Factors affecting the loading efficiency of water-soluble drugs in PLGA microspheres.
Poly(lactide-co-glycolide), PLGA, microspheres containing blue dextran as a hydrophilic model drug were prepared by a solvent evaporation method from w/o/w emulsions using a micro homogenizer. Effects of surfactant concentration in oil phase, stirring time period and stirring rate in the preparation procedure of primary emulsion (w/o) upon drug-loading efficiency were evaluated. Stirring rate during preparation of primary emulsion and surfactant concentration in oil phase affected drug-loading efficiency and the particle size of primary emulsion. Microspheres having the higher drug-loading efficiency were obtained when size differences between the primary emulsions and the secondary ones were large. That is, when the diameter of the primary emulsion is much smaller than that of the secondary emulsion, PLGA microspheres with high-loading efficiency of blue dextran were obtained.


Organic crystal lattices in the axial filament of silica spicules of Demospongiae.
The skeletal system of Demospongiae consists of siliceous spicules, which are composed of an axial channel containing an organic axial filament (AF) surrounded by a compact layer of hydrated amorphous silica. Here we report the ultrastructural investigations of the AF of siliceous spicules from two Demospongiae: Suberites domuncula and Tethya aurantium. Electron microscopy, electron diffraction and elemental mapping analyses on both longitudinal and transversal cross-sections yield that spicules's AF consist of a three-dimensional crystal lattice of six-fold symmetry. Its structure, which is the result of a biological growth process, is a crystalline assembly characterized by a lattice of organic cages (periodicity in the range of 6nm) filled with enzymatically-produced silica. In general, the six-fold lattice symmetry is reflected by the morphology of the AF, which is characterized by six-fold facets. This seems to be the result of a lattice energy minimization process similar to the situation found during the growth of inorganic crystals. Our structural exploitation of three-dimensional organic lattices generated by biological systems is expected to contribute for explaining the relation between axial filament's ultrastructure and spicule's ultimate morphology.


Circular dichroism of immune complexes, IgG and Fab gamma with unique antigenic determinants from rheumatoid serum.
IgG-IgG and IgG-IgM complexes were isolated from one rheumatoid arthritis (RA) serum by affinity chromatography to immobilized F(ag')2 gamma of specific antibodies against unique determinants in the complexes. Both IgG nd IgM, when isolated from these complexes, contained the unique determinants. The circular dichroism (CD) spectrum of IgG differed from that of normal IgG at neutral pH. At pH 3 both IgG and IgM displayed normal CD spectra, and only one third of the molecules now had affinity for the immobilized ligand. The molecules with affinity at pH 3 exhibited an abnormal CD spectrum at pH 3, and a normal CD spectrum was obtained only of those components that lacked affinity. One-third of the Fab gamma isolated from the IgG and IgG complexes with the unique determinants contained the unique determinants that were lacking in the rest of the same principal the Fc gamma fragments. The CD of the two Fab gamma preparations showed the same principal differences as the CD of the molecules with and without affinity to the ligand at acidic pH.


ATP contents and structure of rat liver mitochondria in the presence of 2-mercaptopropionylglycine.
2-Mercaptopropionylglycine was found to be efficient in the treatment of chronic hepatitis. Interest was focussed on the possible mode of action of that reagent at the subcellular level. ATP contents in mitochondria were increased after anaerobic preincubation and after addition of ADP and 2-mercaptopropionylglycine. Concomitantly, we found an increase in condensed configuration of mitochondria. If the reagent was added before ATP-Mg2+ (ADP) the mitochondrial structure was well preserved, though, throughout of orthodox configuration. In comparison the control specimens were grossly swollen. It is proposed that the reagent may act at the level of mitochondrial energy coupling.


New oral solid dosage form for furosemide oral administration.
Furosemide (FURO) is a drug labeled in class IV of the Biopharmaceutics Classification System (BCS) as it is both poor soluble and poor permeable. The aim of this work was to improve FURO biopharmaceutical properties by its formulation in a new solid oral dosage form. It consists in the realization of the composite MgAl-HTlc-FURO, obtained by FURO intercalation into the inorganic matrix hydrotalcite (MgAl-HTlc), and its successive formulation in tablets intended to be swallowed whole and to disintegrate rapidly in the stomach. These formulations were prepared by direct compression of a simple powder mixture constituted by MgAl-HTlc-FURO, a super disintegrant (Explotab, PolyplasdoneXL, PolyplasdoneXL-10, PolyplasdoneINF 10 or L-HPCLH-21) and a filler. The prepared formulations were submitted to disintegration time tests, and only those displaying the lowest disintegration time in gastric medium were submitted to in vitro release studies. Drug dissolution profiles from MgAl-HTlc-FURO tablets were compared with those containing crystalline FURO alone or physically mixed to MgAl-HTlc instead of MgAl-HTlc-FURO. The results revealed that tablets containing MgAl-HTlc-FURO give the best dissolution profile and that L-HPCLH-21 is able to promote the highest drug release in gastric medium, resulting in the most suitable super disintegrant in comparison with the other tested.


A simple conjunctival biopsy.
Biopsy of conjunctival goblet cells may be carried out by pressing a piece of Millipore filter on the conjunctival surface. This can then be stained with PAS and hematoxylin and observed under the microscope after the filter has been cleared with oil. Either spots of mucous corresponding to the openings of the goblet cells are seen, or the filter adheres to the surface and pulls off one or more layers of epithelial cells and goblet cells. The procedure can be carried out on the unanesthetized eye and does not cause discomfort.


New aspects of Helicobacter pylori infection involvement in gastric oncogenesis.
Gastric adenocarcinoma not located in the cardia still remains second only to lung cancer as the leading cause of cancer-related mortality worldwide, whereas adenocarcinoma of the cardia and gastroesophageal junction has been rapidly rising over the past two decades. Gastric malignancy can be subdivided into diffuse and intestinal pathologic entities that have different epidemiological and prognostic features. Various genetic and environmental factors lead to either abnormal gene overexpression or inappropriate expression of normal genes, whose products confer the malignant phenotype. Advances have been made in genetic changes mostly of the intestinal type; its development is probably a multistep process, as has been well described in colon carcinogenesis. Oncogene overexpression, tumor suppressor loss, and defective DNA mismatch repair is associated with gastric cancer. The most common genetic abnormalities tend to be loss of heterozygosity of particularly tumor suppressor p53 gene or "adenomatous polyposis coli" gene. The latter leads to gastric carcinogenesis through changes related to E-cadherin-catenin complex, which plays a critical role in normal tissue architecture maintenance. Mutation of any of its components results in loss of cell-cell adhesion, thereby contributing to malignancy. Putative trophic factors have also been involved in gastric oncogenesis. E-cadherin/CDH1 gene germline mutations have been recognized in families with an inherited predisposition to diffuse-type malignancy. This review focuses mainly on Helicobacter pylori infection involved in gastric carcinogenesis through various mechanisms, including repopulation of the stomach with bone marrow-derived stem cells that may facilitate gastric cancer progression, thereby necessitating eradication of this bacterium.


Properties and purification of a glucose-regulated protein from chick embryo fibroblasts.
A glucose-regulated protein of molecular weight 78,000 (GRP-78) had been purified from a membrane fraction isolated from viral transformed chick embryo fibroblasts. Purification was achieved by extraction of the membrane fraction with Triton X-100, and chromatography on diethylaminoethyl-cellulose and hydroxyapatite. The purified protein exhibited one single spot on two-dimensional polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and has a pI of about 5.3. A monospecific antiserum to GRP-78 was generated in a goat. Immunofluorescence studies using affinity purified antibodies to GRP-78 revealed that this protein was not exposed on the cell surface but was localized in a granular vesicular network inside the cell that resembles the distribution of endoplasmic reticulum. The availability of purified GRP-78 and a specific antiserum to it should prove useful in elucidating the role of this protein in glucose metabolism and its relationship to malignant transformation.


Contributions of NMDA receptors to network recruitment and rhythm generation in spinal cord cultures.
N-methyl-d-aspartic acid (NMDA) receptors are implicated in fictive locomotion; however, their precise role there is not clear. In cultures of dissociated cells from foetal rat spinal cord, synchronous bursting (but not fictive locomotion) can be induced by disinhibition, which is produced by blocking glycinergic and gamma-aminobutyric acid (GABA)A-dependent synaptic conductances. In this study, we investigate the role of NMDA-R in rhythm generation during disinhibition with multielectrode arrays and patch-clamp. We previously determined that bursting activity is generated by repetitive recruitment of a network through recurrent excitation. Blocking NMDA-R with d(-)-2-amino-5-phosphonopentanoic acid (APV) decreased the burst duration, suggesting a role of such receptors in the maintenance of high network activity during the bursts. In addition, APV reduced burst rate in about a third of the experiments, suggesting a contribution of NMDA-R in network recruitment. When (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrate (AMPA)/kainate receptors were blocked with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in the presence of disinhibition, the burst rate was reduced and burst onset was slowed in two-thirds of the experiments. In the remaining experiments, bursting ceased completely with CNQX. Neither APV nor CNQX changed the spatial patterns of activity in the network, suggesting a co-operation of both receptors in rhythm generation. While NMDA alone was not able to create a rhythm, it accelerated bursting in the presence of disinhibition, made it more regular and slowed down network recruitment. These effects were most likely due to the depolarization of the interneurons in the network. We conclude that NMDA-R contribute to rhythm generation in spinal cultures by supporting recurrent excitation and network recruitment and by depolarizing the network.


Interleukin-1 inhibits keratan sulfate production by rabbit chondrocytes: possible role of prostaglandin E2.
We investigated the importance of prostaglandin E2 (PGE2) release in interleukin-1 (IL-1)-induced inhibition of aggrecan synthesis by chondrocytes. Keratan sulfate (KS) production was measured in parallel with PGE2 release in chondrocytes. IL-1 inhibited KS production and stimulated PGE2 release. In the presence of PGE2, there was a dose-dependent decrease in baseline KS production. Indomethacin and dexamethasone partially blocked the IL-1-induced PGE2 release while KS production recovered. Our results suggest that IL-1 inhibits KS production, in part, by stimulating the release of PGE2.


Rapid Access Arrhythmia Clinics (RAACs) Versus Usual Care: Improving Efficiency and Safety of Arrhythmia Management.
Rapid access cardiology services have been proposed for assessment of acute cardiac conditions via an outpatient model-of-care that potentially could reduce hospitalisations. We describe a new Rapid Access Arrhythmia Clinic (RAAC) and compare major safety endpoints to usual care. We matched 312 adult patients with suspected arrhythmia in RAAC to historical age and sex-matched controls discharged from hospital within Western Sydney Local Health District with suspected arrhythmia. The primary endpoint was a composite of time to first unplanned cardiovascular hospitalisation or cardiac death over 12 months. The average age of RAAC patients was 52.2±18.8 years and 51.6±18.8 years for controls, and 48.4% were female in both groups. Mean time from referral to first attended RAAC appointment was 10.5 days. Most were referred from emergency (177, 56.7%) and cardiologists at time of discharge (65, 20.8%). The most common reason for referral was palpitations (180, 57.7%). In total, 155 (49.7%) had a documented arrhythmia, with the most common being atrial fibrillation/flutter (88, 28.2%). The primary endpoint occurred in 35 (11.2%) patients in the RAAC pathway (97.1[95% CI 70-131.3] per 1,000 person-years), compared to 72 (23.1%) patients for usual care controls (229.5[95% CI 180.2-288.1] per 1,000 person-years). Using a propensity score analysis, RAAC pathway significantly reduced the primary endpoint by 59% compared to usual care (HR 0.41, 95% CI 0.27-0.62; p<0.001). RAACs for the early investigation and management of suspected arrhythmia is superior to usual care in terms of reduction in unplanned cardiovascular hospitalisation and death.


Six-minute walk distance predicts 30-day readmission in hospitalized heart failure patients.
Identification of patients with heart failure (HF) at high risk of hospital readmission is critical to refine processes for reducing readmission rates. We hypothesized that patients with higher 6-min walk (6MW) distance at the time of hospital discharge are at low risk for early readmission. We prospectively enrolled 265 patients admitted with HF and left ventricular systolic dysfunction. 6MW testing was administered prior to discharge. Multivariate logistic regression analysis was performed to determine the relationship between 6MW distance and 30-day readmission, stratifying by ≤400 m and >400 m. Two hundred ten patients underwent 6MW testing prior to discharge. Patients with 6MW >400 m had a 30-day readmission rate of 15.9%, whereas patients with 6MW ≤400 m had a 30-day readmission rate of 30.3% (p = 0.016). Patients requiring readmission within 30 days had a median 6MW of 30 m, whereas patients not requiring readmission at 30 days walked 338 m (p = 0.012). 6MW distance predicted freedom from readmission at 30 days (OR: 0.435, 95% CI 0.21-0.9, p = 0.025). Other independent predictors of 30-day readmission included history of gout (0.117, 0.021-0.637, p = 0.013), use of angiotensin-converting enzyme inhibitor or accepted alternative (0.372, 0.169-0.820, p = 0.014) and blood urea nitrogen level (1.019, 1.003-1.035, p = 0.020). Low 6MW distance predicts early hospital readmission in patients with HF. Programs seeking to produce systems that are effective in reducing early hospital readmission may desire to incorporate 6MW testing during HF hospital care.


Feasibility, Acceptability, and Performance of a Continuous Temperature Monitor in Older Adults and Staff in Congregate-Living Facilities.
Residents of congregate-living facilities are susceptible to disability and mortality from infection given the presence of advanced age, multimorbidity, and frailty-as demonstrated in the recent COVID pandemic. This study assessed the feasibility, acceptability, and applicability of a continuous temperature monitoring device in a congregate-living facility with residents of independent living, assisted living, and their care-providing staff. We hypothesized that a wearable device compared with daily manual temperature assessment would be well tolerated and more effective at detecting temperature variances than current standard of care body temperature assessment. Feasibility study. Residents of assisted and independent living and staff of a retirement community. Thirty-five participants, including residents in assisted- and independent-living facilities (25) and staff (10) were enrolled in a 90-day feasibility study and wore a continuous temperature sensor from March to July 2021. Primary outcomes included study completion, ability to reapply the sensor, temperature data acquisition, and data availability from the sensors. A secondary analysis of the temperature data involved comparing the method of obtaining temperature using the continuous monitoring device against standard of care using traditional manual thermometers. Overall, 91.3% of residents, who were in the study during the first reapplication, were able to apply the device without assistance (21 of 23), and 80% of resident participants completed the study (20 of 25). For staff participants, completion rates and reapplication rates were 100%. Data acquisition rates from the continuous temperature devices were much higher than manual temperatures. Four episodes of fever were detected by the devices; manual temperature checks did not identify these events. Continuous temperature monitoring in an older adult population and the staff in congregate-living facilities is feasible and acceptable. This approach identified fever undetected by current standard of care indicating the capability of this device for earlier detection of fevers.


Weight and mortality in Finnish men.
Mortality rates of 22,995 Finnish men aged 25 and over followed up for a median of 12 years were analyzed in relation to body mass index (BMI) at the initial examination. All-cause mortality followed a "U"-shaped distribution, being greatest for the thinnest and fattest men at all ages, or about 1.5-fold for those with BMI less than 19.0 kg/m2 and BMI greater than or equal to 34.0 kg/m2, as compared with men of normal weight (BMI 22.0-24.9 kg/m2). Mortality from cardiovascular diseases (CVD) increased with increasing BMI beyond the normal range. This depended mostly on the association of BMI with the biological risk factors of CVD. Mortality rates from CVD were also elevated among thin men under age 55, which could not be explained by the effect of the biological variables. Mortality rates from non-cardiovascular diseases, including cancers were inversely related to BMI among men of all ages. The high overall mortality of thin men was partly but not entirely attributable to smoking, low social class and antecedent disease. We conclude that both thinness and overweight are detrimental to longevity, but through differing mechanisms and disease patterns.


Clinical characteristics, prognostic factors, and maternal and neonatal outcomes of SARS-CoV-2 infection among hospitalized pregnant women: A systematic review.
Pregnant women represent a potentially high-risk population in the COVID-19 pandemic. To summarize clinical characteristics and outcomes among pregnant women hospitalized with COVID-19. Relevant databases were searched up until May 29, 2020. Case series/reports of hospitalized pregnant women with laboratory-confirmed COVID-19. PRISMA guidelines were followed. Methodologic quality was assessed via NIH assessment tools. Overall, 63 observational studies of 637 women (84.6% in third trimester) with laboratory-confirmed SARS-CoV-2 infection were included. Most (76.5%) women experienced mild disease. Maternal fatality, stillbirth, and neonatal fatality rates were 1.6%, 1.4%, and 1.0%, respectively. Older age, obesity, diabetes mellitus, and raised serum D-dimer and interleukin-6 were predictive of poor outcomes. Overall, 33.7% of live births were preterm, of which half were iatrogenic among women with mild COVID-19 and no complications. Most women underwent cesarean despite lacking a clear indication. Eight (2.0%) neonates had positive nasopharyngeal swabs after delivery and developed chest infection within 48 hours. Advanced gestation, maternal age, obesity, diabetes mellitus, and a combination of elevated D-dimer and interleukin-6 levels are predictive of poor pregnancy outcomes in COVID-19. The rate of iatrogenic preterm birth and cesarean delivery is high; vertical transmission may be possible but has not been proved.


Nerve supply to the soft palate muscles with special reference to the distribution of the lesser palatine nerve.
Descriptions of the innervation of the soft palate muscles in previous studies have varied according to the author. In the present study, distribution of the lesser palatine nerve, through which motor fibers of the facial nerve are considered to reach soft palate muscles, and that of the pharyngeal plexus in the soft palate were investigated in order to reexamine the innervation of the soft palate muscles according to anatomical evidence. Observations suggested that the levator veli palatini and palatopharyngeus were doubly innervated by branches of the lesser palatine nerve and pharyngeal plexus, and that the musculus uvulae was innervated by only the lesser palatine nerve. The soft palate is considered to be located in the border region between the areas of distribution of the lesser palatine nerve and pharyngeal plexus. This may be why controversies exist in previous studies about the innervation of the soft palate muscles.


Urinary cortisol excretion and mood ratings in aircraft cabin crew during a tour of duty involving a disruption in circadian rhythm.
A psychophysiological study was carried out on 28 cabin crew, comprising two teams, who were to travel from Sydney to Los Angeles and return, with stopovers in Los Angeles of 58 and 82 hr respectively. Every urine sample for a period of nine days, commencing 2 days before the flight, was collected. The volume and time the sample was passed were recorded so that urinary cortisol secretion rates could be calculated. Mood was also rated on a scale scored 0-9 at the same time the urine sample was collected. A control group matched for age, sex ratio, and degree of manual labour involved in their occupation, but not involved with the flights, was included in the study for comparison. On the basis of urinary cortisol excretion rates, the crews in Sydney before the flight and in Los Angeles were more highly stressed than the control group. The urinary cortisol excretion rates were significantly greater than those of the control group in Sydney before the flight, in Los Angeles, and during the return flight, but not on the flight out. The high excretion rates before the flight were attributed to an apprehension factor, whereas the elevated values in Los Angeles and during the flight back were attributed to a disruption in circadian rhythm. A factor analysis of mood ratings showed three major factors assessing vitality, distress, and relaxation. Analysis of variance of the mood ratings showed significant changes over the tour of duty for 13 of the 14 moods.


Patients' vs. Physicians' Assessments of Emergencies: The Prudent Layperson Standard.
To compare perception of the need for emergency care by emergency department (ED) patients vs. emergency physicians (EPs). Mailed survey to EPs and a convenience sample of ED patients. Survey rated urgency of acute sore throat, ankle injury, abdominal pain, and hemiparesis, as well as the best definition of "emergency." Responses were compared with chi-square (p < .05). 119/140 (85%) of EPs and 1453 ED patients responded. EPs were more likely to judge acute abdominal pain (79.8% vs. 43.4%, p < 0.001, odds ratio (OR) 5.16, 95% confidence interval (CI) 3.19-8.40) and hemiparesis (100% vs. 82.6%, p < 0.001, OR 24.9, 95% CI 3.75-94.4) as an emergency. Similar proportions of ED patients and EPs considered sore throat (12.2% vs. 7.6%, p = 0.18, OR 0.59, CI 0.27-1.23) and ankle injury (46.9% vs. 38.6%, p = 0.10, OR 0.71, CI 0.48-1.06) an emergency. EPs (35%) and ED patients (40%) agreed to a similar degree with the "prudent layperson" definition, "a condition that may result in death, permanent disability, or severe pain." (p = .36, OR 1.22, CI 0.81-1.84). EPs were more likely to add, "the condition prevented work," (27% vs. 16%, p = 0.003, OR 0.51, CI 0.33-0.81). Patients more often added, "occurred outside business hours" (15% vs. 4%, p = 0.002, OR 4.0, CI = 1.5-11.3). For serious complaints, ED patients' thresholds for seeking care are higher than judged appropriate by EPs. Stroke is not uniformly recognized as an emergency. Absent consensus for the "correct" threshold, the prudent layperson standard is appropriate.


Enhanced insulin binding to blood-brain barrier in vivo and to brain microvessels in vitro in newborn rabbits.
Insulin is a known growth factor in nonneural tissue, and recent studies have shown that there are insulin receptors throughout the adult and fetal central nervous system. Since insulin has only limited access to the adult brain, this study was undertaken to determine if insulin has increased availability to the newborn brain where it may act as a neonatal brain growth promoter. In vivo brain uptake of 125I-insulin after a single-pass carotid injection was measured in newborn, 3-wk-old and 11-wk-old (adult) rabbits. The brain uptake index (BUI) relative to a 3HOH reference was 22.0 +/- 1.1% (mean +/- SEM) for newborn, 12.8 +/- 0.6% for 3-wk-old, and 6.5 +/- 0.1% for adults. Specific 125I-insulin binding to isolated cerebral microvessels was similarly increased in the newborn (60.6 +/- 3.3%/mg protein) compared with the 3-wk-old (23.8 +/- 1.7) and adult animals (13.6 +/- 1.9). Scatchard analysis revealed that the difference was due to an increase in receptor number with only minimal changes in the affinity. The increased availability of circulating insulin to the newborn brain was further corroborated by elevated CSF/serum and brain/serum insulin ratios in the newborn versus adult. These results suggest that insulin has increased access to the newborn brain where it may function as a growth factor.


Myofascial force transmission is increasingly important at lower forces: firing frequency-related length-force characteristics of rat extensor digitorum longus.
Effects of submaximal stimulation frequencies on myofascial force transmission were investigated for rat anterior crural muscles with all motor units activated. Tibialis anterior and extensor hallucis longus (TAEHL) muscles were kept at constant muscle-tendon complex length, but extensor digitorum longus muscle (EDL) was lengthened distally. All muscles were activated simultaneously at 10, 20, 30 and 100 Hz within an intact anterior crural compartment. At lower frequencies, significant proximo-distal EDL force differences exist. Absolute EDL proximo-distal active force differences were highest at 100 Hz (deltaF(dist-prox) = 0.4 N). However, the normalized difference was highest at 10 Hz (deltaF(dist-prox) = 30%F(dist)). Firing-frequency dependent shifts of the ascending limb of the EDL length-force curve to higher lengths were confirmed for a muscle within an intact compartment, although effects of firing frequency assessed at proximal and distal EDL tendons differed quantitatively. As EDL was lengthened distally, TAEHL distal isometric active force decreased progressively. The absolute decrease was highest for 100 Hz (deltaF(from initial) = -0.25 N). However, the highest normalized decrease was found for 10 Hz stimulation (deltaF(from initial) = -40%). At submaximal stimulation frequencies, myofascial force transmission is present and the fraction of force transmitted myofascially increases with progressively lower firing frequencies. Evidently, the stiffness of epimuscular myofascial paths of force transmission decreases less than the stiffness of serial sarcomeres and myotendinous pathways. It is concluded that low firing frequencies as encountered in vivo enhance the relative importance of epimuscular myofascial force transmission with respect to myotendinous force transmission.


Electroencephalographic monitoring for ischemia during carotid endarterectomy: visual versus computer analysis.
In a retrospective study, we compared the use of computer-generated spectral electroencephalographic descriptors with a neurologist's interpretation of raw EEG data. Data were collected from patients undergoing carotid endarterectomy and anesthetized with isoflurane in nitrous oxide and oxygen. The EEG was recorded on magnetic tape during the period immediately before and after occlusion. These tapes were then analyzed off-line using a computer to generate averaged changes in 18 spectral descriptors. A strip-chart of raw EEG before and after the carotid occlusion was interpreted by a neurologist, who assigned changes in the EEG following occlusion to one of four visual inspection groups, depending on the severity of change. A descriptive examination of the distribution of changes in spectral descriptors revealed that no single descriptor adequately reflected the neurologist's interpretation of the raw EEG. Using data from 20 patients, the percent change from preocclusion to postocclusion values for total power, spectral edge frequency, spectral variance, and log spectral variance was examined. Only for the visual inspection group judged by the electroencephalographer to have the most severe ischemic change was there a significant difference in total power and log spectral variance. Although computer-processed EEG devices are of value as trending devices for detecting visual patterns associated with inadequate cerebral perfusion, single descriptors in this study did not consistently reflect a neurologist's diagnosis of ischemia. Single descriptors of spectral EEG analysis may not be sufficient to use as alarm variables in the recognition of cerebral ischemia.


Stability mechanism of SiO2/SDS dispersion for foam flooding in hydrocarbon reservoirs: experimental research and molecular simulation.
The dispersion of silica dioxide (SiO2)/sodium lauryl sulfate (SDS) has been widely used in hydrocarbon reservoirs, but its instability is still a problem in practical engineering applications. The dispersion morphology of SiO2 nanoparticles before and after modification was studied by TEM, and the thermal stability of different foam dispersions was evaluated by FoamScan. In this paper, the mechanism of foam stability was investigated by combining the measurement of interfacial energy of nanoparticles at the gas-liquid interface with dynamics simulation of molecular diffusion. The results showed that SiO2/SDS dispersions had good thermal stability due to the synergistic effect of SiO2 nanoparticles and SDS. The addition of SiO2 nanoparticles improved the interfacial energy and interfacial activity at the gas-liquid interface, meanwhile limited the movement of SDS molecules and water molecules, which was beneficial for foam stability. Notably, the addition of modified SiO2 nanoparticles further enhanced the interfacial energy at the gas-liquid interface and strengthened the restriction of water/SDS molecular movement, thereby slowing down the drainage and decay of the foam dispersions. The mechanism investigation of SiO2/SDS dispersions was of benefit to foam flooding in hydrocarbon reservoirs.


Inheritance of occlusal topography: a twin study.
This was to determine the relative contribution of genetic factors on the morphology of occlusal surfaces of mandibular primary first molars by employing the twin study model. The occlusal morphology of mandibular primary first molar teeth from dental casts of 9 monozygotic (MZ) twin pairs and 12 dizygotic (DZ) twin pairs 4 to 7 years old, were digitized by contact-type three-dimensional (3D) scanner. To compare the similarity of occlusal morphology between twin sets, each twin pair of occlusal surfaces was superimposed to establish the best fit by using computerized least squared techniques. Heritability was computed using a variance component model, adjusted for age and gender. DZ pairs demonstrated a greater degree of occlusal morphology variance. The total amount of difference in surface overlap was 0.0508 mm (0.0018 (inches) for the MZ (n=18) sample and 0.095 mm (0.0034 inches) for the DZ (n=24) sample and were not statistically significant (p=0.2203). The transformed mean differences were not statistically significantly different (p=0.2203). Heritability estimates of occlusal surface areas for right and left mandibular primary first molars were 97.5% and 98.2% (p<0.0001), respectively. Occlusal morphology of DZ twin pairs was more variable than that of MZ twin pairs. Heritability estimates revealed that genetic factors strongly influence occlusal morphology of mandibular primary first molars.


Gap junction intercellular communication propagates cell death in cancerous cells.
Gap junction intercellular communication (GJIC) or cell coupling has an important function in maintaining tissue homeostasis and is thus a critical factor in the life and death balance of cells. While the role of GJIC in cell growth regulation has been much studied, its involvement in apoptosis remains unclear. In this study we elucidated the possibility that cell death is propagated via gap junctions, employing the rat bladder carcinoma cell line BC31. BC31 cells proliferate quickly, are tumorigenic, and are well-coupled via gap junctions that contain the gap junction protein Connexin43 (Cx43). In addition, these cells are predisposed to spontaneous death by apoptosis, particularly upon achieving confluency. We found that many dying BC31 cells express Cx43 just as their non-apoptotic counterparts do. Furthermore, Cx43 in apoptotic cells could be functionally competent, supporting coupling of these cells with their non-apoptotic neighbors, and as a result, clusters of coordinately dying cells were observed. The role of Cx43 and GJIC in propagating cell death was shown by analysing clones of BC31 cells expressing a mutant of Cx43 that is a dominant negative inhibitor of GJIC, and by using beta-glycyrrhetinic acid to inhibit intrinsic cell coupling in BC31 cells: in both cases the formation of clusters of dying cells was abrogated, and the intensity of cell death was considerably decreased. These results suggest that GJIC spreads cell-killing signals initially generated by a single cell that spontaneously initiates apoptosis, into healthy surrounding cells, thus increasing the level of cell death. Treatment of BC31 cells with the sleep-inducing lipid Oleamide, which selectively restricts gap junction permeability to Ca(2+) ions, did not abrogate coordinated cell death by clusters, indicating that Ca(2+) ions are the most probable cell-killing signals spread through gap junctions.


[National second-opinion network for testicular cancer patients. Results of a user survey].
The national second opinion project of the German Testicular Cancer Study Group (GTCSG) has served to improve the quality of care provided to testicular cancer patients since 2006. A recent online survey was carried out to characterize the users of the second opinion offer and clarify their motivation for participating in the project. Furthermore, the aim was to identify weaknesses of the project which could be improved. A total of 440 users of the second opinion project were contacted of whom 192 participated in the survey. In summary, the data collected showed a high degree of satisfaction among the participants who appreciated the second opinions received. Some issues with a need for improvement, predominantly in the structural organisational area, were disclosed. These served as a basis for a recently completed revision of the project immanent internet-based communication platform with a new data mask facilitating the introduction of patients with relapsed tumors. Interestingly, a high proportion of survey participants expressed the desire for establishment of a similar second opinion project for patients with penile cancer (77.1% of the participants).


Clinical benefit of tolvaptan in patients with acute decompensated heart failure and chronic kidney disease.
Tolvaptan, a vasopressin type 2 receptor antagonist, has an aquaretic effect without affecting renal function. The effects of long-term tolvaptan administration in heart failure patients with renal dysfunction have not been clarified. Here, we assessed the clinical benefit of tolvaptan during a 6-month follow-up in acute decompensated heart failure (ADHF) patients with severe chronic kidney disease (CKD; estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m(2)). We compared 33 patients with ADHF and severe CKD who were administered tolvaptan in addition to loop diuretics (TLV group), with 36 patients with ADHF and severe CKD who were administered high-dose loop diuretics (≥40 mg) alone (LD group). Alterations in serum creatinine and eGFR levels from the time of hospital discharge to 6-month follow-up were significantly different between the groups, with those in the TLV group being more favorable. Furthermore, Kaplan-Meier analysis revealed that rehospitalization for heart failure (HF) was significantly lower in the TLV group compared with the LD group. In ADHF patients with severe CKD, tolvaptan use for 6 months reduced worsening of renal function and rehospitalization rates for HF when compared with conventional diuretic therapy. In conclusion, tolvaptan could be a safe and effective agent for long-term management of HF and CKD.


Allogeneic bone marrow transplantation for active Epstein-Barr virus-related lymphoproliferative disease and hemophagocytic lymphohistiocytosis in an infant with severe combined immunodeficiency syndrome.
A 5-month-old male presented with fever, hepatosplenomegaly, leukocytosis with atypical lymphoblasts, anemia and thrombocytopenia. Severe combined imunodeficiency syndrome (T-, B+, NK+), B lymphoproliferative disease and hemophagocytic lymphohistiocytosis triggered by Epstein-Barr virus (EBV) were diagnosed. As his clinical situation deteriorated rapidly, BMT was performed with unmanipulated marrow stem cells from his EBV-positive HLA-identical sister after conditioning with dexamethasone (1.75 mg/kg/day), cyclophosphamide (114 mg/kg) and etoposide (10 mg/kg), with no immunosuppression given post transplant. Engraftment occurred on day 6 with explosive proliferation of donor CD8(+) T cells. The patient died 3 days later from acute respiratory distress syndrome. Autopsy revealed full donor engraftment and no signs of hemophagocytic lymphohistiocytosis or B lymphoproliferative disease. Thus, transplanted T cells can expand very rapidly within days after BMT and clear EBV lymphoproliferative disease and hemophagocytic lymphohistiocytosis.


Symptoms mediate the relationship between childhood trauma and non-suicidal self-injury: A hospital-based study of adolescents with mood disorder.
Childhood trauma has a significant impact on the development of adolescents, which may lead to interpersonal and psychological problems. Determining the incidence and consequences of childhood trauma in psychiatric clinical practice is of great significance. A survey was conducted among adolescents with mood disorders. Childhood Trauma Questionnaire (CTQ), the Adolescent Non-Suicidal-Self-Injury Behavior Function Assessment Scale (ANBFAS) and a series of psychological scales were filled face to face. Path analysis was used to examine the causation structure of childhood trauma-related symptoms. A total of 117 participants (74.5%) had experienced at least one type of trauma. Interpersonal and psychological features of adolescent patients with childhood trauma were detailed in this study. The path analysis model showed that the relationships between childhood trauma and NSSI were mediated by depressive symptoms and thinking disorders, respectively, whereas depressive symptoms individually mediated the correlation between childhood trauma and sleep disturbances in adolescent patients with psychiatric disorders (χ2 /df = 1.23). For adolescent patients with childhood trauma, psychological counseling for interpersonal relationships should start with families and peers. It is important to treat their depressive symptoms and thinking disorders and alleviate NSSI behavior and sleep disorders.


Localized flap melt after Nd-YAG laser treatment in recurrent post-LASIK epithelial ingrowth.
Neodymium: Yttrium-Aluminum-Garnet (Nd-YAG) laser treatment of epithelial ingrowth was found promising with high success rates in cases of primary post-LASIK epithelial ingrowth. However, the application range of this procedure is not well-known. For the first time, the authors report the outcome of a patient treated with Nd-YAG laser for multiple recurrences of post-laser in situ keratomileusis epithelial ingrowth.


Metastable attractors explain the variable timing of stable behavioral action sequences.
The timing of self-initiated actions shows large variability even when they are executed in stable, well-learned sequences. Could this mix of reliability and stochasticity arise within the same neural circuit? We trained rats to perform a stereotyped sequence of self-initiated actions and recorded neural ensemble activity in secondary motor cortex (M2), which is known to reflect trial-by-trial action-timing fluctuations. Using hidden Markov models, we established a dictionary between activity patterns and actions. We then showed that metastable attractors, representing activity patterns with a reliable sequential structure and large transition timing variability, could be produced by reciprocally coupling a high-dimensional recurrent network and a low-dimensional feedforward one. Transitions between attractors relied on correlated variability in this mesoscale feedback loop, predicting a specific structure of low-dimensional correlations that were empirically verified in M2 recordings. Our results suggest a novel mesoscale network motif based on correlated variability supporting naturalistic animal behavior.


Secretin-assisted CT of the pancreas: improved pancreatic enhancement and tumour conspicuity.
The primary aim of this prospective pilot study was to determine if the administration of intravenous secretin prior to contrast-enhanced computed tomography (CT) improves pancreatic enhancement and pancreatic tumor conspicuity. The second aim was to determine the optimal timing for secretin administration prior to contrast-enhanced CT. Local ethics committee approval was obtained. 35 patients (18 men, 17 women; mean age, 67.6 years; age range; 25 to 86 years) with known or suspected pancreatic malignancy or an abdominal malignancy underwent a helical CT of the pancreas. The pancreas was first localised on an unenhanced scan using 10mm sections. Following 120 ml of intravenous 300 mg/ml of non ionic contrast medium (CM), injected at a rate of 5 ml/s, images of the pancreas (3mm slice thickness) and liver (8mm slice thickness) were obtained at 40 and 70 seconds respectively. A second CT was obtained 1-5 days after the first one using the same CT and intravenous contrast medium injection parameters. However 100 IU of secretin was given as an intravenous bolus between 0 and 5 min prior to intravenous contrast medium administration. Each patient acted as their own control. The attenuation in Hounsfield Units (HU) was recorded on non-contrast, pancreatic phase and portal venous phases for both secretin and non-secretin CTs, in the pancreas and pancreatic tumors (where present). Tumor conspicuity was calculated (in the 19 patients with pancreatic adenocarcinomas) by subtracting pancreatic tumor attenuation from pancreatic attenuation. Statistical evaluation comparing pre and post secretin enhancement was performed using matched paired t-tests. A significant increase in pancreatic enhancement was observed when secretin was injected at 2 to 3 min before contrast material injection (the increase in pancreatic density following secretin at 2 min was 31.5+/-10 HU (29.2%) (p=.035); and at 3 min was 23.2+/-7.8 HU (22.7%) (p=.041). Pancreatic tumor conspicuity in the pancreatic phase was most marked when secretin was injected between 2 to 4 min before contrast medium, with 4 min showing a statistically significant increase in tumor conspicuity, 48.2+/-14.2 HU (p=.04). Imaging in the pancreatic phase 2 to 4 min after administration of intravenous secretin leads to greater enhancement of the pancreas with greater tumor conspicuity, than imaging without secretin.


Proteome analysis of isolated myenteric plexus reveals significant changes in protein expression during postnatal development.
The enteric nervous system in vertebrates is the most complex part of the peripheral nervous system. Concerning chemical coding, ultrastructure and neuronal circuits, it is more similar to the central than to the peripheral nervous system. Its networks, the myenteric and submucous plexus are integrated in the gut wall. The enteric nervous system is a system of high plasticity, which not only changes during pre- and postnatal development, but also with disease or changing dietary habits. The Aim of this study was to elucidate changes in protein expression during the first two postnatal weeks in the rat myenteric plexus. Colonic and duodenal myenteric plexus from newborn (P1) and fourteen-day old (P14) Sprague-Dawley rats was isolated following a procedure that combines enzymatic digestion and mechanical agitation. The neuronal tissue was collected and processed for two-dimensional gel electrophoresis (2-DE). The obtained 2-D gels were stained with silver for image analysis or with colloidal Coomassie for subsequent protein identification. Gels from the various samples showed a high degree of consistence concerning protein-spots found in all preparations. Nevertheless, there was a number of proteins that were clearly detected in one sample but not, or only in significantly smaller amounts in the other. Several differentially expressed proteins in the postnatal myenteric plexus were identified with MALDI-TOF mass spectrometry. Especially stathmin, polyubiquitin and heterogeneous nuclear ribonucleoprotein seem to play an important role in pre- and postnatal development. 2-DE combined with mass spectrometry can help to identify pathological relevant proteins in the enteric nervous system, and so deliver a valuable tool for the early diagnosis of also central nervous system diseases by using biopsies from the gut.


Two enzymatic methods for determination of the phosphate content of phosphoproteins.
Two new enzymatic methods are described for the determination of the amount of inorganic phosphate covalently bound to macromolecules. In the first method, the inorganic matter obtained after ashing is incubated with [1-14C] pyruvate in the presence of pyruvate oxidase and the enzymatically formed 14CO2 is collected. The other method uses glycogenolytic enzymes to generate NADH which is then measured fluorometrically. The use of these two phosphate-dependent enzymes allows the measurement of phosphate at up to 1000 times greater sensitivity than is obtainable with the phosphomolybdic acid method, thus permitting phosphate analyses to be performed on microgram quantities of proteins.


Undifferentiated and differentiated L6 myoblast plasma membranes. II: Comparison of the morphological and biochemical characteristics of isolated plasma membranes.
Plasma membrane vesicles isolated from undifferentiated and differentiated L6 myoblasts show a comparable phase and ultrastructural morphology. Both are agglutinated by Concanavalin A and wheat germ agglutinin, contain approx. 20 polypeptides and have a comparable intramembranous particle density and topography.


[Cochlear implants in children with mental disabilities].
Nowadays, profoundly deaf children with associated psychotic disorders can sometimes benefit from a cochlear implant program. These fragile children who have a specific development need a reinforced observation and follow up, and active parental collaboration. From a series of 8 children with psychotic disorders implanted between 1999 and 2006, we present 4 representative cases of our practise, which have at least 3 years post implant. The questions that should occur about the conditions of the cochlear implantation are discussed in the light of the results of our observations. No children deteriorated them selves. All of them use their cochlear implant continuously. Cochlear implant is a tool in a global approach towards mobilization of communication resources in such children.


Controversies in Facial Cosmetic Surgery.
Facial cosmetic surgery techniques are constantly updated to meet the expectations of patients who demand less invasive procedures and less recovery time. Current trends in lower eyelid surgery call for periorbital fat repositioning instead of excision of fat. Controversies still exist in chin augmentations regarding osseous genioplasty versus alloplastic chin implant. The benefits, disadvantages, and considerations of these procedures are discussed.


Epidemiologic parameters and evaluation of control measure for 2009 novel influenza a (H1N1) in Xiamen, Fujian Province, China.
Containment of influenza A H1N1 virus spread was implemented successfully in Xiamen, with large-scale inoculation to reduce morbidity. To identify beneficial elements and to guide decision-making in epidemic containment, we analyzed the epidemiologic parameters and evaluated the control measures. We determined various parameters from laboratory-confirmed cases, including incubation period, duration of illness and reproductive number (R0), and evaluated the control measures. There were 1414 cases with dates of onset between June 14, 2009 and March 22, 2010. The incidence was 56.79/100,000, and mortality was 0.12/100,000. The incidence during the community epidemic phase was 6.23 times higher than in the containment phase. A total of 296,888 subjects were inoculated with domestic influenza H1N1 virus cleavage vaccine. An epidemic curve showed that vaccination in students cut the peak incidence of illness significantly. Men (relative risk (RR) = 1.30, 95% confidence interval (CI): 1.17-1.45) and persons aged 0-14 years were at greater risk of infection. The incidence increased with younger age (χ2 = 950.675, p = ∞). Morbidity was lower in urban than in rural areas (RR = 0.56, 95%CI: 0.50-0.62). The median incubation time was 2 days, median duration of symptoms was 7 days, and the within-school reproductive number was 1.35. Our analysis indicated that the characteristics of this novel influenza virus were similar to those of seasonal influenza. The principle of "interception of imported cases" applied at Xiamen ports, and vaccination of students effectively limited the spread of the influenza pandemic and reduced the epidemic peak.


Draft Genome Sequence of Enteropathogenic Escherichia coli, Isolated from the Bloody Stool Sample of a Common Marmoset (Callithrix jacchus).
Here, we report the draft genome sequence of Escherichia coli strain R811. This bacterium was isolated from the bloody stool sample of a common marmoset, and was categorized as enteropathogenic E. coli because it possessed eae.


A feeding model of oyster larvae (Crassostrea angulata).
There is a need to develop more efficient rearing systems for the aquaculture of economically important bivalves, such as oysters. Here, we constructed a model that describes the feeding behavior of larval Crassostrea angulata oysters and tested it in an experimental setting. Larval ingestion rate is closely correlated with larval length. Based on our model, we showed that larval swimming speed, velum diameter and the filtration coefficient, which also determine the ingestion rate, are also correlated with larval length. Our model integrates morphological, locomotory and feeding behavior parameters to establish a relation between them and so provides a mathematical way to describe variation in the feeding behavior of bivalve larvae. The results of this study could facilitate the precise management of the aquaculture of bivalve larvae, in particular the optimum prey density and feeding rate of these important organisms.


Domains of the SFL1 protein of yeasts are homologous to Myc oncoproteins or yeast heat-shock transcription factor.
We identified a yeast suppressor gene for flocculation (SFL1), which complemented a newly isolated sfl1 mutant. This mutation causes asexual cell aggregation. SFL1 encodes a 767-amino acid protein which has two domains significantly homologous to Myc oncoproteins and the yeast heat shock transcription factor (HSTF). The Myc homologous region in SFL1 overlaps with the conserved region in a series of interesting proteins: MyoD1, Drosophila achaete-scute, twist, daughterless gene products and immunoglobulin enhancer-binding proteins. In addition, the N-terminal region of the SFL1 gene product shows extensive homology to the DNA-binding domain of HSTF. Mutational analysis of SFL1 demonstrates that it is required for normal cell-surface assembly in vegetative growth. We propose that the SFL1 gene product may be a transcription factor which is involved in regulation of the gene(s) related to yeast flocculation.


A comparison of professionally employed lesbians and heterosexual women on the MMPI.
The hypothesis tested is whether lesbianism implies psychopathology. The MMPI was given to 26 nonpatient lesbians who were professionally employed full time, and the results were compared to those for a group of 29 similarly employed heterosexual women. With the exception of the Sc scale, no difference was found on the clinical scales. The lesbian group achieved a significantly higher elevation than the nonlesbians on the Mf and Sc scales. Further analysis of the data on the Sc subscales indicated no difference on the pathological part of the scale, but rather a difference in degree of social alienation. Analysis of the data according to a second variable, living status, found significant differences and has important implications for future studies of the lesbian population. Single women, regardless of sexual orientation, scored significantly higher on scales K and Pa and on the Pa subscale naivete. A significant interaction between sexual orientation and living status was achieved on one scale, the F scale.


Astaxanthin stability and color change of krill during subcritical water treatment.
Pacific krill (Euphausia pacifica) contains high amounts of astaxanthin, a carotenoid pigment with strong antioxidative activities. In this study, the effects of subcritical water temperatures (100-180 °C) and times (0-10 min) on color changes (L*, a*, and b*) and astaxanthin degradation in Pacific krill were investigated. In addition, an aqueous solution of pure astaxanthin and that of crude astaxanthin from Pacific krill, both at a concentration of 5 mg/L, were subjected to treatment under subcritical water conditions using a flow-type reactor to compare the degradation of free astaxanthin and astaxanthin fatty acid esters. To compare the results of the different treatment conditions on the properties of astaxanthin, the severity factor (log R0) was calculated, which ranged from 0.38 to 3.52. The extractability of astaxanthin enhanced when the subcritical water treatment was carried out at log R0 values of 2.00-2.44. In contrast, astaxanthin underwent 50% degradation at log R0 > 2.44. The changes in the a* values correlated well with the astaxanthin content in the treated krill, while the b* and L* values might relate to the browning components forming owing to Maillard reaction. The results show that free astaxanthin was less stable than crude astaxanthin under subcritical water treatment.


Erratum: Patient satisfaction with cardiac rehabilitation: association with utilization, functional capacity, and heart-health behaviors [Corrigendum].
[This corrects the article on p. 821 in vol. 11, PMID: 28479853.].


Fatigue in early rheumatoid arthritis: data from the Early Rheumatoid Arthritis Network.
Fatigue is a disabling symptom in people with RA. This study aims to describe the prevalence, risk factors and longitudinal course of fatigue in early RA. Demographic, clinical, quality of life (QoL), comorbidities and laboratory data were from the Early RA Network (ERAN), a UK multicentre inception cohort of people with RA. Fatigue was measured using the vitality subscale of the 36-item Short Form Health Survey, where higher values represent better QoL. Baseline prevalences of fatigue classifications were age and sex standardized. Linear regression, hierarchical growth curve modelling and group-based trajectory modelling (GBTM) were utilized. At baseline (n = 1236, 67% female, mean age 57 years), the mean vitality was 41 (s.d. 11) and disease duration was 11 months (interquartile range 7-18). Age- and sex-standardized prevalence rates of fatigue and severe fatigue were 44% (95% CI 39, 50) and 19% (95% CI 15, 23), respectively. Fatigue changed little over 3 years and five measurement occasions β = -0.13 (95% CI -0.23, -0.02). GBTM identified two subgroups, which we named 'Fatigue' (53%) and 'No-fatigue' (47%). Female sex, worse pain, mental health and functional ability were associated with greater fatigue and predicted Fatigue group membership (area under the receiver operating characteristics curve = 0.81). Objective measures of inflammation-swollen joint count and ESR-were not significantly associated with fatigue. Fatigue is prevalent and persistent in early RA. Diverse characteristics indicative of central mechanisms are associated with persistent fatigue. Management of fatigue might require interventions targeted at central mechanisms in addition to inflammatory disease modification. People who require such interventions might be identified at presentation with early RA.


Clinical, Biochemical, and Molecular Features in 37 Saudi Patients with Very Long Chain Acyl CoA Dehydrogenase Deficiency.
Very long chain acyl CoA dehydrogenase (VLCAD) deficiency (OMIM#201475) is an autosomal recessive disorder of fatty acid beta oxidation caused by defect in the ACADVL. The aim of this study was to analyze the clinical, biochemical, and molecular features of VLCAD deficiency in Saudi Arabia, including the treatment and outcome. We carried out a retrospective chart review analysis of 37 VLCAD deficiency patients from two tertiary centers in Saudi Arabia, over a 14-year period (2002-2016). Twenty-three patients were managed at King Abdul-Aziz Medical City and fourteen patients at King Fahad Medical City. Severe early onset VLCAD deficiency is the most frequent phenotype in our patients, caused by four different mutations in ACADVL; 31 patients (83.7%) had a homozygous nonsense mutation in exon 2 of ACADVL c.65C>A;p. Ser22X. Twenty-three patients died before the age of 2 years, despite early detection by newborn screening and implementation of treatment, including supplementation with medium chain triglycerides. This study reports the clinical, biochemical, molecular findings, treatment, and outcome of patients with VLCAD deficiency over the last 14 years. We identified the most common variant and one new variant in ACADVL. Despite early diagnosis and treatment, the outcome of VLCAD deficiency in this Saudi Arabian population remains poor. Preventive measures, such as prenatal diagnosis, could be implemented.


Comprehensive characterization of tumor immune landscape following oncolytic virotherapy by single-cell RNA sequencing.
An important mechanism of oncolytic virotherapy in ameliorating cancer immunotherapy is by inducing significant changes in the immune landscape in the tumor microenvironment (TME). Despite this notion and the potential therapeutic implications, a comprehensive analysis of the immune changes in carcinomas induced by virotherapy has not yet been elucidated. We conducted single-cell RNA sequencing analysis on carcinomas treated with an HSV-2-based oncolytic virus to characterize the immunogenic changes in the TME. We specifically analyzed and compared the immune cell composition between viral treated and untreated tumors. We also applied CellChat to analyze the complex interactions among the infiltrated immune cells. Our data revealed significant infiltration of B cells in addition to other important immune cells, including CD4+, CD8+, and NK cells following virotherapy. Further analysis identified distinct subset compositions of the infiltrated immune cells and their activation status upon virotherapy. The intensive interactions among the infiltrated immune cells as revealed by CellChat analysis may further shape the immune landscape in favor of generating antitumor immunity. Our findings will facilitate the design of new strategies in incorporating immunotherapy into virotherapy for clinical translation. Moreover, the significant infiltration of B cells makes it suitable for combining virotherapy with immune checkpoint inhibitors.


Initial in vivo results of a hybrid retinal photocoagulation system.
We describe initial in vivo experimental results of a new hybrid digital and analog design for retinal tracking and laser beam control. An overview of the design is given. The results show in vivo tracking rates which exceed the equivalent of 38 degrees/s in the eye. A robotically assisted lesion pattern is created for laser surgery to treat conditions such as diabetic retinopathy and retinal breaks.


A 14-gene region of rat chromosome 8 in SHR-derived polydactylous congenic substrain affects muscle-specific insulin resistance, dyslipidaemia and visceral adiposity.
The SHR and the PD/Cub are two established rodent models of human metabolic syndrome. Introgression of a ca 30 cM region of rat chromosome 8 from PD/Cub onto the genetic background of SHR was previously shown to influence several of the metabolic syndrome-related traits along with causing the PLS in the SHR-Lx congenic strain. In the process of identification of the causative alleles, we have produced several congenic sublines. The differential segment of SHR-Lx PD5 congenic substrain [SHR.PD(D8Rat42-D8Arb23)/Cub] spans approximately 1.4 Mb encompassing only 14 genes. When comparing the metabolic, morphometric and gene expression profiles of the SHR-Lx PD5 vs. SHR, the polydactyly and several distinct metabolic features observed in the original SHR-Lx congenic were still manifested, suggesting that the responsible genes were "trapped" within the relatively short differential segment of PD/Cub origin in SHR-Lx PD5. Particularly, the SHR-Lx PD5 displayed substantial reduction of insulin sensitivity confined to skeletal muscle. Among the candidate genes, the promyelocytic leukaemia zinc-finger Plzf (Zbtb16) transcription repressor is most likely responsible for the Lx mutation resulting in PLS and could also be involved in the alteration of metabolic pathways. The sequence analysis of the Plzf gene revealed a SNP leading to a threonine to serine substitution in SHR at aminoacid position 208 (T208S). In summary, we have isolated a 1.4 Mb genomic region syntenic to human chromosome 11q23, which, apart from causing polydactyly-luxate syndrome (PLS), affects total body weight, adiposity, lipid profile, insulin sensitivity of skeletal muscle and related gene expression as shown in the SHR-Lx PD5 congenic substrain.


Mucin 15 is expressed in human placenta and suppresses invasion of trophoblast-like cells in vitro.
Trophoblast invasion is crucial for the development of normal placentas. Mucins are suggested to be involved in cancer invasion. However, the function of mucins in trophoblast invasion has never been reported. This study was to investigate the expression of mucin (MUC) 15 in human placenta and its role in trophoblast invasion. MUC15 mRNA in human tissues was analyzed by Northern blot. MUC15 mRNA and protein in human placenta were detected by real-time RT-PCR and Western blot, respectively. The distribution of MUC15 was revealed by immunohistochemistry. The effects of MUC15 on trophoblast invasion in vitro were analyzed by matrigel invasion assay in human choriocarcinoma JAR and JEG-3 cells. MUC15 was expressed most highly in human placenta. MUC15 mRNA and protein increased with gestational age (P < 0.05, first versus third trimester). Immunohistochemistry showed that MUC15 protein was expressed by both cytotrophoblasts and syncytiotrophoblasts, especially at the apical membrane of syncytiotrophoblasts. In addition, MUC15 was found to be present in the glandular epithelium of the decidua. Overexpression of MUC15 substantially decreased matrigel invasion of JAR and JEG-3 cells by 87.5 +/- 1.1 and 83.8 +/- 5.7%, respectively, versus control, which was closely associated with an increase in mRNA expression of tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2. Knockdown of MUC15 with small interfering RNA significantly reversed these effects (P < 0.05). Differential expression of MUC15 in human placentas may play a critical role in the regulation of trophoblast invasion.


Sox proteins and neural crest development.
Among the families of transcription factors expressed at the neural plate border in response to neural crest-inducing signals, Sox proteins have emerged as important players in regulating multiple aspects of neural crest development. Here, we summarize the expression of six Sox genes, namely Sox8, Sox9, Sox10, LSox5, Sox4 and Sox11, in neural crest progenitors and their derivatives, and review some aspects of their function pertaining to neural crest development in several species.


The impact of COVID-19 on psychiatric and mental health services in Europe: suffering experienced by professionals.
The COVID-19 pandemic has not only impacted intensive care units, but all healthcare services generally. This PsyGipo2C project specifically investigates how psychiatry and mental health professionals have been affected by the reorganizations and constraints imposed, which have reshaped their often already difficult working conditions. Our research combined quantitative and qualitative methods, surveying and interviewing health professionals of all occupations working in psychiatric and mental health services. A questionnaire was completed by 1241 professionals from 10 European countries, and 13 group interviews were conducted across 5 countries. In addition to this, 31 individual interviews were conducted in Belgium and France. Among the questionnaire respondents, 70.2% felt that their workload had increased, particularly due to their tasks being diversified and due to increased complexity in the provision of care. 48.9% felt that finding a work-life balance had become more difficult, and 59.5% felt their health had been affected by the crisis. The impact of the health crisis nevertheless varied across professions: our data provides insight into how the health measures have had a differential impact on professional tasks and roles across the various categories of occupations, obliging professionals to make various adaptations. The distress incurred has been linked not only to these new constraints in their work, but also to the combination of these with other pressures in their personal lives, which has consequently compromised their well-being and their ability to cope with multiple demands. The COVID-19 health crisis has had varying impacts depending on the profession and access to remote work, sometimes leading to conflicts within the teams. The suffering expressed by the professionals was tied to their values and patterns of investment in work. Our research also highlights how these professionals made little use of the psychological supports offered, probably due to a reluctance to acknowledge that their mental health was affected.


Cloning of cDNA encoding human H-protein, a constituent of the glycine cleavage system.
A cDNA that encodes human H-protein, a constituent protein of the glycine cleavage system, was cloned with anti-rat H-protein antibody as a probe from a human liver cDNA library constructed with an expression vector, lambda gt11. The longest size of cDNA of the isolated clones was about 750 base long (lambda HH15B9). On the other hand, we determined the primary structure of human H-protein from the amino terminal Ser by the 12th Val, including a hexapeptide, -Glu-Lys-His-Glu-Trp-Val-. In addition to the finding that most cDNA inserts cloned hybridized with the synthetic DNA probe composed of the possible sequences for the hexapeptide, we confirmed that lambda HH15B9 encodes the partial primary structure of H-protein in an open reading frame.


Chronic eosinophilic ascites in a very young child.
A case of chronic eosinophilic ascites with onset in early infancy is described. An intensive diagnostic work-up ruled out other known causes of ascites in childhood. The final diagnosis was made at 2 years of age when a large number of eosinophils was detected in the ascitic fluid. The outcome was complicated by an ex vacuo intraperitoneal haemorrhage. Steroids were able to control the disease only after complete aspiration (1600 ml) of the ascitic fluid. On discontinuation of treatment, peritoneal inflammation recurred indicating steroid-dependency. eosinophilic ascites, a very rare disorder in children, should be considered in the differential diagnosis of even very young children presenting with ascites.


The effect of environmental temperature on protein and energy changes following burn injury in the rat.
The metabolic response to a standard burn injury in rats (25% of body surface area) was investigated at environmental temperature 20 degrees C and 30 degrees C. With an intake of 15 g diet (20% w/w protein) per day, burned rats at 20 degrees C were found to be in negative energy balance mainly due to increased insensible (evaporative) losses, and they lost weight. Fat was the main endogenous source of energy, although protein was also catabolised from both carcass and pelt. At 30 degrees C, insensible losses of burned rats were still high, but they had lower sensible (mainly radiative) losses leading to a positive energy balance and a gain in weight. This consisted mainly of carcass water, fat and protein. Urine catecholamines were higher in burned rats at 20 degrees C than at 30 degrees C and correlated with heat loss, urine nitrogen and urine 3-methylhistidine, supporting the hypothesis that catecholamines play a central role in mediating the protein and energy changes following burn injury. For the first 4-6 days, urine nitrogen and 3-methylhistidine excretion increased in rats at 30 degrees C, suggesting that this early part of the metabolic response is obligatory. These findings support the use of raised environmental temperatures to reduce the metabolic response to burns.


Continuous sheet of lens epithelium on an intraocular lens: pathological confirmation of specular microscopy.
A monolayer of proliferating lens epithelium on the anterior surface of an intraocular lens was found cytologically and confirmed histologically in a postmortem examination of one eye of a 57-year-old man. The man had had extracapsular cataract surgery five years earlier. This pathological finding confirms observations with specular microscopy.


Right ventricular outflow tract systolic excursion: a useful method for determining right ventricular systolic function.
Assessment of right ventricular (RV) systolic function is not an easy task. Although RV fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE) are useful in the assessment of RV function, their use can be sometimes limited. Right ventricular outflow tract systolic excursion (RVOT_SE) is a new way to evaluate RV systolic function. The aim of this study was to assess the correlation between RVOT_SE and other RV systolic function assessment methods. RVOT_SE was defined as the systolic excursion of the RV outflow tract anterior wall endocardium. A total of 104 patients with a wide range of RV systolic function, ejection fraction, and pulmonary artery systolic pressure were studied. We also measured another four ways to evaluate RV systolic function, FAC, TAPSE, right ventricular outflow tract fractional shortening (RVOT_FS), and tricuspid annular systolic excursion velocity S' (Tissue S'). There was a strong correlation between RVOT_SE and each one of the four studied ways to evaluate RV systolic function. Multivariate regression analysis showed that the independent variables correlated with RVOT_SE were RVOT_FS (p < 0.0001), FAC (p = 0.005) and TAPSE (p = 0.023). RVOT_SE diagnosed patients with reduced RV systolic function with 98 % sensitivity and 96 % specificity. There was no correlation between RVOT_SE and ejection fraction, or between RVOT_SE and pulmonary artery systolic pressure in patients with reduced RV systolic function. Intra-observer and inter-observer reproducibility were favorable for RVOT_SE and all four studied ways. RVOT_SE is a simple, accurate, and promising method for evaluating RV systolic function.


Myricetin facilitates potassium currents and inhibits neuronal activity of PVN neurons.
The effects of myricetin on hypothalamic paraventricular nucleus (PVN) neurons in rats were investigated. By whole-cell patch clamp detection in hypothalamic brain slices, we showed that the action potential frequency in type-I PVN neurons dose-dependently decreased after myricetin treatment. Further studies demonstrated that myricetin may enhance potassium currents and shifts the voltage-dependence of activation of potassium currents to more negative potentials by 6.07 mV. Using calcium free/cadmium perfusion solution could reverse myricetin-induced enhancement of potassium currents in PVN neurons. These results suggested that inhibition of hypothalamic PVN neurons by myricetin might be attributed to the enhancement of potassium currents.


Triclosan in a sewage treatment process--balances and monitoring data.
In a German sewage treatment plant that processes 200000 m(3) wastewater per day, the concentrations of 2,4,4'-trichloro, 2'-hydroxy-phenylether (triclosan) in the in-flowing ( approximately 1000 ng x l(-1)) as well as in the out-flowing water ( approximately 50 ng x l(-1)) are compared to the concentrations measured in sludge (1200 ng x g(-1)). Considering the mass flow of water and sludge in the respective plant, balances including water and sludge are calculated. Thirty percent of the triclosan is sorbed with weak bonds to the sludge, while some amounts are sorbed as bound residues in the sludge. About 5% is dissolved in the out-flowing water. Thus most of the in-flowing material is not recovered as the parent compound but it is likely that it is transformed to other metabolites or unrecovered bound residues. These data are compared to the monitoring of sewage sludge of 20 different plants in this region, most of which are smaller, though. The concentrations found in these sludges vary from 1000-8000 ng x g(-1).


Hemolytic disease of the newborn following maternal self-injection of blood.
A teenage primigravida with no prior history of transfusion presented with anti-D, anti-C, and anti-E in her serum and subsequently developed anti-Fya. The infant had hemolytic disease of the newborn. The antibodies were provoked by the girl's self-injection of her partner's blood for emotional gratification. Clinicians and transfusion services should be aware that hemolytic disease of the newborn in a first pregnancy can be caused by self-inflicted maternal immunization. Close communication between clinicians and transfusion service is emphasized.


Child temperament is associated with energy intake and its day-to-day variability among preschoolers-Results from a cross-sectional DAGIS study.
Although research has linked children's temperament with weight outcomes, the associations between temperament and dietary outcomes, particularly energy intake, remain understudied. Furthermore, little is known about how temperament is associated with diet in the early childhood education and care (ECEC) context, which is an important environment for many children. This study examined whether temperament is associated with mean energy intake and its day-to-day variability. In addition, the associations were examined separately in the contexts of home and ECEC. The study used data from 505 Finnish children from a cross-sectional DAGIS study conducted in 2015-2016. Parents reported their child's temperament with a questionnaire and food consumption with a food record for two weekdays (outside daycare hours) and one weekend day. Early educators at an ECEC centre reported the child's food consumption during the daycare hours on the same weekdays as the parents kept food records at home. Associations were examined with linear regression models. Children with higher surgency had a higher mean daily energy intake. When examined separately at home and in the ECEC centre, the association was found only in the ECEC centre. Children with higher negative affectivity had greater day-to-day variability in energy intake. This association, however, was not observed when examined separately at home and at the ECEC centre. The results indicate that temperament may shape children's energy intake. Moreover, the role of the ECEC context in children's eating may be different depending on a child's temperamental dispositions, which warrants further research.


Effects of the volume conductor on the apparent orientation of a known cardiac dipole.
The surface electrocardiogram (EKG) is dependent on two major factors: the cardiac generator and the volume conductor. This investigation assessed the effects of the volume conductor in man on the apparent orientation of a simulated cardiac dipole. The apparent orientation of the dipole was calculated from measured surface potentials from about 60 locations on the body of five patients with implanted cardiac pacemakers. The real orientation of the dipole (an implanted pacemaker) was determined radiographically. The effects of both inhomogeneity and boundary characteristics of the volume conductor on the apparent orientation of the dipole were assessed using a new inverse algorithm. The difference between the orientation of the real and the calculated dipoles averaged 30 degrees (range 15 degrees--40 degrees) when the torso was assumed to be an infinite-homogeneous volume conductor. When the configuration of the torso was accounted for, however, the difference between the orientation of the real and calculated dipoles was reduced to 9 degrees (range 5 degrees--13 degrees). Thus, by taking into account the geometry of the torso and neglecting the inhomogeneities in the volume conductor, it is possible to calculate the orientation of a dipole in the cardiac region with an accuracy of about 9 degrees. It is reasonable to assume that the orientation of real activation wave fronts from localized areas of the heart could be calculated with a similar degree of accuracy.


The extracorporeal perfusion of the swine uterus as an experimental model: The effect of tocolytic drugs.
Comparison of the effect of tocolytic drugs on isolated swine uterus preparations. Forty swine uteri were perfused with the aim to preserve a viable organ, which should be responsive to oxytocic hormones and tocolytic pharmaca. An intrauterine catheter recorded the pressure changes. After initiation of rhythmical uterine contractions we administered known tocolytic drugs (fenoterol, ritodrine, terbutaline, propofol, acetylsalicylic acid, alcohol, atosiban, verapamil, and glyceryl trinitrate) in various concentrations. Perfusate pH and lactate, partial oxygen and carbon dioxide tensions, and oxygen saturation in the perfusate showed good preservation of the organ for up to 8h. All substances showed a tocolytic effect on the swine uterus. The effect varied substantially with regard to the length of the contraction free intervals, which was our main effect parameter. Fenoterol, acetylsalicylic acid, and alcohol showed the most and glyceryl trinitrate the least powerful effect. A direct comparison of various tocolytic substances in the same experimental model showed the best effect for fenoterol. Furthermore, we could demonstrate that the swine uterus perfusion system is a suitable model to study the influence of various conditions like the administration of drugs or the induction of oxidative stress on the uterus function.


Manual Cardiopulmonary Resuscitation Versus CPR Including a Mechanical Chest Compression Device in Out-of-Hospital Cardiac Arrest: A Comprehensive Meta-analysis From Randomized and Observational Studies.
Mechanical chest compression devices have been developed to facilitate continuous delivery of high-quality cardiopulmonary resuscitation (CPR). Despite promising hemodynamic data, evidence on clinical outcomes remains inconclusive. With the completion of 3 randomized controlled trials, we conduct a meta-analysis on the effect of in-field mechanical versus manual CPR on clinical outcomes after out-of-hospital cardiac arrest. With a systematic search (PubMed, Web of Science, EMBASE, and the Cochrane Libraries), we identified all eligible studies (randomized controlled trials and nonrandomized studies) that compared a CPR strategy including an automated mechanical chest compression device with a strategy of manual CPR only. Outcome variables were survival to hospital admission, survival to discharge, and favorable neurologic outcome. Twenty studies (n=21,363) were analyzed: 5 randomized controlled trials and 15 nonrandomized studies, pooled separately. For survival to admission, the pooled estimate of the randomized controlled trials did not indicate a difference (odds ratio 0.94; 95% confidence interval 0.84 to 1.05; P=.24) between mechanical and manual CPR. In contrast, meta-analysis of nonrandomized studies demonstrated a benefit in favor of mechanical CPR (odds ratio 1.42; 95% confidence interval 1.21 to 1.67; P<.001). No interaction was found between the endorsed CPR guidelines (2000 versus 2005) and the CPR strategy (P=.27). Survival to discharge and neurologic outcome did not differ between strategies. Although there are lower-quality, observational data that suggest that mechanical CPR used at the rescuer's discretion could improve survival to hospital admission, the cumulative high-quality randomized evidence does not support a routine strategy of mechanical CPR to improve survival or neurologic outcome. These findings are irrespective of the endorsed CPR guidelines during the study periods.


Complementation analysis reveals a potential role of human ARV1 in GPI anchor biosynthesis.
ARV1 is involved in regulating lipid homeostasis but also in the biosynthesis of glycosylphosphatidylinositol (GPI) in Saccharomyces cerevisiae. Here, we examined whether human ARV1 can complement the role of yeast ARV1 in GPI biosynthesis. Overexpression of human ARV1 could rescue the phenotypes associated with GPI anchor synthesis defect in the yeast arv1Δ mutant. The results suggest that Arv1 function in GPI biosynthesis may be conserved in all eukaryotes, from yeast to humans.


Sesamin ameliorates mucosal tissue injury of mesenteric ischemia and reperfusion in an experimental rat model.
Mesenteric ischemia/reperfusion (I/R) injury is a serious clinical condition. There were a lot of experimental studies performed in the treatment of I/R injury. To our knowledge, this is the first experimental study with effects of sesamin on I/R injury model. We aimed to investigate the protective effect of sesamin on mesenteric I/R injury model. A total of 32 male Sprague-Dawley rats were divided into four groups. Control group: superior mesenteric artery (SMA) exposed without clamping. I/R group: SMA was clamped for 60 min and then reperfused for 2 h. Sesamin group (S): 30 mg/kg sesamin were given for 5 days, and SMA exposed without clamping. I/R + S group: 30 mg/kg sesamin were given for 5 days, SMA was clamped for 60 min, and then reperfused for 2 h. Plasma and tissue oxidant parameters were investigated as well as histopathological evaluation. Plasma and tissue total antioxidant status (TAS) levels were significantly higher in I/R + S group compared to the rest (p < 0.005). The plasma TAS levels in I/R group was significantly low. The highest tissue TAS levels were detected in I/R + S group. The high levels of plasma and tissue TOS were found in I/R + S group. Plasma and tissue OSI levels were significantly higher in I/R group. Histopathologic evaluation showed that the mean level of intestinal tissue injury score in I/R group was 2.75 and 1.38 in I/R + S group. Sesamin helps to protect the intestinal tissue at the cellular level by reducing the oxidative stress and inflammation at both the plasma and tissue levels in the experimental I/R model.


Tumor Infiltrating Lymphocytes and CD8+ T Cell Subsets as Prognostic Markers in Patients with Surgically Treated Laryngeal Squamous Cell Carcinoma.
To evaluate the prognostic significance of tumor infiltrating lymphocytes (TILs) and of CD8+ T-cell subsets in patients with surgically treated laryngeal squamous cell carcinoma (LSCC), LSCC from 283 patients were examined. TIL density was morphologically assessed on whole sections. CD8+ cell counts/mm2 were evaluated on multiple tissue microarray cores per tumor (median counts for high/low CD8+/mm2). TIL density and CD8+ counts weakly correlated with each other (Spearman's rho = 0.348). Heterogeneous CD8+ counts/mm2 were demonstrated in 28% of the tumors. In univariate analysis, a significant interaction was observed between CD8 expression and nodal status with respect to outcome; in node-positive patients, those with high CD8+ tumors had 77% lower risk of relapse (interaction p < 0.001) and 74% lower risk for death (interaction p = 0.002) compared to patients with low CD8+ tumors. In multivariate analysis, higher TIL density independently conferred lower risk for relapse in the entire cohort (HR 0.87; 95% CI 0.77-0.98; Wald's p = 0.017) and in node-positive patients (HR 0.41; 95% CI 0.23-0.75; p = 0.003) and, similarly, for death (p = 0.025 and p = 0.003, respectively). High CD8+ was not a significant independent prognostic marker in any analysis setting. The assessment of CD8+ infiltrates does not seem to offer additional prognostic information over the morphologically assessed TIL density. It also appears that the favorable prognostic impact of higher TIL density and CD8+ infiltrates mostly concerns node-positive but not node-negative disease. If validated in larger node-positive cohorts, these findings are worth considering for the diagnostic development of immune cell infiltrates in LSCC.


Monitoring of residual disease by next-generation deep-sequencing of RUNX1 mutations can identify acute myeloid leukemia patients with resistant disease.
We studied the utility and clinical relevance of RUNX1 (runt-related transcription factor 1) mutations and their application as residual disease detection markers using next-generation deep-sequencing. Mutation screening was prospectively performed in 814 acute myeloid leukemia patients. At diagnosis, 211/814 (25.9%) patients harbored mutations with a median clone size of 39% (range: 2-96%). Furthermore, in 57 patients paired samples from diagnosis and relapse were analyzed. In 47/57 (82.5%) cases the same alterations detected at diagnosis were present at relapse, whereas in 1/57 (1.8%) cases the mutation from the diagnostic sample was no longer detectable. Discrepancies were observed in 9/57 (15.8%) cases, also including the occurrence of novel RUNX1 mutations not restricted to those regions affected at diagnosis. Moreover, in 103 patients the prognostic impact of residual levels of RUNX1 mutations during complete remission was studied. Separation of patients according to median residual mutation burden into 'good responders' and 'poor responders' (median: 3.61%; range: 0.03-48.0%) resulted in significant differences of both event-free (median 21.0 vs. 5.7 months, P<0.001) and overall survival (OS; median 56.9 vs. 32.0 months, P=0.002). In conclusion, deep-sequencing revealed that RUNX1 mutations qualify as patient-specific markers for individualized disease monitoring. The measurement of mutation load may refine the assignment into distinct risk categories and treatment strategies.


New media guide to support members' PR.
Shirley Dent, BVA's media manager, announces the launch of a new media guide to help members promote their own and the profession's work in local media.


Semi-supervised deep embedded clustering with pairwise constraints and subset allocation.
Semi-supervised deep clustering methods attract much attention due to their excellent performance on the end-to-end clustering task. However, it is hard to obtain satisfying clustering results since many overlapping samples in industrial text datasets strongly and incorrectly influence the learning process. Existing methods incorporate prior knowledge in the form of pairwise constraints or class labels, which not only largely ignore the correlation between these two supervision information but also cause the problem of weak-supervised constraint or incorrect strong-supervised label guidance. In order to tackle these problems, we propose a semi-supervised method based on pairwise constraints and subset allocation (PCSA-DEC). We redefine the similarity-based constraint loss by forcing the similarity of samples in the same class much higher than other samples and design a novel subset allocation loss to precisely learn strong-supervised information contained in labels which consistent with unlabeled data. Experimental results on the two industrial text datasets show that our method can yield 8.2%-8.7% improvement in accuracy and 13.4%-19.8% on normalized mutual information over the state-of-the-art method.


Quantitative assessment of ventricular function in sickle cell disease: effect of long-term erythrocytapheresis.
Previous studies on cardiac function in patients with sickle cell disease (SCD) demonstrated abnormalities of systolic and diastolic function including elevated left ventricular myocardial performance index (LVMPI) on chronic transfusion protocols. LVMPI has been validated as a useful and easy non-invasive measure of overall cardiac function. Up to now, there are no reported studies on cardiac function in patients with SCD maintained on long-term erythrocytapheresis (LTE). We recorded LVMPI in 22 patients with SCD aged 3-20 years and we compared the results between non-transfused patients (NT-SCD) and patients on LTE (T-SCD). Males with SCD had higher mean LVMPI than females (P = 0.04). There were significant differences among T-SCD, severe NT-SCD, and mild NT-SCD patients with respect to hemoglobin (Hb) levels (P = .003) and TR velocity (P = .03). T-SCD patients showed elevated LVMPI compared to NT-SCD patients with severe and mild disease (P = 0.002). Pair-wise comparisons demonstrated that T-SCD patients had LVMPI that was significantly higher than NT-SCD (mild) patients (P = 0.01). Our study demonstrates that patients SCD on LTE have cardiac dysfunction based on elevated LVMPI. This may be a reflection of the global severity of disease. Our findings merit further investigation with serial monitoring of LVMPI on a larger number of patients with SCD.


The effect of a multi-disciplinary obesity intervention compared to usual practice in those ready to make lifestyle changes: design and rationale of Whanau Pakari.
Child obesity internationally has been identified as one of the major threats to future population health. Indigenous people and those from lower socio-economic backgrounds are over-represented in obesity statistics. There is a need for evidence of effect of interventions for child obesity with long-term follow-up. Whether engaging with those that are more motivated to make lifestyle changes is a useful strategy has not been fully explored. We hypothesise that in obese/overweight children, assessed as psychologically "ready for change", delivery of a 12-month multi-disciplinary intervention programme results in a significant reduction in body mass index standard deviation score. Whanau Pakari is an unblinded randomised controlled clinical trial comparing a 12 month intervention programme with standard practice, with 6 monthly assessments for 2 years, conducted in Taranaki, New Zealand (a region where 15.8 % of the population are indigenous). It specifically targets indigenous people and those in more deprived households. Obese/overweight children and adolescents aged 5-16 years are eligible. Exclusion criteria are medical/psychological conditions leading to inability to undertake physical activity/participate in group sessions; those not "ready" to make lifestyle changes; and those without a committed family member. Assessments of health parameters, dietary history, physical activity and overall health-related quality of life/psychological functioning are completed in the participant's home. Fasting blood tests are obtained at baseline, 12 and 24 months. The primary outcome is body mass index standard deviation score. Secondary outcomes include quality of life, dietary behaviour and physical activity, cardiovascular and metabolic profile (blood pressure, resting heart rate, waist circumference), glycaemic control (fasting glucose and glycated Haemoglobin), fasting insulin, and lipids. A general linear mixed model will be used to assess change from baseline using the 6, 12, 18 and 24 month measures, adjusting for age, gender, socioeconomic status and ethnicity, and whether at the contemplative or preparation/action stages of readiness for change. This trial will inform the development of management programmes for obese children and adolescents that are appropriate for indigenous populations. It will investigate whether those at the preparation/action stage of "readiness" to make lifestyle changes are more successful in making changes than those who are contemplative. Australian New Zealand Clinical Trials Registry (ANZCTR):12611000862943. (Date registered 15/08/2011).


Four hundred fifty consecutive laparoscopic Roux-en-Y gastric bypasses with no mortality and declining leak rates and lengths of stay in a bariatric training program.
We reviewed our obesity surgery database for 2 experienced bariatric surgeons since their last patient death in October 2003 through July 2007. Data on all patients undergoing planned laparoscopic Roux-en-Y gastric bypass (L-GBP) by the two attending bariatric surgeons at the Medical College of Virginia Hospitals were reviewed. The operations were performed by fellows in minimally invasive surgery, assisted by the 2 attending physicians in more than 90% of patients. Surgical technique included a handsewn imbrication of a gastrojejejunostomy and jejunojejunostomy, each performed with a linear stapler. Routine sampling of a juxtaanastamotic drain for amylase levels was substituted for routine upper gastrointestinal contrast studies during the study period. All patients, except those who had earlier extensive upper abdominal surgery in that time period, were offered a laparoscopic approach (5.7% were converted to open procedures). The mean (+/- SD) age was 42.4+/-11 years; body mass index was 49.5+/-9 kg/m(2). Women represented 80.5% of patients. The leak rate declined from 9.7% in 2004 to 2.0% in 2006 (p < 0.05, chi-square test); there have been no leaks in any patient since July 2006, including the 40 patients in 2007. Hospital length of stay declined from 4.7+/-5.7 days in 2004 to 2.9+/-3.3 days in 2006 (p < 0.05, Wilcoxon rank test). At 1-year followup, 270 patients had lost 66.1%+/-17% of initial excess weight, which was similar to that in our open gastric bypasses. Comorbid conditions improved or resolved in 67.6% of patients with diabetes, 56.1% of those with hypertension, 75% of those with sleep apnea, 87.8% of those with urinary stress incontinence, 95.9% of those with gastroesophageal reflux disease, and in 100% of those with stasis ulcers. Overall complication rates of wound infection (1.5%), incisional hernia (1.7%), internal hernia (0.2%), and intestinal obstruction (1.7%) were low. Results for laparoscopic Roux-en-Y gastric bypass improve with experience and can be taught in an academic training program, with low morbidity and mortality. Routine postoperative upper gastrointestinal contrast studies are unnecessary and may lengthen hospital stay.


[Frontal astrocytoma with spinal cord metastasis. Report of a case and review of the literature].
A case of a right frontal astrocytoma with spinal metastatic lesion in the region of the third dorsal vertebra is reported. The metastatic nodule was removed six months after the craniotomy. In the literature concerning to the dissemination of tumors cells is suggested that there is not a causal relationship between CSF seeding and operative intervention. Access to the ventricular system or basal cisterns is of primary importance in the production of metastases.


Incidence and Risk Factors of Cancer in the Anal Transitional Zone and Ileal Pouch following Surgery for Ulcerative Colitis and Familial Adenomatous Polyposis.
Proctocolectomy with ileal pouch-anal anastomosis is the intervention of choice for ulcerative colitis and familial adenomatous polyposis requiring surgery. One of the long-term complications is pouch cancer, having a poor prognosis. The risk of high-grade dysplasia and cancer in the anal transitional zone and ileal pouch after 20 years is estimated to be 2 to 4.5% and 3 to 10% in ulcerative colitis and familial polyposis, respectively. The risk factors for ulcerative colitis are the presence of pre-operative dysplasia or cancer, disease duration > 10 years and severe villous atrophy. For familial polyposis, the risk factors are the number of pre-operative polyps > 1000, surgery with stapled anastomosis and the duration of follow-up. In the case of ulcerative colitis, a pouchoscopy should be performed annually if one of the following is present: dysplasia and cancer at surgery, primary sclerosing cholangitis, villous atrophy and active pouchitis (every 5 years without any of these factors). In the case of familial polyposis, endoscopy is recommended every year including chromoendoscopy. Even if anal transitional zone and ileal pouch cancers seldom occur following proctectomy for ulcerative colitis and familial adenomatous polyposis, the high mortality rate associated with this complication warrants endoscopic monitoring.


[Color duplex ultrasonography, percutaneous transpopliteal venography and photoplethysmography assess venous reflux in the lower extremities].
To assess the scope of photoplethysmography (PPG), color duplex ultrasonography, percutaneous transpopliteal venography for evaluating chronic venous disease. Color duplex ultrasonography, percutaneous transpopliteal venography, and PPG and were used in 40 patients their results were compared. Color duplex ultrasonography and percutaneous transpopliteal venography for evaluating venous reflux was not significant (P > 0.05) in the femoral-popliteal venous segment. The accuracy of PPG in evaluating venous reflux was 67% compared with that of color duplex ultrasonography. PPG as the first test is often used for chronic venous disease. Color duplex ultrasonography can provide sufficient information for treatment of patients the. Percutaneous transpopliteal venography is necessary when noninvasive test can not provide sufficient information.