One-year follow-up of posterior chamber toric phakic intraocular lens implantation for moderate to high myopic astigmatism.
To assess the 1-year clinical outcomes of toric Visian Implantable Collamer Lens (ICL; STAAR Surgical, Nidau, Switzerland) implantation for moderate to high myopic astigmatism. Prospective, observational case series. Fifty-six eyes of 32 consecutive patients, with spherical equivalent errors of -4.00 to -17.25 diopters (D) and cylindrical errors of -0.75 to -4.00 D, who underwent toric ICL implantation. Before and 1 week and 1, 3, 6, and 12 months after surgery, the safety, efficacy, predictability, stability, and adverse events of the surgery were assessed in eyes undergoing toric ICL implantation. Ocular higher-order aberrations (HOAs) and contrast sensitivity (CS) function also were evaluated before and 1 year after surgery. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), safety index, efficacy index, predictability, stability, adverse events, HOAs, and CS function. The logarithm of the minimum angle of resolution (logMAR) UCVA and logMAR BSCVA were -0.11 (corresponding to Snellen equivalent 20/16) ± 0.12 and -0.19 (corresponding to 20/12.5) ± 0.08 1 year after surgery, respectively. The safety and efficacy indices were 1.17 ± 0.21 and 1.00 ± 0.29. At 1 year, 91% and 100% of the eyes were within 0.5 and 1.0 D, respectively, of the targeted correction. Manifest refraction changes of -0.07 ± 0.27 D occurred from 1 week to 1 year. For a 4-mm pupil, fourth-order aberrations were changed, not significantly, from 0.05 ± 0.02 μm before surgery to 0.06 ± 0.03 μm after surgery (P = 0.38, Wilcoxon signed-rank test). Similarly, for a 6-mm pupil, fourth-order aberrations were not significantly changed, merely from 0.20 ± 0.08 μm before surgery to 0.23 ± 0.11 μm after surgery (P = 0.15). The area under the log CS function was significantly increased from 1.41 ± 0.15 before surgery to 1.50 ± 0.13 after surgery (P < 0.001). No vision-threatening complications occurred during the observation period. In the authors' experience, the toric ICL performed well in correcting moderate to high myopic astigmatism during a 1-year observation period, suggesting its viability as a surgical option for the treatment of such eyes.


[A new slit-lamp fluorophotometer for the clinical evaluation of corneal epithelial barrier function].
A new objective slit-lamp fluorophotometer was developed to examine corneal epithelial barrier function. This instrument has several new characteristics. The photodetector system is placed directly in front of the cornea and the focal diamond is accurately positioned at the corneal surface, permitting measurement of the barrier function of peripheral parts of the cornea. Due to the filter characteristics, measurement can be done even in a relatively bright room. Only one second is needed for measurement, eliminating blink interruption. Linear relationships were found between measurement count and fluorescein concentration. 0.5% and 3 microliters of fluorescein was applied to the eyes of healthy volunteers. In non-washed eyes, the concentration changes were consistent with tear turnover, and in washed eyes, the changes reflected the barrier function of the corneal epithelium and showed correlation with age. This instrument is also useful for determining autofluorescence. A significant relation was seen between autofluorescence and age.


Dexmedetomidine enhances glymphatic brain delivery of intrathecally administered drugs.
Drug delivery to the central nervous system remains a major problem due to biological barriers. The blood-brain-barrier can be bypassed by administering drugs intrathecally directly to the cerebrospinal fluid (CSF). The glymphatic system, a network of perivascular spaces promoting fluid exchange between CSF and interstitial space, could be utilized to enhance convective drug delivery from the CSF to the parenchyma. Glymphatic flow is highest during sleep and anesthesia regimens that induce a slow-wave sleep-like state. Here, using mass spectrometry and fluorescent imaging techniques, we show that the clinically used α2-adrenergic agonist dexmedetomidine that enhances EEG slow-wave activity, increases brain and spinal cord drug exposure of intrathecally administered drugs in mice and rats. Using oxycodone, naloxone, and an IgG-sized antibody as relevant model drugs we demonstrate that modulation of glymphatic flow has a distinct impact on the distribution of intrathecally administered therapeutics. These findings can be exploited in the clinic to improve the efficacy and safety of intrathecally administered therapeutics.


Sonographic parenchymal and brain perfusion imaging: preliminary results in four patients following decompressive surgery for malignant middle cerebral artery infarct.
To investigate new methods of diagnostic transcranial sonography for brain parenchymal, vascular and perfusion imaging, we performed 3-D native tissue harmonic transcranial sonography (3D-nthTCS), 3-D transcranial color-coded duplex sonography (3D-TCCS), and "loss-of-correlation" imaging (LOC-TCCS) in four patients following early hemicraniectomy due to space-occupying "malignant" middle cerebral artery infarction (MMCAI). Three-dimensional datasets, utilizing 3D-nthTCS and 3D-TCCS, were created and up to 10 axial 2-D B-mode image planes, similar to CCT, reconstructed in each patient. Three-dimensional reconstructions of the circle of Willis documented one persistent carotid-T occlusion and three recanalizations of the MCA. LOC-TCCS, based on stimulated acoustic emission from an ultrasound (US) contrast agent, demonstrated a perfusion deficit in 2 of 3 patients, with regard to their infarcts. Concluding, 3D-nthTCS, 3D-TCCS and LOC-TCCS are promising tools for bedside monitoring, early prognosis and treatment evaluation for MMCAI in the postoperative period. Further studies should be performed to standardize these new methods and evaluate their applications through the intact calvarina.


Long-term neural recording characteristics of wire microelectrode arrays implanted in cerebral cortex.
This paper describes a detailed protocol for obtaining chronic, multi-site unit recordings in cerebral cortex of awake animals for periods of three months or more. The protocol includes details for making relatively simple and inexpensive implantable multichannel electrodes that consist of arrays of separate microwires. The results reported in this paper suggest that a viable implant will have discriminable unit activity on about 80% of the electrodes, resulting in, on average, the simultaneous unit recording of upwards of 60 units during a daily recording session. The active electrodes during one recording session tend to remain active in subsequent recording sessions for several weeks. Using the methods described here, implants have been constructed which incorporate several different electrode materials, coatings, sizes, and electrode separation within a single array. These microwire electrode arrays provide the basic technology for obtaining unit recordings for several months. This provides a model system for studying biocompatibility of neural implants, which is a critical component for the development of neural implants that have an indefinite working span.


Phospholipase D involvement in the plant oxidative burst.
Pathogen-triggered generation of reactive oxidants, termed the oxidative burst, contributes to disease resistance in both plant and animal kingdoms. Since phospholipase D plays a key role in the neutrophil oxidative burst signaling cascade and is highly abundant in plants, we investigated its participation in the plant oxidative burst. Thin layer chromatography of extracted phospholipids revealed no changes in phosphatidic acid levels in soybean cells undergoing oxidant production, and no changes in phosphatidyl-ethanol biosynthesis could be detected when ethanol was present during elicitation. An inhibitor of phosphatidic acid hydrolase, propranolol, did not modify burst parameters or phosphatidic acid levels during the burst, suggesting our inability to detect phosphatidic acid accumulation was not due to rapid elimination. Furthermore, exogenous phosphatidic acid did not elicit a burst or enhance elicitor-stimulated bursts. Finally, ethanol, a substitute nucleophile, did not abrogate the burst. With data showing the presence of phospholipase D in soybean cells, these data argue that soybean phospholipase D does not participate in signaling the oxidative burst. This constitutes the first major difference between the plant and animal oxidative burst signal transduction pathways.


Striking elevation of serum IgA, IgA-containing immune complexes, and IgA rheumatoid factor in clinically silent dermatitis herpetiformis.
We describe a patient with dermatitis herpetiformis with immunoglobulin A (IgA)-containing circulating immune complexes and IgA rheumatoid factor who presented with acute renal insufficiency; a renal biopsy specimen showed IgA nephropathy. The renal function and proteinuria spontaneously returned to normal despite markedly elevated levels of IgA-containing circulating immune complexes, IgA rheumatoid factor, and IgA antibodies to some environmental antigens. IgA1 was the predominant subclass. IgA2-containing immune complexes and IgM rheumatoid factor were not detected. Cultures of peripheral blood mononuclear cells produced increased quantities of IgA and IgA rheumatoid factor spontaneously and after pokeweed mitogen stimulation. These data indicate that renal function can improve and remain normal despite the presence of increased levels of IgA-containing circulating immune complexes and IgA rheumatoid factor.


Recombination may cause genotoxicity.


Auxin modulates the enhanced development of root hairs in Arabidopsis thaliana (L.) Heynh. under elevated CO(2).
Root hairs may play a critical role in nutrient acquisition of plants grown under elevated CO(2) . This study investigated how elevated CO(2) enhanced the development of root hairs in Arabidopsis thaliana (L.) Heynh. The plants under elevated CO(2) (800 µL L(-1)) had denser and longer root hairs, and more H-positioned cells in root epidermis than those under ambient CO(2) (350 µL L(-1)). The elevated CO(2) increased auxin production in roots. Under elevated CO(2) , application of either 1-naphthoxyacetic acid (1-NOA) or N-1-naphthylphthalamic acid (NPA) blocked the enhanced development of root hairs. The opposite was true when the plants under ambient CO(2) were treated with 1-naphthylacetic acid (NAA), an auxin analogue. Furthermore, the elevated CO(2) did not enhance the development of root hairs in auxin-response mutants, axr1-3, and auxin-transporter mutants, axr4-1, aux1-7 and pin1-1. Both elevated CO(2) and NAA application increased expressions of caprice, triptychon and rho-related protein from plants 2, and decreased expressions of werewolf, GLABRA2, GLABRA3 and the transparent testa glabra 1, genes related to root-hair development, while 1-NOA and NPA application had an opposite effect. Our study suggests that elevated CO(2) enhanced the development of root hairs in Arabidopsis via the well-characterized auxin signalling and transport that modulate the initiation of root hairs and the expression of its specific genes.


Incidence of developmental defects at the no observed adverse effect level (NOAEL).
Bioassay data from Teratology, Vol. 1 (1968) through Vol. 40 (1990), were utilized which were sufficient to establish no observed adverse effect levels (NOAEL's) for 120 experiments on 93 developmental toxicants in animals. The observed incidence (risk) at the NOAEL was calculated as the proportion of affected fetuses minus the proportion affected in the control animals. This calculation did not require any dose-response modeling. Data were primarily from experiments on rats and mice with a few studies on rabbits and hamsters. There did not appear to be differences in risks at the NOAEL among these four species. For each experiment, the risk at the NOAEL was tabulated for all of the adverse effects which shared the same NOAEL. Since the observed risk at the NOAEL for either dead/resorbed or abnormal fetuses exceeded 1% in about one-fourth of the cases, this suggests that a benchmark dose with a risk on this order would eliminate the higher risks and serve as a basis for establishing reference doses. If the lower confidence limit on a benchmark dose is used in place of the NOAEL, better experimental designs with more animals would result in tighter confidence limits, giving larger (less stringent) reference doses than poorer experiments.


Tuberculosis knowledge, attitudes and practices: a cross-sectional study in the Somali population living in Finland.
In Finland, the epidemiology of tuberculosis is changing: incidence declined from 13/100 000 in 1995 to 4 in 2016 and the proportion of foreign-borns among all TB cases increased from 5% to 50%. The most common country of origin among foreign-born TB patients was Somalia. Knowledge, attitudes and practices (KAP) studies are used to collect information for planning and tailoring health care services. KAP studies in Finland have been used for other diseases but not to study Somalis in regards to TB. The KAP were assessed by a piloted questionnaire. Convenience sampling was performed, and the questionnaire was administered in mosques, shops and Islamic events. Knowledge and attitudes were assessed by creating composite scores. Associations between sociodemographic characteristics and knowledge and attitudes were investigated using logistic regression to compute odds ratios (OR) and 95% confidence intervals (CI). A total of 407 participants took part; 49% were male. Low level of knowledge was held by 53% of participants, and favourable attitude regarding TB by 63%. Knowledge was not associated with gender or country of birth. Female participants were twice more likely to have a favourable attitude than males (adjusted OR, 2.37; 95%CI, 1.40-4.01). Those with high knowledge are twice more likely to have a favourable attitude towards TB (adjusted OR, 2.21; 95%CI, 1.32-3.69). The population held a favourable attitude towards TB, but knowledge gaps and misconceptions regarding TB were found. The results of this study can be used for designing health communication and targeted preventive measures for the Somali population.


Pd- and Ni-catalyzed cross-coupling reactions of functionalized organozinc reagents with unsaturated thioethers.
A variety of unsaturated thioethers have been subjected to cross-coupling reactions with functionalized zinc reagents in the presence of a transition-metal catalyst. Three different catalytic systems based on Pd(OAc)(2) or [Ni(acac)(2)] and the ligands S-Phos or DPE-Phos gave the best results. N-Heterocyclic thioethers based on a pyridine, pyrimidine, pyrazine, pyridazine, triazine, benzothiazole, benzoxazole, pyrrole, or quinazoline ring, as well as thiomethylacetylenes, serve as electrophiles in this cross-coupling reaction. Aryl-, heteroaryl-, benzylic, and alkylzinc halides with sensitive functionalities, such as ester, nitrile, or ketone groups react at ambient temperature with unsaturated thioethers using a Ni catalyst. The corresponding Pd-catalyzed reactions require slightly higher temperatures. Large-scale cross-coupling experiments (10-20 mmol) with N-heterocycles are also reported.


[Use of adenosine and high-energy phosphates in cardiac anesthesiology].
Usage of adenosine and high-energy phosphates in cardiac anesthesiology is widely discussed. Implementation of above substances can be achieved via three possible ways: during the preparation of patients for cardiac surgery, during surgery and after the surgery during intensive postoperative care. Optimum methods for cardiac protection, which could guarantee safe, lasting heart function preservation after the surgery are investigated till now. Advantages and disadvantages of adenosine application during preoperative and postoperative periods as well as in cardiac surgery are presented. Possibilities to use phosphocreatine for cardioprotection will be discussed as well.


Generalization of a conditioned inhibitor of response suppression in rats.
Following acquisition of conditioned suppression of barpresses to a visual conditiondd stimulus (CS), rats were subjected to a particular variety of differentiation training procedures. An auditory conditioned inhibitor (CI), which preceded and accompanied the CS on some trials, signaled that inescapable shock will not be given on that trial. When the CI acquired the capacity to attenuate markedly the suppressive effects of the CS presented within the CI + CS compound, the frequency dimension of the CI was varied during generalization tests. Reliable within-subjects gradients of barpress enhancement were obtained when tone test frequencies were presented alone. Frequency gradients obtained from CI variation in compound with the CS were rather flat and reflected some residual suppression of the on-going barpressing.


Validation of the 30-item General Health Questionnaire in postpartum women.
Two hundred consecutive women from five Southampton general practices who were between 8 and 14 weeks postpartum were visited at home. Each subject was given the 30-item General Health Questionnaire (GHQ-30) and a standardized psychiatric interview. Thirty-seven (18%) were identified as 'cases' by the psychiatric interview. Eighty-nine (44.5%) scored highly on the GHQ. Analysis of the results indicates that slight modification of the content and a raised cut-off point of the GHQ-30 make it a useful screening instrument for postpartum psychiatric disorder.


Chlorophyll fluorescence emission spectrum inside a leaf.
Chlorophyll a fluorescence can be used as an early stress indicator. Fluorescence is also connected to photosynthesis so it can be proposed for global monitoring of vegetation status from a satellite platform. Nevertheless, the correct interpretation of fluorescence requires accurate physical models. The spectral shape of the leaf fluorescence free of any re-absorption effect plays a key role in the models and is difficult to measure. We present a vegetation fluorescence emission spectrum free of re-absorption based on a combination of measurements and modelling. The suggested spectrum takes into account the photosystem I and II spectra and their relative contribution to fluorescence. This emission spectrum is applicable to describe vegetation fluorescence in biospectroscopy and remote sensing.


Prevention of Fascial Dehiscence with Onlay Prophylactic Mesh in Emergency Laparotomy: A Randomized Clinical Trial.
Fascial dehiscence (FD) occurs in up to 14.9% of high-risk patients undergoing emergency laparotomy. Although prophylactic mesh can prevent FD, its use in emergency operations remains controversial. A prospective randomized clinical trial was conducted at the Hospital das Clínicas from Faculdade de Medicina da Universidade de São Paulo in Brazil. It was performed among high-risk patients, defined according to Rotterdam risk model, undergoing midline emergency laparotomy. The patients were randomized into the suture group (SG), with slowly absorbable running sutures placed with a 36-mm-long needle at a suture-to-wound length ratio of 4:1, and the prophylactic mesh group (PMG), with fascial closure as in the SG but reinforced with onlay polypropylene mesh. The primary end point was incidence of FD at 30 days post operation. We analyzed 115 patients; 52 and 63 were allocated to the SG and PMG, respectively. In all, 77.4% of the cases were for colorectal resection. FD occurred in 7 (13.5%) patients in the SG and none in the PMG (p = 0.003). There was no difference between the groups in number of patients with surgical site occurrence (SSO) or SSO requiring procedural intervention. However, some specific SSOs had higher incidences in the mesh group: surgical site infection (20.6% versus 7.7%; p = 0.05), seroma (19.0% versus 5.8%; p = 0.03), and nonhealing incisional wound (23.8% versus 5.8%; p = 0.008). Of SSOs in the PMG and SG, 92.3% and 73.3%, respectively, resolved spontaneously or with bedside interventions. Prophylactic onlay mesh reinforcement in emergency laparotomy is safe and prevents FD. Surgical site infection, seroma, and nonhealing incisional wound were more common in the mesh group, but associated with low morbidity within 30 days post operation.


Comparative binding to DR4 and DR5 receptors of TRAIL and BNNTs/PAHE/mPEG-DSPE/TRAIL nanoparticles.
TRAIL is a member of the tumor necrosis factor family of cytokines, which induces apoptosis of cancer cells, thanks to its binding to its cognate receptors DR5 and DR4. We have recently demonstrated that nanovectorization of TRAIL with single-walled carbon nanotubes enhanced TRAIL affinity to DR5. In this paper, 1-pyrenebutyric acid N-hydroxysuccinimide ester functionalized boron nitride nanotubes (BNNTs) were used to anchor the TRAIL protein. The resulting BNNT/1-pyrenebutyric acid N-hydroxysuccinimide ester nanotubes were mixed with methoxy-poly(ethylene glycol)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-conjugates so as to allow a good dispersion of these nanoparticle TRAIL (NPT) in aqueous solution. The difference of binding between NPT and soluble TRAIL to DR4 and DR5 receptors was then studied by the use of affinity chromatography. DR4 and DR5 receptors were thus immobilized on a chromatographic support, and the binding of the 2 ligands TRAIL and NPT to DR4 and DR5 was studied in the temperature range 30°C to 50°C. Negative enthalpy (ΔH) values indicated that van der Waals interactions and hydrogen bonding are engaged favorably at the ligand-receptor interface. It was shown that their rank-ordered affinities were strongly different in the sequence TRAILDR4 < NPTDR4 < TRAILDR5 < NPTDR5 , and the highest affinity for NPT to DR4 and DR5 receptors observed at low pHs was due to the less accessibility of the His molecular switch to be protonated when TRAIL was immobilized on BNNTs. Taken together, our results demonstrated that nanovectorization of TRAIL with BNNTs enhanced its binding to both DR4 and DR5 receptors at 37°C. Our novel nanovector could potentially be used for delivering TRAIL to cells for cancer treatment.


Improved delay-dependent asymptotic stability criteria for delayed neural networks.
This brief is concerned with asymptotic stability of neural networks with uncertain delays. Two types of uncertain delays are considered: one is constant while the other is time varying. The discretized Lyapunov-Krasovskii functional (LKF) method is integrated with the technique of introducing the free-weighting matrix between the terms of the Leibniz-Newton formula. The integrated method leads to the establishment of new delay-dependent sufficient conditions in form of linear matrix inequalities for asymptotic stability of delayed neural networks (DNNs). A numerical simulation study is conducted to demonstrate the obtained theoretical results, which shows their less conservatism than the existing stability criteria.


Transanal total mesorectal excision: surgical technique description and outcomes.
Minimally invasive techniques (MIS) have been evolving quickly in colorectal surgery during the last two decades. Transanal total mesorectal excision (taTME) was developed as a combination of skills acquired from different MIS approaches such as Transanal Endoscopic Microsurgery (TEM), Transanal Minimally Invasive Surgery (TAMIS) and Natural Orifices Transluminal Endoscopic Surgery (NOTES). TaTME allows for a better visualization of surgical planes of dissection and achievement of rectal resection following oncologic principles. We here present the standardized taTME technique in use at the Hospital Clínic de Barcelona and our published outcomes in rectal cancer.


Immunogenicity of the Shigella flexneri serotype Y (SFL 124) vaccine strain expressing cloned glucosyl transferase gene of converting bacteriophage SfX.
The glucosyl transferase gene (gtr) from bacteriophage phage X (SfX) caused partial conversion of serotype Y (group antigen 3, 4) to X (group antigen 7, 8) when introduced into a candidate vaccine strain of Shigella flexneri serotype Y (SFL124). The gtr gene caused conversion of O-antigens but did not eliminate the adsorption of the corresponding phage SfX. The hybrid strain expressing both group antigens 7, 8 and 3, 4 showed 75% protection when immunized guinea pigs were challenged with a wild-type S. flexneri serotype X strain. No protection was observed against serotype Y challenge, although group antigen 3, 4 was detected in the LPS of the hybrid strain. This suggests the importance of O-antigen immunity in the host defense against shigellosis.


Effects of adenosine on sympathetic vasoconstriction in dog gracilis muscle.
The effects of intra-arterial infusions of adenosine (ADO) on sympathetic vasconstrictor responses were studied in the gracilis nerve-muscle preparation of the dog under constant flow conditions. Sympathetic nerves to the muscle were activated at a frequency of 1 Hz for 2 min during infusions of ADO, 2-chloroadenosine, nitroglycerine or hydralazine. ADO concentrations of 1, 10 and 50 microM decreased perfusion pressure by 19, 42 and 57 mm Hg, respectively, from a control (saline infusion) perfusion pressure of 110 mm Hg. Sympathetic vasoconstrictor responses were attenuated only at 50 microM ADO. Sympathetic responses during 1 and 10 microM ADO infusion were the same as during infusion of 10 and 100 microM nitroglycerine, which produced the same degree of vasodilation as 1 and 10 microM ADO, respectively. Except for greater vasodilator potency, 2-chloroadenosine infusions produced effects similar to ADO. Infusion of hydralize produced concentration-dependent decreases in control perfusion pressure and sympathetic vasoconstrictor responses. These results indicate that intra-arterial administration of ADO or one of its stable analogs (2-chloroadenosine) does not cause inhibition of sympathetic vasoconstrictor responses except at concentrations that cause nearly maximal vasodilation.


Evaluation of a new method for determining tracheal tube length in children.
Most paediatric tracheal tubes are marked in centimetres from the tip. In 105 children, nasotracheal tube length was set at the level of the vocal cords such that all 3.0 and 3.5 mm internal diameter tubes were placed with the 3 cm mark at the cords, all 4.0 and 4.5 tubes were set at 4 cm at the cords and all 5.0 and 5.5 tubes were set at 5 cm at the cords. Subsequent chest X ray showed that 79% of the tracheal tubes were in the ideal midtracheal position, one tube was marginally short and 20% of the tubes were marginally long. Neither bronchial intubation nor accidental extubation occurred in any subject. This is an effective method to determine tracheal tube length which may be used for both oral and nasal intubation.


Problems in estimating the extent of coprophagy in the rat.
The quantity of re-ingested faeces was calculated by comparing faecal dry matter of unrestricted rats and coprophagy-restricted rats after correcting for differences in food intake. Due to high day-to-day variations of produced and re-ingested faeces it was not possible to calculate precisely the extent of coprophagy of an individual rat at a particular day with this difference method. Reliable quantitative estimates require at least two rats and a collection period of 7 d. When fed on a nutritionally complete diet, rats re-ingested 0-11% of their faeces. When fed on low-protein diets (66 g egg albumin/kg) or diets diluted with 200 g cellulose/kg, coprophagy was not significantly increased. A high re-ingestion rate (6-25%) was observed with thiamin and pantothenic acid deficiencies. After re-ingestion of faeces had been prevented for 1 week, the amount of faeces re-ingested during the subsequent week without tail-cups was increased twofold. It is concluded that rats are able to regulate the amount of faeces eaten precisely according to their requirements.


Altered exercise pulmonary function after left ventricular assist device implantation.
The use of LVADs as a bridge to heart transplantation is increasing steadily as more surgical centers add this effective strategy for end-stage heart failure patients. Fundamental exercise physiology in the presence of LVADs has been described previously, and data is available that supports the safety and efficacy of exercise in this population. Variants to the expected exercise response that may be secondary to LVAD implantation, such as the pulmonary restrictive pattern that developed in the patient described in this case study, may occur. Clinicians should consider assessment and monitoring of pulmonary function in this patient population, especially in patients with exercise-induced dyspnea and perhaps patients with pre-existing pulmonary limitation.


Quantification of N-acetyl-L-aspartic acid in urine by isotope dilution gas chromatography-mass spectrometry.
A method for quantification of N-acetyl-L-aspartic acid by isotope dilution gas chromatography-mass spectrometry using 15N-[2H3]acetyl-L-aspartic acid is described. The method is sufficiently sensitive to be used with solvent extraction techniques commonly employed for urinary organic acid analysis. The mean concentration of N-acetyl-L-aspartic acid in 80 normal and abnormal control urine specimens was 19.7 +/- 10.8 mg/g creatinine (12.7 +/- 7.8 mmol/mol creatinine). Seven patients, ages 9 months to 7 years, with Canavan-van Bogaert syndrome had urinary N-acetyl-L-aspartic acid levels from 606 to 4760 mg/g creatinine. The method can also be used with cerebrospinal fluid, in which the concentration of N-acetyl-L-aspartic acid is about one-tenth of that in urine.


Multicritical Point on the de Almeida-Thouless Line in Spin Glasses in d>6 Dimensions.
The de Almeida-Thouless (AT) line in Ising spin glasses is the phase boundary in the temperature T and magnetic field h plane below which replica symmetry is broken. Using perturbative renormalization group (RG) methods, we show that, when the dimension d of space is just above six, there is a multicritical point (MCP) on the AT line, which separates a low-field regime, in which the critical exponents have mean-field values, from a high-field regime, where the RG flows run away to infinite coupling strength; as d approaches six from above, the MCP approaches the zero-field critical point exponentially in 1/(d-6). Thus, on the AT line, perturbation theory for the critical properties breaks down at a sufficiently large magnetic field even above 6 dimensions, as well as for all nonzero fields when d≤6, as was known previously. We calculate the exponents at the MCP to first order in ϵ=d-6>0. The fate of the MCP as d increases from just above six to infinity is not known.


Noradrenergic and serotonergic modulation to treat vasomotor symptoms.
Hot flushes are a major clinical problem for many menopausal women. Their aetiology is unknown. Centrally acting neurotransmitters are involved, but this involvement is yet to be fully characterized. In clinical trials with optimal patient selection and compliance, estrogen can reduce the frequency of hot flushes by 70-80%, and placebo by 20-40%. For some women, however, there are contraindications to the use of estrogen, and others are unwilling to use it. Furthermore, hot flushes may persist in spite of adequate estrogen replacement, and to improve symptoms physicians then have either to add another drug to the regimen or find an alternative to estrogen. The most commonly used non-hormonal alternatives for climacteric symptoms are neurotransmitter modulators such as the selective serotonin reuptake inhibitors. These reduce the frequency of hot flushes by 60%. The mechanism of this effect appears to differ from that underlying their effect on mood. They are generally well tolerated and rates of adverse events are far lower than those reported in studies of the use of these agents for depression. The limited efficacy of clonidine suggests that adrenergic mechanisms may be involved and data are awaited for more specific selective noradrenaline reuptake inhibitors. Thus, non-hormonal treatments are not as effective as estrogens in relieving hot flushes but may have a place as an alternative.


Pathologic anatomy and CT correlations in the glioblastoma multiforme.
6 cases of glioblastoma multiforme, 1 anaplastic astrocytoma, and 1 astrocytoma were studied pathologically post mortem. The specimens were compared to antemortem CT scans, when available. By use of whole brain sections, each glioblastoma was divided into a central area of necrosis, a surrounding rim of hypercellular neoplasm, and a peripheral zone of infiltration. The dimensions and areas of these three zones were quantified. The striking findings of the study were the often small diameter of the hypercellular region and the frequently narrow peripheral zone of detectable infiltrating cells. Comparison of the autopsy specimens with CT scans confirmed previous studies of the glioblastoma. The radiographic central area of low density is necrosis; the enhancing rim is a markedly hypercellular region, and the perilesional low density encompasses a population of infiltrating tumor cells.


Immunotherapy in Melanoma: Recent Advances and Promising New Therapies.
The incidence and mortality of melanoma are on the rise. Historically, patients diagnosed with metastatic melanoma were faced with a grim prognosis, with survival rates of 15% at 5 years. Prior to 2011, no drug or therapeutic regimen had been shown to improve overall survival (OS) in metastatic melanoma. Chemotherapeutic agents, such as dacarbazine or temozolomide, are often given to patients for palliative purposes; high-dose interleukin 2 and biochemotherapy are immunotherapeutic options that could be offered to patients with a good performance status at specialized centers. Neither has been shown to impact OS, but durable complete responses are seen in a minority of patients. Since 2011, 4 new drugs have been approved by the US Food and Drug Administration for the treatment of metastatic melanoma, all of which improve survival. Three of these agents (vemurafenib, dabrafenib, and trametinib) are targeted therapies, with ipilimumab being the only new immunotherapy. With a focus on immunotherapeutic agents, this review seeks to summarize the treatment options currently available for metastatic melanoma and to examine those on the near horizon.


Assessing the relationship of paraoxonase-1 Q192R polymorphisms and the severity of lung disease in SM-exposed patients.
Late respiratory complications in patients suffering from pulmonary lesions due to sulfur mustard (SM) gas are asthma, chronic obstructive pulmonary disease and bronchiectasis. Recently PON1 antioxidant activity draws attention as the enzyme which prevents the oxidation of lipoproteins during oxidative stress. In this study we aimed to investigate PON1 192 polymorphisms and paraoxonase and arylesterase activity in the serum of SM-exposed lung disease patients. Also, we examined the detection of PON1 and apoA1 proteins in BAL fluid. 101 male patients were included who were categorized to three groups of mild, moderate and severe suffering from pulmonary lesions due to SM. Significant reduction in paraoxonase activity [Healthy: 412.46 ± 89.1 U/L, Severe: 89.66 ± 20.7 U/L] (p < 0.0001) and arylesterase activity [Healthy: 25826.4 ± 4425.23 U/L, Severe: 16760.43 ± 3814.9 U/L] (p < 0.0001) with increase in severity of disease was demonstrated statistically. With respect to the distribution of the PON1 polymorphism, the RR genotype was more frequent in severe patients [37.2%] than healthy group [10%] (p < 0.05) and no significant regression was found between genotype and PON1 activity. On the other hand, the results of PON1 and apoA1 detection illustrated that only apoA1 protein was found in BAL fluid. According to our findings it seems that increase in the stress oxidative in chemical injured veterans with pulmonary complications comes with reduction in PON1 enzyme activity and appearance of RR genotype rises up with the increase in disease severity. Since a significant correlation between enzyme activity and genotype was not observed altering these two variables with each other requires more studies.


Anatomical methods for voxelation of the mammalian brain.
Voxelation allows high-throughput acquisition of three-dimensional gene expression patterns in the brain through analysis of spatially registered voxels (cubes). The method results in multiple volumetric maps of gene expression analogous to the images reconstructed in biomedical imaging techniques. An important issue for voxelation is the development of approaches to anchor correctly harvested voxels to the underlying anatomy. Here, we describe experiments to identify fixation and cryopreservation protocols for improved registration of harvested voxels with neuroanatomical structures. Paraformaldehyde fixation greatly reduced RNA recovery as judged by ribosomal RNA abundance. However, gene expression signals from paraformaldehyde-fixed samples were not appreciably diminished as judged by average signal-noise ratios from microarrays, highlighting the difficulties of accurate quantitation of cross-linked RNA. Additional use of cryoprotection helped to improve further RNA recovery and signal from fixed tissue. It appears that the best protocol to provide the necessary resolution of neuroanatomical information in voxelation entails a controlled dose of fixation and thorough cryoprotection, complemented by histological staining.


Comprehensive multiresidue method for the simultaneous determination of 74 pesticides and metabolites in traditional Chinese herbal medicines by accelerated solvent extraction with high-performance liquid chromatography/tandem mass spectrometry.
In this paper, a multiresidue method for the simultaneous target analysis of 74 pesticides and metabolites in traditional Chinese herbal medicines (TCHMs) was developed using accelerated solvent extraction (ASE) coupled with HPLC/MS/MS. Pesticide residues were extracted from the different samples using ASE, then purified by gel permeation chromatography and graphitized carbon black/primary, secondary amine SPE. Gradient elution was used in conjunction with positive mode electrospray ionization MS/MS to detect 74 pesticides and metabolites from Cortex Cinnamomi, Flos Carthami, Folium Ginkgo, Herba Pogostemonis, Radix Ginseng, and Semen Ginkgo using a single chromatographic run. The analytical performance was demonstrated by the analysis of extracts spiked at three concentration levels ranging from 0.005 to 0.125 mg/kg for each pesticide and metabolite. In general, recoveries ranging from 70 to 110%, with RSDs better than 15%, were obtained. The recovery and repeatability data were in good accordance with European Union guidelines for pesticide residue analysis. The LOD for most of the targeted pesticides and metabolites tested was below 0.01 mg/kg.


Can continuity-of-care requirements for surgery residents be demonstrated in the current teaching environment?
In 1994, the Residency Review Committee in Surgery began evaluating the ability of programs to provide adequate continuity-of-care experiences to residents, based on 6 criteria requiring resident participation in each phase of a surgical patient's care. The Residency Review Committee document further described resident and patient experiences as being synonymous. No previous studies were found that examined the 6 criteria or compared them with the patient's experience with continuity. Study objectives were 2-fold: (1) to assess the 6 required continuity-of-care experiences provided to general surgery residents and (2) to compare resident experiences to the patient's experience with continuity. Surgery residents from 2 academic years, representing each postgraduate year, were studied. Patients had (1) undergone an operation involving a resident and (2) remained hospitalized for longer than 24 hours but less than 10 days. Data were collected from a retrospective randomized review of each patient's medical records. Of the 114 cases, 23.7% showed that the same resident participated in all phases of care. In the remaining cases, residents provided preoperative care in 70.2%, directed the postoperative hospitalized care in 86.8%, and provided postdischarge care in 37.7%. Patients saw an average +/- SD of 4.6 +/- 1.5 surgical providers during the entire course of their surgical care. In conclusion, continuity experiences were provided to surgery residents in varying quantities and combinations, with one quarter of the residents experiencing "perfect continuity." Resident continuity experiences and patient continuity were not synonymous. Although improved medical record documentation may have enhanced these results, continuity-of-care remains difficult to demonstrate in view of the current surgery teaching environment.


Dimensional changes of extended-pour alginate impression materials.
Recently, manufacturers have marketed alginate impression materials, claiming dimensional stability for up to 100 hours to allow shipping to a dental laboratory for digital model fabrication. The purpose of this study was to evaluate the dimensional changes of these newer materials after storage at different temperatures and times. Two extended-pour alginates (claiming 100 hours of accuracy) (Kromopan; Lascod, Florence, Italy; and Triphasix; Parkell, Edgewood, NY), 2 traditional alginates (Jeltrate; Dentsply-Caulk, York, Pa; and Kromatica; Matech, Sylmar, Calif), and 1 vinyl polysiloxane (VP Mix; Henry Schein, Melville, NY) were used to impress a scored aluminum die. The distance between the score lines was measured on the impressions at 10 minutes, 24 hours, and 100 hours after mix, and the percentages of dimensional change were calculated. Temperature effects were studied by storage at cold (-9°C), room (22°C), or hot (46°C) temperatures for 8 hours. All alginates had statistically significant dimensional changes at 24 and 100 hours (0.69%-6.13%). VP Mix exhibited no statistically significant changes for any storage condition. The Kromopan (100 hour) and Kromatica (traditional) alginates were the most stable (0.85%-2.22% at 100 hours). Triphasix (100 hour) and Jeltrate (traditional) were the least stable (1.53%-4.73% at 100 hours). Cold-temperature storage resulted in the most dimensional changes (1.96%-4.73% at 100 hours). Room-temperature storage resulted in the least dimensional changes (0.97%-1.53% at 100 hours). All alginate impression materials in the study had significant changes at 24 and 100 hours in all storage conditions tested.


[Content determination of four diester diterpenoid alkaloids in leaves of Aconitum kusnezoffii by HPLC].
This present study is to develop an HPLC method for simultaneous determination of four diester diterpenoid alkaloids, beiwutine, mesaconitine, hypaconitine and aconitine in the leaves of Aconitum kusnezoffii, so as to provide evidence of the quality control of this herb. The four constituents were measured on a Waters XBridge CC₁₈ column(4.6 mmχ250 mm, 5 μm). The mobile phase was acetonitrile-40 mmol·L⁻¹ ammonium acetate solution(adjusted pH to 10.5 with ammonia solution)(33:67) with isocratic elution at a flow rate of 1.0 mL·min⁻¹; the detection wavelength was 235 nm; the column temperature was 30 °C, and the injection volume was 10 μL. Next, this contents of the four diester diterpenoid alkaloids in 12 samples were 0.025 5-0.088 5, 0.039 1-0.071 5, 0.026 6-0.081 0 and 0.008 12-0.031 2 mg·g⁻¹, respectively. Next, this method has been successfully applied to the analysis of A. kusnezoffii folium in different harvest periods. The contents of the four alkaloids decreased primarily, and then increased with the postponing of harvest. The established method is proved to be accurate and sensitive for the determination of alkaloids in A. kusnezoffii folium, and may be useful for the quality improvement of this herbal medicine. Moreover, these results indicated the scientific significance for the toxicity and the suitable harvest time of this herb.


Improved pulmonary function by acid sphingomyelinase inhibition in a newborn piglet lavage model.
In acute inflammatory lung disease in newborn infants, exogenous surfactant only transiently improves lung function. We hypothesized that the transient nature of this protection is in part explained by elevated acid sphingomyelinase (a-SMase) activity that may inactivate surfactant and promote proinflammatory responses. We investigated the intermediate-term effects (>12 h) of a-SMase inhibition in a neonatal piglet model of repeated airway lavage by the intratracheal use of the a-SMase inhibitor imipramine, together with exogenous surfactant as a carrier substance. After surfactant washout and induction of pulmonary inflammation, lung function was monitored over 24 hours of mechanical ventilation and followed by ex vivo analyses. In addition, we studied the effect of lipopolysaccharide inhalation in a-SMase-deficient mice at 48 hours. Surfactant washout increased both pulmonary a-SMase activity and ceramide content; this was attenuated by surfactant and prevented in the surfactant plus imipramine group. Compared with surfactant alone, Pa(O(2)), dynamic compliance, and extravascular lung water were improved in the final 12 hours in the surfactant plus imipramine group. At 24 hours, lavage fluid leukocyte counts and IL-8 concentrations decreased, and physical surfactant film properties improved. In the mouse model at 48 hours, a-SMase-deficient mice showed reduced pulmonary ceramide levels and attenuated leukocyte influx into the alveolar space. We conclude that stabilization of exogenous surfactant by adding imipramine to create a "fortified surfactant preparation" improves lung function in a clinically relevant piglet model, and that this effect can be attributed to the inhibition of a-SMase as evidenced in the mouse model.


Effects of anesthetic technique on blood loss and complications after simultaneous bilateral total knee arthroplasty.
Anesthetic technique affects perioperative outcomes, but less was known in simultaneous bilateral total knee arthroplasty (BTKA). A single center, retrospective analysis was carried out to prove the hypothesis that utilization of regional anesthesia would result in favorable perioperative outcomes. Medical records of patients admitted for simultaneous BTKA between 2004 and 2013 were analyzed. Two groups, the general anesthesia (GA) and regional anesthesia (RA) group, were identified. Patient preoperative characteristics were compared. Perioperative outcomes measured included blood loss, transfusion requirement, length of hospitalization, operating time, and 30-day perioperative complications. A total of 513 patients were identified, 54.6% were performed under GA, and 45.4% under RA. Patient characteristics were similar between the two groups, except that patients operated under GA were younger than those under RA. RA was associated with significantly less perioperative blood loss (981 vs. 1075 mL, p = 0.017) and 30-day complications (6.4 vs. 13.2%, p = 0.016). Systemic and organ specific infections were particularly lower in the RA group (0.4 vs. 3.9%, p = 0.009). Transfusion requirement, length of hospitalization, and operating time were similar between the two groups. After correcting for covariates, RA offered a 92 mL (p = 0.023) reduction in blood loss and 49% less overall complications (p = 0.047), compared to GA. Patients who underwent simultaneous BTKA under RA had lesser blood loss and lower complication rate than GA. The impact of RA can be further exploited to improve perioperative outcomes of simultaneous BTKA in addition to various other interventions.


Genetic analysis of recently identified osteoporosis susceptibility genes in southern Chinese.
Fifty-six genomic loci recently were identified as associated with bone mineral density (BMD) in a large meta-analysis study of mainly European-descent subjects. Circulating factors related to calcium and phosphate metabolism, eg, serum levels of calcium, phosphate, vitamin D metabolites, PTH, and alkaline phosphatase (ALP), may affect bone turnover and metabolism. We aimed to investigate the effects of these reported variants, as well as their interactions with 5 studied circulating factors, on BMD in a southern Chinese prospective cohort (n = 2670). The identified interactions were further replicated in an independent cohort of 800 Chinese females. Approximately half (n = 27) of the reported variants were successfully replicated in our sample of southern Chinese individuals. We further demonstrated a significant interaction between MARK3 and serum ALP levels (Pmeta = 9.89 ×10(-6)); the effect of MARK3 rs11623869 on BMD was stronger in the presence of high serum levels of ALP. In addition, several interactions between other genes and circulating factors were suggested. Our study has provided an independent replication of associations between several reported loci and BMD in a large sample of southern Chinese individuals. These replicated loci may represent osteoporosis susceptibility genes in both Chinese and European-descent populations. Furthermore, we have shown that serum ALP levels modified the association of MARK3 with BMD. Understanding the mechanisms of the interactions between BMD-related loci and circulating factors may help to determine the pathogenesis of susceptibility to osteoporosis and could have implications for clinical care.


Transseptal catheterization without needle puncture.
The aim was to see if probing the fossa ovalis for transseptal puncture during balloon mitral valvuloplasty will reduce time consumed for the procedure. Twenty-five patients had probing of fossa ovalis for left atrial entry (group I). In 30 patients (group II), standard needle puncture was done for left atrial entry. Puncture time and fluoroscopy time were noted and oxymetry was done. Later, a further 60 patients underwent probing of fossa ovalis for validation of the technique. Puncture times in groups I and II were 84.7 +/- 27.5 and 116.1 +/- 37.9 s, respectively (p < 0.02). Fluoroscopy time was 51.2 +/- 19.6 and 73.6 +/- 22.3 s in groups I and II, respectively (p < 0.03). During validation of the technique, 54 of 60 patients (90%) had successful left atrial entry through probing. Atrial level shunt was not seen. Probing the fossa achieves left atrial entry in 90% of patients. It avoids needle puncture and reduces puncture time as well as fluoroscopy time. It is a safe technique.


Mannose receptor-mediated gene transfer into macrophages using novel mannosylated cationic liposomes.
A novel mannosylated cholesterol derivative, cholesten-5-yloxy-N-(4-((1-imino-2-beta-D-thiomannosyl -ethyl)amino)bu tyl) formamide (Man-C4-Chol), was synthesized in order to perform mannose receptor-mediated gene transfer with liposomes. Plasmid DNA encoding luciferase gene (pCMV-Luc) complexed with liposomes, consisting of a 6:4 mixture of Man-C4-Chol and dioleoylphosphatidylethanolamine (DOPE), showed higher transfection activity than that complexed with 3beta[N-(N', N'-dimethylaminoethane)-carbamoyl]cholesterol (DC-Chol)/DOPE(6:4) and N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA)/DOPE(1:1) liposomes in mouse peritoneal macrophages. The presence of 20 mM mannose significantly inhibited the transfection efficiency of pCMV-Luc complexed with Man-C4-Chol/DC- Chol/DOPE(3:3:4) and Man-C4-Chol/DOPE(6:4) liposomes. High gene expression of pCMV-Luc was observed in the liver after intravenously injecting mice with Man-C4-Chol/DOPE(6:4) liposomes, whereas DC-Chol/DOPE(6:4) liposomes only showed marked expression in the lung. The gene expression with Man-C4-Chol/DOPE(6:4) liposome/ DNA complexes in the liver was observed preferentially in the non-parenchymal cells and was significantly reduced by predosing with mannosylated bovine serum albumin. The gene expression in the liver was greater following intraportal injection. These results suggest that plasmid DNA complexed with mannosylated liposomes exhibits high transfection activity due to recognition by mannose receptors both in vitro and in vivo. Gene Therapy (2000) 7, 292-299.


Differential distribution of transforming growth factor-alpha immunohistochemistry within whole gastric mucosa in rats.
Transforming growth factor-alpha (TGF-alpha) plays an important role in both proliferation and differentiation of mucosal cells at the gastrointestinal level, including stomach, where it is constitutively produced. This study evaluated the immunohistochemical distribution of TGF-alpha within whole gastric mucosa in rats, through the examination of seriate sections. Each stomach was opened along the greater curvature, pinned upon a cork plate, fixed in formalin and cut in 2-mm parallel strips which were sequentially superimposed on a glass slide. Sections were immunostained for TGF-alpha and pictures were taken from three areas: greater and lesser curvature; mucosa lying between the two curvatures. The sections were graded on the basis of the intensity of TGF-alpha staining, which was scored as follows: 0) no staining; 1) weakly positive; 2) intensely positive. The percent number of immunopositive cells and a mean intensity were calculated. Gastric mucosa showed a marked immunopositivity to TGF-alpha, mainly in parietal cells whose cytoplasm displayed moderate to intense staining. Positive cells (and the mean intensity) of total mucosa were 15.7+/-6.1% (1.13+/-0.42). However, they were not uniformly distributed, being 26.3+/-1.9% (1.67+/-0.24) in the mucosa lying between the two curvatures, 12.4+/-2.5% (1.52+/-0.22) along the lesser curvature and 8.3+/-2.1% (0.31+/-0.17) along the greater curvature. These results show that parietal cells of rat gastric mucosa exhibit immunoreactivity to TGF-alpha. Considering the gastroprotective effects of this factor, its non-homogeneous distribution within different areas may be of importance in understanding the lesion pattern of gastric damage after the administration of noxious agents.


Specific binding and laterality of human extrastriatal dopamine D2/D3 receptors in late onset type 1 alcoholic patients.
Late onset type 1 alcoholism has been suggested to be associated with decreased dopaminergic transmission. Our hypothesis was that late onset type 1 alcoholics have also abnormal extrastriatal dopamine D(2)/D(3) receptor distribution. We performed binding, heterogeneity and laterality analysis of extrastriatal and striatal dopamine D(2)/D(3) receptors in nine late onset male alcoholics and in 12 age-matched healthy males. A radioligand, [(123)I]epidepride was used in high resolution single-photon emission tomography (SPET). Specific binding of epidepride in the left temporal pole was significantly (P<0.05) lower in type 1 alcoholics (0.74+/-0.14 ml/ml) than in controls (0.89+/-0.14 ml/ml). In alcoholics, there was no normal left-to-right asymmetry of the temporal cortical heterogeneity of epidepride distribution observed in control males (0.89+/-0.19 vs. 1.10+/-0.19; P<0.05). The results suggest that the specific binding of dopamine D(2)/D(3) receptors in late type 1 alcoholics is decreased and its laterality in the temporal brain is altered from normal.


The hidden blood loss after hip fracture.
Despite advances in surgical and anaesthetic techniques the mortality after hip fracture has not significantly changed in the last 40 years. Pre-operative anaemia is a risk factor for peri-operative death. We speculate that a significant proportion of the blood loss related to hip fractures has occurred prior to surgery. Identifying patients at risk of pre-operative anaemia can facilitate appropriate medical optimisation. This study is unique in its attempt to quantify the blood loss associated with the initial hip injury. In a retrospective study all patients with both a diagnosis of hip fracture and an operative delay of >48 h were assessed. The information collected included: fracture classification, serial haemoglobins and patient co-morbidities. The exclusion criteria included a pre-injury diagnosis of anaemia, anti-coagulation and gastrointestinal bleeds. Between 2007/2008 sixty-eight intracapsular and fifty extracapsular hip fracture patients had serial haemoglobins and operative delays of >48 h (mean 75 h, range 48-270 h). The mean lowest recorded haemoglobin prior to surgery for both extracapsular and intracapsular fractures were 95.0 g/L (+/-SEM 2.2) and 108.5 g/L (+/-SEM 2.2) respectively. This difference was statistically significant (Student's t-test p<0.05). The mean haemoglobin drop in the extracapsular and intracapsular fracture groups was 20.2 g/L (range 0-49 g/L) and 14.9 g/L (range 0-59 g/L) respectively. Hip fracture patients have a large drop in haemoglobin that is associated with the initial trauma rather than the operation. This highlights the need for anaesthetic and orthopaedic staff to be vigilant to the risk of pre-operative anaemia in this cohort of frail patients even when the initial haemoglobin is apparently normal.


In phyllodes tumour of the breast expression of c-kit but not of ALDH1A1 is associated with adverse clinico-pathological features.
Attempts at identification of an ideal prognostic/predictive biomarker in phyllodes tumour (PT) have not been fruitful so far. Studies evaluating c-kit expression in PT have shown contradictory results. Recently aldehyde dehydrogenase 1A1 (ALDH1A1) was proposed as a stem cell marker for malignant PT but its expression has not been studied in benign and borderline tumours. We aimed to evaluate expression and prognostic significance of c-kit and ALDH1A1 in different grades of PT. Epithelial and stromal c-kit and ALDH1A1 expression were studied in 104 PT cases (86 primary and 18 recurrent tumours) and compared with different clinico-pathological features and recurrence rates. Stromal c-kit expression at 1 % cutoff correlated with increasing tumour grade, larger tumour size, hypercellularity, nuclear atypia, stromal overgrowth, infiltrative margins and mitotic count. These associations, however, were lost with higher (5 or 10 %) cutoffs. Conversely, decreased c-kit expression in the epithelial component correlated with increasing tumour grade, regardless of the cutoffs used. Stromal ALDH1A1 expression did not have significant associations with tumour grade or other adverse clinico-pathological features, regardless of different cutoffs. None of the cases showed significant epithelial ALDH1A1 expression. Expression of c-kit was associated with poorer overall survival (p = 0.011), while ALDH1A1 expression was associated with shorter recurrence-free survival (p = 0.036). In conclusion, c-kit expression was associated with higher tumour grade and adverse clinico-pathological features. However, these associations are cutoff dependent, partly explaining the variability in previously reported studies. ALDH1A1 expression did not have significant correlations with tumour grade and adverse clinico-pathological variables.


Alterations of oligodendrocytes and demyelination in the spinal cord of patients with mitochondrial encephalomyopathy.
The spinal cords of 2 autopsied patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) were examined. Histologically, the spinal cords showed a spongy state due to the presence of distended myelinated fibers with enlarged periaxonal spaces. Ultrastructurally, the affected fibers showed extensive microvacuolation of the inner myelin sheath with occasional vesicular changes. The presence of macrophages near the degenerated myelin was a frequent finding. The stripping of myelin lamellae by macrophage was observed, with frequent appearance of denuded axons. Furthermore, prominent morphological changes were observed in oligodendrocytes. These findings indicate that demyelination, probably secondary to the degeneration of oligodendrocytes, occurs in the spinal cord of MELAS.


Sensitivity and Specificity of Laser-Scanning In Vivo Confocal Microscopy for Filamentous Fungal Keratitis: Role of Observer Experience.
To determine sensitivity and specificity of laser-scanning in vivo confocal microscopy (LS-IVCM) for detection of filamentous fungi in patients with microbial keratitis and to evaluate the effect of observer's imaging experience on these parameters. Retrospective reliability study. This study included 21 patients with filamentous fungal keratitis and 24 patients with bacterial keratitis (as controls). The etiology of infection was confirmed based on the response to specific therapy regardless of culture results. All patients had undergone full-thickness corneal imaging by a LS-IVCM (Heidelberg Retina Tomograph 3 with Rostock Cornea Module; Heidelberg Engineering, Heidelberg, Germany). The images were evaluated for the presence of fungal filaments by 2 experienced observers and 2 inexperienced observers. All observers were masked to the clinical and microbiologic data. The mean number of images obtained per eye was 917 ± 353. The average sensitivity of LS-IVCM for detecting fungal filaments was 71.4% ± 0% for the experienced observers and 42.9% ± 6.7% for the inexperienced observers. The average specificity was 89.6% ± 3.0% and 87.5% ± 17.7% for these 2 groups of observers, respectively. Although there was a good agreement between the 2 experienced observers (κ = 0.77), the inexperienced observers showed only a moderate interobserver agreement (κ = 0.51). The LS-IVCM sensitivity was higher in patients with fungal infections who had positive culture or longer duration of the disease. Although LS-IVCM has a high specificity for diagnosing filamentous fungal keratitis, its sensitivity is moderate and highly dependent on the level of the observer's experience and training with this imaging modality.


Posterior plagiocephaly: proactive conservative management.
The pathology, diagnosis and management of posterior plagiocephaly remains highly controversial. While the rationale for surgical management of true lambdoid synostosis is undisputed, opinions vary greatly on how to manage severe, unresolving, non-synostotic cases. We reviewed 39 cases of posterior plagiocephaly, 37 of which were treated conservatively. Of these, 34 patients had a significant improvement over the following year with sleep posture modification and/or physiotherapy. While only eight cases returned to complete normality, the remainder had deformities that were deemed mild by both mothers and surgeons, and did not merit surgery. Defining recalcitrant cases remains elusive as standard imaging is often unhelpful. While 3-D CT offers a much more accurate diagnosis of true lambdoid synostosis with bony union and allows objective assessment of the deformity, serial scans involve radiation doses that are difficult to justify. Clinical follow-up is the only reliable method at present.


Profile of Patients Hospitalized through the Emergency Room to the Medicine Ward and their Short-term Outcome at a Tertiary Care Hospital in Delhi.
With an increasing number of sicker patients, limited hospital beds, and an emphasis on day care, the profile of patients hospitalized to medicine wards has undergone a radical re-definition. The increasing share of patients hospitalized through the emergency department for acute care to medicine wards has left little space for hospitalization through the outpatient department (OPD). There are some global data available on the profile of patients presenting to the emergency rooms (ERs) and their subsequent outcome. Data from developing countries, especially India, in this regard are lacking. This cross-sectional study included all patients hospitalized to the medicine ward through the medical emergency services, provided by the Department of Medicine, each Wednesday and every sixth Sunday for the entire year (a total of 62 days), from November 2010 through October 2011, and followed their outcome up to seven days after hospitalization. Of the 3,618 cases presenting to medicine emergency on these days, 1,547 (42.3%) were advised admission. Nine hundred sixty-seven reported to the medicine wards. One hundred eleven (7.73%) expired within 24 hours; others absconded, were lost in transit, did not consent to participation, or were discharged. During the next seven days, 452 (46.7%) recovered sufficiently and were discharged to go home. Two hundred thirty (23.8%) left the hospital without informing the medical staff. Fourteen (1.4%) patients were transferred to other departments. One hundred thirty-seven (8.8%) patients died during the next six days of hospitalization. After Multivariate Logistic Regression analysis, abnormal Glasgow Coma Scale (GCS) score, high systolic blood pressure (BP), age, increased total leucocyte count, increased globulin, low bicarbonate in arterial blood, low Mini Mental Status Examination (MMSE) score, and a raised urea >40 mg/dL were found to be associated significantly with mortality. Of the 1,547 patients who needed urgent hospitalization, 248 (16%) died within the first week, one-half of them within the first 24 hours. An advanced age, abnormal GCS score, low MMSE score, increased systolic BP, leukocytosis, acidosis, and uremia were found to be associated with a fatal outcome. Therefore, nearly one-half of the patients who would have a fatal short-term outcome were likely to do so within the first 24 hours, making the first day of presentation "the golden day" period.


Controlled 3D Assembly of Graphene Sheets to Build Conductive, Chemically Selective and Shape-Responsive Materials.
Driven by the surface activity of graphene, electrically conductive elastomeric foams have been synthesized by the controlled reassembly of graphene sheets; from their initial stacked morphology, as found in graphite, to a percolating network of exfoliated sheets, defining hollow spheres. This network creates a template for the formation of composite foams, whose swelling behavior is sensitive to the composition of the solvent, and whose electrical resistance is sensitive to physical deformation. The self-assembly of graphene sheets is driven thermodynamically, as graphite is found to act as a 2D surfactant and is spread at high-energy interfaces. This spreading, or exfoliation, of graphite at an oil/water interface stabilizes water-in-oil emulsions, without the need for added surfactants or chemical modification of the graphene. Using a monomer such as butyl acrylate for the emulsion's oil phase, elastomeric foams are created by polymerizing the continuous oil phase. Removal of the aqueous phase then results in robust, conductive, porous, and inexpensive composites, with potential applications in energy storage, filtration, and sensing.


Infrared tympanic thermography as a substitute for a probe in the evaluation of ear temperature for post-mortem interval determination: a pilot study.
Reported methods which have been used to measure tympanic temperatures on cadavers up to now are quite invasive. They involve the use of a probe which can perforate the tympanic membrane and frequently causes bleeding from the ear. For this reason a non traumatic method for estimating tympanic temperature should be applied. Infrared tympanic thermometry seems to be a plausible option. Reliability of infrared tympanic thermometry (ITT) has been largely assessed on living individuals but only one author up to now has assessed its applicability for post-mortem interval determination. Thus the authors set out to test the difference between ear temperatures taken with a probe vs. ITT, differences between left and right ear and reproducibility of measurements of ITT. The aim of the study was to verify whether ITT could be a plausible option for measuring ear temperature for PMI estimation. Ear temperatures were taken on 25 cadavers (15 males, 10 females). Temperatures were taken alternately by similarly trained personnel by two technical methods (Checktemp 1 thermocouple probe and First Temp Genius infrared thermometer) for a total of 93 measurements. Statistical analysis of the data was performed using SAS statistical software. The range of temperature measured was from 20 to 28 degrees C, statistical analysis revealed no differences within the two technical methods, both for right and left ear (ITT: 22.33+/-0.35 vs. probe: 23.08+/-0.25; P=0.087). The study shows the ITT method can be considered as a possible alternative to the probe for measuring ear temperative and further studies should be considered.


Effect of a patellar realignment brace on patellofemoral relationships: evaluation with kinematic MR imaging.
The effect of a newly developed patellar realignment brace was evaluated in 21 patellofemoral joints (19 patients) with patellar subluxation (13 joints with lateral subluxation and eight with medial subluxation) by using active-movement, loaded kinematic magnetic resonance (MR) imaging. Sixteen patellofemoral joints (76%) demonstrated a qualitative correction of or improvement in patellar subluxation (ie, centralization of the patella or a decrease in the displacement of the patella) after application of the brace. Four of the five "failures" occurred in patellofemoral joints that had patella alta and/or dysplastic bone anatomy. These results indicate that the patellar realignment brace was able to counteract patellar subluxation in the majority of patellofemoral joints studied, as shown by active-movement, loaded kinematic MR imaging. This brace appears to be useful for conservative treatment of patients with patellofemoral joint pain secondary to patellar malalignment and maltracking.


Lack of evidence for immunological reactions to polygelatin.
Gelatin-based plasma substitutes resemble denatured collagen in that sequence dependent antigenic sites of collagen may be preserved in these preparations and cause side reactions of such plasma substitutes. We have measured the binding of 125I-collagen in denatured conformation to antibodies and to cold-insoluble globulin (CIG) in sera of patients undergoing orthopedic surgery. About two thirds of the sera bound significant amounts of denatured collagen to immunoglobulins and to CIG. Yet, there was no correlation in individual patients or in groups of patients between the collagen binding capacity of sera and the occurrence of allergic reactions upon infusions of Haemaccel. Furthermore, antibodies to denatured collagen induced in animals did not cross-react with gelatin-based plasma substitutes. Thus, it is not likely that side reactions after infusion of gelatin-based plasma substitutes are caused by immunological reactions between antigens and performed antibodies.


Predicted shortage of vascular surgeons in the United States: population and workload analysis.
To estimate the size of the future workforce in vascular surgery (VS) and the added cost associated with addressing the projected shortage in the United States. The net supply (number of Vascular Surgeons [VSN] currently practicing, new graduates entering the workforce, and those retiring) for each decade was calculated. The projected population for each decade was determined by U.S. Census Bureau figures. Some assumptions of this model included: (1) In 2008, the population was 300,000,000; (2) There were 2783 board certified VSN in 2008; (3) VSN will practice 30 years from board certification to retirement; (4) There will be 105 board certifications and 93 retirements per year; (5) Vascular operations will remain at 284 per 100,000 population; (6) Salaries of trainees will be $50,000 with benefits of 30% and $15,000 of additional direct medical education costs. Population and workload analysis suggests that there will be a shortage of 330 surgeons (9.8%) and 399 surgeons (11.6%) by 2030, respectively. The cost of training enough VSN (in a six-year program) by 2030 will be between $1,166,400,000 and $1,199,520,000. A conservative estimate by both population and workload analysis, disregarding aging of the population, lifestyle choices of future VSN, and increasing demand for services, indicates a shortage of VSN in the future. Unless the Balanced Budget Act of 1997 is revised by Congress, the cost to train the additional VS workforce remains a significant barrier.


Neurologic aspects of 49,XXXXY syndrome.
49,XXXXY syndrome is a rare sex chromosome aneuploidy syndrome characterized by mental retardation, severe speech impairment, craniofacial abnormalities, multiple skeletal defects, and genital abnormalities. We describe a 13-year-old boy with 49,XXXXY syndrome, language impairment, seizures, and left-hemisphere magnetic resonance imaging abnormalities and review the distinctive neurologic, cognitive, and behavioral phenotypes associated with this disorder. Finally, we discuss testosterone supplementation in the treatment of this syndrome.


Relation between serum high molecular weight adiponectin and serum ferritin or prohepcidin in patients with type 2 diabetes.
An increase of serum ferritin, an indicator of body iron store, is associated with insulin resistance and with an increased risk of type 2 diabetes in the general population. A low serum adiponectin is also associated with insulin resistance. Recently, hepcidin was identified as a regulator of iron metabolism. We investigated whether serum adiponectin was associated with serum ferritin or prohepcidin, a precursor of hepcidin, in healthy subjects and patients with type 2 diabetes. We studied 65 healthy subjects and 104 patients with type 2 diabetes. A serum ferritin concentration ≥ 300 ng/ml for men or ≥ 150 ng/ml for women was defined as hyperferritinemia. Serum ferritin was significantly higher and serum prohepcidin was significantly lower in diabetic patients than in control subjects. Serum total and high molecular weight (HMW) adiponectin correlated negatively with serum ferritin in control subjects or diabetic patients, while serum total and HMW adiponectin correlated positively with serum prohepcidin in diabetic patients, but not in control subjects. Serum total and HMW adiponectin were lower in patients with hyperferritinemia than in those without it. In conclusion, serum ferritin was increased in type 2 diabetic patients, while serum prohepcidin was decreased. A high serum ferritin was associated with insulin resistance, and with low serum total and HMW adiponectin in patients with type 2 diabetes.


Prospective memory: a new focus for research.
Prospective memory is required for many aspects of everyday cognition, its breakdown may be as debilitating as impairments in retrospective memory, and yet, the former has received relatively little attention by memory researchers. This article outlines a strategy for changing the fortunes of prospective memory, for guiding new research to shore up the claim that prospective memory is a distinct aspect of cognition, and to obtain evidence for clear performance dissociations between prospective memory and other memory functions. We begin by identifying the unique requirements of prospective memory tasks and by dividing memory's prospective functions into subdomains that are analogous to divisions in retrospective memory (e.g., short- versus long-term memory). We focus on one prospective function, called prospective memory proper; we define this function in the spirit of James (1890) as requiring that we are aware of a plan, of which meanwhile we have not been thinking, with the additional consciousness that we made the plan earlier. We give an operational definition of prospective memory proper and specify how it differs from explicit and implicit retrospective memory and how it might be empirically assessed.


Firefighter attitudes, norms, beliefs, barriers, and behaviors toward post-fire decontamination processes in an era of increased cancer risk.
Firefighters are exposed to carcinogens such as volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) during fires and from their personal protective equipment (PPE). Recent research has shown that decontamination processes can reduce contamination on both gear and skin. While firefighter cultures that honor dirty gear are changing, little is known about current attitudes and behaviors toward decontamination in the fire service. Four hundred eighty-five firefighters from four departments completed surveys about their attitudes, beliefs, perceived norms, barriers, and behaviors toward post-fire decontamination processes. Overall, firefighters reported positive attitudes, beliefs, and perceived norms about decontamination, but showering after a fire was the only decontamination process that occurred regularly, with field decontamination, use of cleansing wipes, routine gear cleaning, and other behaviors all occurring less frequently. Firefighters reported time and concerns over wet gear as barriers to decontamination.


Differential impact of body position on the severity of disordered breathing in heart failure patients with obstructive vs. central sleep apnoea.
Obstructive (OSA) and central sleep apnoea (CSA) are a common comorbidity in patients with heart failure. The purpose of this study was to assess and compare the impact of body position on the severity of sleep apnoea in these two groups of patients. Standard polysomnography was performed in consecutive, clinically stable, optimally treated patients with moderate-to-severe heart failure and systolic dysfunction. Patients with an apnoea-hypopnoea index (AHI) ≥15/h (n = 120) were included in the study. The severity of sleep-disordered breathing was quantified by the AHI, the mean value of oxygen desaturations (O2 desat) and the apnoea ratio. Data from the right and left positions were combined into a single lateral position. Positional sleep apnoea was defined as a >50% reduction in the AHI between the supine and the lateral position. Twenty-nine and 91 subjects had dominant OSA and CSA, respectively. The AHI markedly decreased from the supine to the lateral position in both groups [OSA: (median [q1,q3]) 50.3 [36.9, 67.6]/h vs. 10.4 [7.0, 18.5]/h, P < 0.0001; CSA: 47.4 [37.6, 56.0]/h vs. 19.3 [11.9, 33.3]/h]. The reduction was greater in OSA patients (p = 0.027). Similarly, O2 desat and the apnoea ratio decreased in the lateral position (P < 0.0001). Positional sleep apnoea was observed in 76% of OSA and 53% of CSA patients (P = 0.028). This study demonstrates that the lateral sleeping position has a major beneficial effect on the severity of sleep-disordered breathing in heart failure patients, and that this improvement is greater in subjects with OSA than in those with CSA.


SV40 early region and large T antigen in human brain tumors, peripheral blood cells, and sperm fluids from healthy individuals.
SV40 T antigen (Tag) coding sequences were detected by PCR amplification followed by Southern blot hybridization in human brain tumors and tumor cell lines, as well as in peripheral blood cells and sperm fluids of healthy donors. SV40 early region sequences were found in 83% of choroid plexus papillomas, 73% of ependymomas, 47% of astrocytomas, 33% of glioblastoma multiforme cases, 14% of meningiomas, 50% of glioblastoma cell lines, and 33% of astrocytoma cell lines and in 23% of peripheral blood cell samples and 45% of sperm fluids from normal individuals. None of the 13 normal brain tissues were positive for SV40 DNA, nor were seven oligodendrogliomas, two spongioblastomas, one neuroblastoma, one meningioma, or four neuroblastoma cell lines. Expression of SV40 early region was found by reverse transcription PCR, and SV40-specific Tag was detected by indirect immunofluorescence in glioblastoma cell lines. DNA sequence analysis, performed in four positive samples, confirmed that the amplified PCR products belong to the SV40 early region. Sixty-one % of the neoplastic patients positive for SV40 sequences had an age excluding exposure to SV40-contaminated polio vaccines, suggesting a contagious transmission of SV40. The possible role of SV40 Tag in the etiopathogenesis of human brain tumors and the spread of SV40 by horizontal infection in the human population are discussed.


Cellular basis of diabetic nephropathy: 1. Study design and renal structural-functional relationships in patients with long-standing type 1 diabetes.
This study was designed to elucidate the cellular basis of risk of or protection from nephropathy in patients with type 1 diabetes. Entry criteria included diabetes duration of > or =8 years (mean duration, 22.5 years) and glomerular filtration rate (GFR) >30 ml x min(-1) x 1.73 m(-2). Patients were classified, on the basis of the estimated rate of mesangial expansion, as "fast-track" (upper quintile) or "slow-track" (lower quintile). A total of 88 patients were normoalbuminuric, 17 were microalbuminuric, and 19 were proteinuric. All three groups had increased glomerular basement membrane (GBM) width and mesangial fractional volume [Vv(Mes/glom)], with increasing severity from normoalbuminuria to microalbuminuria to proteinuria but with considerable overlap among groups. Vv(Mes/glom) (r = 0.75, P < 0.001) and GBM width (r = 0.63, P < 0.001) correlated with albumin excretion rate (AER), whereas surface density of peripheral GBM per glomerulus [Sv(PGBM/glom)] (r = 0.50, P < 0.001) and Vv(Mes/glom) (r = -0.48, P < 0.001) correlated with GFR. Vv(Mes/glom) and GBM width together explained 59% of AER variability. GFR was predicted by Sv(PGBM/glom), AER, and sex. Fast-track patients had worse glycemic control, higher AER, lower GFR, more hypertension and retinopathy, and, as expected, worse glomerular lesions than slow-track patients. Thus, there are strong relationships between glomerular structure and renal function across the spectrum of AER, but there is considerable structural overlap among AER categories. Given that normoalbuminuric patients may have advanced glomerulopathy, the selection of slow-track patients based on glomerular structure may better identify protected patients than AER alone.


Unraveling cis-regulatory mechanisms at the abdominal-A and Abdominal-B genes in the Drosophila bithorax complex.
Genome sequencing has revealed that in metazoans, only a small percentage of DNA actually codes for functional proteins. Research efforts have focused on elucidating the purpose of the rest of the genome, which was initially largely thought of as mere 'junk' DNA. One genomic region that is proving to be a rich source of new information is the Drosophila bithorax complex (BX-C). At this homeotic gene complex, many different classes of cis-regulatory elements, such as insulators, silencers, enhancers, and promoters, work together to tightly control gene expression during development. Recent studies have begun to unravel the intricate nature of these regulatory interactions. The BX-C was first discovered and characterized by Ed Lewis over three decades ago. In his seminal 1978 Nature paper, Lewis speculated that "substances" originating from the nongenic regions of the BX-C may regulate expression of the neighboring abdominal-A and Abdominal-B homeotic genes. A number of discoveries in the last few years suggest that he was right. The activation of some of the cis-sequences at the complex appears to be controlled by nongenic transcription, providing a further level of regulatory complexity to regions of nonprotein coding DNA. The hope is that these studies of gene regulation at the BX-C in the humble fruit fly will provide clues as to how vast intergenic regions contribute to the incredible complexity of gene regulation in other species, including humans.


Accuracy of blood flow values determined by arterial spin labeling: a validation study in isolated porcine kidneys.
To validate the accuracy of quantitative blood flow values determined using pulsed arterial spin labeling (ASL) in the preserved and reperfused porcine kidney. Ex vivo porcine kidneys were perfused with whole blood under physiological conditions, in particular including pulsatile flow. Total flow through the kidney was determined using an ultrasound flowmeter. ASL measurements at two different inversion times and four different flow rates in the range of 70-210 mL/100 mL*minute were performed. Absolute values of blood flow and arterial transit times were determined in the kidney cortex. The quantitative values were in good agreement with the reference values obtained after calibration of the total flow. The greatest difference observed was 13%. Isolated organ hemoperfusion allows validating perfusion imaging techniques. The experimental setup enables long-term radiotherapeutic or toxicological studies using noninvasive ASL to monitor blood flow quantitatively.


A case of antenatal Bartter syndrome with sensorineural deafness.
Bartter syndrome type IV, also known as Bartter syndrome with sensorineural deafness (BSND), is caused by loss-of-function mutations in the BSND gene, which encodes barttin, an accessory subunit of chloride channels located in the kidney and inner ear. Patients with BS IV have a highly variable clinical phenotype. This report concerns a Korean male patient with antenatal Bartter syndrome due to a homozygous BSND p.G47R mutation, who presented with severe perinatal symptoms followed by a relatively benign course with preserved renal function after early infancy. In addition, the clinical features and the laboratory data of the patient were compared with those of previously reported patients with the same mutation.


Applicability of Xpert MTB/RIF assay for routine diagnosis of tuberculosis: a four-year single-center experience.
The aim of this study is to assess the Xpert MTB/RIF assay for diagnosis of the Mycobacterium tuberculosis complex in clinical samples and to compare the results by reference to the diagnostic method, Bactec MGIT 960. A total of 7407 samples were included from patients not primarily suggesting pulmonary or extrapulmonary tuberculosis (TB), collected from patients required to be screened for TB and excluding TB diagnoses since it was a differential diagnosis. Also included were a total of 411 samples from patients primarily suggesting pulmonary or extrapulmonary TB. In the first group, 152 of 7407 samples yielded positive results with the Bactec MGIT 960, 131 (1.77%) were found positive with Löwenstein-Jensen medium, and 295 (3.99%) were found positive with Ziehl-Neelsen staining. In the second group, 24 (5.8%), 17 (4.1%), and 28 (6.8%) of 411 samples were found positive. Xpert MTB/RIF [27 (6.6%) of 411 samples] detected 3 additional samples as positive, and these 3 cases were clinically compatible with TB. The Xpert MTB/RIF assay shows superior performance for the diagnosis of TB. Its usefulness in culture-negative patients and the best method for integrating this diagnostic method into current tuberculosis diagnostic algorithms both need further study.


Incident reporting practices in the preanalytical phase: Low reported frequencies in the primary health care setting.
Incident reporting is commonly used to improve patient safety. The preanalytical phase of laboratory testing contains several manual error-prone tasks where mistakes can affect patient outcomes. However, the practical use of incident reports in this area has not been previously investigated in the primary health care setting, where the majority of the patients come in contact with health care. All staff responsible for venous blood sampling in 70 primary health care centres and in two hospital clinical laboratories (317 respondents, response rate 94%) completed a questionnaire. Of the primary health care staff, 69% reported that they had never filed an incident report regarding venous blood sampling. Barriers for not filing incident reports often/always included lack of time (44%) and a complicated reporting procedure (27%). A higher proportion of staff with re-education (43%) had filed at least one incident report as compared to those without re-education (20%, p < 0.001). No differences in incident reporting practices were found between primary health care and hospital clinical laboratory staff. The investigated incident reporting system is likely to underreport incidents in the preanalytical phase. Therefore, the ability to discover preventable system vulnerabilities needs refinement.


Functional anatomy of the peripheral olfactory system of the African lungfish Protopterus annectens Owen: macroscopic, microscopic, and morphometric aspects.
An anatomical functional study of the olfactory system of Protopterus annectens along the course of the primary olfactory neuron was made by means of macroscopic and microscopic methods on samples of specimens weighing from 3 to 1.250 gm. The olfactory organ, opening by anterior and posterior nostrils into the oral cavity, may be considered a macrosmatic fish type according to the repartition of receptor areas along parallel grooves and on the basis of its active irrigation mechanism. A morphometric study of Protopterus, using a set of seven specimens weighing from 4 to 350 gm, is compared with two morphometric studies on Silurid fishes and reveals some original features concerning the increase of the surface area of the receptor epithelium. The olfactory organ is meant to function in water; its isolation from the aerial environment is carried out by closing the apertures with edema linked to the hypothyroid and cholinergic crisis during the starvation stage; it represents an adaptation to the life in a special environment. This study does not support the assimilation of the posterior intrabuccal opening to a choana, nor the presence of a functional vomeronasal organ. The olfactory nerve shows a definite degree of organization, but it was not possible to recognize any vomeronasal nerve linked with the former. The histological organization of the bulbar relay is of a primitive type; it was impossible to locate an accessory olfactory bulb corresponding to a functional vomeronasal organ, the presence and the innervation of which by the nervus terminalis is discussed.


The effects of fractional microablative CO2 laser therapy on sexual function in postmenopausal women and women with a history of breast cancer treated with endocrine therapy.
To examine the outcomes of sexual function in postmenopausal women and women with a history of breast cancer treated with endocrine therapy who were experiencing the symptoms of GSM for which they were treated with fractional microablative CO2 laser. From July 2015 to October 2016, a retrospective chart review of women who underwent fractional microablative CO2 laser therapy (MonaLisa Touch, DEKA) for GSM was conducted. Several validated questionnaires were used to assess changes in symptoms and sexual function including the Female Sexual Function Index (FSFI), the Wong-Baker Faces Scale (WBFS), and the Female Sexual Distress Scale-Revised (FSDSR). Comparisons of mean symptom scores were described at baseline and six weeks after each treatment. There was a statistically significant improvement in every domain of FSFI, WBFS, and FSDS-R when comparing baseline symptom scores to after treatment three symptom scores for all patients. The secondary outcome was to evaluate the differences, if any, in outcomes of sexual function between postmenopausal women and women with a history of breast cancer treated with endocrine therapy. Both groups had statistically significant improvements in many domains studied. Fractional microablative CO2 laser therapy (MonaLisa Touch, DEKA) is an effective modality in treating the symptoms of GSM in postmenopausal women and women with a history of breast cancer treated with endocrine therapy.


Culturing fibroblasts in 3D human hair keratin hydrogels.
Human hair keratins are readily available, easy to extract, and eco-friendly materials with natural bioactivities. Keratin-based materials have been studied for applications such as cell culture substrates, internal hemostats for liver injury, and conduits for peripheral nerve repair. However, there are limited reports of using keratin-based 3D scaffolds for cell culture in vitro. Here, we describe the development of a 3D hair keratin hydrogel, which allows for living cell encapsulation under near physiological conditions. The convenience of making the hydrogels from keratin solutions in a simple and controllable manner is demonstrated, giving rise to constructs with tunable physical properties. This keratin hydrogel is comparable to collagen hydrogels in supporting the viability and proliferation of L929 murine fibroblasts. Notably, the keratin hydrogels contract less significantly as compared to the collagen hydrogels, over a 16-day culture period. In addition, preliminary in vivo studies in immunocompetent animals show mild acute host tissue response. These results collectively demonstrate the potential of cell-loaded keratin hydrogels as 3D cell culture systems, which may be developed for clinically relevant applications.


Pornography Use and Marital Separation: Evidence from Two-Wave Panel Data.
As pornography use continues to increase in the U.S., studies have sought to understand its potential influence on marital relationships. Yet, the primary focus of such studies has been pornography's association with marital quality, not stability. Consequently, we still know relatively little about whether pornography consumption at one time predicts marital disruption later on. Drawing on data from the 2006 and 2012 waves of the nationally representative Portraits of American Life Study (N = 445), this article examined whether married Americans who viewed pornography in 2006, either at all or in greater frequencies, were more likely to experience a marital separation by 2012. Binary logistic regression analyses showed that married Americans who viewed pornography at all in 2006 were more than twice as likely as those who did not view pornography to experience a separation by 2012, even after controlling for 2006 marital happiness and sexual satisfaction as well as relevant sociodemographic correlates. The relationship between pornography use frequency and marital separation, however, was technically curvilinear. The likelihood of marital separation by 2012 increased with 2006 pornography use to a point and then declined at the highest frequencies of pornography use. Ancillary analyses, however, showed that this group of married Americans with high frequencies of 2006 pornography viewing and low likelihood of later marital separation was not statistically distinguishable from either abstainers or moderate viewers in terms of marital separation likelihood. All findings held regardless of gender. Data limitations and implications for future research are discussed.


Routine treatment duration for clients attending a community based anxiety disorders clinic.
To determine the average duration of treatment at a community-based anxiety disorders clinic. Data were collected on primary disorder, the presence of co-occurring disorders and treatment length (both in terms of number of sessions and weeks of therapy) for 248 consecutive clients. The mean number of sessions was 13, and average treatment length was 29 weeks. There was substantial variation in treatment duration (range for number of sessions = 1-128, range for treatment duration = 0-186 weeks). Clients with anxiety disorders were often treated in relatively few sessions, in line with randomised controlled trials (RCTs). However, a number of clients required many more sessions and were treated for a longer period of time than clients in RCTs. Health services should be cautious in mandating limits to therapy duration for anxiety disorders given the wide range in the duration of treatment for clients in our sample.


Expression of bone morphogenetic proteins in stromal cells from human bone marrow long-term culture.
Highly purified primitive hemopoietic stem cells express BMP receptors but do not synthesize bone morphogenetic proteins (BMPs). However, exogenously added BMPs regulate their proliferation, differentiation, and survival. To further explore the mechanism by which BMPs might be involved in hemopoietic differentiation, we tested whether stromal cells from long-term culture (LTC) of normal human bone marrow produce BMPs, BMP receptors, and SMAD signaling molecules. Stromal cells were immunohistochemically characterized by the presence of lyzozyme, CD 31, factor VIII, CD 68, S100, alkaline phosphatase, and vimentin. Gene expression was analyzed by RT-PCR and the presence of BMP protein was confirmed by immunohistochemistry (IHC). The supportive role of the stromal cell layer in hemopoiesis in vitro was confirmed by a colony assay of clonogenic progenitors. Bone marrow stromal cells express mRNA and protein for BMP-3, -4, and -7 but not for BMP-2, -5, and -6 from the first to the eighth week of culture. Furthermore, stromal cells express the BMP type I receptors, activin-like kinase-3 (ALK-3), ALK-6, and the downstream transducers SMAD-1, -4, and -5. Thus, human bone marrow stromal cells synthesize BMPs, which might exert their effects on hemopoietic stem cells in a paracrine manner through specific BMP receptors.


[New definition of metabolic syndrome: does it have the same cardiovascular risk?].
The International Diabetes Federation (IDF) has recently published the new criteria for the diagnosis of metabolic syndrome. The aim of this study was to compare the clinical characteristics and cardiovascular risk of the new patients with MS compared to the previous National Cholesterol Education Program ATP III definition, its differential characteristics and cardiovascular risk. Cross sectional study in a hypertension clinic. Coronary risk was calculated (Framingham function NCEP-ATP III) and other cardiovascular markers, urinary albumin excretion (UAE in mg/24 hours) and high sensitivity C-reactive protein (CRP) were assessed. A total 2,404 patients were evaluated, 1,901 non-diabetic and 503 diabetic hypertensive subjects. The non-diabetics 726 (38.2%) had MS with the previous NCEP ATP-III definition, the number increasing sharply to 1,091 (57.4%) with the new IDF definition. The proportion did not increase in diabetics (93% vs. 92%). Concordance in the diagnosis was 78% in non-diabetics and 91% in diabetics. The new patients had a similar coronary risk (Framingham) but lower values of other cardiovascular markers: logUAE 1.00 (0.49) mg/24 hours vs. 1.06 (0.55) mg/24 hours (p = 0.003), and CRP 1.9 (2.7) mg/L vs. 2.5 (3.2) mg/L (median, interquartile range; p < 0.001). The new IDF definition of MS increases the number of patients with MS. The new patients have a similar coronary risk (Framingham) but the new parameters used to assess cardiovascular risk (UAE and CRP) were lower. The relationship of the new definition of MS and cardiovascular risk remains to be defined.