLCNDV-Le DNA-A contains the AV2 and AV1 open reading frames (ORFs) in the virion-sense orientation and five additional ORFs named AC1, AC2, AC3, AC4 and AC5 in the complementary-sense orientation. The DNA-B contains BV1 ORF in the virion-sense orientation and BC1 ORF in the complementary-sense orientation. No DNA betasatellites were found associated with ToLCNDV-Le in naturally infected samples. Phylogenetic analysis clustered ToLCNDV-Le with the ToLCNDV-ES strain of western Mediterranean Basin isolates. Consequently, the ToLCNDV-ES-[IT-Zu-Le18] name is proposed as the descriptor for ToLCNDV-Le. Using recombination detection program RDP4, one putative recombination breakpoint (Rbp) was identified close to nucleotide positions 2197-2727, covering approximately half of the AC1 region, including the AC4 ORF and the 3' UTR. RDP4 indicated the event represents an Rbp of an isolate similar to ToLCNDV [Pk-06] (Acc. No. EF620534) found in Luffa acutangula in Pakistan and identified as putative minor parent into the background of ToLCNDV [BG-Jes-Svr-05] (Acc. No. AJ875157), found in tomato in Bangladesh, and identified as putative major parent. To the best of our knowledge, this is the first report of a ToLCNDV-ES recombinant isolate in the AC1-AC4 region in Italy.


Tuberculous bronchitis in children.
Of 63 children with primary pulmonary tuberculosis who were examined bronchoscopically without particular regard for the usual criteria for the procedure, 18 (28.5 per cent) had visible tuberculous bronchitis.Certain endobronchial lesions resolved spontaneously, others responded to bronchoscopic treatment, and still others persisted despite all efforts.X-ray observations and clinical signs were of limited value in determining prior to bronchoscopy which child would have visible bronchial disease. Bronchoscopy is essential for both diagnosis and treatment of these lesions. Tuberculous bronchitis should be suspected whenever a child who is being treated for pulmonary tuberculosis by conservative means does not improve.


Two-dimensional nMR study of bleomycin and its zinc(II) complex: reassignment of 13C resonances.
Two-dimensional NMR experiments--one bond 1H-13C correlation spectroscopy and heteronuclear multiple bond correlation spectroscopy, both performed in the reverse detection mode--have been employed to unambiguously assign all of the 13C resonances of the antibiotic bleomycin and its zinc(II) complex. Previous 1H resonance assignments of bleomycin (Chen et al. (1977) Biochemistry 16, 2731-2738) were confirmed on the basis of homonuclear Hartmann-Hahn and homonuclear COSY experiments. The 13C assignments differ substantially from those previously obtained by other investigators (Naganawa et al., (1977) J. Antibiot. 30, 388-396; Dabrowiak et al., (1978) Biochemistry 17, 4090-4096) but are in agreement with those reported by Akkerman et al. (1988) (Magn. Reson. Chem. 26, 793-802). The more recent study employed similar two-dimensional correlation experiments (performed in the direct detection mode) in conjunction with attached proton tests. Their study often required model compound data to identify carbonyls adjacent to aliphatic moieties. Previous 13C NMR studies of the structure, pH titration, and molecular dynamics of bleomycin and its zinc complex have been reinterpreted in terms of the revised assignments.


Automated telecommunication to obtain longitudinal follow-up in a multicenter cross-sectional COPD study.
It can be challenging to maintain longitudinal follow-up of subjects in clinical studies. COPDGene is a multicenter, observational study designed to identify genetic factors associated with COPD and to characterize COPD-related phenotypes. To obtain follow-up data on patient's vital status and outcomes, the COPDGene Longitudinal Follow-up (LFU) Program was developed to supplement its parent study. We used a telecommunication system that employed automated telephone contact or web-based questions to obtain longitudinal follow-up data in our subjects. A branching questionnaire asked about exacerbations, new therapies, smoking status, development of co-morbid conditions, and general health status. Study coordinators contacted subjects who did not respond to one of the automated methods. We enrolled 10,383 subjects in the COPDGene study. As of August 29, 2011, 7,959 subjects completed 19,955 surveys. On the first survey, 68.8% of subjects who completed their survey did so by electronic means, while 31.3% required coordinator phone follow-up. On each subsequent survey the number of subjects who completed their survey by electronic means increased, while the number of subjects who required coordinator follow-up decreased. Despite many of the patients in the cohort being chronically ill and elderly, there was broad acceptance of the system with over half the cohort using electronic response methods. The COPDGene LFU Study demonstrated that telecommunications was an effective way to obtain longitudinal follow-up of subjects in a large multicenter study. Web-based and automated phone contacts are accepted by research subjects and could serve as a model for LFU in future studies.