Recent developments in factor-facilitated ribosome assembly.
Escherichia coli ribosomal subunits can be reconstituted in vitro under highly optimized conditions. These reconstitution systems have proven invaluable for the study of ribosomal subunit assembly. While E. coli ribosomal subunits can self-assemble in vitro there has been much speculation regarding the existence of extra-ribosomal assembly factors that act in functional subunit formation in vivo. Recently, a biochemical assay has been implemented to identify factors that facilitate a single, critical step in 30S subunit assembly in vitro. These studies have revealed that the DnaK (heat shock protein 70) chaperone system can facilitate 30S subunit assembly in vitro. The 30S subunits, formed in the presence of the chaperones under otherwise non-permissive conditions, are highly similar to 30S subunits formed under standard reconstitution conditions. It has become evident that the manner in which the "factor-assembled" 30S subunits are purified is critical for monitoring formation of functional ribosomal particles. Given that methodologies for in vitro reconstitution and functional analysis of ribosomal subunits have been described in detail previously, this manuscript will focus on isolation of functional 30S subunits that have been assembled in the presence of exogenous factors in vitro. Also, recent efforts toward understanding the roles of exogenous factors in 50S subunit and eukaryotic ribosome assembly will be briefly discussed.


The syndrome of inappropriate ADH secretion secondary to vinblastine-bleomycin therapy.
A clinical picture compatible with the syndrome of inappropriate ADH (antidiuretic hormone) secretion was observed in two patients receiving vinblastine-bleomycin chemotherapy. The mechanism by which this response is brought about is unclear. Penetration of Vinka alkaloids into CSF of humans is poor in the absence of extensive meningeal involvement, and hence an indirect method of action by a reduction in the osmotic threshold for vasopressin release has been suggested. By administering vinblastine on days 1 and 4 (instead of days 1 and 2, as suggested in the high-response regimen consisting of vinblastine, bleomycin, and cis-platinum) we have found better bone marrow tolerance and have not noticed the inappropriate ADH syndrome.


A cross-sectional assessment of health-related quality of life (HRQoL) among hypertensive patients in Pakistan.
To describe the health-related quality of life (HRQoL) profile of hypertensive population in Pakistan. A cross-sectional descriptive study was undertaken with a cohort of 385 hypertensive patients attending two public hospitals in Quetta city, Pakistan. The EuroQoL EQ-5D scale was used for the assessment of HRQoL. EQ-5D is a standardized instrument for use as a measure of health outcome and is used in the clinical and economic evaluation of health care as well as population health surveys. The HRQoL was scored using values derived from the UK general population survey. P ≤ 0.05 was taken as significant. Two hundred and sixty-five (68.85%) respondents were men with 3.01 ± 0.939 years of history of hypertension. Majority (n = 186, 48.3%) were categorized in age group of 28-37 years with mean age of 39.02 ± 6.596. Education, income and locality had significant relation with HRQoL score. HRQoL was measured poor in our study patients (0.4674 ± 0.2844). Hypertension has an adverse effect on patients' well-being and HRQoL. Results from this study could be useful in clinical practice, particularly in early treatment of hypertension, at point where improving HRQoL is still possible.


Treadmill-belt width, but not feedback from the lower visual field, influences the noise characteristics of step width time series.
Step kinematic variability, which has been associated with gait-related fall risk, is thought to be attributed to neuromotor noise. Altered neuromotor control of step kinematics would be expected to manifest as changes in the noise-related characteristics of the step kinematic time series. This study determined the effects of eliminating feedback from the lower visual field and reducing treadmill-belt width on the noise characteristics of step width time series and statistical measures of step width variability during treadmill walking. We hypothesized that eliminating feedback from the lower visual field and reducing treadmill-belt width would both alter the noise characteristics of step width time series, reflected by decreased fractal scaling, and increase statistical measures of step width variability. Eighteen young adults performed four randomly ordered walking trials during which we manipulated visual feedback from the lower visual field (normal and obstructed) and treadmill-belt width (wide and narrow). Reducing treadmill-belt width, but not eliminating feedback from the lower visual field, significantly reduced the fractal scaling of step width time series, indicating a shift towards white, uncorrelated noise. These results suggest that accounting for the influence of treadmill-belt width on step width time series may be an important consideration in both laboratory and clinical settings. Further work is needed to clarify the effects of vision on measures of step width, identify the mechanism(s) underlying the observed shift towards white, uncorrelated noise associated with reduced treadmill-belt width, and to assess the potential relationship between the noise characteristics of step width time series and fall risk.


A Study of Clinicopathological Profile of Salivary Gland Swellings.
Salivary gland diseases usually present as a swelling of the affected gland. These lesions are commonly encountered in day to day practice. A salivary gland swelling can present in a variety of locations, depending on the salivary gland affected. The purpose of the study is to know the incidence of salivary gland swellings and the usefulness of FNAC in evaluating these swellings. The present study is a time bound prospective study of fifty consecutive cases of salivary gland swellings admitted in our hospital during the period November 2014-August 2016. Most of the patients underwent pre-operative work up with FNAC and patients indicated for surgery underwent surgery and HPE. Salivary gland swelling occurred more commonly in 3rd decade of life and equal number of cases were seen in both genders. Most of the patients presented with salivary gland swelling (98%). 21 (42%) were non neoplastic, 29 (58%) were neoplastic swellings, 18 (36%) were benign of which pleomorphic adenoma was the most common and 11 (22%) were malignant of which adenoid cystic carcinoma was the most common. Parotid gland was the most common gland involved. Fine needle aspiration cytology was highly sensitive for benign tumours and highly specific for malignant tumours. FNAC should be first choice of investigation in evaluating the salivary gland pathologies. Early diagnosis and subsequent appropriate management carries good prognosis.


Description of HLA-DRB1*14:02:09, a novel HLA allele identified in a Colombian donor.
HLA-DRB1*14:02:09 differs from HLA-DRB1*14:02:01:02 by a single nucleotide substitution in codon 169 of exon 3.


Addressing health disparities through promoting equity for individuals with intellectual disability.
Intellectual disabilities (ID) are conditions originating before the age of 18 that result in significant limitations in intellectual functioning and conceptual, social and practical adaptive skills. IDs affect 1 to 3% of the population. Persons with ID are more likely to have physical disabilities, mental health problems, hearing impairments, vision impairments and communication disorders. These co-existing disabilities, combined with the limitations in intellectual functioning and in adaptive behaviours, make this group of Canadians particularly vulnerable to health disparities. The purpose of this synthesis article is to explore potential contributory factors to health vulnerabilities faced by persons with ID, reveal the extent and nature of health disparities in this population, and examine initiatives to address such differences. The review indicates that persons with ID fare worse than the general population on a number of key health indicators. The factors leading to vulnerability are numerous and complex. They include the way society has viewed ID, the etiology of ID, health damaging behaviours, exposure to unhealthy environments, health-related mobility and inadequate access to essential health and other basic services. For persons with ID there are important disparities in access to care that are difficult to disentangle from discriminatory values and practice. Policy-makers in the United States, England and Scotland have recently begun to address these issues. It is recommended that a clear vision for health policy and strategies be created to address health disparities faced by persons with ID in Canada.


Is the therapeutic index better with gemcitabine-based chemoradiation than with 5-fluorouracil-based chemoradiation in locally advanced pancreatic cancer?
To retrospectively compare the toxicity and efficacy of concurrent gemcitabine-based chemoradiation with that of concurrent 5-fluorouracil (5-FU)-based chemoradiation in patients with unresectable pancreatic cancer. Between September 1996 and May 2000, 114 patients with localized unresectable adenocarcinoma of the pancreas were treated with concurrent chemoradiation. Locally advanced unresectable disease was defined as low-density tumor in contact with the superior mesenteric artery (SMA) or celiac artery, or occlusion of the superior mesenteric-portal venous confluence. Fifty-three patients were selected to receive gemcitabine in 7 weekly cycles (250-500 mg/m(2)) with concurrent radiotherapy (median dose 30 Gy, range 30-33 Gy in 10-11 fractions). The remaining 61 patients received continuous-infusion 5-FU (200-300 mg/m(2)) with concurrent radiotherapy (30 Gy in 10 fractions). Radiotherapy was delivered to the primary tumor and regional lymphatics. Patients receiving gemcitabine and those receiving 5-FU had a similar mean Karnofsky performance status (KPS, 89% vs. 86%), distribution of tumor grade (43% vs. 33% poorly differentiated), and percent weight loss (all p = NS). However, patients treated with gemcitabine had a significantly larger median maximum cross-sectional tumor area (TA, 8.8 cm(2) vs. 5.7 cm(2), p = 0.046) and were significantly younger (median age 60 vs. 68 years, p <0.001). Severe acute toxicity (ST) was defined as toxicity requiring a hospital stay of more than 5 days, mucosal ulceration with bleeding, more than 3 dose deletions of gemcitabine or discontinuation of 5-FU, or toxicity resulting in surgical intervention or death. Kaplan-Meier analysis was used to calculate the actuarial rate of local progression on imaging (LP), the rate of distant metastasis (DM), and the overall survival (OS) rate. The imaging was reviewed in resected patients. Patients receiving gemcitabine developed significantly more ST during treatment (23% vs. 2%, p < 0.0001) than did those receiving 5-FU. Patients treated with gemcitabine had a similar 10-month LP rate (62% vs. 61%), 10-month DM rate (55% vs. 47%), 1-year OS rate (42% vs. 28%), and median OS duration (11 months vs. 9 months) to patients treated with 5 FU (all p = NS). Five patients who received gemcitabine and 1 patient who received 5-FU underwent margin-negative pancreaticoduodenectomy after chemoradiation. Three patients had a short segment (<or= 1 cm in length) of low-density tumor abutting the SMA, 1 had involvement of the common hepatic artery, and 1 had a short-segment occlusion of the superior mesenteric vein, amenable to venous resection and reconstruction. The other patient was thought to have inflammatory changes discontiguous with the tumor surrounding the SMA, which resolved after therapy. TA >10 cm(2) (p = 0.03) and poor differentiation (p = 0.07) were associated with a worse survival duration; however, other factors, such as KPS and weight loss >10% and age did not influence OS. Despite the selection of healthier patients to receive gemcitabine, there was a significantly higher severe toxicity rate than with 5-FU. The median and 1-year survivals were not significantly different with the use of concurrent gemcitabine; however, the tumors treated were significantly larger. Additionally, a small number of patients with minimal arterial involvement whose disease met our radiographic definition of unresectable disease had margin-negative resections after treatment with gemcitabine-based chemoradiation. These possible benefits and the high rate of severe toxicity define a very narrow therapeutic index for concurrent gemcitabine-based chemoradiation given by this schedule of administration.


Genetic mapping and candidate gene analysis for melon resistance to Phytophthora capsici.
Phytophthora blight is one of the most serious diseases affecting melon (Cucumis melo) production. Due to the lack of highly resistant germplasms, the progress on disease-resistant research is slow. To understand the genetics of melon resistance to Phytophthora capsici, an F2 population containing 498 individuals was developed by crossing susceptible line E31 to highly resistant line ZQK9. Genetic analysis indicated that the resistance in ZQK9 was controlled by a dominant gene, tentatively named MePhyto. Through bulked-segregant analysis (BSA-Seq) and chromosome walking techniques, the MePhyto gene was mapped to a 52.44 kb interval on chromosome 12. In this region, there were eight genes and their expression patterns were validated by qRT-PCR. Among them, one wall-associated receptor kinase (WAK) gene MELO3C002430 was significantly induced in ZQK9 after P. capsici inoculation, but not in E31. Based on the non-synonymous mutation site in MELO3C002430, a cleaved amplified polymorphic sequence (CAPS) marker, CAPS2430, was developed and this maker was co-segregated with MePhyto in both F2 population and a collection of 36 melon accessions. Thus MELO3C002430 was considered as the candidate gene and CAPS2430 was a promising marker for marker-assisted selection (MAS) in breeding. These results lay a foundation for revealing the resistance mechanism of melon to P. capsici.


Reduction of 51Cr-permeability of tissue culture cells by infection with herpes simplex virus type 1.
Infection of different strains of tissue culture cells with herpes simplex virus type 1 (HSV-1) resulted in a reduced 51Cr-permeability. A stability of the cellular membrane to Triton X-100, toxic sera and HSV-specific complement-mediated immune-cytolysis could be observed simultaneously. The results differed with respect to the cell strain used in the experiments.


The effects of photobiomodulation using LED on the repair process of skin graft donor sites.
The benefits of photobiomodulation (PBM) applied to wounds are well-described in the literature; however, its effects in skin graft donor sites have been poorly studied. The aim of this study is to evaluate the effects of LED PBM on re-epithelialization and wound quality of the skin donor site and on pain during repair process. This is a case series study that part of the patients received standard treatment and the others received standard treatment combined with PBM. Data collection was performed at the Burn Unit at a Public Hospital, Brazil. The study had 21 participants and 25 donor sites, 13 in the control group (conventional treatment with Membracel® bandage) and 12 in the experimental group (Membracel® + LED). Irradiation parameters were 1.53 J/cm2, 2.55 mW/cm2, 660 nm, 600 s in the immediate postoperative period as well as on the 1st, 3rd, 5th, and 7th days postoperatively. Pain was measured using the visual analog scale. The Bates-Jensen scale was used to monitor the re-epithelialization process and measurements were performed of donor skin sites in the postoperative period. Quantitative variables were expressed as mean ± standard deviation or median and interquartile range [p25; p75]. The comparison of the distribution of these variables between groups was performed using the Mann-Whitney test. No differences between groups were found for re-epithelialization time, area or quality of the wound. Regarding pain, a significant reduction was found on the 5th postoperative day in the experimental group compared to the control group. PBM did not induce changes in the re-epithelialization period, wound area or wound quality scores of the Bates-Jensen Scale but did induce a reduction in pain compared to the group treated with Membracel® alone.


Pain in scleral pocket incision cataract surgery using topical and peribulbar anesthesia.
To evaluate the pain produced during different phases of phacoemulsification cataract surgery using a scleral pocket incision under topical versus peribulbar anesthesia. Department of Ophthalmology, Oulu University Hospital, Oulu, Finland. This prospective study comprised 100 cataract patients who were randomly selected to have phacoemulsification with a scleral pocket incision using either topical or peribulbar anesthesia. Topical anesthesia comprised oxybuprocaine 0.4% drops. Peribulbar anesthesia was given with an inferolateral transconjuctival injection of an even mixture of lidocaine 2% and bupivacaine 0.5% with hyaluronidase. Inadvertent eye movement during surgery was recorded. Pain occurring during intravenous line cannulation, introduction of the anesthetic agent, and phacoemulsification was measured using a visual analog scale (from 0 to 10) and a descriptive verbal 5-step scale. Patients were asked about pain immediately after each phase. The pain during cannulation was similar in both groups (P = .498). The peribulbar injection was statistically significantly more painful than induction of topical anesthesia (2.11 and 0.10, respectively; P < .001). Surgery was statistically significantly more painful in the topical group than in the peribulbar group (2.76 and 0.85, respectively; P < .001). The mean pain score during all 3 phases was similar (1.43 topical group and 1.51 peribulbar group; P = .500). On the verbal scale, surgery was more painful under topical than under peribulbar anesthesia (P < .001). There were no statistical differences in pain during the peribulbar injection and during cannulation (P = .461 and P = .462, respectively). Inadvertent eye movement occurred more often in the topical anesthesia group. Considering the entire procedure, total pain using topical anesthesia was acceptable and equal to that using peribulbar anesthesia for phacoemulsification with a scleral pocket incision. Pain during phacoemulsification was greater under topical anesthesia but not significantly different from the pain during the peribulbar injection.


The neglected functions of intrinsically disordered proteins and the origin of life.
The example of gelatine shows that extended proteins behave quite differently than globular ones: with water they form a gel. Historically the colloid view of protoplasm was discredited in favour of membrane-(pump)-theory (MPT), but unjustified. In his association-induction hypothesis Ling demonstrates that MPT is full of contradictions and that the colloid view has to be re-considered. In that case IDP's play a crucial role in this. What Ling calls the 'living state' consists of the unitary protoplasmic structure from which it was experimentally demonstrated that it can survive and keep Na+ and K+ concentrations without a delineating membrane. It consists of unfolded polypeptide chains whereby the repetitive backbone peptide groups orient and polarise many layers of water, in which Na+ and other solutes have reduced solubility and whereby the polypeptide β- and ϒ-carboxyl-groups adsorb K+. This 'associated' state is the resting state: a coherent high-energy low-entropy meta-stable state. It can be kept by adsorbed ATP (NTP) eventually for years without consumption of ATP as demonstrated by Clegg on Artemia embryo's. Stimuli can transform this state into a lower-energy higher-entropy action state with dissociation of ADP and Pi and newly synthesised ATP can reinstall it. Rest-to-action and action-to-rest were shown to be real phase-shifts. Ling's theory is a complete quantitative theory with corroborated equations for solute distribution, transport, cell potentials and osmotic behaviour and describing the cell's energy cycle. IDP's are involved in all this. The new view on IDP's leads to new insights on the origin of life.


Excitation energy transfer study of the spatial relationship between the carbonyl and metal cofactors in pig plasma amine oxidase.
9-Hydrazinoacridine irreversibly labeled pig plasma amine oxidase by covalent attachment to the active carbonyl cofactor. The visible absorption spectrum of the modified protein displays new absorption bands at 495 and 525 nm. Its emission spectrum exhibited maxima at 415 and 440 nm. In addition, both absorption and emission spectra were insensitive to pH changes between 6 and 10. Phase modulation fluorometry was used to determine fluorescence lifetimes of Zn2+- and Co2+-substituted acridinyl plasma amine oxidase. Energy transfer efficiency was 22%; the distance separating the Co2+ ion (in the copper binding site) and the acridine moiety (the amine substrate binding site) ranges between 11.7 and 14.7 A. This work defines the proximity of the metal and substrate (and hence the carbonyl cofactor) and precludes any direct interaction between Cu2+ and pyrroloquinoline quinone or between Cu2+ and the substrate.


QRS Duration or QRS Morphology: What Really Matters in Cardiac Resynchronization Therapy?
The beneficial effects of cardiac resynchronization therapy (CRT) have been well established in large, randomized trials. Despite the documented success of this treatment strategy, a significant proportion of patients with heart failure do not achieve the desired response. The aim of this review was to delineate factors contributing to a successful CRT response, emphasizing the interrelated roles of QRS morphology and QRS interval duration. More data are available on QRS duration, as this factor has been used as an enrollment criterion in clinical trials. Response to CRT seems to increase as the QRS duration becomes longer, with greatest benefit in QRS duration ≥150 ms. Recent data have placed more emphasis on QRS morphology, demonstrating variability in clinical response between patients with left bundle branch block, non-left bundle branch block, and right bundle branch block morphology. Notably, myocardial scarring and cardiac dimensions, among other variables, may alter heterogeneity in ventricular activation. Understanding the electrophysiological underpinnings of the QRS complex has become important not only to predict response but also to facilitate the patient-specific delivery of resynchronization therapy.


[From setting up to creating an IPA collective].
The Nancy Regional University Hospital is strongly committed to the development of advanced practice nursing. Currently, 23 advanced practice nurses (APNs) are working at the hospital. The care department, which is responsible for their future positioning, has supported their implementation. The desire to work together on common projects quickly became apparent, and a group of APNs was formed over time, culminating in the creation of a collective. This feedback is the first step towards a multi-faceted partnership, and highlights an example of organization around this new profession.


Personality changes following heart transplantation: The role of cellular memory.
Personality changes following heart transplantation, which have been reported for decades, include accounts of recipients acquiring the personality characteristics of their donor. Four categories of personality changes are discussed in this article: (1) changes in preferences, (2) alterations in emotions/temperament, (3) modifications of identity, and (4) memories from the donor's life. The acquisition of donor personality characteristics by recipients following heart transplantation is hypothesized to occur via the transfer of cellular memory, and four types of cellular memory are presented: (1) epigenetic memory, (2) DNA memory, (3) RNA memory, and (4) protein memory. Other possibilities, such as the transfer of memory via intracardiac neurological memory and energetic memory, are discussed as well. Implications for the future of heart transplantation are explored including the importance of reexamining our current definition of death, studying how the transfer of memories might affect the integration of a donated heart, determining whether memories can be transferred via the transplantation of other organs, and investigating which types of information can be transferred via heart transplantation. Further research is recommended.


Treatment of multiple huge liver cysts in a hybrid operating room: a case report.
Liver cysts are common, with most cases being asymptomatic. In symptomatic cases, the disease is amenable to treatment. However, huge or multiple liver cysts with vascular narrowing and associated systemic symptoms are extremely rare. Furthermore, the performance of a reliable and effective surgery in such cases remains a major problem. Here, we report a case of multiple giant liver cysts with impaired blood flow surgically treated in a hybrid operating room. A 73-year-old male presented to a previous doctor with leg edema and dyspnea on exertion; computed tomography revealed that the cause complaint was right lung and heart compression and inferior vena cava (IVC) stenosis due to huge liver cysts in the caudal lobe. The patient was referred to our hospital because of disease recurrence despite percutaneous aspiration of the cyst. Multiple liver cysts were observed in addition to the drained cysts, two of which were located on both sides of the IVC and caused IVC stenosis. We performed open surgery for the liver cysts and used the hybrid operating room for intraoperative IVC angiography and measuring the hepatic vein and portal vein (PV) pressure. We performed unroofing of the hepatic cyst and cauterization of the cyst wall on the hepatic side. Angiography was performed before and after unroofing of the liver cysts, and IVC stenosis release was confirmed. IVC pressure measured at the peripheral side of the stenosis and PV pressures were continuously measured during surgery and were confirmed to have decreased during the opening of the liver cysts. The patient had a good postoperative course and was discharged on the 10th postoperative day. No recurrence was observed 6 months postoperatively. Cyst unroofing surgery using angiography in a hybrid operating room is a useful treatment for deep hepatic lesions in that vascular stenosis improvement can be intraoperatively confirmed. Moreover, in cases wherein the cyst compresses the vasculature, intraoperative monitoring of IVC and PV pressures can be used to prove that the liver cyst is hemodynamically involved.


Loss of the actin regulator cyclase-associated protein 1 (CAP1) modestly affects dendritic spine remodeling during synaptic plasticity.
Dendritic spines form the postsynaptic compartment of most excitatory synapses in the vertebrate brain. Morphological changes of dendritic spines contribute to major forms of synaptic plasticity such as long-term potentiation (LTP) or depression (LTD). Synaptic plasticity underlies learning and memory, and defects in synaptic plasticity contribute to the pathogeneses of human brain disorders. Hence, deciphering the molecules that drive spine remodeling during synaptic plasticity is critical for understanding the neuronal basis of physiological and pathological brain function. Since actin filaments (F-actin) define dendritic spine morphology, actin-binding proteins (ABP) that accelerate dis-/assembly of F-actin moved into the focus as critical regulators of synaptic plasticity. We recently identified cyclase-associated protein 1 (CAP1) as a novel actin regulator in neurons that cooperates with cofilin1, an ABP relevant for synaptic plasticity. We therefore hypothesized a crucial role for CAP1 in structural synaptic plasticity. By exploiting mouse hippocampal neurons, we tested this hypothesis in the present study. We found that induction of both forms of synaptic plasticity oppositely altered concentration of exogenous, myc-tagged CAP1 in dendritic spines, with chemical LTP (cLTP) decreasing and chemical LTD (cLTD) increasing it. cLTP induced spine enlargement in CAP1-deficient neurons. However, it did not increase the density of large spines, different from control neurons. cLTD induced spine retraction and spine size reduction in control neurons, but not in CAP1-KO neurons. Together, we report that postsynaptic myc-CAP1 concentration oppositely changed during cLTP and cTLD and that CAP1 inactivation modestly affected structural plasticity.


Prenatal diagnosis of beta-thalassemia using selective hemolysis of maternal cells contaminating fetal blood sample.
The prenatal diagnosis of the severe, hereditary anemias may be impossible when a placental blood sample which contains a high percentage of maternal rather than fetal cells is obtained. An incubation system described by Boyer et al. [3] with minor modifications, was applied to mixtures of blood from prematures and adults in order to increase the proportion of premature cells. After 40 min incubation, 95% or more of adult red cells were destroyed, whereas 30-60% of premature red cells were recovered, as determined by several independent methods. In a pregnancy at risk for beta-thalassemia, a placental blood sample which was purely fetal was obtained. Complete lack of in vitro beta-globin synthesis showed the fetus to have homozygous beta-thalassemia. When fetal blood was mixed with maternal blood in a ratio of 1:15, beta-globin synthesis in the mixture was comparable to that of normal fetuses. In contrast, when the cell mixture was subjected to selective hemolysis prior to separation of globins, beta-globin synthesis again was not detectable. Thus, using selective hemolysis, the correct diagnosis could be established from a blood sample containing only about 6% of fetal cells.


Quantification and rejection of ocular artifacts in auditory evoked fields in schizophrenics.
In a magnetoencephalographic investigation of the auditory evoked field (AEF) in 17 schizophrenics and 17 controls, 37% of the schizophrenics and 12% of the controls showed eye artifacts in every second trial or even more frequently. In the uncorrected average fields, the ratio between the power of artifacts and the power of the magnetoencephalogram (MEG) exceeded the value of 0.1 for 48% of the schizophrenics and for 29% of the controls. Ocular artifacts biased the locations of equivalent current dipoles of the M100 component towards deeper positions. A regression algorithm for the correction of ocular artifacts in raw data and an identification technique of ocular artifacts based on the topography of transmission coefficients is described. A linear dependence of ocular artifacts in AEF on the electrooculogram (EOG) was confirmed. Possible errors introduced by the correction are discussed. Transmission coefficients should be calculated for several individual trials with the same type of artifact. Errors due to evoked potentials in the EOG were found to be comparable in amplitude to noise in the AEF. Examples of transmission coefficients from the EOG to the MEG are given.


Monitoring Prostate Tumor Growth in an Orthotopic Mouse Model Using Three-Dimensional Ultrasound Imaging Technique.
Prostate cancer (CaP) is the most commonly diagnosed and the second leading cause of death from cancer in males in USA. Prostate orthotopic mouse model has been widely used to study human CaP in preclinical settings. Measurement of changes in tumor size obtained from noninvasive diagnostic images is a standard method for monitoring responses to anticancer modalities. This article reports for the first time the usage of a three-dimensional (3D) ultrasound system equipped with photoacoustic (PA) imaging in monitoring longitudinal prostate tumor growth in a PC-3 orthotopic NODSCID mouse model (n = 8). Two-dimensional and 3D modes of ultrasound show great ability in accurately depicting the size and shape of prostate tumors. PA function on two-dimensional and 3D images showed average oxygen saturation and average hemoglobin concentration of the tumor. Results showed a good fit in representative exponential tumor growth curves (n = 3; r(2) = 0.948, 0.955, and 0.953, respectively) and a good correlation of tumor volume measurements performed in vivo with autopsy (n = 8, r = 0.95, P < .001). The application of 3D ultrasound imaging proved to be a useful imaging modality in monitoring tumor growth in an orthotopic mouse model, with advantages such as high contrast, uncomplicated protocols, economical equipment, and nonharmfulness to animals. PA mode also enabled display of blood oxygenation surrounding the tumor and tumor vasculature and angiogenesis, making 3D ultrasound imaging an ideal tool for preclinical cancer research.


Do some neurological conditions induce brain plasticity processes?
Paillard [Paillard J. Réflexions sur l'usage du concept de plasticité en Neurobiologie. J Psychol Norm Pathol 1976;1:33-47] defined adaptive plasticity as the capacity of the system to change its own structure and expand its behavioural repertoire. We review the literature on brain damage patients, in whom, adaptive plasticity was observed via neuropsychological and functional neuroimaging examinations. Attentional and memory system alterations and some resulting changes considered as compensatory mechanisms are commented. We have selected a single case presenting with developmental amnesia [Vargha-Khadem F, Gadian DG, Watkins KE, Connelly A, Van Paesschen W, Mishkin M. Differential effects of early hippocampal pathology on episodic and semantic memory. Science 1997;277(5324):376-80; Maguire EA, Vargha-Khadem F, Mishkin M. The effects of bilateral hippocampal damage on fMRI regional activations and interactions during memory retrieval. Brain 2001;124(Pt 6):1156-70] and several groups of multiple sclerosis patients studied recently [e.g. Mainero C, Pantano P, Caramia F, Pozzilli C. Brain reorganization during attention and memory tasks in multiple sclerosis: insights from functional MRI studies. J Neurol Sci 2006;245(1/2):93-8; Morgen K, Sammer G, Courtney SM, Wolters T, Melchior H, Blecker CR, et al. Distinct mechanisms of altered brain activation in patients with multiple sclerosis. Neuroimage 2007;37(3):937-46; Nebel K, Wiese H, Seyfarth J, Gizewski ER, Stude P, Diener HC, et al. Activity of attention related structures in multiple sclerosis patients. Brain Res 2007;1151:150-60]. Convergence evidence via the two approaches - neuropsychological and functional fMRI - was shown as functional and structural brain plasticity was demonstrated in the selected works. Some common characteristics of brain plasticity emerge from this review independently of the neurological conditions we reviewed.


Walleye dermal sarcoma virus Orf B functions through receptor for activated C kinase (RACK1) and protein kinase C.
Walleye dermal sarcoma virus is a complex retrovirus that is associated with walleye dermal sarcomas that are seasonal in nature. Fall developing tumors contain low levels of spliced accessory gene transcripts A and B, suggesting a role for the encoded proteins, Orf A and Orf B, in oncogenesis. In explanted tumor cells the 35 kDa Orf B accessory protein is localized to the cell periphery in structures similar to focal adhesions and along actin stress fibers. Similar localization was observed in mammalian cells. The cellular protein, receptor for activated C kinase 1 (RACK1), bound Orf B in yeast two-hybrid assays and in cell culture. Sequence analysis of walleye RACK1 demonstrated high conservation to other known RACK1 sequences. RACK1 binds to activated protein kinase C (PKC). Orf B associates with PKCalpha, which is constitutively activated and localized at the membrane. Activated PKC promoted cell survival, proliferation, and increased cell viability in Orf B-expressing cells.


Hybrids of aurantiamide acetate and isopropylated genipin as potential anti-inflammatory agents: The design, synthesis, and biological evaluation.
A novel series of hybrids designed on the basis of aurantiamide acetate and isopropylated genipin were synthesized and biologically evaluated as anti-inflammatory agents. Among them, compound 7o exhibited the best inhibitory activity against TNF-α secretion (IC50 = 16.90 μM) and was selected for further in vitro and in vivo functional study. The results demonstrated that 7o was capable of suppressing the expression of LPS-induced iNOS and COX-2, as well as reducing the production of NO at the concentration of 5 μM, which may be resulted from its regulation of NF-κB signaling and MAPK signaling. Moreover, compound 7o exhibited favorable in vivo anti-inflammatory activity with an inhibition rate of 53.32% against xylene-induced ear swelling in mice at the dose of 5 mg/kg.


Automatic multiorgan segmentation in thorax CT images using U-net-GAN.
Accurate and timely organs-at-risk (OARs) segmentation is key to efficient and high-quality radiation therapy planning. The purpose of this work is to develop a deep learning-based method to automatically segment multiple thoracic OARs on chest computed tomography (CT) for radiotherapy treatment planning. We propose an adversarial training strategy to train deep neural networks for the segmentation of multiple organs on thoracic CT images. The proposed design of adversarial networks, called U-Net-generative adversarial network (U-Net-GAN), jointly trains a set of U-Nets as generators and fully convolutional networks (FCNs) as discriminators. Specifically, the generator, composed of U-Net, produces an image segmentation map of multiple organs by an end-to-end mapping learned from CT image to multiorgan-segmented OARs. The discriminator, structured as an FCN, discriminates between the ground truth and segmented OARs produced by the generator. The generator and discriminator compete against each other in an adversarial learning process to produce the optimal segmentation map of multiple organs. Our segmentation results were compared with manually segmented OARs (ground truth) for quantitative evaluations in geometric difference, as well as dosimetric performance by investigating the dose-volume histogram in 20 stereotactic body radiation therapy (SBRT) lung plans. This segmentation technique was applied to delineate the left and right lungs, spinal cord, esophagus, and heart using 35 patients' chest CTs. The averaged dice similarity coefficient for the above five OARs are 0.97, 0.97, 0.90, 0.75, and 0.87, respectively. The mean surface distance of the five OARs obtained with proposed method ranges between 0.4 and 1.5 mm on average among all 35 patients. The mean dose differences on the 20 SBRT lung plans are -0.001 to 0.155 Gy for the five OARs. We have investigated a novel deep learning-based approach with a GAN strategy to segment multiple OARs in the thorax using chest CT images and demonstrated its feasibility and reliability. This is a potentially valuable method for improving the efficiency of chest radiotherapy treatment planning.


Di(2-ethylhexyl) phthalate mediates IL-33 production via aryl hydrocarbon receptor and is associated with childhood allergy development.
Few studies assess cord blood biomarkers to predict prenatal exposure to di(2-ethylhexyl) phthalate (DEHP) on the development of allergic diseases later in childhood. IL-33 has been indicated to play an important role in allergic diseases. We evaluated the association of prenatal DEHP exposure and IL-33 in cord blood on the development of allergic diseases. We also investigated the mechanism of DEHP in human lung epithelial cells and asthma animal models. 66 pregnant women were recruited, and their children followed when they were aged 3 years. Maternal urinary DEHP metabolites were determined using liquid chromatography-electrospray-ionization-tandem mass spectrometry. The effect of DEHP on IL-33 production was investigated in human lung epithelial cells and club cell-specific aryl hydrocarbon receptor (AhR) deficiency mice. ELISA and RT-PCR, respectively, measured the IL-33 cytokine concentration and mRNA expression. The concentrations of maternal urinary DEHP metabolites and serum IL-33 in cord blood with childhood allergy were significantly higher than those in the non-childhood allergy group. DEHP and MEHP could induce IL-33 production and reverse by AhR antagonist and flavonoids in vitro. Enhanced ovalbumin-induced IL-4 and IL-33 production in bronchoalveolar lavage fluid (BALF) by DEHP exposure and suppressed in club cell-specific AhR null mice. Kaempferol has significantly reversed the DEHP effect in the asthma animal model. Cord blood IL-33 level was correlated to childhood allergy and associated with maternal DEHP exposure. IL-33 might be a potential target to assess the development of DEHP-related childhood allergic disease. Flavonoids might be the natural antidotes for DEHP.


In vivo MRI cell tracking using perfluorocarbon probes and fluorine-19 detection.
This article presents a brief review of preclinical in vivo cell-tracking methods and applications using perfluorocarbon (PFC) probes and fluorine-19 ((19) F) MRI detection. Detection of the (19) F signal offers high cell specificity and quantification ability in spin density-weighted MR images. We discuss the compositions of matter, methods and applications of PFC-based cell tracking using ex vivo and in situ PFC labeling in preclinical studies of inflammation and cellular therapeutics. We also address the potential applicability of (19) F cell tracking to clinical trials.


Periodontal management of an adolescent with Down's syndrome--a case report.
A case of periodontitis in a young adolescent Japanese girl with Down's syndrome is presented in this report. The patient received a monthly preventive course of dental care consisting of mechanical plaque control and oral hygiene instruction. After 2.5 years she recovered from progression of periodontal disease both clinically and microbiologically. The importance of clinical care for periodontitis in Down's syndrome patients is discussed.


Identification of Mycobacterium DNA in an Egyptian Pott's disease of 5,400 years old.
The antiquity of tuberculosis in the Old World is controversial because the morphology of the lesion in skeletal remains is non-specific. We report the recovery of a DNA fragment from a 5,400-year-old Predynastic Egyptian skeleton that exhibits a kyphotic, 'hunchback' spinal deformity consistent with Pott's disease and suggestive of tuberculous vertebral involvement. The recovered DNA fragment was sequenced and is consistent with an original Mycobacterium sequence. We cannot prove that it is M. tuberculosis, M. bovis or an ancient mycobacteria resembling the two current forms because the observed modifications in the sequence could be attributed to the antiquity of Mycobacterium and/or to the effects of Taq polymerase. This provides the most specific evidence for the antiquity of human Mycobacterium disease in the world.


The development of selective attention: holistic perception versus resource allocation.
In two experiments, a speeded sorting task was administered to children. In each sorting, the child was instructed to sort a deck of cards according to values on one dimension while the values of a second irrelevant dimension were held constant, were correlated, or were varied orthogonally. Experiment 1 evaluated developmental changes in perceived structure as compared with such changes in the control of attention. Different groups of kindergarten, 2d-, and 5th-grade children performed the task with spatially integrated vs spatially separated dimensions. The results indicate that with spatially integrated dimensions there is a trend from holistic to featural perception and an increase in attentional control with increasing age. Spatially separate dimensions are perceived dimensionally at all ages, but show a trend in attentional development. In Experiment 2, the spatially integrated dimensions of Experiment 1 were made separable by portraying different targets within a configuration in different colors. The theoretical implications of the results are discussed.


Electron microscopic investigations on stages of dog piroplasms cultured in vitro: Asian isolates of Babesia gibsoni and strains of B. canis from France and Hungary.
Stages obtained from two Asian Babesia gibsoni-isolates cultured in vitro were studied by means of transmission electron microscopy and compared to strains of B. canis cultured in vitro. While the developmental stages of the latter preserved their shape in culture, many of the initially small stages of the B. gibsoni strains grew considerably and often looked rather similar to B. canis.


Development and calibration of a model for the potential establishment and impact of Aedes albopictus in Europe.
The Asian tiger mosquito (Aedes albopictus) is one of the most invasive disease vectors worldwide. The species is a competent vector of dengue, chikungunya, Zika viruses and other severe parasites and pathogens threatening human health. The capacity of this mosquito to colonize and establish in new areas (including temperate regions) is enhanced by its ability of producing diapausing eggs that survive relatively cold winters. The main drivers of population dynamics for this mosquito are water and air temperature and photoperiod. In this paper, we present a mechanistic model that predicts the potential distribution, abundance and activity of Asian tiger mosquito in Europe. The model includes a comprehensive description of: i) the individual life-history strategies, including diapause, ii) the influence of weather-driven individual physiological responses on population dynamics and iii) the density-dependent regulation of larval mortality rate. The model is calibrated using field data from several locations along an altitudinal gradient in the Italian Alps, which enabled accurate prediction of cold temperature effects on population abundance, including identification of conditions that prevent overwintering of the species. Model predictions are consistent with the most updated information on species' presence and absence. Predicted population abundance shows a clear south-north decreasing gradient. A similar yet less evident pattern in the activity of the species is also predicted. The model represents a valuable tool for the development of strategies aimed at the management of Ae. albopictus and for the implementation of effective control measures against vector-borne diseases in Europe.


Palatal Swellings: A Proposed Classification and a Case Report of Pleomorphic Adenoma of Minor Salivary Gland of the Palate.
Palatal swellings are a commonly encountered diagnostic entity. They can be infectious, neoplastic, odontogenic, vascular, congenital or secondary manifestation of a systemic disease. While individual palatal lesions are well documented in the literature, there is lack of a comprehensive classification of such entities. Proper classification helps in prompt and accurate diagnosis, facilitating proper management. This article proposes a comprehensive classification of palatal swellings based on their location, clinical findings and aetiology, and describes a case report of pleomorphic adenoma of the minor salivary gland of the palate.


Functional and structural evaluation of bovine heart cytochrome c oxidase incorporated into bicelles.
Bilayered long- and short-chain phospholipid assemblies, known as bicelles, have been widely used as model membranes in biological studies. However, to date, there has been no demonstration of structural or functional viability for the fundamental mitochondrial electron transport complexes reconstituted into or interacting with bicelles. In the present work, bicelles were formed from the mixture of long- and short-chain phospholipids, specifically 14:0 and 6:0 phosphatidylcholines (1,2-dimyristoyl-sn-glycero-3-phosphocholine, (DMPC) and 1,2-dihexanoyl-sn-glycero-3-phosphocholine, (DHPC)). Isolated from bovine heart, cytochrome c oxidase was successfully incorporated into bicelles. Bicelles and cytochrome c oxidase incorporated into bicelles ("proteobicelles") were characterized by absorption spectroscopy, dynamic light scattering, atomic force microscopy, sedimentation velocity and differential scanning calorimetry. It was demonstrated that at total concentration of phospholipids CL = 24 mM and the molar ratio (q) of long-chain DMPC over short-chain DHPC equal to 0.4, the diameter of bicelles formed at neutral pH is in the range of 30-60 nm with the thickness of bicelles of about 4 nm. Adding cytochrome c oxidase to bicelles unified the size of the resulting proteobicelles to about 160 nm. Cytochrome c oxidase in bicelles was fully reducible by artificial donors of electrons, exhibited "normal" reaction with external ligands, and was fully active. Both, sedimentation velocity analysis and temperature-induced denaturation indicated that enzyme in bicelles is monomeric. We concluded that cytochrome c oxidase in bicelles maintains its structural and functional integrity, and that bicelles can be used for more comprehensive investigation of cytochrome c oxidase and most likely other mitochondrial electron transfer complexes.


XIST Loss Promotes Mediator Activity to Enhance Tumorigenic Potential.
XIST controls homeostasis in mammary stem cells, balancing self-renewal and differentiation.


[Engineering of Escherichia coli for convenient expression of [FeFe]-hydrogenase].
A new method used to heterologously express [FeFe]-hydrogenase in Escherichia coli was investigated in our present study. By homologous recombination, three assistant genes (hydE, hydF and hydG) for hydrogenase were integrated into the chromosome of E. coli BW 25113-10, in which all hydrogenase genes were inactivated. A hydrogenase structural gene hydA from Clostridium butyricum was used to test the hydrogenase maturation ability of the recombined E. coli. BW 25113-13. The corrected integration of the three assistant genes was confirmed by PCR, and RT-PCR results indicated that the three accessory genes were transcripted in the recombinant. The active expression of hydA indicated that the constitutively expressed accessory proteins could assist the maturation of the [FeFe]-hydrogenases. A simplified [FeFe]-hydrogenase expression recombinant E. coli BW25113-13 was constructed. It would lay foundations for the functional screening of [FeFe]-hydrogenases and the construction of novel hydrogen producing pathways in E. coli.


Production and purification of the bacterial autolysin N-acetylmuramoyl-L-alanine amidase B from Pseudomonas aeruginosa.
The bacterial cell wall heteropolymer peptidoglycan is not a static structure as it is constantly being made and recycled throughout the bacterium's life cycle. This turnover of peptidoglycan is a highly coordinated event involving a complement of autolytic enzymes that include those with specificity for either the carbohydrate or the peptide linkages of peptidoglycan. One major class of these autolysins are the N-acetylmuramoyl-L-alanine amidases which cleave the amide linkage between the stem peptides and the lactyl moiety of muramoyl residues. They are required in the periplasm for cell separation during division and in both the periplasm and cytoplasm to trim soluble released PG fragments during turnover for recycling. The gene encoding N-acetylmuramoyl-L-alanine amidase B in Pseudomonas aeruginosa was cloned and over-expressed in Escherichia coli. The recombinant protein with a C-terminal His-tag was purified to apparent homogeneity by a combination of affinity and cation-exchange chromatographies using Ni(2+)NTA-agarose and Source S, respectively. Four separate assays involving zymography, light scattering, HPLC and MALDI-TOF mass spectrometry were used to confirm the activity of the protein as an N-acetylmuramoyl-L-alanine amidase.


Open-label study to investigate the safety and efficacy of adjunctive perampanel in pediatric patients (aged 4 to <12 years) with inadequately controlled focal-onset seizures: Japanese subgroup analysis.
To evaluate the safety and tolerability of adjunctive perampanel in a Japanese subpopulation of Study 311 (NCT02849626), which was a global, multicenter, open-label, single-arm study of children (aged 4 to <12 years) with inadequately controlled focal-onset seizures (FOS), with or without focal to bilateral tonic-clonic seizures (FBTCS) or generalized tonic-clonic seizures (GTCS). Study 311 comprised a Core Study, Extension A, and Extension B; this report focuses on the Japanese patient subgroup in the Core Study only. In the Core Study, Japanese patients (FOS only) received adjunctive perampanel ≤12 mg/day in a 23-week Treatment Phase. Endpoints included safety/tolerability (primary) and median percent change in seizure frequency per 28 days from baseline. Patients were stratified by age and concomitant enzyme-inducing anti-seizure medication (EIASM) use. Of 65 enrolled Japanese patients, 56 completed the Core Study and nine withdrew. The most common reason for discontinuation was adverse events (AEs) (n = 4 [6.2%]). The mean (standard deviation) daily dose of perampanel in Japanese FOS patients was 5.8 (2.2) mg/day. During the Core Study, treatment-emergent AEs (TEAEs) were reported by 89% of Japanese patients, most commonly nasopharyngitis (28%) and somnolence (28%). The median percent reduction in seizure frequency per 28 days from baseline was 37% and the lower limit of the 95% CI was greater than 10.5%, satisfying the pre-defined efficacy criteria. Perampanel was effective regardless of age or concomitant EIASM use. Perampanel as adjunctive therapy is generally safe, well-tolerated, and efficacious in Japanese children aged 4 to <12 years with FOS (with/without FBTCS).


Bond length contraction in gold nanoparticles.
The structure of nanoparticles typically differs from its bulk counterpart. Predominantly, the structures of gold nanoparticles have been under exceedingly intense discussion since the discovery of their high catalytic activity. We found an increasing bond length contraction with decreasing particle size for citrate-stabilized gold nanoparticles in aqueous solution as determined by in situ extended X-ray absorption fine structure (EXAFS) spectroscopy. Particle sizes and size distributions were determined by small-angle X-ray scattering. The analysis of the obtained EXAFS spectra employing ab initio calculations reveals that the Au-Au bond length undergoes a contraction of 2 pm for nanoparticles with a radius of 2.9 nm. NIST reference material RM 8011 gold nanoparticles with a radius of 4.4 nm exhibit a smaller contraction of approximately 1 pm. Finally, gold atoms in RM 8013 particles with a radius of 25.7 nm show distances of 288 pm--identical to the distance in gold foil--and exhibits bulk-like properties. The observed bond length contraction of gold nanoparticles in solution is significantly smaller than previously reported for gold nanoparticle deposited on surfaces, which is up to 15 pm. This indicates that the bond length contraction effect of "free" and "surface-immobilized" nanoparticles differ fundamentally. Such difference could be essential for the understanding of nanoparticle-supported catalysis.


[Specific and nonspecific effects of blood transfusion on heart graft survival in the rat].
We investigated the role of various blood-transfusions regimens including donor specific and third-party blood transfusions in rat heart transplantations. One ml donor blood (BN; RT1n) given to the recipients (Lew, RT1(1)) of (Lew.BN)F1 rats 7 days prior to grafting prolonged heart survival (24 +/- 8 vs 9.9 +/- 2.7 in control). Heart graft survival was much less when donor blood was given to recipients 1 month before grafting. There was no complementary effect between BT from donor and from third party blood or vice-versa. In addition, although donor blood prolonged graft survival (19.7 +/- 7.5 vs 9.9 +/- 2.7) when given the day of surgery, post surgery sequential BT from the donor (day 0-3-7 and 14 after transplantation) did not further increased survival (14 +/- 4.6). The effect of donor-BT was RT1a specific since third-party blood (1 ml) was ineffective (9.5 +/- 1) whereas 1 ml of congenic RT1n rat (Lew. 1 N) blood increases heart survival: 14 +/- 2.14 vs 9.9 +/- 2.2 in control animals. Although only 1 ml of donor blood enhanced specifically the heart allografts of the corresponding RT1 phenotype, weekly repeated third-party BT (n = 8) did also prolong graft survival (13.7 +/- 3.4) suggesting that aside from classical and powerful model of active RT1 specific effect of BT, a nonspecific, dose-related mechanism can occur.


Handedness and sleep duration.
The differences in habitual sleep duration and absolute deviations in habitual sleep duration from the normative mean between 60 left-, 36 mixed- and 125 right-handed college students were tested. It was found that mixed-handers tend to sleep less and as a group show significantly greater deviations in habitual sleep durations than either left- or right-handers. The heuristic value of this relationship for future research was discussed briefly.


Characterization of electron transfer dissociation in the Orbitrap Velos HCD cell.
Electron transfer dissociation (ETD) is commonly employed in ion traps utilizing rf fields that facilitate efficient electron transfer reactions. Here, we explore performing ETD in the HCD collision cell on an Orbitrap Velos instrument by applying a static DC gradient axially to the rods. This gradient enables simultaneous three dimensional, charge sign independent, trapping of cations and anions, initiating electron transfer reactions in the center of the HCD cell where oppositely charged ions clouds overlap. Here, we evaluate this mode of operation for a number of tryptic peptide populations and the top-down sequence analysis of ubiquitin. Our preliminary data show that performing ETD in the HCD cell provides similar fragmentation as ion trap-ETD but requires further optimization to match performance of ion trap-ETD.


Intracellular growth of Legionella pneumophila serogroup 1 monoclonal antibody type 2 positive and negative bacteria.
Epidemiological evidence suggests that monoclonal antibody type 2 positive (MAB 2+) Legionella pneumophila serogroup 1 (LP1) more often causes disease than do MAB 2- isolates, and there is evidence that MAB 2- LP1 grow less well in cells than do MAB 2+ bacteria. We tested the intracellular growth rates of ten randomly selected MAB 2- LP1 isolates, by using guinea-pig alveolar macrophages, and human monocyte-derived macrophages. Save a low virulence control, all ten MAB 2- isolates grew as well in cells as a virulent MAB 2+ isolate. Heterogeneity of MAB 2- LP1 growth in cells exists, making poor intracellular growth an unlikely explanation for why MAB 2+ LP1 appear to cause disease more often.


Neurodegeneration in the olfactory bulb and olfactory deficits in the Ccdc66 -/- mouse model for retinal degeneration.
The Ccdc66-deficient (Ccdc66 -/-) mouse model exhibits slow progressive retinal degeneration. It is unclear whether CCDC66 protein also plays a role in the wildtype (WT; Ccdc66 +/+) mouse brain and whether the lack of Ccdc66 gene expression in the Ccdc66 -/- mouse brain may result in morphological and behavioral alterations. CCDC66 protein expression in different brain regions of the adult WT mouse and in whole brain during postnatal development was quantified by SDS-PAGE and Western blot. Ccdc66 reporter gene expression was visualized by X-gal staining. Selected brain regions were further analyzed by light and electron microscopy. In order to correlate anatomical with behavioral data, an olfactory habituation/dishabituation test was performed. CCDC66 protein was expressed throughout the early postnatal development in the WT mouse brain. In adult mice, the main olfactory bulb exhibited high CCDC66 protein levels comparable to the expression in the retina. Additionally, the Ccdc66 -/- mouse brain showed robust Ccdc66 reporter gene expression especially in adult olfactory bulb glomeruli, the olfactory nerve layer and the olfactory epithelium. Degeneration was detected in the Ccdc66 -/- olfactory bulb glomeruli at advanced age. This degeneration was also reflected in behavioral alterations; compared to the WT, Ccdc66 -/- mice spent significantly less time sniffing at the initial presentation of unknown, neutral odors and barely responded to social odors. Ccdc66 -/- mice develop substantial olfactory nerve fiber degeneration and alteration of olfaction-related behavior at advanced age. Thus, the Ccdc66 -/- mouse model for retinal degeneration adds the possibility to study mechanisms of central nervous system degeneration.


Longitudinal Analysis of Neighborhood Food Environment and Diabetes Risk in the Veterans Administration Diabetes Risk Cohort.
Diabetes causes substantial morbidity and mortality among adults in the US, yet its incidence varies across the country, suggesting that neighborhood factors are associated with geographical disparities in diabetes. To examine the association between neighborhood food environment and risk of incident type 2 diabetes across different community types (high-density urban, low-density urban, suburban, and rural). This is a national cohort study of 4 100 650 US veterans without type 2 diabetes. Participants entered the cohort between 2008 and 2016 and were followed up through 2018. The median (IQR) duration of follow-up was 5.5 (2.6-9.8) person-years. Data were obtained from Veterans Affairs electronic health records. Incident type 2 diabetes was defined as 2 encounters with type 2 diabetes International Classification of Diseases, Ninth Revision or Tenth Revision codes, a prescription for diabetes medication other than metformin or acarbose alone, or 1 encounter with type 2 diabetes International Classification of Diseases Ninth Revision or Tenth Revision codes and 2 instances of elevated hemoglobin A1c (≥6.5%). Data analysis was performed from October 2020 to March 2021. Five-year mean counts of fast-food restaurants and supermarkets relative to other food outlets at baseline were used to generate neighborhood food environment measures. The association between food environment and time to incident diabetes was examined using piecewise exponential models with 2-year interval of person-time and county-level random effects stratifying by community types. The mean (SD) age of cohort participants was 59.4 (17.2) years. Most of the participants were non-Hispanic White (2 783 756 participants [76.3%]) and male (3 779 555 participants [92.2%]). The relative density of fast-food restaurants was positively associated with a modestly increased risk of type 2 diabetes in all community types. The adjusted hazard ratio (aHR) was 1.01 (95% CI, 1.00-1.02) in high-density urban communities, 1.01 (95% CI, 1.01-1.01) in low-density urban communities, 1.02 (95% CI, 1.01-1.03) in suburban communities, and 1.01 (95% CI, 1.01-1.02) in rural communities. The relative density of supermarkets was associated with lower type 2 diabetes risk only in suburban (aHR, 0.97; 95% CI, 0.96-0.99) and rural (aHR, 0.99; 95% CI, 0.98-0.99) communities. These findings suggest that neighborhood food environment measures are associated with type 2 diabetes among US veterans in multiple community types and that food environments are potential avenues for action to address the burden of diabetes. Tailored interventions targeting the availability of supermarkets may be associated with reduced diabetes risk, particularly in suburban and rural communities, whereas restrictions on fast-food restaurants may help in all community types.


Gene expression profiling in acute Stanford type B aortic dissection.
To compare the gene expression profiles of the aorta specimens between patients with Stanford type B aortic dissection (AD) and controls. Samples of descending aorta were collected from patients with type B AD (n = 12) and from multiorgan donors as controls (n = 12). Phalanx whole genome microarray was used to analyze differential gene expression. Of the 6375 probes validated, 623 genes were found to be differentially expressed between patients with type B AD and controls (fold change ≥2). Gene ontology analysis identified significantly enriched gene groups pertaining to cell-cell adhesion, extracellular matrix, cell-matrix adhesion, cytoskeleton, immune and inflammatory response, and apoptosis. Genes encoding components related to integrity and strength of the aortic wall were downregulated, whereas those related to inflammatory response were upregulated in type B AD. The altered patterns of gene expression indicate preexisting structural defects that are probably a consequence of insufficient remodeling of the aortic wall.


Dynamic heterogeneity of cerebral hypoperfusion after prolonged cardiac arrest in dogs measured by the stable xenon/CT technique: a preliminary study.
After prolonged cardiac arrest and reperfusion, global cerebral blood flow (gCBF) is decreased to about 50% normal for many hours. Measurement of gCBF does not reveal regional variation of flow or permit testing of hypotheses involving multifocal no-flow or low-flow areas. We employed the noninvasive stable Xenon-enhanced Computerized Tomography (Xe/CT) local CBF (LCBF) method for use in dogs before and after ventricular fibrillation (VF) cardiac arrest of 10 min. This was followed by external cardiopulmonary resuscitation (CPR) and control of cardiovascular pulmonary variables to 7 h postarrest. In a sham (no arrest) experiment, the three CT levels studied showed normal regional heterogeneity of LCBF values, all between 10 and 75 ml/100 cm3 per min for white matter and 20 and 130 ml/100 cm3 per min for gray matter. In four preliminary CPR experiments, the expected global hyperemia at 15 min after arrest, was followed by hypoperfusion with gCBF reduced to about 50% control and increased heterogeneity of LCBF. Trickle flow areas (LCBF less than 10 ml/100 cm3 per min) not present prearrest, were interspersed among regions of low, normal, or even high flow. Regions of 125-500 mm3 with trickle flow or higher flows, in different areas at different times, involving deep and superficial structures migrated and persisted to 6 h, with gCBF remaining low. These preliminary results suggest: no initial no-reflow foci (less than 10 ml/100 cm3 per min) larger than 125 mm3 persisting through the initial global hyperemic phase; delayed multifocal hypoperfusion more severe than suggested by gCBF measurements; and trickle flow areas caused by dynamic factors.


Low prebiopsy state irritability scores at the clinical onset of invasive breast carcinoma.
The research findings regarding the role of psychiatric illness in breast cancer are not yet clear. This report investigates the differences between patients with invasive breast carcinoma (IBC) and patients with benign breast disease regarding the psychiatric history and the current prebiopsy psychopathology. The psychiatric history of 124 females, aged 70 or less, was evaluated by interview and the DSM-IV criteria were used to establish the diagnoses. The Present State Examination (PSE)-Index of Definition (ID)-CATEGO computer program was used to define current psychopathology. Known risk factors of breast cancer were included in the analyses. After biopsy, 59 patients had IBC and 65 had benign breast diseases. Multiple logistic regression analyses showed that low psychiatric history and low irritability were independent predictors of IBC regarding the DSM-IV and the PSE-ID-CATEGO, respectively. Low psychiatric history and low prebiopsy state irritability differentiates IBC patients from noncancer patients.


Dark matter RNA: an intelligent scaffold for the dynamic regulation of the nuclear information landscape.
Perhaps no other topic in contemporary genomics has inspired such diverse viewpoints as the 95+% of the genome, previously known as "junk DNA," that does not code for proteins. Here, we present a theory in which dark matter RNA plays a role in the generation of a landscape of spatial micro-domains coupled to the information signaling matrix of the nuclear landscape. Within and between these micro-domains, dark matter RNAs additionally function to tether RNA interacting proteins and complexes of many different types, and by doing so, allow for a higher performance of the various processes requiring them at ultra-fast rates. This improves signal to noise characteristics of RNA processing, trafficking, and epigenetic signaling, where competition and differential RNA binding among proteins drives the computational decisions inherent in regulatory events.


Inflammation and Coagulation as Mediators in the Relationships Between Religious Attendance and Functional Limitations in Older Adults.
The aim of this study was to examine inflammation and coagulation, which are positively linked to disability and inversely linked to increased religious attendance, as mediators in the cross-sectional relationships between religious attendance and functional status. Frequency of attendance and limitations in basic activities of daily living (ADLs), instrumental activities (IADLs), and mobility were assessed in 1,423 elders. More frequent attendance was associated with fewer ADL, IADL, and mobility limitations, and with lower levels of inflammation and coagulation including interleukin-6, soluble vascular cell adhesion molecule, and D-dimer. Inflammation and coagulation partially mediated the associations between attendance and function. Eight percent of the effect of attendance on ADL (p = .014), 5% of the effect on IADL (p = .003), and 8% of the effect on mobility (p = .001) limitations were due to inflammation and coagulation. Relationships between attendance and function may be due in part to lower levels of inflammation and coagulation among elders who attend services.


Effects of Work Environments and Occupational Fatigue on Care Left Undone in Rotating Shift Nurses.
This study aimed to examine the effects of work environments and occupational fatigue on care left undone in rotating shift nurses, and to identify the indirect (mediation) effect of work environments on care left undone through nurses' occupational fatigue in South Korean acute care hospitals. This study employed a cross-sectional design using an online survey to collect data from 488 rotating shift nurses of acute care hospitals in Korea between November and December 2018. A mobile schedule management application for shift nurses was used to advertise the study and to send a link to the online survey. The survey included questions on the nurses' work environment characteristics, care left undone activities, and the Korean version of the Occupational Fatigue Exhaustion/Recovery scale. Poisson regression was used to explore the relationships among work environments, occupational fatigue, and care left undone. Hayes' Model 4 and a bootstrapping analysis were used to identify the mediating effect of occupational fatigue on the relationship between work environments and care left undone. The average number of tasks left undone was 3.45 (SD = 2.19). The higher the acute and chronic fatigue levels noted among nurses, the higher were the occurrences of care left undone. Conversely, the higher the intershift recovery level, the lower were the occurrences of care left undone. The results showed a positive relationship between care left undone and overtime hours and the number of patients per nurse. Moreover, nurses' occupational fatigue mediated the relationship between work environments and care left undone. Night shifts per month and the number of consecutive days off had an indirect effect on care left undone through occupational fatigue. High levels of occupational fatigue and poor intershift recovery among nurses can lead to care left undone. Nurses' occupational fatigue mediates the effect of work environment on care left undone. It is crucial for healthcare administrators and leaders to develop policies and mandatory regulations to facilitate better working conditions for nurses, consequently reducing their occupational fatigue and decreasing the occurrence of care left undone in acute care hospitals.


Laparoscopic cholecystectomy without routine operative cholangiography does not result in significant problems related to retained stones.
This study investigated whether failure to identify common bile duct stones at laparoscopic cholecystectomy results in significant postoperative complications related to retained stones. We performed a retrospective analysis of the case notes of 377 consecutive patients undergoing laparoscopic cholecystectomy without routine operative cholangiography under a single surgeon in a district general hospital between 1995 and 1999. Highly selective preoperative endoscopic retrograde cholangiopancreatography (ERCP) was employed to identify and manage suspected bile duct stones in pancreatitis, jaundice, persistently elevated liver function tests, or a dilated common bile duct. Eighteen (4.8%) of 377 patients presented postoperatively with symptoms/signs suggesting biliary pathology. Two (0.5%) were confirmed to have retained duct stones/debris (ultrasound/ERCP); both recovered with conservative treatment. Only 1 patient of 274 (0.4%) without preoperative ERCP subsequently presented with a symptomatic retained stone, the other having been stented preoperatively. Highly selective preoperative ERCP without routine operative cholangiography is not associated with a significant increase in morbidity/mortality related to retained stones following laparoscopic cholecystectomy.


Mammalian phospholipid homeostasis: homeoviscous adaptation deconstructed by lipidomic data driven modelling.
One of the mostly widely cited theories of phospholipid homeostasis is the theory of homeoviscous adaptation (HVA). HVA states that cells maintain membrane order (frequently discussed in terms of membrane fluidity or viscosity) within tight conditions in response to environmental induced changes in membrane lipid composition. In this article we use data driven modelling to investigate membrane order, using methodology we previously developed to investigate another theory of phospholipid homeostasis, the intrinsic curvature hypothesis. A set of coarse-grain parameters emerge from our model which can be used to deconstruct the relative contribution of each component membrane phospholipid to net membrane order. Our results suggest, for the membranes in the mammalian cells we have studied, that a ratio control function can be used to model membrane order. Using asynchronous cell lines we quantify the relative contribution of around 130 lipid species to net membrane order, finding that around 16 of these phospholipid species have the greatest effect in vivo. Then using lipidomic data obtained from partially synchronised cultures of HeLa cells we are able to demonstrate that these same 16 lipid species drive the changes in membrane order observed around the cell cycle. Our findings in this study suggest, when compared with our previous work, that cells maintain both membrane order and membrane intrinsic curvature within tight conditions.


Does this patient have Clostridioides difficile infection? A systematic review and meta-analysis.
The clinical features and predictors of Clostridioides difficile infection overlap with many conditions. We performed a systematic review to evaluate the diagnostic utility of clinical features (clinical examination, risk factors, laboratory tests, and radiographic findings) associated with C. difficile. Systematic review and meta-analysis of diagnostic features for C. difficile. MEDLINE, EMBASE, CINAHL, and Cochrane databases were searched up to September 2021. Studies that reported clinical features of C. difficile, a valid reference standard test for confirming diagnosis of C. difficile, and a comparison among patients with a positive and negative test result. Adult and paediatric patients across diverse clinical settings. Sensitivity, specificity, likelihood ratios. Stool nucleic acid amplification tests, enzyme immunoassays, cell cytotoxicity assay, and stool toxigenic culture. Rational Clinical Examination Series and Quality Assessment of Diagnostic Accuracy Studies-2. Univariate and bivariate analyses. We screened 11 231 articles of which 40 were included, enabling the evaluation of 66 features for their diagnostic utility for C. difficile (10 clinical examination findings, 4 laboratory tests, 10 radiographic findings, prior exposure to 13 antibiotic types, and 29 clinical risk factors). Of the ten features identified on clinical examination, none were significantly clinically associated with increased likelihood of C. difficile infection. Some features that increased likelihood of C. difficile infection were stool leukocytes (LR+ 5.31, 95% CI 3.29-8.56) and hospital admission in the prior 3 months (LR+ 2.14, 95% CI 1.48-3.11). Several radiographic findings also strongly increased the likelihood of C. difficile infection like ascites (LR+ 2.91, 95% CI 1.89-4.49). There is limited utility of bedside clinical examination alone in detecting C. difficile infection. Accurate diagnosis of C. difficile infection requires thoughtful clinical assessment for interpretation of microbiologic testing in all suspected cases.


N-glycan profiling alterations of serum and immunoglobulin G in immune thrombocytopenia.
The glycosylation alterations of serum and IgG are involved in a variety of autoimmune and inflammatory diseases and have shown great potential in biomarker field. The diagnosis of immune thrombocytopenia (ITP) is exclusive. Our study aimed to discover the potential glyco-biomarkers for auxiliary diagnosis of ITP. The serum samples were obtained from 61 ITP patients and 35 healthy controls, and IgG samples were purified from 34 out of 61 ITP patients and 35 healthy controls. DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis (DSA-FACE) was used to analyze serum and IgG N-glycan profiling. 6 of 12 serum N-glycan peaks, 6 of 7 IgG N-glycan peaks, serum fucosylation, and IgG galactosylation were significantly different between ITP patients and healthy controls (p < 0.05). IgG peak 7 showed good diagnostic efficacy for discriminating ITP patients from healthy individuals (AUC 0.967). ITP patients with severe thrombocytopenia had a significantly lower serum fucosylation than ITP patients with mild and moderate thrombocytopenia (p < 0.05). Serum fucosylation and serum peak 5 were correlated with platelet counts in ITP patients with severe thrombocytopenia, and the absolute values of correlation coefficient were both over 0.5. The specific N-glycan patterns of serum and IgG were observed in ITP patients. IgG peak 7 was a potential biomarker for auxiliary diagnosis of ITP.


Effect of the glycosyltransferases on the capsular polysaccharide synthesis of Streptococcus suis serotype 2.
Streptococcus suis serotype 2 (S. suis 2) is a serious zoonotic pathogen causing septicemia and meningitis in piglets and humans. The capsular polysaccharide (CPS) is an essential virulence factor for S. suis 2 to infect the host. The synthesis of CPS repeating units involves multiple glycosyltransferases. In this study, four genes (cps2E, cps2G, cps2J and cps2L) encoding different glycosyltransferases involved in CPS synthesis were researched in S. suis 2. Four deletion mutants (Δcps2E, Δcps2G, Δcps2J and Δcps2L) with their CPS incomplete and their sialic acid content significantly decreased were constructed in S. suis 2 SC19. All these four mutant strains showed enhanced adhesion to Hep-2 cells and increased sensitivity to phagocytosis. Flow cytometric analysis also revealed that these four mutants were more susceptible to the attack by the complement system. In a mouse model of infection, the mutant strains were rapidly cleared by the immune system, compared with the wild-type strain. In summary, this study characterized four genes (cps2E, cps2G, cps2J and cps2L) involved in CPS synthesis of S. suis 2 SC19 and it revealed that these genes were all crucial for SC19 to invade and survive in the host.


The structure of an abequose - containing O-polysaccharide isolated from Pectobacterium aquaticum IFB5637.
Soft rot and blackleg diseases, caused by pectinolytic bacteria from the numerous species of Dickeya and Pectobacterium, pose a serious threat to the world potato production. Besides, infections triggered by these pectinolytic bacteria lead to huge economic losses in the cultivation of other crops, vegetables, and ornamentals. Strains belonging to the genus Pectobacterium tend to be isolated from various environments such as rotten or asymptomatic plants, weeds, soil or water. The main virulence factors of these phytopathogenic bacteria involve plant cell wall degrading enzymes (PCWDEs) i.e. pectinases, cellulases and proteases. Among accessory virulence factors, there is often lipopolysaccharide (LPS) listed. This constituent of the external part of bacterial cell wall contains lipid A, inner and outer core in addition to O-polysaccharide (OPS). LPS plays an important role in plant-microbe interactions, in particular during the first step of pathogen recognition. In this study we present the chemical structure of OPS of the first Pectobacterium aquaticum strain (IFB5637) isolated from water in Poland. The OPS consists of two common hexoses, such as mannose and glucose, as well as an abequose (3,6-dideoxy-d-xylo-hexose), the first 3,6-dideoxyhexose identified among the Pectobacteriaceae family: According to our best knowledge this is the first determined structure of the OPS of P. aquaticum.


[Adrenal tumors].
Adrenal tumors can be primary or secondary entities. Primary tumors are able to secrete hormones which may cause significant effects clinically. Typical tumor-related adrenal diseases are Conn's syndrome (hyperaldosteronism), Cushing's syndrome (hypercortisolism), and pheochromocytoma (catacholamine excess). Primary adrenal tumors are rarely malignant, but adrenocortical neoplasias show a relation between tumor size and rate of malignancy. Diagnostic methods for adrenal tumors include hormone tests and imaging. The first choice of treatment is surgical removal, today preferably by minimally invasive approaches.


Purification and properties of alanine dehydrogenase from Halobacterium salinarium.
1. L-Alanine dehydrogenase (L-alanine:NAD+ oxidoreductase (deaminating), EC 22.214.171.124) was purified about 500-fold from Halobacterium salinarium. 2. The enzyme appears to be homogeneous in polyacrylamide gel electrophoresis. The apparent molecular weight is about 60 000. 3. Activity and stability of the enzyme are largely affected by different salts. Full activity of the NADH-dependent reductive amination of pyruvate occurs at 4.3 M NaCl. This activation can be achieved also by KCl and several other salts instead of NaCl. 4. The NAD+-dependent oxidative deamination of L-alanine occurs only in the presence of high concentrations of KCl. This reaction is not stimulated by NaCl. The Km values for the substrates NADH, pyruvate and NH+4 are also salt dependent. 5. The thermal stability of the enzyme is considerably higher in the presence of high concentrations of NaCl than in the presence of KCl. 6. The enzyme is completely inactivated by the removal of salt. Full reactivation is achieved by addition of salt in the presence of 2-mercaptoethanol. Inactivation proceeds about ten times faster than reactivation. The inactivation after the withdrawal of salt and the reactivation following the readdition of salt show a characteristic hysteresis loop.


Zygoma and Mandibular Angle Reduction: Contouring Surgery to Correct the Square Face in Asians.
Changing the facial appearance with facial contouring surgery is popular, especially in East Asian countries where a square face is a common chief complaint. Mandibular angle reduction, malar reduction, genioplasty, and chin and body contouring surgery can be performed as independent or ancillary procedures during orthognathic surgery. Many techniques have been developed and different osteotomy designs have been proposed to enhance outcomes and minimize complication risks. Here, we review the surgical techniques and considerations for mandibular angle and malar reduction, the two most commonly performed contouring surgeries in East Asia to correct the square face.


Framework residue 71 is a major determinant of the position and conformation of the second hypervariable region in the VH domains of immunoglobulins.
Analysis of the immunoglobulins of known structure reveals systematic differences in the position and main-chain conformation of the second hypervariable region of the VH domain (H2). We show that the major determinant of the position of H2 is the size of the residue at site 71, a site that is in the conserved framework of the VH domain. It is likely that for about two thirds of the known VH sequences the size of the residue at this site is also a major determinant of the conformation of H2. This effect can override the predisposition of the sequence, as in the case of the H2 loop of J539, which is an exception to the rules relating sequence and conformation of short hairpin loops. Understanding the relationship between the residue at position 71 and the position and conformation of H2 has applications to the prediction and engineering of antigen-binding sites of immunoglobulins.


Sublethal doses of exogenous hydrogen peroxide prime human neutrophils to formyl peptide.
Hydrogen peroxide (H2O2) is an oxidative agent important in inflammation and ischemia. Neutrophils (PMNs) are a main source of H2O2 in the inflammatory focus. However, after recruitment into the inflammatory or ischemic zone of the heart, the PMN itself might serve as a target for exogenous H2O2. In the present work we found that PMNs are very resistant to the cytotoxic action of H2O2 (LD50 for PMNs is about 30-50 mM, whereas for endothelial cells it is about 200-300 microM). Unexpectedly, treatment of PMNs by H2O2 at a sublethal dose of 10 mM leads to a subsequent increase in the generation of superoxide anion in response to the chemoattractant peptide FMLP (twofold increase in O2- generation 30 min after treatment by H2O2 as compared with nontreated control cells). H2O2 itself does not induce O2- generation by PMNs. Therefore, any H2O2 that accumulated in the inflammatory or ischemic zone might alter the functional activity of PMNs and prime them to subsequent agonist activation.


[Endoscopic dilatation of ureteroileal stenosis in Bricker diversions. Apropos of 11 patients].
Eleven patients with stenosis of an uretero-ileal anastomosis following Bricker's operation underwent endoscopic dilatation of these stenoses via an inferior approach with Eder-Puestow's apparatus or Savary's dilators. The preliminary results were favourable in 7 patients with clinical, endoscopic and radiological improvement. An uretero-ileal drainage catheter was inserted in each case and was changed regularly after the operation. In one patient, a stone trapped in the anastomosis was able to be removed via the endoscopic procedure. No complications were observed. The two technical failures required surgical re-operation in one case and dilatation via a superior approach with an inflatable balloon catheter. This technique demonstrates the value of gastrointestinal endoscopy in the treatment of certain complications in patients with a urinary diversion using a segment of the intestinal tract.


Microscope-Based Augmented Reality with Intraoperative Computed Tomography-Based Navigation for Resection of Skull Base Meningiomas in Consecutive Series of 39 Patients.
The aim of surgery for skull base meningiomas is maximal resection with minimal damage to the involved cranial nerves and cerebral vessels; thus, implementation of technologies for improved orientation in the surgical field, such as neuronavigation and augmented reality (AR), is of interest. Included in the study were 39 consecutive patients (13 male, 26 female, mean age 64.08 ± 13.5 years) who underwent surgery for skull base meningiomas using microscope-based AR and automatic patient registration using intraoperative computed tomography (iCT). Most common were olfactory meningiomas (6), cavernous sinus (6) and clinoidal (6) meningiomas, meningiomas of the medial (5) and lateral (5) sphenoid wing and meningiomas of the sphenoidal plane (5), followed by suprasellar (4), falcine (1) and middle fossa (1) meningiomas. There were 26 patients (66.6%) who underwent gross total resection (GTR) of the meningioma. Automatic registration applying iCT resulted in high accuracy (target registration error, 0.82 ± 0.37 mm). The effective radiation dose of the registration iCT scans was 0.58 ± 1.05 mSv. AR facilitated orientation in the resection of skull base meningiomas with encasement of cerebral vessels and compression of the optic chiasm, as well as in reoperations, increasing surgeon comfort. No injuries to critical neurovascular structures occurred. Out of 35 patients who lived to follow-up, 33 could ambulate at their last presentation. A microscope-based AR facilitates surgical orientation for resection of skull base meningiomas. Registration accuracy is very high using automatic registration with intraoperative imaging.


In vitro cytotoxicity assessment of monocationic and dicationic pyridinium-based ionic liquids on HeLa, MCF-7, BGM and EA.hy926 cell lines.
Dicationic ionic liquids (ILs) generally possess higher thermal and electrochemical stability than the analogous monocationic ILs, which makes them more suitable for high-temperature applications as solvents for organic reactions, lubricants or stationary phase in gas chromatography. However, knowledge on dicationic IL cytotoxicity is still scarce. Here we explore the cytotoxicity of twelve mono- and dicationic pyridinium-based ILs on HeLa, MCF-7, BGM and EA.hy926 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell cycle arrest assays, apoptosis experiments and orange staining were carried out. The results showed that dicationic ILs are generally less cytotoxic than their monocationic counterparts. In monocationic ILs, cytotoxicity was stronger when they contain long alkyl chains, because of their higher lipophilicity. However, the full effect of the length of the linkage alkyl chain of dicationic ILs on cytotoxicity is not clear probably because the chain is "trapped" between both cationic moieties. IL cytotoxicity is highly dependent on the cell type, and HeLa cells exposed to [C12Pyr]Br die via apoptosis. The present study increases our knowledge of IL cytotoxicity on human and monkey cells and clarifies the cell death mechanism. The results suggest that dicationic ILs offer the potential to replace some monocationic ILs because of their lower cytotoxicity.


Biofeedback EMG alternative therapy for chronic low back pain: Study protocol of a pilot randomized controlled trial.
Chronic pain affects about 100 million U.S. adults, with chronic low back pain (CLBP) cited as the most prevalent type. Although there is evidence that non-pharmacological therapies seem to be effective for treating low back pain, there is limited evidence of the effectiveness of EMG biofeedback with non-specific chronic low back pain (NCLBP). The purpose of this study is, therefore, to determine the efficacy of a portable EMG biofeedback device on pain in individuals with CLBP. This study is a prospective, single-center, assessor-blind, two-arm, parallel randomized controlled trial to be conducted at Brigham and Women's Hospital, Boston, MA. Eighty patients with CLBP will be randomized in a 2:1 ratio to receive sEMG-BF (surface EMG biofeedback) or continued care (no intervention). All participants will receive treatment virtually weekly for 8 weeks. The primary outcome will be pain intensity (Brief Pain Inventory). The secondary outcomes will include pain interference (Brief Pain Inventory), disability (The Oswestry Disability Index (ODI)), anxiety and depression (Hospital Anxiety and Depression Scale). All outcomes will be assessed at baseline, immediately post-intervention, and 3 months follow-up. To our knowledge, this study will be the first powered randomized controlled trial to compare the effectiveness of a virtual sEMG-BF protocol specifically designed for CLBP. The outcome of the study may provide evidence for the effectiveness of biofeedback using digital therapeutics to relieve pain in individuals with CLBP. Clinical Trials Registry (http://ClinicalTrials.gov Identifier: NCT04607460). Registered on October 29, 2020.


Alkaline phosphatase in nasal secretion of cattle: biochemical and molecular characterisation.
Nasal secretion (NS) was investigated as a source of information regarding the mucosal and systemic immune status of cattle challenged by respiratory disease. A method for the collection of substantial volumes (~12 ml) of NS from cattle was developed to establish a reference range of analytes that are present in the NS of healthy cattle. Biochemical profiles of NS from a group of 38 healthy Holstein-Friesian cows revealed high alkaline phosphatase (AP) activity of up to 2392 IU/L. The character and source of the high activity of AP in bovine NS was investigated. Histochemical analysis confirmed the localization of the AP enzyme activity to epithelial cells and serous glands of the nasal respiratory mucosa. Analysis of mRNA levels from nasal mucosa by end point RT-PCR and PCR product sequencing confirmed that the AP was locally produced and is identical at the nucleotide level to the non-specific AP splice variant found in bovine liver, bone and kidney. Analysis by isoelectric focussing confirmed that AP was produced locally at a high level in nasal epithelium demonstrating that AP from nasal secretion and nasal mucosa had similar pI bands, though differing from those of the liver, kidney, bone and intestine, suggesting different post-translational modification (PTM) of AP in these tissues. A nasal isozyme of AP has been identified that is present at a high activity in NS, resulting from local production and showing distinctive PTM and may be active in NS as an anti-endotoxin mediator.


Use of terpene-based products, with and without anhydrous alcohol, as clearing agents in trichrome staining technique for intestinal protozoa.
BDH xylene substitute, a terpene-based product, and its mixture with anhydrous alcohol were found to be excellent replacements for xylene and carbol-xylene, respectively, in the trichrome staining technique applied to sodium acetate-acetic acid-Formalin-fixed fecal smears for detection of intestinal protozoa.


Visualization of growth signal transduction cascades in living cells with genetically encoded probes based on Förster resonance energy transfer.
Fluorescence probes based on the principle of Förster resonance energy transfer (FRET) have shed new light on our understanding of signal transduction cascades. Among them, unimolecular FRET probes containing fluorescence proteins are rapidly increasing in number because these genetically encoded probes can be easily loaded into living cells and allow simple acquisition of FRET images. We have developed probes for small GTPases, tyrosine kinases, serine-threonine kinases and phosphoinositides. Images obtained with these probes have revealed that membrane protrusions such as nascent lamellipodia or neurites provide an active signalling platform in the growth factor-stimulated cells.


Patient perspectives on facilitators and barriers to equitable engagement with digital CBT-I.
Digital cognitive behavioral therapy for insomnia has significant advantages for dissemination and scalability vs. in-person cognitive behavioral therapy for insomnia and is, therefore, well-positioned to be the first-line intervention for insomnia. However, only about half of patients remit following digital cognitive behavioral therapy for insomnia. Evidence suggests that treatment engagement is a critical driver of digital cognitive behavioral therapy for insomnia effectiveness, and barriers to engagement disproportionately impact people from under-resourced communities. For digital cognitive behavioral therapy for insomnia to be effective and scalable, we need to identify facilitators and barriers to digital cognitive behavioral therapy for insomnia engagement. Responses from an exit survey about participant experiences with digital cognitive behavioral therapy for insomnia were analyzed using mixed methods. The survey included quantitative measures of treatment engagement and a free-response item, which was coded and analyzed for themes using both inductive and deductive approaches. Analyses revealed five themes that were relevant for engagement: (1) digital person-to-person components, (2) type and extent of information, (3) user's sense of autonomy, (4) app functionality, and (5) importance of tailored content. Facilitators included enjoyment of digital cognitive behavioral therapy for insomnia elements, particularly those that enhanced a sense of connection (eg, a digital therapist avatar); content presented clearly and at an appropriate pace; and smooth app functionality. Barriers included desire for additional human support, perception that digital cognitive behavioral therapy for insomnia did not account for clinical complexities, and factors that interfered with implementation of key treatment recommendations. Many barriers and facilitators are influenced by health literacy and technological literacy. Those with access to health and technological literacy are better equipped to engage with digital cognitive behavioral therapy for insomnia. Recommendations for adaptations and enhancements are discussed.