Abnormally Small Neuromuscular Junctions in the Extraocular Muscles From Subjects With Idiopathic Nystagmus and Nystagmus Associated With Albinism.
Infantile nystagmus syndrome (INS) is often associated with abnormalities of axonal outgrowth and connectivity. To determine if this manifests in extraocular muscle innervation, specimens from children with idiopathic INS or INS and albinism were examined and compared to normal age-matched control extraocular muscles. Extraocular muscles removed during normal surgery on children with idiopathic INS or INS and albinism were immunostained for neuromuscular junctions, myofiber type, the immature form of the acetylcholine receptor, and brain-derived neurotrophic factor (BDNF) and compared to age-matched controls. Muscles from both the idiopathic INS and INS and albinism groups had neuromuscular junctions that were 35% to 71% smaller based on myofiber area and myofiber perimeter than found in age-matched controls, and this was seen on both fast and slow myosin heavy chain isoform-expressing myofibers (all P < 0.015). Muscles from subjects with INS and albinism showed a 7-fold increase in neuromuscular junction numbers on fast myofibers expressing the immature gamma subunit of the acetylcholine receptor. The extraocular muscles from both INS subgroups showed a significant increase in the number and size of slow myofibers compared to age-matched controls. Brain-derived neurotrophic factor was expressed in control muscle but was virtually absent in the INS muscles. These studies suggest that, relative to the final common pathway, INS is not the same between different patient etiologies. It should be possible to modulate these final common pathway abnormalities, via exogenous application of appropriate drugs, with the hope that this type of treatment may reduce the involuntary oscillatory movements in these children.


Carotid intima-media thickening and in vivo LDL oxidation in patients with essential hypertension.
Low density lipoproteins (LDL) from hypertensive patients are more prone to in vitro oxidation and undergo a more pronounced oxidation in vivo. Due to the pro-atherogenic activity of oxidatively modified LDL, the correlation between the carotid intima-media thickening (IMT) and the markers of in vivo LDL oxidation was investigated in hypertensive patients. A cross-sectional study on 101 normocholesterolemic patients with newly diagnosed and untreated essential hypertension was performed. The occurrence of in vivo LDL oxidation was evaluated by measuring the titers of autoantibodies against Cu(2+)-oxidised LDL (oxLDL) and malondialdehyde-derivatised LDL (MDA-LDL). The extent and degree of atherosclerosis and the IMT were measured by means of carotid and femoral ultrasonography with a duplex scanner equipped with a high resolution probe. We did not find significant correlations between in vivo LDL oxidation parameters and the extent of atherosclerotic lesion in the entire group of hypertensive patients. However, a significant direct correlation was detected between the carotid IMT and the titer of autoantibodies against both oxLDL and MDA-LDL in hypertensive patients without advanced atherosclerotic plaques. The results obtained support the hypothesis that enhanced LDL oxidation may be one of the pathophysiological events related to the formation and progression of early atherosclerotic lesions (IMT) in carotid arteries of hypertensive patients.


[Women with epilepsy planning pregnancy].
There are many important health issues for women with epilepsy, in particular for women of childbearing age. Recent surveys have shown that only a minority of such patients received information on important issues concerning pregnancy. Pre-pregnancy counselling should include information on interactions of antiepileptic drugs (AEDs) and oral contraceptives, risk of teratogenicity, use of folic acid, the importance of monotherapy with the lowest effective dosage of an AED, and the safety of breast feeding as well as other special aspects of epilepsy and pregnancy. Planned pregnancy and counselling before conception is crucial. With a multidisciplinary approach the majority of pregnancies will have a favourable outcome. The article addresses these issues and describes practical considerations for the counselling of women with epilepsy who are planning pregnancy.


Synaptic inputs and timing underlying the velocity tuning of direction-selective ganglion cells in rabbit retina.
There are two types of direction-selective ganglion cells (DSGCs) identified in the rabbit retina, which can be readily distinguished both morphologically and physiologically. The well characterized ON-OFF DSGCs respond to a broad range of image velocities whereas the less common ON DSGCs are tuned to slower image velocities. This study examined how the synaptic inputs shape the velocity tuning of DSGCs in an isolated preparation of the rabbit retina. The receptive-field properties were mapped by extracellular spike recordings and compared with the light-evoked excitatory and inhibitory synaptic conductances that were measured under voltage-clamp. The synaptic mechanisms underlying the generation of direction selectivity appear to be similar in both cell types in that preferred-direction image motion elicits a greater excitatory input and null-direction image motion elicits a greater inhibitory input. To examine the temporal tuning of the DSGCs, the cells were stimulated with either a grating drifted over the receptive-field centre at a range of velocities or with a light spot flickered at different temporal frequencies. Whereas the excitatory and inhibitory inputs to the ON-OFF DSGCs are relatively constant over a wide range of temporal frequencies, the ON DSGCs receive less excitation and more inhibition at higher temporal frequencies. Moreover, transient inhibition precedes sustained excitation in the ON DSGCs, leading to slowly activating, sustained spike responses. Consequently, at higher temporal frequencies, weaker excitation combines with fast-rising inhibition resulting in lower spike output.


30 Immunotherapy in advanced NSCLC-from the 'tsunami' of therapeutic knowledge to a clinical practice algorithm: results from an international expert panel meeting of the Italian Association of Thoracic Oncology (AIOT).
Although lung cancer remains the leading cause of death from cancer worldwide, the advent of immunotherapy is changing the survival of patients affected by non-small cell lung cancer (NSCLC). A multitude of clinical trials are evaluating different immune checkpoints inhibitors in this new field of thoracic oncology. At the beginning of the immunotherapy era, nivolumab, pembrolizumab and atezolizumab showed high efficacy in patients with advanced NSCLC in second-line setting, receiving approvals for clinical practice. Nivolumab and atezolizumab are approved independently from programmed death lig and 1 (PD-L1) expression, while pembrolizumab is currently approved only for patients with PD-L1 expression ≥1%. The role of PD-L1 expression acquired more interest considering first-line clinical trials, in which the role of immunotherapy as monotherapy was confirmed only for pembrolizumab in patients with PD-L1 expression ≥50%. These data were analysed in this paper, focusing on the implications in clinical practice and how to use them to an accurate clinical benefit of patients with advanced NSCLC. We report a review based on a MEDLINE/PubMed, searched for randomised phase 2/3 trials evaluating immune checkpoint inhibitors and NSCLC, that moved to an approval from Food and Drug Administration (FDA) and European Medicine Agency (EMA). The evidence discussed in this manuscript and the final therapeutic algorithm, coming out from an International Experts Panel Meeting of the Italian Association of Thoracic Oncology.


Extracapsular en bloc resection in pituitary adenoma surgery.
A pituitary pseudocapsule often contains tumor tissue and should be removed for radical resection. It can be used as a surgical plane for more radical resection of the tumor in many cases of pituitary adenomas. We evaluated the advantages and disadvantages of extracapsular en bloc capsulectomy. From 1992 until 2011, 1,089 treated patients were grouped according to the resection technique: en bloc capsulectomy, fragmented capsulectomy, or piecemeal resection. Their surgical and endocrinological outcomes and complications were evaluated. Extracapsular tumor resection was performed in 263 patients; en bloc capsulectomy in 94 patients and fragmented capsulectomy in 169, whereas piecemeal resection was performed in 826. Extracapsular resection was performed more frequently in prolactin- and thyroid-stimulating hormone-secreting tumors. Total resection was more frequently achieved in extracapsular resection and its chance was 100% when tumors were removed in an en bloc fashion. For the functioning pituitary adenomas, endocrinological remission was achieved in all patients whose tumors were removed in an en bloc fashion and there was no recurrence. Postoperative cerebrospinal fluid (CSF) rhinorrhea developed in 4.2 and 2.7% in the extracapsular resection group and the piecemeal resection groups, respectively. The chance of postoperative aggravation of pituitary function was not statistically different between groups. Extracapsular resection is critical for radical tumor resection and endocrinological remission. The removal of a pseudocapsule does not increase the risk of postoperative hypopituitarism nor postoperative CSF rhinorrhea.


Chronic physical illness, psychiatric disorder and disability in the workplace.
While agreement is growing that mental illness burdens the North American economy, how it impacts productivity--particularly compared to physical illness--is unclear. Hypothesizing that lost work days are only the tip of the iceberg, we also examined the association of mental and chronic physical illness with partial work days and days requiring extra effort to function. Data from 4225 employed individuals, aged 18-54, were analyzed. These were a subset of respondents to the Ontario Health Survey's Mental Health Supplement, a 1990/91 epidemiologic survey of households across Ontario, Canada. Psychiatric disorder was assessed using the University of Michigan' modification of WHO's Composite International Diagnostic Interview (UM-CIDI). Similar to US reports, professional/managerial groups had lower rates of affective and anxiety disorders and fewer disability days compared to the rest of the workforce. However, no single occupational group was consistently at greater risk for either physical or psychiatric problems. Even after accounting for sociodemographic characteristics and work conditions, mental and physical status had clear, but different, impacts on productivity. Physical conditions alone had a fairly constant effect across all types of disability days and were the largest contributor to total work day loss. They also significantly impacted partial and extra effort days but were far less important than conditions involving a mental disorder. Respondents with mental health problems, either alone or in combination with physical illnesses, appeared more likely to go to work but to require greater effort to function. WHO projects that mental illness will become the second most important cause of global disease burden in the next century. Our findings suggest that among working individuals, it affects productivity more subtly than does physical illness. However, with an estimated eight percent of Ontario's workforce experiencing more than two months annually of decreased productivity, it still incurs significant social and economic costs.


Revisiting the effects of powdered activated carbon on membrane fouling mitigation in an anaerobic membrane bioreactor by evaluating long-term impacts on the surface layer.
Two submerged anaerobic membrane bioreactors (AnMBRs) with and without powdered activated carbon (PAC) were studied to revisit the effect of PAC on membrane fouling performance by long-term operation when treating synthetic sewage. The results showed that PAC remained efficient for membrane fouling control after long-term operation (over 140 d), and it reduced the fouling rate at a hydraulic retention time of 8 h from 3.12 to 0.89 kPa/d. PAC mainly mitigated the membrane fouling by restraining the formation of a cake layer while generating a gel layer on the membrane surface, which was attributed to the PAC-induced microbial community change in mixed liquor and the membrane surface. Microbial community analysis indicated the genera Pseudomonas (26.5%) and Methanothrix (79.21%) were the predominant bacteria and archaea, respectively, in the gel layer, and this result is completely different from the presence of a high abundance of Levilinea (7.1%), Aminivibrio (4.9%) and Methanothrix (90.04%) in the cake layer on the membrane surface without PAC. The significant difference in the predominant microbes in the membrane surface layer was attributed to the reduced enrichment of Levilinea and Methanothrix with PAC addition.


On-road exposure to highway aerosols. 2. Exposures of aged, compromised rats.
Ambient particulate pollution is associated with adverse health effects in epidemiological studies of the elderly with cardiopulmonary diseases. We hypothesize that ultrafine particles (UFP) contribute to these effects, especially when they are freshly generated and occur at high number concentrations. Studies to determine adverse effects have been performed using laboratory-generated surrogates, diluted exhaust from stationary engines, or concentrated ambient UFPs. Methodological difficulties exist with such experiments, and questions remain about how well these particles model those found in ambient air. Freshly generated UFPs are present at high concentrations on highways and vehicle passengers are directly exposed to them. We wished to expose rats to these UFPs to test their potential to cause effects. Since such exposures have not been done before, one objective of our study was to demonstrate the feasibility of an on-road exposure study. Secondly, we wished to determine if there are significant exposure-related effects in aged, compromised rats. Old rats (21-mo F-344) were exposed directly on highways to either the aerosol (<1 microm)/gas phase, gas phase only, or filtered air using an on-road exposure system. Some rats were pretreated with a low dose of inhaled endotoxin or with instilled influenza virus to induce lung inflammation. The exposures in compartmentalized whole-body chambers consisted of 6-h driving periods on I-90 between Rochester and Buffalo once or 3 days in a row. Endpoints related to lung inflammation, inflammatory cell activation, and acute-phase responses were measured after exposure. The on-road exposure system did not affect measured endpoints in filtered air-exposed rats, indicating that it was well tolerated by them. We observed the expected increases in response (inflammation, inflammatory cell activation) to the priming agents. We also found a significant particle-associated increase in plasma endothelin-2, suggesting alterations in vascular endothelial cell activation. In addition, we observed main effects of particles related to the acute-phase response and inflammatory-cell activation. Interactions between on-road particles and the priming agents were also found. These results suggest that exposures to on-road particle mixtures have effects on the pulmonary and cardiovascular system in compromised, old rats. Furthermore, they demonstrate that on-road exposures are feasible and could be performed in future studies with more continuous particle exposures.


Hidden charge states in soft-x-ray laser-produced nanoplasmas revealed by fluorescence spectroscopy.
Highly charged ions are formed in the center of composite clusters by strong free-electron laser pulses and they emit fluorescence on a femtosecond time scale before competing recombination leads to neutralization of the nanoplasma core. In contrast to mass spectrometry that detects remnants of the interaction, fluorescence in the extreme ultraviolet spectral range provides fingerprints of transient states of high energy density matter. Spectra from clusters consisting of a xenon core and a surrounding argon shell show that a small fraction of the fluorescence signal comes from multiply charged xenon ions in the cluster core. Initially, these ions are as highly charged as the ions in the outer shells of pure xenon clusters with charge states up to at least 11+.


Vitamin D.
The vitamin D endocrine system plays an essential role in calcium homeostasis and bone metabolism, but research during the past two decades has revealed a diverse range of biological actions that include induction of cell differentiation, inhibition of cell growth, immunomodulation, and control of other hormonal systems. Vitamin D itself is a prohormone that is metabolically converted to the active metabolite, 1,25-dihydroxyvitamin D [1,25(OH)(2)D]. This vitamin D hormone activates its cellular receptor (vitamin D receptor or VDR), which alters the transcription rates of target genes responsible for the biological responses. This review focuses on several recent developments that extend our understanding of the complexities of vitamin D metabolism and actions: the final step in the activation of vitamin D, conversion of 25-hydroxyvitamin D to 1,25(OH)(2)D in renal proximal tubules, is now known to involve facilitated uptake and intracellular delivery of the precursor to 1alpha-hydroxylase. Emerging evidence using mice lacking the VDR and/or 1alpha-hydroxylase indicates both 1,25(OH)(2)D(3)-dependent and -independent actions of the VDR as well as VDR-dependent and -independent actions of 1,25(OH)(2)D(3). Thus the vitamin D system may involve more than a single receptor and ligand. The presence of 1alpha-hydroxylase in many target cells indicates autocrine/paracrine functions for 1,25(OH)(2)D(3) in the control of cell proliferation and differentiation. This local production of 1,25(OH)(2)D(3) is dependent on circulating precursor levels, providing a potential explanation for the association of vitamin D deficiency with various cancers and autoimmune diseases.


Stereo improves 3D shape discrimination even when rich monocular shape cues are available.
We measured the ability to discriminate 3D shapes across changes in viewpoint and illumination based on rich monocular 3D information and tested whether the addition of stereo information improves shape constancy. Stimuli were images of smoothly curved, random 3D objects. Objects were presented in three viewing conditions that provided different 3D information: shading-only, stereo-only, and combined shading and stereo. Observers performed shape discrimination judgments for sequentially presented objects that differed in orientation by rotation of 0°-60° in depth. We found that rotation in depth markedly impaired discrimination performance in all viewing conditions, as evidenced by reduced sensitivity (d') and increased bias toward judging same shapes as different. We also observed a consistent benefit from stereo, both in conditions with and without change in viewpoint. Results were similar for objects with purely Lambertian reflectance and shiny objects with a large specular component. Our results demonstrate that shape perception for random 3D objects is highly viewpoint-dependent and that stereo improves shape discrimination even when rich monocular shape cues are available.


Cold-induction of afadin in brown fat supports its thermogenic capacity.
The profound energy-expending nature of brown adipose tissue (BAT) thermogenesis makes it an attractive target tissue to combat obesity-associated metabolic disorders. While cold exposure is the strongest inducer of BAT activity, the temporal mechanisms tuning BAT adaptation during this activation process are incompletely understood. Here we show that the scaffold protein Afadin is dynamically regulated by cold in BAT, and participates in cold acclimation. Cold exposure acutely increases Afadin protein levels and its phosphorylation in BAT. Knockdown of Afadin in brown pre-adipocytes does not alter adipogenesis but restricts β3-adrenegic induction of thermogenic genes expression and HSL phosphorylation in mature brown adipocytes. Consistent with a defect in thermogenesis, an impaired cold tolerance was observed in fat-specific Afadin knockout mice. However, while Afadin depletion led to reduced Ucp1 mRNA induction by cold, stimulation of Ucp1 protein was conserved. Transcriptomic analysis revealed that fat-specific ablation of Afadin led to decreased functional enrichment of gene sets controlling essential metabolic functions at thermoneutrality in BAT, whereas it led to an altered reprogramming in response to cold, with enhanced enrichment of different pathways related to metabolism and remodeling. Collectively, we demonstrate a role for Afadin in supporting the adrenergic response in brown adipocytes and BAT function.


BRET-based effector membrane translocation assay monitors GPCR-promoted and endocytosis-mediated Gq activation at early endosomes.
G protein-coupled receptors (GPCRs) are gatekeepers of cellular homeostasis and the targets of a large proportion of drugs. In addition to their signaling activity at the plasma membrane, it has been proposed that their actions may result from translocation and activation of G proteins at endomembranes-namely endosomes. This could have a significant impact on our understanding of how signals from GPCR-targeting drugs are propagated within the cell. However, little is known about the mechanisms that drive G protein movement and activation in subcellular compartments. Using bioluminescence resonance energy transfer (BRET)-based effector membrane translocation assays, we dissected the mechanisms underlying endosomal Gq trafficking and activity following activation of Gq-coupled receptors, including the angiotensin II type 1, bradykinin B2, oxytocin, thromboxane A2 alpha isoform, and muscarinic acetylcholine M3 receptors. Our data reveal that GPCR-promoted activation of Gq at the plasma membrane induces its translocation to endosomes independently of β-arrestin engagement and receptor endocytosis. In contrast, Gq activity at endosomes was found to rely on both receptor endocytosis-dependent and -independent mechanisms. In addition to shedding light on the molecular processes controlling subcellular Gq signaling, our study provides a set of tools that will be generally applicable to the study of G protein translocation and activation at endosomes and other subcellular organelles, as well as the contribution of signal propagation to drug action.


Abdominal scar endometriosis: A case report and review of literature.
Endometriosis is defined as the presence of functioning endometrial tissue outside the uterine cavity. Abdominal wall or cutaneous endometriomas are quite uncommon with an incidence of less than 1%. Abdominal wall endometrioma can occur in a previous surgical scar, commonly following obstetrical and gynecological surgeries. Cutaneous endometriosis is difficult to diagnose because of its nonspecific symptoms and is often confused with other dermatological and surgical diseases thereby delaying the diagnosis and management. We are reporting a case of scar endometriosis at the site of previous cesarean scar involving the rectus sheath. The pathogenesis, diagnosis, and treatment of this rare condition are being discussed. Awareness of the clinical features and presentation of this rare condition is essential for timely diagnosis and management.


A 5-year follow-up study of Alfredson's heel-drop exercise programme in chronic midportion Achilles tendinopathy.
Eccentric exercises have the most evidence in conservative treatment of midportion Achilles tendinopathy. Although short-term studies show significant improvement, little is known of the long-term (>3 years) results. To evaluate the 5-year outcome of patients with chronic midportion Achilles tendinopathy treated with the classical Alfredson's heel-drop exercise programme. Part of a 5-year follow-up of a previously conducted randomised controlled trial. Methods 58 patients (70 tendons) were approached 5 years after the start of the heel-drop exercise programme according to Alfredson. At baseline and at 5-year follow-up, the validated Victorian Institute of Sports Assessment-Achilles (VISA-A) questionnaire score, pain status, alternative treatments received and ultrasonographic neovascularisation score were recorded. In 46 patients (58 tendons), the VISA-A score significantly increased from 49.2 at baseline to 83.6 after 5 years (p<0.001) and from the 1-year to 5-year follow-up from 75.0 to 83.4 (p<0.01). 39.7% of the patients were completely pain-free at follow-up and 48.3% had received one or more alternative treatments. The sagittal tendon thickness decreased from 8.05 mm (SD 2.1) at baseline to 7.50 mm (SD 1.6) at the 5-year follow-up (p=0.051). At 5-year follow-up, a significant increase of VISA-A score can be expected. After the 3-month Alfredson's heel-drop exercise programme, almost half of the patients had received other therapies. Although improvement of symptoms can be expected at long term, mild pain may remain.


Minimum variance optimal rate allocation for multiplexed H.264/AVC bitstreams.
Consider the problem of transmitting multiple video streams to fulfill a constant bandwidth constraint. The available bit budget needs to be distributed across the sequences in order to meet some optimality criteria. For example, one might want to minimize the average distortion or, alternatively, minimize the distortion variance, in order to keep almost constant quality among the encoded sequences. By working in the rho-domain, we propose a low-delay rate allocation scheme that, at each time instant, provides a closed form solution for either the aforementioned problems. We show that minimizing the distortion variance instead of the average distortion leads, for each of the multiplexed sequences, to a coding penalty less than 0.5 dB, in terms of average PSNR. In addition, our analysis provides an explicit relationship between model parameters and this loss. In order to smooth the distortion also along time, we accommodate a shared encoder buffer to compensate for rate fluctuations. Although the proposed scheme is general, and it can be adopted for any video and image coding standard, we provide experimental evidence by transcoding bitstreams encoded using the state-of-the-art H.264/AVC standard. The results of our simulations reveal that is it possible to achieve distortion smoothing both in time and across the sequences, without sacrificing coding efficiency.


Transfer collaborative filtering from multiple sources via consensus regularization.
Collaborative filtering is one of the most successful approaches to build recommendation systems. Recently, transfer learning has been applied to recommendation systems for incorporating information from external sources. However, most existing transfer collaborative filtering algorithms tend to transfer knowledge from one single source domain. Rich information is available in many source domains, which can better complement the data in the target domain than that from a single source. However, it is common to get inconsistent information from different sources. To this end, we proposed a TRA nsfer collaborative filtering framework from multiple sources via C onsE nsus R egularization, called TRACER for short. The TRACER framework handles the information inconsistency with a consensus regularization, which enforces the outputs from multiple sources to converge. In addition, our algorithm is to learn and transfer knowledge at the same time while most of the traditional transfer learning algorithms are to learn knowledge first and then transfer it. Experiments conducted on two real-world data sets validate the effectiveness of the proposed algorithm.


A qualitative analysis of STEM female's coping strategy under the COVID-19 pandemic.
The purpose of the research was to realize the STEM female's career coping under the pandemic. We conducted in-depth interviews with three STEM female engineers in Silicon Valley, California. After analyzing the research results, we found that: (1) In response to the impact of the pandemic, technology companies and female workers have demonstrated their ability to respond quickly; (2) While working from home, STEM females experienced five notable challenges, but also developed corresponding coping strategies; (3) Corporate systems and teamwork in the STEM fields utilize external resources to help female workers respond effectively to the pandemic.


Pediatric Laryngeal Granular Cell Tumor: Case Report and Literature Review.
Granular cell tumors (GCTs) are rare benign tumors that can occur in any part of the body. They are most commonly found in the head and neck region, especially the tongue. Laryngeal GCTs are rare, accounting for only 3% to 10% of all GCTs. This case report describes a 4-year-old boy with a laryngeal GCT. The patient presented with a history of hoarseness for 2 years. Stroboscopy revealed a large mass occupying the entire length of the left vocal cord. The mass was successfully removed by microlaryngeal surgery with laser ablation. The patient's symptoms resolved after surgery, and he had an uneventful recovery. This case highlights the importance of considering GCTs in the differential diagnosis of patients with hoarseness. Early diagnosis and treatment can lead to excellent outcomes.


Statistical learning in typically developing children: the role of age and speed of stimulus presentation.
It is possible that statistical learning (SL) plays a role in almost every mental activity. Indeed, research on SL has grown rapidly over recent decades in an effort to better understand perception and cognition. Yet, there remain gaps in our understanding of how SL operates, in particular with regard to its (im)mutability. Here, we investigated whether participant-related variables (such as age) and task-related variables (such as speed of stimulus presentation) affect visual statistical learning (VSL) in typically developing children. We tested 183 participants ranging in age from 5 to 12 years and compared three speeds of presentation (using stimulus durations of 800, 400 and 200 msecs). A multiple regression analysis revealed significant effects of both age and speed of presentation - after attention during familiarization and gender had been taken into consideration. VSL followed a developmental trajectory whereby learning increased with age. The amount of learning increased with longer presentation times (as shown by Turk-Browne, Jungé & Scholl, 2005, in their study of adults). There was no significant interaction between the two variables. These findings assist in elucidating the nature of statistical learning itself. While statistical learning can be observed in very young children and at remarkably fast presentation times, participant- and task-related variables do impact upon this type of learning. The findings reported here may serve to enhance our understanding of individual differences in the cognitive and perceptual processes that are thought to rely, at least in part, on SL (e.g. language processing and object recognition).


Cerebellar liponeurocytoma: immunohistochemical and ultrastructural study of a case.
The clinical, histopathological, and ultrastructural features of a cerebellar liponeurocytoma are reported. The tumor, a 3-cm mass localized in the right cerebellar hemisphere, was resected from a 61-year-old man clinically presenting with symptoms of intracranial hypertension. The lesion was composed of small, in some areas closely packed, medulloblastoma-like cells with prominent areas of lipidization phenomena. Moreover, mitoses, cellular atypia, and numerous vascular structures were focally observed. Glial and neuronal differentiation was immunohistochemically noted (glial fibrillary acidic protein, synaptophysin, neurofilaments, and neuron-specific enolase positivity). The p53 oncoprotein was detected in the majority of neoplastic cells and a moderate proliferation activity, evaluated by Mib-1 antibody, was focally appreciated. Ultrastructural study did not show evident neuritic processes, synapses, or dense core neuroendocrine granules. This cerebellar tumor previously called lipidized medulloblastoma and recently renamed cerebellar liponeurocytoma is considered an adult neoplasm with excellent prognosis histologically presenting prominent lipidized areas and, at the immunohistochemical and ultrastructural level, both glial and neuronal differentiation. The present study provides the first description of a less differentiated and histologically more aggressive form of this unusual tumor.


Evolution of male pregnancy associated with remodeling of canonical vertebrate immunity in seahorses and pipefishes.
A fundamental problem for the evolution of pregnancy, the most specialized form of parental investment among vertebrates, is the rejection of the nonself-embryo. Mammals achieve immunological tolerance by down-regulating both major histocompatibility complex pathways (MHC I and II). Although pregnancy has evolved multiple times independently among vertebrates, knowledge of associated immune system adjustments is restricted to mammals. All of them (except monotremata) display full internal pregnancy, making evolutionary reconstructions within the class mammalia meaningless. Here, we study the seahorse and pipefish family (syngnathids) that have evolved male pregnancy across a gradient from external oviparity to internal gestation. We assess how immunological tolerance is achieved by reconstruction of the immune gene repertoire in a comprehensive sample of 12 seahorse and pipefish genomes along the "male pregnancy" gradient together with expression patterns of key immune and pregnancy genes in reproductive tissues. We found that the evolution of pregnancy coincided with a modification of the adaptive immune system. Divergent genomic rearrangements of the MHC II pathway among fully pregnant species were identified in both genera of the syngnathids: The pipefishes (Syngnathus) displayed loss of several genes of the MHC II pathway while seahorses (Hippocampus) featured a highly divergent invariant chain (CD74). Our findings suggest that a trade-off between immunological tolerance and embryo rejection accompanied the evolution of unique male pregnancy. That pipefishes survive in an ocean of microbes without one arm of the adaptive immune defense suggests a high degree of immunological flexibility among vertebrates, which may advance our understanding of immune-deficiency diseases.


Insight into the relationship between forced vital capacity and transfer of the lungs for carbon monoxide in patients with idiopathic pulmonary fibrosis.
Forced vital capacity (FVC) is routinely used to quantify the severity and identify the progression of idiopathic pulmonary fibrosis (IPF). Although less commonly used, lung transfer of carbon monoxide (TLCO) correlates better with the severity of IPF than does FVC. Aiming at studying how FVC behaves in relation to TLCO, we analysed cross-sectional data from 430 IPF patients, of which 221 had at least 2 assessments (performed 2.4 ± 1.9 years apart) available for longitudinal analyses. Thresholds for identifying "abnormal" FVC and TLCO values were the statistically-defined lower limits of normal (LLN). For patients with longitudinal data, mean annual absolute declines of FVC and TLCO were calculated. The correlation between FVC and TLCO (%predicted) was weak (R2=0.21). FVC was "abnormal" (i.e., <LLN) in 38% of patients while 84% of patients had an "abnormal" TLCO. A large majority of the 268 patients with a "normal" FVC had nevertheless an "abnormal" TLCO (n = 209; 78%). On longitudinal analysis, 67/221 patients had an annual absolute decline in FVC≥5%, 34/221 had an annual absolute decline in TLCO ≥10%, and 22 had both. In IPF, a "normal" FVC should be viewed with caution as it is most often associated with an "abnormal" TLCO, a parameter that is strongly correlated with the morphological extent of the disease. Only 1/3 of the patients with a FVC-based progression criterion also had a TLCO progression criterion. In contrast, 2/3 of patients with a TLCO progression criterion also had a FVC progression criterion.


Study between axillary and rectal temperature measurements in children.
We compared axillary and rectal temperatures in 216 patients to assess the reliability of axillary temperature for determining fever in children under 14 years of age. Beyond the neonatal period, the mean rectal temperature was significantly higher than the axillary temperature. The sensitivity of axillary temperature in detecting fever was 87.5% among neonates but only 46% among older children. Axillary temperature correlated well with rectal temperature in neonates but not older children. There was no direct mathematical relationship between axillary and rectal temperature. Axillary temperature should be taken in neonates as it is less hazardous; rectal temperature should be used beyond this age.


Carnobacterium inhibens sp. nov., isolated from the intestine of Atlantic salmon (Salmo salar).
Strain K1T, isolated from the gastrointestinal tract of Atlantic salmon (Salmo salar), has the capacity to inhibit the growth of the fish pathogens Vibrio anguillarum and Aeromonas salmonicida. Strain K1T is a motile Gram-positive psychrophilic rod that lacks both catalase and oxidase, which does not grow on acetate containing media, but grows at pH 9 and in TSB with up to 6% sodium chloride content. Strain K1T is facultatively anaerobic and tryptone as a sole source of nutrient promotes growth. The most abundant cellular fatty acid of strain K1T is oleic acid (18:1cis9). Based on 16S rDNA sequence comparisons, it is suggested that strain K1T is phylogenetically closely related to C. alterfunditum. However, the unique phenotypic attributes of strain K1T suggest that it represents a new species. The name Carnobacterium inhibens is proposed, for which the type strain is K1T (= CCUG 31728T).


A comparative study on the utility of telehealth in the provision of rheumatology services to rural and northern communities.
There is a critical shortage of specialty rheumatology services in Canada. The impact is felt more in rural and northern regions than on urban areas of the country. In response to the need, this study was conducted to compare the satisfaction of referring physicians with rheumatology services through conventional visiting specialty clinics; email consults and regularly scheduled videoconference. Three rural communities of similar size and availability of physician services were assigned to one of the following means of providing outreach rheumatology services: visiting rheumatologist clinics, email access to rheumatologist and scheduled videoconference consults. A case based pre/post test, and post satisfaction questionnaire were administered to the primary care physicians in these communities. Patient outcomes, and physician ability and confidence in managing specific arthritis problems, were measured. Physicians responded positively to all methods of rheumatology service provision. The videoconference group were the most positive. The reasons were: immediate feedback to referring physician and patient, effective case based learning and transfer of knowledge, and improved accessibility. Videoconference is preferred to visiting clinics and email as a method for rheumatology services to rural/northern communities. It is cost effective and there is knowledge transfer between the rheumatologist and the referring physicians.


Role of pGlu-serpinin, a novel chromogranin A-derived peptide in inhibition of cell death.
Chromogranin A (CgA) is a member of the granin family of molecules found in secretory granules of endocrine and neuro-endocrine cells. Here, we have identified a new 23-mer CgA-derived peptide secreted from pituitary AtT-20 cells, which we named pyroGlu-serpinin (pGlu-serpinin). LC-MS studies of peptides in conditioned medium of AtT-20 cells indicate that pGlu-serpinin is derived from initial processing of mouse CgA at paired basic residues, Arg461-Arg462 and Arg433-Arg434, to yield a previously described 26 amino acid peptide, serpinin. Three amino acids are then cleaved from the N terminus of serpinin, yielding a peptide with an N-terminal glutamine, which is then subsequently pyroglutaminated. Immunocytochemistry showed co-localization of pGlu-serpinin with adrenocorticotropic hormone in secretory granules of AtT-20 cells, and it was released in an activity-dependent manner. Functional studies demonstrated that pGlu-serpinin was able to prevent radical oxygen species (hydrogen peroxide)-induced cell death of AtT-20 cells and cultured rat cerebral cortical neurons at a concentration of 1 and 10 nM, respectively. These data indicate that pGlu-serpinin has anti-apoptotic effects that may be important in neuroprotection of central nervous system neurons and pituitary cells. Furthermore, pGlu-serpinin added to the media of AtT-20 cells up-regulated the transcription of the serine protease inhibitor, protease nexin-1 (PN-1) mRNA. pGlu-serpinin's ability to increase levels of PN-1, a potent inhibitor of plasmin released during inflammatory processes causing cell death, may play a role in protecting cells under adverse pathophysiological conditions.


L. monocytogenes-induced actin assembly requires the actA gene product, a surface protein.
The intracellular pathogenic bacterium L. monocytogenes can spread directly from cell to cell without leaving the cytoplasm. The mechanism of this movement, generated through bacterially induced actin polymerization, is not understood. By analyzing an avirulent Tn917-lac mutant defective for actin polymerization, we have identified a bacterial component involved in this process. The transposon had inserted in actA, the second gene of an operon. Gene disruption of downstream genes and transformation of the mutant strain with actA showed that the actA gene encodes a surface protein necessary for bacterially induced actin assembly. Our results indicate that it is a 610 amino acid protein with an apparent molecular weight of 90 kd.


The ConsuMEER study: a randomised trial towards the effectiveness of protein-rich ready-made meals and protein-rich dairy products in increasing protein intake of community-dwelling older adults after switching from self-prepared meals towards ready-made meals.
The risk of undernutrition in older community-dwelling adults increases when they are no longer able to shop or cook themselves. Home-delivered products could then possibly prevent them from becoming undernourished. This single-blind randomised trial tested the effectiveness of home-delivered protein-rich ready-made meals and dairy products in reaching the recommended intake of 1·2 g protein/kg body weight (BW) per d and ≥25 g of protein per meal. Community-dwelling older adults (n 98; mean age 80·4 (sd 6·8) years) switched from self-prepared to home-delivered hot meals and dairy products for 28 d. The intervention group received ready-made meals and dairy products high in protein; the control group received products lower in protein. Dietary intake was measured at baseline, after 2 weeks (T1), and after 4 weeks (T2). Multilevel analyses (providing one combined outcome for T1 and T2) and logistic regressions were performed. Average baseline protein intake was 1·09 (se 0·05) g protein/kg BW per d in the intervention group and 0·99 (se 0·05) g protein/kg BW per d in the control group. During the trial, protein intake of the intervention group was 1·12 (se 0·05) g protein/kg BW per d compared with 0·87 (se 0·03) g protein/kg BW per d in the control group (between-group differences P < 0·05). More participants of the intervention group reached the threshold of ≥25 g protein at dinner compared with the control group (intervention T1: 84·8 %, T2: 88·4 % v. control T1: 42·9 %, T2: 40·5 %; P < 0·05), but not at breakfast and lunch. Our findings suggest that switching from self-prepared meals to ready-made meals carries the risk of a decreasing protein intake, unless extra attention is given to protein-rich choices.


Comparison of two simple stitches and modified Mason-Allen suture for medial meniscus posterior root tear based on the progression of meniscal posterior extrusion: A retrospective cohort study.
Purpose: Medial meniscus (MM) posterior root (PR) tear leads to severe MM posterior extrusion (PE), resulting in rapid knee cartilage degeneration. MMPR repairs are recommended to reduce MMPE, especially during knee flexion. However, the difference in MMPE between different repair techniques remains unknown. This study aimed to investigate preoperative and postoperative MMPE following several pullout repair techniques. We hypothesized that a technique using two simple stitches (TSS) would be more useful than FasT-Fix-dependent modified Mason-Allen suture (F-MMA) to prevent the progression of MMPE in knee extension. Methods: This retrospective study included 35 patients who underwent MMPR repair. To compare MMPE, patients were divided into two groups according to the use of F-MMA while grasping the posterior capsule and TSS without grasping it. Open magnetic resonance imaging was performed at 10° and 90° knee flexion preoperatively, and at 3 and 12 months postoperatively, and the MMPE of both groups was evaluated. Results: A significant difference was observed between preoperative and 3-month postoperative MMPE at 90° knee flexion in both groups (p < .01). A significant difference was observed in 3- and 12-month postoperative MMPE at 10° knee flexion between both groups (p = .04/.02), whereas no significant difference in the preoperative MMPE at 10° knee flexion was observed between them (p = .45). Conclusions: Both repairs were found to be useful to reduce MMPE in knee flexion. Further, F-MMA repair increased MMPE in knee extension, unlike TSS repair. These findings suggest that TSS might have more advantages for load distribution when standing or walking.


Inhibiting cortisol response accelerates recovery from a photic phase shift.
Jetlag results when a temporary loss of circadian entrainment alters phase relationships among internal rhythms and between an organism and the outside world. After a large shift in the light-dark (LD) cycle, rapid recovery of entrainment minimizes the negative effects of internal circadian disorganization. There is evidence in the existing literature for an activation of the hypothalamic-pituitary-adrenal (HPA) axis after a photic phase shift, and it is possible that the degree of HPA-axis response is a determining factor of reentrainment time. This study utilized a diurnal rodent, Octodon degus, to test the prediction that the alteration of cortisol levels would affect the reentrainment rate of circadian locomotor rhythms. In experiment 1, we examined the effects of decreased cortisol (using metyrapone, an 11beta-hydroxylase inhibitor) on the rate of running-wheel rhythm recovery after a 6-h photic phase advance. Metyrapone treatment significantly shortened the length of time it took animals to entrain to the new LD cycle (11.5% acceleration). In experiment 2, we examined the effects of increased cortisol on the rate of reentrainment after a 6-h photic phase advance. Increasing plasma cortisol levels increased the number of days (8%) animals took to reentrain running-wheel activity rhythms, but this effect did not reach significance. A third experiment replicated the results of experiment 1 and also demonstrated that suppression of HPA activity via dexamethasone injection is capable of accelerating reentrainment rates by approximately 33%. These studies provide support for an interaction between the stress axis and circadian rhythms in determining the rate of recovery from a phase shift of the LD cycle.


Gene mutations in primary ciliary dyskinesia related to otitis media.
Otitis media with effusion (OME) is the most common cause of conductive hearing loss in children and is strongly associated with primary ciliary dyskinesia (PCD). Approximately half of the children with PCD require otolaryngology care, posing a major problem in this population. Early diagnosis of PCD is critical in these patients to minimise the collateral damage related to OME. The current gold standard for PCD diagnosis requires determining ciliary structure defects by transmission electron microscopy (TEM) or clearly documenting ciliary dysfunction via digital high-speed video microscopy (DHSV). Although both techniques are useful for PCD diagnosis, they have limitations and need to be supported by new methodologies, including genetic analysis of genes related to PCD. In this article, we review classical and recently associated mutations related to ciliary alterations leading to PCD, which can be useful for early diagnosis of the disease and subsequent early management of OME.


[The immune activity of cytoflavine in the treatment of the diffuse septic peritonitis].
Influence of citoflavin on dynamics of functional condition of mitogen-induced immunocompetent blood cells at patients with widespread purulent peritonitis is studied. It is established that investigated immunocompetent cells have regulating effect on migration of neutrophil leukocytes at widespread purulent peritonitis during all postoperative period. PHA-activated mononuclear cells don't cause inhibition of migration of neutrophil granulocytes, observed in norm. At the same time the LPS-activated monocytes lead to migration strengthening of neutrophil granulocytes, in comparison with the data received in norm. Usage of citoflavin at patients with widespread purulent peritonitis renders corrective action on immunocompetent cells, changing their properties of regulation of migratory activity of neutrophil granulocytes. It is revealed that such action of citoflavin is connected with function restoration of mononuclear cells to inhibit migration of neutrophil leukocytes and with restoration of stimulation of migration of neutrophil leukocytes under the influence of the LPS-activated monocytes to the values received in norm. The revealed effects at use of citoflavin are most expressed by the 5th day of the postoperative period.


Effect of nitrous oxide use on long-term neurologic and neuropsychological outcome in patients who received temporary proximal artery occlusion during cerebral aneurysm clipping surgery.
The authors explored the relationship between nitrous oxide use and neurologic and neuropsychological outcome in a population of patients likely to experience intraoperative cerebral ischemia: those who had temporary cerebral arterial occlusion during aneurysm clipping surgery. A post hoc analysis of a subset of the data from the Intraoperative Hypothermia for Aneurysm Surgery Trial was conducted. Only subjects who had temporary arterial occlusion during surgery were included in the analysis. Metrics of short-term and long-term (i.e., 3 months after surgery) outcome were evaluated via both univariate and multivariate logistic regression analysis. An odds ratio (OR) greater than 1.0 denotes a worse outcome in patients receiving nitrous oxide. The authors evaluated 441 patients, of which 199 received nitrous oxide. Patients receiving nitrous oxide had a greater risk of delayed ischemic neurologic deficits (i.e., the clinical manifestation of vasospasm) (OR, 1.78, 95% confidence interval [CI], 1.08-2.95; P = 0.025). However, at 3 months after surgery, there was no difference in any metric of gross neurologic outcome: Glasgow Outcome Score (OR, 0.67; CI, 0.44-1.03; P = 0.065), Rankin Score (OR, 0.74; CI, 0.47-1.16; P = 0.192), National Institutes of Health Stroke Scale (OR, 1.02; CI, 0.66-1.56; P = 0.937), or Barthel Index (OR, 0.69; CI, 0.38-1.25; P = 0.22). The risk of impairment on at least one test of neuropsychological function was reduced in those who received nitrous oxide (OR, 0.56; CI, 0.36-0.89; P = 0.013). In this patient population, use of nitrous oxide was associated with an increased risk for the development of delayed ischemic neurologic deficits; however, there was no evidence of detriment to long-term gross neurologic or neuropsychological outcome.


Mediterranean diet and survival among patients with coronary heart disease in Greece.
The Mediterranean diet has been hypothesized to reduce fatality among patients with coronary heart disease. We examined the association between the degree of adherence to the traditional Mediterranean diet and survival of persons with diagnosed coronary heart disease at enrollment, in a population-based prospective investigation of 1302 Greek men and women, who were followed up for an average of 3.78 years (the European Prospective Investigation Into Cancer and Nutrition cohort). Information on usual dietary intakes during the year preceding enrollment was recorded through a validated food frequency questionnaire. Adherence to the Mediterranean diet was assessed by a 10-unit Mediterranean diet score that incorporates the salient characteristics of this diet. Proportional hazards regression was used to assess the relation of overall degree of adherence to the Mediterranean diet with mortality overall or by cause (cardiac vs noncardiac). Higher adherence to the Mediterranean diet by 2 units was associated with a 27% lower mortality rate among persons with prevalent coronary heart disease at enrollment (total deaths, 131; adjusted mortality ratio, 0.73; 95% confidence interval, 0.58-0.93). The reduced mortality was more evident and amounted to 31% (total deaths, 85; adjusted mortality ratio, 0.69; 95% confidence interval, 0.52-0.93) when only cardiac deaths were considered as the relevant outcome. Associations between individual food groups contributing to the Mediterranean diet score and mortality were generally not significant. Greater adherence to the traditional Mediterranean diet is associated with a significant reduction in mortality among individuals diagnosed as having coronary heart disease.


Evidence synthesis, practice guidelines and real-world prescriptions of new generation antidepressants in the treatment of depression: a protocol for cumulative network meta-analyses and meta-epidemiological study.
Depressive disorders are the most common, burdensome and costly mental disorders. Their treatments have developed through the past decades and we now have more than a dozen new generation antidepressants, while a series of guidelines have been published to provide recommendations over the years. However, there still may exist important gaps in this evidence synthesis and implementation process. Systematic reviews may not have been conducted in the most unbiased, informative and timely manners; guidelines may not have reflected the most up-to-date evidence; clinicians may not have changed their clinical decision-makings in accordance with the relevant evidence. The aim of this study is to examine the gaps between the ideally synthesised evidence, guideline recommendations and real-world clinical practices in the prescription of new generation antidepressants for major depression through the past three decades. We will conduct cumulative network meta-analyses (cNMAs) based on the comprehensive systematic review which has identified published and unpublished head-to-head randomised controlled trials comparing the following antidepressants in the acute phase treatment of major depression: agomelatine, amitriptyline, bupropion, citalopram, clomipramine, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, trazodone, venlafaxine, vilazodone and vortioxetine. The primary outcomes will be the proportions of patients who responded (efficacy) and who withdrew from treatment for any reasons (acceptability). We will conduct a random effects cNMA to synthesise evidence and obtain a comprehensive ranking of all new generation antidepressants based on their surface under the cumulative ranking curves. We will identify series of international clinical practice guidelines for the treatment of major depression of adults and summarise their recommendations. We will estimate real-world prescription patterns of antidepressants in the nationally representative samples in USA in the Medical Expenditure Panel Survey. We will compare and evaluate the gaps between the rankings according to cNMAs conducted at 5-year intervals between 1990 and 2015, recommendations in guidelines published in the ensuing 5 years and actual practices thereafter. This review does not require ethical approval. We will disseminate our findings through publications in peer-reviewed journals and presentations at conferences. UMIN000031898.


Risk of Anterior Cruciate Ligament Injury in Athletes on Synthetic Playing Surfaces: A Systematic Review.
The effect of synthetic playing surfaces on the risk of injury in athletes is frequently debated in the orthopaedic literature. Biomechanical studies have identified increased frictional force at the shoe-surface interface, theoretically increasing the risk of injury relative to natural grass. This increase in frictional force is potentially relevant for the risk of anterior cruciate ligament (ACL) rupture, where noncontact mechanisms are frequent. However, clinical studies examining this issue have shown mixed results. The purpose of this study was to systematically review the available literature on risk of ACL rupture on natural grass versus artificial turf. We hypothesized that the risk of ACL rupture on synthetic playing surfaces would not be higher than that of natural grass playing surfaces. Systematic review. A systematic keyword search was performed of OVID, EMBASE, the Cochrane Library of Systematic Reviews, and the PROSPERO International Prospective Register of Systematic Reviews. Candidate articles were included if they reported the risk ratio of ACL rupture on natural grass versus synthetic playing surfaces, were of level 3 evidence or better, and included only ACL injuries sustained during organized athletic events. Exclusion criteria included a study with non-field-related sports and the use of historical cohorts for calculating risk ratios. A total of 10 studies with 963 ACL injuries met criteria for inclusion, all of which reported on soccer and football cohorts. Among these, 4 studies (753 ACL injuries) found an increased risk of ACL injury on artificial playing surfaces. All 4 of these articles were conducted using American football cohorts, and they included both earlier-generation surfaces (AstroTurf) and modern, 3rd-generation surfaces. Only 1 study in football players found a reduced risk of ACL injury on synthetic playing surfaces. No soccer cohort found an increased risk of ACL injury on synthetic surfaces. High-quality studies support an increased rate of ACL injury on synthetic playing surfaces in football, but there is no apparent increased risk in soccer. Further study is needed to clarify the reason for this apparent discrepancy.


Inlet protein aggregation: a new mechanism for lubricating film formation with model synovial fluids.
This paper reports a fundamental study of lubricant film formation with model synovial fluid components (proteins) and bovine serum (BS). The objective was to investigate the role of proteins in the lubrication process. Film thickness was measured by optical interferometry in a ball-on-disc device (mean speed range of 2-60 mm/s). A commercial cobalt-chromium (CoCrMo) metal femoral head was used as the stationary component. The results for BS showed complex time-dependent behaviour, which was not representative of a simple fluid. After a few minutes sliding BS formed a thin adherent film of 10-20 nm, which was attributed to protein absorbance at the surface. This layer was augmented by a hydrodynamic film, which often increased at slow speeds. At the end of the test deposited surface layers of 20-50 nm were measured. Imaging of the contact showed that at slow speeds an apparent 'phase boundary' formed in the inlet just in front of the Hertzian zone. This was associated with the formation of a reservoir of high-viscosity material that periodically moved through the contact forming a much thicker film. The study shows that proteins play an important role in the film-forming process and current lubrication models do not capture these mechanisms.


Colistin: new lessons on an old antibiotic.
Colistin has been re-introduced into clinical practice for the treatment of carbapenem-resistant Gram-negative bacteria. Studies in the last decade attempted to reconstruct the path that present-day medications undergo prior to clinical use. In this review, we summarize the results of recent clinical studies. Colistin was associated with lower mortality than no effective treatment and higher unadjusted mortality than β-lactams in non-randomized clinical studies. However, it was administered to sicker patients with carabapenem-resistant bacteria. Overall, nephrotoxicity rates were not higher with colistin in these studies, and colistin-induced nephrotoxicity is reversible in most patients. The emergence of colistin resistance has been described in high-use settings. Synergy with carbapenem, rifampin and other antibiotics has been reported in vitro. Randomized controlled trials are ongoing or in planning to assess this and other aspects of colistin use in clinical practice.


Steady-state kinetics of peroxidation of 2-chloro-10-(3-dimethylaminopropyl)-phenothiazine catalyzed by horseradish peroxidase
The steady-state kinetics of peroxidation of 2-chloro-10-(3-dimethylaminopropyl)-phenothiazine (Aminazine) catalyzed by horseradish peroxidase was studied. Aminazine was shown to be a substrate of peroxidase which is oxidized with a slow rate. The values of the catalytic constant (kcat) and Km were measured within the pH range from 4.5 to 7.0. In the presence of Aminazine, there was an increase in the rate of peroxidation of potassium ferrocyanide. Binding of an activator to the peroxidase active center caused an increase in the enzyme affinity for ferrocyanide, although had no effect on the kcat value within the pH range from 5 to 7.


Organic amendments and control of foot rot of Piper betle caused by Phytophthora parasitica var. piperina.
Experiments have been performed to control foot rot of Piper betle by organic amendments and antagonists in soil. Soil amended with corn straw gave best control. Corn straw supplemented with nitrogen (NH4NO3) gave still better control. The effect of different antagonists growing on corn-straw and til (Sesamum indicum) oil cake amendments showed that Trichoderma viride gave best control. Aspergillus terreus failed to control the disease although it showed great antifungal activity under controlled condition in Petri dishes.


Sterically stabilized liposomes: improvements in pharmacokinetics and antitumor therapeutic efficacy.
The results obtained in this study establish that liposome formulations incorporating a synthetic polyethylene glycol-derivatized phospholipid have a pronounced effect on liposome tissue distribution and can produce a large increase in the pharmacological efficacy of encapsulated antitumor drugs. This effect is substantially greater than that observed previously with conventional liposomes and is associated with a more than 5-fold prolongation of liposome circulation time in blood, a marked decrease in uptake by tissues such as liver and spleen, and a corresponding increased accumulation in implanted tumors. These and other properties described here have expanded considerably the prospects of liposomes as an effective carrier system for a variety of pharmacologically active macromolecules.


Urinary continence and quality of life in the first year after radical perineal prostatectomy.
We attempt to characterize the return of urinary continence and urinary domain related quality of life objectively after radical perineal prostatectomy (RPP). A total of 92 RPP candidates were prospectively enrolled in a quality of life (QOL) survey using a validated assessment tool and evaluated before surgery, and then after surgery at 1 month and subsequent 3-month intervals. The time to regain continence based on 3 different definitions and the time to recover baseline urinary domain related QOL was calculated. Median time to regain continence after RPP ranged from 3.0 to 3.3 months depending on the definition of continence. Median time for patients to regain continence depending on age (younger than 55, 55 to 64 and older than 64) and medical comorbidities (none, 1 and 2 or more) varied between 1.4 +/- 0.3, 3.0 +/- 0.9 and 3.3 +/- 0.4 months, respectively (p = 0.028), and 1.4 +/- 0.2, 3.3 +/- 0.2 and 3.5 +/- 2.6 months, respectively (p = 0.009). Twelve months after RPP 84%, 66% and 82% of patients regained individual baseline urinary summary, function and bother scores, respectively. Postoperative radiation (XRT) represented the only independent predictor of the time to recover baseline urinary domain summary scores in a multivariate analysis (p = 0.042) with a median delay in the XRT (10 patients) and nonXRT group (82 patients) of 8.0 and 6.7 months, respectively. Based on self-reported questionnaire data, a majority of patients regain urinary continence and urinary domain related QOL within 12 months after RPP. The time course of recovery from radical prostatectomy represents an important outcome criterion that should be shared with patients considering treatment options.


Donor risk factors for graft failure in a 20-year study of penetrating keratoplasty.
To determine donor risk factors for graft failure and late endothelial failure (LEF) 20 years after penetrating keratoplasty (PK). Prospective, observational study of 500 consecutive PKs performed by one surgeon. After excluding eyes undergoing second grafts, fellow eyes of bilateral cases, and patients who withdrew research authorization, 388 eyes (388 patients) were available for analysis. At specific intervals during 20 years of follow-up after PK, the central corneal endothelium was analyzed by specular microscopy and risk factors for graft failure and LEF were determined. The 41 grafts examined at 20 years represented 22% of the available clear grafts. Mean (SD) donor endothelial cell loss since the preoperative examination was 74% (9%), with no change in endothelial cell density between 15 and 20 years (P = .93; 36 eyes). Eighty-three grafts were known to have failed, of which 26 were because of LEF. Transplant recipients with a diagnosis of keratoconus had a lower risk of graft failure (P = .03) and LEF (P < or = .03) compared with those with endothelial dysfunction. Neither the method (McCarey-Kaufman or K-Sol media [n = 275] or organ culture [n = 113]) nor the length of donor preservation was associated with graft failure or LEF. Lower preoperative endothelial cell density (P = .02) and higher endothelial cell loss at 2 months (P = .004) increased the risk of LEF for a recipient diagnosis of endothelial dysfunction but not keratoconus. Recipient diagnosis is a risk factor for graft failure. The length of corneal preservation is not associated with graft failure or with LEF, but these results should be confirmed in a study in which donor corneas are preserved using current methods and with more complete follow-up.


Exercise and smoking habits in patients with and without low back and leg pain.
The exercise and smoking habits of low back or leg pain sufferers vs. persons not having low back or leg pain are compared. The type, frequency and length of exercise is determined from a study of 576 low back or leg pain sufferers compared to 50 persons who state they are symptomatic. The same was done for smoking habits. Thirty-three percent of low back or leg pain sufferers smoked as compared to 14% of those without pain. Forty-seven percent of low back or leg pain sufferers as compared to 86% of non-sufferers exercised regularly. The level of physical activity and general exercise have been found to improve strength, mobility and endurance; this might prevent future back injury. Our study is to determine differences in the exercise habits of persons with low back and/or leg pain vs. those who do not have pain, with the intention being to see if pain sufferers exercise less.


Effects of combined training with breathing resistance and sustained physical exertion to improve endurance capacity and respiratory muscle function in healthy young adults.
[Purpose] In this study, combined training with breathing resistance and sustained physical exertion was carried out to evaluate its physiological effects and its effect on improve endurance capacity. [Subjects and Methods] The subjects were nine healthy adults (mean age 20.4, SD ± 1.7 years). The combined training group (n = 5) carried out 6 weeks of combined training using a cycle ergometer, with exercise load tests and respiratory function tests performed before and after the training. The results of the training were compared to a control group (n = 4) that only performed the cycling exercise without the combined training with breathing resistance. [Results] In the combined training group, ventilatory threshold, maximal load of the cycle ergometer in exercise load tests, and maximal voluntary ventilation increased after training. These increases after training were all significant, but none of these variables changed significantly in the control group. [Conclusion] The results imply that in comparison to conventional training methods, combined training with breathing resistance and sustained physical exertion is beneficial for increasing endurance capacity and respiratory muscle function. This result provides important information regarding the effects of the new training method for improving endurance capacity.


Cereal-based biorefinery development: utilisation of wheat milling by-products for the production of succinic acid.
A novel wheat-based bioprocess for the production of a nutrient-complete feedstock for the fermentative succinic acid production by Actinobacillus succinogenes has been developed. Wheat was fractionated into bran, middlings and flour. The bran fraction, which would normally be a waste product of the wheat milling industry, was used as the sole medium in two solid-state fermentations (SSF) of Aspergillus awamori and Aspergillus oryzae that produce enzyme complexes rich in amylolytic and proteolytic enzymes, respectively. The resulting fermentation solids were then used as crude enzyme sources, by adding directly to an aqueous suspension of milled bran and middlings fractions (wheat flour milling by-products) to generate a hydrolysate containing over 95g/L glucose, 25g/L maltose and 300mg/L free amino nitrogen (FAN). This hydrolysate was then used as the sole medium for A. succinogenes fermentations, which led to the production of 50.6g/L succinic acid. Supplementation of the medium with yeast extract did not significantly improve succinic acid production though increasing the inoculum concentration to 20% did result in the production of 62.1g/L succinic acid. Results indicated that A. succinogenes cells were able to utilise glucose and maltose in the wheat hydrolysate for cell growth and succinic acid production. The proposed process could be potentially integrated into a wheat-milling process to upgrade the wheat flour milling by-products (WFMB) into succinic acid, one of the future platform chemicals of a sustainable chemical industry.


Factors affecting the maternal-foetal relationship.
Mother's attachment to her unborn child has a strong impact on a pregnant woman's attitude towards her health, postnatal attachment, and the child's physical and emotional growth. The purpose of our study was to identify the factors that impact the maternal-foetal relationship. The study was conducted at the Centre of Obstetrics and Gynaecology of the tertiary-level Vilnius University Hospital Santaros Klinikos in Vilnius, Lithuania. An original questionnaire of nine parts was developed that the questionnaire included information on demographical data, gynaecological and obstetrical history, a relationship assessment scale, the index of happiness, an antenatal depression risk questionnaire, and the Maternal-Antenatal Attachment Scale. The study included 388 pregnant women. It was found that the level of education, obstetrical issues during pregnancy, and the risk of postnatal depression negatively impacted the maternal-foetal relationship (p < 0.05). Mothers who were elder in family birth order, also those whose pregnancy was of a longer duration, who had a better-quality romantic relationship with partner, and whose socioeconomic fulfilment was higher were all found to have a better quality of maternal-foetal bonding (p < 0.05). The early recognition of low attachment and right application of various means of psychologic intervention might improve the quality of pregnancy, maternity, and childhood.


Determination of sialic acids in milks and milk-based products.
Sialic acids are becoming recognized as important components of milk-based products for infants and young children. As such, many companies now label the sialic acid content of their products. To control the labeling, suitable methods are required for this analysis. The objective of this work was to set up a rapid and sensitive method for the determination of the two most commonly occurring sialic acids, N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc), using high-performance liquid chromatography (HPLC). The sialic acids were released from their parent oligosaccharides, glycoproteins, or glycolipids by mild acid hydrolysis using formic acid. They were then derivatized using 1,2-diamino-4,5-methylenedioxybenzene (DMB) and subsequently separated on a Zorbax SB-Aq Rapid Resolution column in less than 2 min. The method developed was validated on various milk-based products and ingredients containing sialic acid at levels from 0.3 to 900 mg/100 g. Spiking experiments indicate that the sialic acid recoveries ranged from 87% to 108%. The expanded measurement uncertainty was typically below 15% for Neu5Gc and typically below 10% for Neu5Ac or the sum of the sialic acids, with a few exceptions. The proposed method is fast, specific, and easy to set up for compliance analysis in a routine laboratory.


Pineal Tumors: clinical diagnosis, with special emphasis on the significance of pineal calcification.
The clinical presentations, findings of neuroradiological examinations, laboratory findings, pathological diagnoses, methods of treatment, and results of follow-up of 43 cases of pineal tumor collected at the Nagoya University Hospital from 1958 to 1979 are reviewed. The definitions of calcification of the pineal body and of pineal tumor are given. There is a significant difference in the incidence of calcification of the pineal body between pineal teratomas and pineal germinomas. Although there is a 100% rate of calcification of the pineal body in cases of pineal germinoma, the rate is very low in cases of pineal teratoma; calcification appears in only a small percentage of the cases of teratoma mixed with germinoma or embryonal carcinoma, or both. In male patients with suprasellar germinoma, there is a high frequency of an associated pineal calcification. No pineal calcification is seen in cases of basal ganglia germinoma. The computed tomographic (CT) findings of pineal teratoma and germinoma are characteristic. CT scanning is superior for early diagnosis of suprasellar and basal ganglia germinomas.


Mediation of a corticosterone-induced reproductive conflict.
Current research in birds suggests that a conflict should exist during reproduction for the role of the glucocorticoid corticosterone (CORT). While elevated levels have been correlated with the increased energetic demand of raising offspring, elevated CORT levels have traditionally been implicated in reproductive abandonment. We examined the relationship between CORT and nest desertion in breeding wild female European starlings (Sturnus vulgaris) incorporating analyses of both total circulating levels and 'free', unbound CORT through analysis of corticosteroid-binding globulin (CBG). Free baseline CORT levels of nest-abandoning birds were significantly higher than nonabandoning birds within each stage, with chick-rearing birds exhibiting the highest free baseline CORT levels, while concurrently remaining the most resistant stage to nest desertion. Elevated free baseline CORT levels in chick-rearing birds were not due to increased total CORT secretion, but rather to a decrease in CBG levels. Overall, our results suggest that CORT and CBG interact to play a role in mediating the increased energetic demand of offspring, while minimizing the chances of nest desertion, thereby alleviating any potential behavioral conflict for CORT during reproduction. Furthermore, these results demonstrate that the traditional view of the role of CORT during reproduction is much more complex than previously appreciated. Together with mounting evidence, we suggest that elevated corticosteroid levels are an inherent and necessary part of reproduction in nonmammalian tetrapods.


A collaborative pastoral care and counseling supervisory model.
Presents a collaborative pastoral care and counseling supervisory model based on constructivism and attachment theories. Addresses issues concerning cognition, learning theory, and anxiety. Identifies the stages in the supervisory process. Discusses ways in which cognitive, emotional, and social development are linked to attachment theory and places this in the context of supervision in pastoral counseling. Reflects on the theological relevance of attachment theory utilizing the biblical parable of the prodigal son.


Mobile phone tools for field-based health care workers in low-income countries.
In low-income regions, mobile phone-based tools can improve the scope and efficiency of field health workers. They can also address challenges in monitoring and supervising a large number of geographically distributed health workers. Several tools have been built and deployed in the field, but little comparison has been done to help understand their effectiveness. This is largely because no framework exists in which to analyze the different ways in which the tools help strengthen existing health systems. In this article we highlight 6 key functions that health systems currently perform where mobile tools can provide the most benefit. Using these 6 health system functions, we compare existing applications for community health workers, an important class of field health workers who use these technologies, and discuss common challenges and lessons learned about deploying mobile tools.


Haemodynamics and myocardial oxygen consumption during isoflurane (forane) anaesthesia in geriatric patients.
The influence of isoflurane on haemodynamics and myocardial oxygen consumption was examined in seven geriatric patients under conditions of controlled ventilation and a normal arterial carbon dioxide tension. During isoflurane/nitrous oxide in oxygen anaesthesia (0.75 and 1.5 vol% inspired isoflurane) no significant changes occurred in cardiac output, stroke volume, heart rate, central venous and pulmonary artery pressure. Arterial pressure decreased, as did total peripheral resistance. A reduction in left ventricular maximum dp/dt (18-39%) was, at least in part, a result of changes in loading conditions. Total body (CaO2--CVO2) and base excess values remained within the normal range. We consider that the oxygen supply was adequate to meet the metabolic demands of the body as a whole. Myocardial oxygen consumption decreased by 25% during 0.75 vol% inspired isoflurane and by 43.5% with deepening of anaesthesia (1.5 vol% isoflurane).


Immunomodulatory innate defence regulator (IDR) peptide alleviates airway inflammation and hyper-responsiveness.
Exacerbation in asthma is associated with decreased expression of specific host defence peptides (HDPs) in the lungs. We examined the effects of a synthetic derivative of HDP, innate defence regulator (IDR) peptide IDR-1002, in house dust mite (HDM)-challenged murine model of asthma, in interleukin (IL)-33-challenged mice and in human primary bronchial epithelial cells (PBECs). IDR-1002 (6 mg/kg per mouse) was administered (subcutaneously) in HDM-challenged and/or IL-33-challenged BALB/c mice. Lung function analysis was performed with increasing dose of methacholine by flexiVent small animal ventilator, cell differentials in bronchoalveolar lavage performed by modified Wright-Giemsa staining, and cytokines monitored by MesoScale Discovery assay and ELISA. PBECs stimulated with tumour necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ), with or without IDR-1002, were analysed by western blots. IDR-1002 blunted HDM challenge-induced airway hyper-responsiveness (AHR), and lung leucocyte accumulation including that of eosinophils and neutrophils, in HDM-challenged mice. Concomitantly, IDR-1002 suppressed HDM-induced IL-33 in the lungs. IFN-γ/TNF-α-induced IL-33 production was abrogated by IDR-1002 in PBECs. Administration of IL-33 in HDM-challenged mice, or challenge with IL-33 alone, mitigated the ability of IDR-1002 to control leucocyte accumulation in the lungs, suggesting that the suppression of IL-33 is essential for the anti-inflammatory activity of IDR-1002. In contrast, the peptide significantly reduced either HDM, IL-33 or HDM+IL-33 co-challenge-induced AHR in vivo. This study demonstrates that an immunomodulatory IDR peptide controls the pathophysiology of asthma in a murine model. As IL-33 is implicated in steroid-refractory severe asthma, our findings on the effects of IDR-1002 may contribute to the development of novel therapies for steroid-refractory severe asthma.


Chronic kidney disease stage is associated with the number of risk factors in type 2 diabetes patients (STages Of NEphropathy in type 2 diabetes and Heart Failure - STONE HF).
To study the association between risk factors and chronic kidney disease (CKD), and characterize medication use in Finnish primary care type 2 diabetes (T2D) patients. Data on clinical characteristics, laboratory measurements, and medications were collected from medical records. The primary outcome measure was notable CKD (stage 3-5, eGFR <60 ml/min/1.73 m2) and/or increased albuminuria. The explanatory variables were individual risk factors and risk factor groups based on their number (0-2, 3-4, 5-6, >7). Spearman's rank correlation coefficient and risk ratio analysis were used to analyze the association between the number of risk factors and CKD stage, and between the number of risk factors and notable CKD, respectively. Altogether, 1335 patients with T2D in 60 Finnish primary care centers were recruited for this cross-sectional study. Three-quarters of T2D patients had 3 risk factors and 36% had ≥ 5 risk factors. Compared to patients with 0-2 risk factors, patients with 3-4, 5-6, and ≥ 7 risk factors had a 5.5-fold, 9.9-fold, and 15.9-fold risk of notable CKD (p < 0.001), respectively. Heart failure was most strongly associated with notable CKD (risk ratio, 3.7; p < 0.001). Number of risk factors was strongly associated with advanced-stage CKD.


A study of the effects of large doses of glutethimide that were used for self-poisoning during pregnancy on human fetuses.
Animal investigations showed some embryolethal and teratogenic effects of glutethimide, a piperidindion derivative non-barbital hypnotic drug. Thus, the objective of this study was to evaluate the effects of very large doses of glutethimide that were used for a suicide attempt during pregnancy on the embryo-fetal development of exposed children. Self-poisoned pregnant women were identified from the population of female patients of the Department of Toxicology Internal Medicine, Korányi Hospital, Budapest who had been admitted from the 3 million people of Budapest and its surrounding region. The rates of congenital abnormalities, intrauterine fetal development (based on birth weight and pregnancy age at delivery) and cognitive-behavioral status of exposed children born to mothers who attempted suicide with glutethimide alone or in combination with other drugs during pregnancy were compared with their sib controls. Of 1044 pregnant women with self-poisoning during pregnancy between 1960 and 1993, 33 used glutethimide for a suicide attempt sixteen of these women delivered live-born infants. The dose of glutethimide ranged between 1000 and 15,000 mg with a mean of 4234 mg. Of the 16 exposed children, five were male and 11 were female. Three exposed children were affected with congenital abnormalities (atrial septal defect type II, pectus carinatum, fetal alcohol syndrome). Of their 16 matched unexposed sib pairs, two had congenital abnormalities. The mean birth weight of the exposed children was somewhat larger due to somewhat longer pregnancy age at delivery. Cognitive status and behavioral scale of the exposed children did not indicate a fetotoxic (including neurotoxic) effect of large doses of glutethimide. Very large doses of glutethimide used for a suicide attempt by 16 pregnant women did not produce teratogenic or fetotoxic (including neurotoxic) effects in their children.


p,p'-DDE induces apoptosis and mRNA expression of apoptosis-associated genes in testes of pubertal rats.
One,1-dichloro-2,2 bis(p-chlorophenyl) ethylene (p,p'-DDE), the major metabolite of 2,2-bis(4-chlorophenyl)-1,1,1-trichloroethane (DDT), is a known persistent organic pollutant and male reproductive toxicant. It has antiandrogenic effect. However, the mechanism by which p,p'-DDE exposure causes male reproductive toxicity remains unknown. To elucidate the mechanism underpinning the testicular effects of p,p'-DDE, we sought to investigate apoptotic effects and mRNA expression of apoptosis-associated genes in the testis of pubertal rats, including Fas, FasL, calpain-1, cytochrome c, Bax, Bcl-w, Bak, and caspase-3, -8, -9, -12. Animals were administered with different doses of p,p'-DDE (0, 20, 60, 100 mg/kg body weight) every other day by intraperitoneal injection for 10 days. The results indicated that p,p'-DDE exposure at over 20 mg/kg body weight showed the induction of apoptotic cell death. p,p'-DDE could induce decrease in SOD and GSH-Px activity of serum in 60 mg/kg body weight group. Significant elevations in the mRNA levels of Fas, FasL, calpain-1, cytochrome c, Bax, Bak, and caspase-3, -8, -9, -12 were observed in testis of rat treated with p,p'-DDE. Taken together, these results lead us to speculate that in vivo exposure to p,p'-DDE might induce testicular apoptosis in pubertal rats through the involvement of Fas/FasL, mitochondria and endoplasmic reticulum-mediated pathways.


Chemical adhesion in dentistry.
The terms used in the chemistry of adhesion are reviewed as well as the role played by surface energies, viscosity, surface roughness, etc. The similarity of chemical bonds in substrate and adhesive which favours adhesion in general, is very rare in dentistry. It is shown how and when a chemical bridge between two different types of materials works in dentistry. Finally, it is made evident why binding to dental hard tissues will not be permanent.


Paracoccus limosus sp. nov., isolated from activated sludge in a sewage treatment plant.
Two strains of gram-negative, catalase- and oxidase-positive, coccus-shaped bacteria, designated NB88(T) and LNB004, were isolated from activated sludge in the Mae-san sewage treatment plant in South Korea. They were characterized in a polyphasic taxonomic study based on phenotypic, phylogenetic and genotypic approaches. Comparative 16S rRNA gene sequence analysis indicated that strains NB88(T) and LNB004 represented a novel subline within the genus Paracoccus in the family Rhodobacteraceae. According to 16S rRNA gene sequence comparisons, strains NB88(T) and LNB004 were indistinguishable and showed 94.5-97.6 % similarity to the type strains of other Paracoccus species. Strain NB88(T) exhibited relatively high levels of DNA hybridization (84±3.5 %) with LNB004 and low hybridization values (<40 %) with type strains of other Paracoccus species. Both strains showed chemotaxonomic characteristics typical of the genus Paracoccus, with Q-10 as the predominant respiratory quinone and C18 : 1ω7c as the major fatty acid, and both strains accumulated poly-β-hydroxybutyrate granules. The DNA G+C contents of strains NB88(T) and LNB004 were 66.4 and 65.1 mol%, respectively. The polar lipid profiles of strains NB88(T) and LNB004 included major amounts of phosphatidylglycerol, phosphatidylcholine and an unknown aminolipid. The taxonomic position of strains NB88(T) and LNB004 was clarified by the low level of DNA-DNA hybridization with closely related strains and the strains could be distinguished from other recognized species by using biochemical tests and molecular genetic analysis. On the basis of their phenotypic and genotypic properties and their phylogenetic distinctiveness, strains NB88(T) and LNB004 should be classified in a novel species of the genus Paracoccus, for which the name Paracoccus limosus sp. nov. is proposed. The type strain is NB88(T) ( = KEMC 5401-184(T) = JCM 17370(T)); strain LNB004 ( = KEMC 5401-001) is a reference strain.


Short-term Follow-up US Leads to Higher False-positive Results Without Detection of Structural Recurrences in PTMC.
To investigate the value of the annual follow-up neck ultrasonography (US) for postoperative surveillance in patients with papillary thyroid microcarcinoma (PTMC). This retrospective study has been approved by our institutional review board (IRB) with waiver for informed consent. A total of 375 patients diagnosed as PTMCs, who underwent total thyroidectomy with radioiodine remnant ablation were included, to identify the recurrence rate and the false-positive rate of annual ultrasound. The number, interval, and the results of follow-up US or fine needle aspiration were obtained from electronic medical records. Four (1.1%, 4/375) recurrences were found 3 years after the initial treatment, and only 1 patient (0.3%, 1/375) had a metastatic lymph node larger than 8 mm in the shortest diameter on US found 7.6 years after initial treatment with biochemical abnormalities. Cumulative risk of having at least 1 false-positive exam was 8.3% by the 8th US, and 8.1% by the 8-9 year follow-up. Cox multivariate regression showed shorter interval of follow-up US and presence of lymph node metastasis at initial surgery are independent predictors affecting the cumulative false-positive results (hazard ratio [HR], 0.60; 95% confidence interval [CI]: 0.49-0.73; P < 0.001 and HR, 2.19; 95% CI: 1.01-4.75; P = 0.048, respectively). Short-term follow-up US can result in higher cumulative false-positive results without detection of meaningful recurrences in patients with PTMCs who do not have biochemical abnormalities.


Effect of vaccination schedule on immune response of Macaca mulatta to cell culture-grown Rocky Mountain spotted fever vaccine.
The effect of vaccination schedule on the immune response of Macaca mulatta to formalin-inactivated chicken embryo cell culture (CEC)-grown Rickettsia rickettsii vaccine was studied. Schedules consisted of inoculation on day 1 only, on days 1 and 15, on days 1 and 30, on days 1, 8, and 15, or on days 1, 15, and 45. Humoral antibody measured by microagglutination and indirect immunofluorescence and resistance to challenge with 10(4) plaque-forming units of yolk sac-grown R. rickettsii were assessed. Seroconversion was noted in all monkeys after the first dose of vaccine. A second dose administered 8 or 15 days after the primary infection, or a third given 7 or 30 days after the second, produced no long-term effect on antibody titer. Only monkeys given two doses of vaccine at a 30-day interval showed an increase in antibody titer during the period before challenge. Vaccination with one, two, or three doses of CEC vaccine prevented development of rash and rickettsemia after challenge. The two-dose schedules appeared to induce the highest degree of resistance to challenge, as indicated by unaltered hematological parameters and body temperature in monkeys. The one- and three-dose schedules were somewhat less effective, in that some challenged monkeys within each group displayed febrile and leukocyte responses associated with Rocky Mountain spotted fever infection. Our data suggest that administration of two doses of CEC vaccine at 15- or 30-day intervals is the immunization schedule of choice.


The ms2io6A37 modification of tRNA in Salmonella typhimurium regulates growth on citric acid cycle intermediates.
The modified nucleoside 2-methylthio-N-6-isopentenyl adenosine (ms2i6A) is present in position 37 (adjacent to and 3' of the anticodon) of tRNAs that read codons beginning with U except tRNA(i.v. Ser) in Escherichia coli. In Salmonella typhimurium, 2-methylthio-N-6-(cis-hydroxy)isopentenyl adenosine (ms2io6A; also referred to as 2-methylthio cis-ribozeatin) is found in tRNA, most likely in the species that have ms2i6A in E. coli. Mutants (miaE) of S. typhimurium in which ms2i6A hydroxylation is blocked are unable to grow aerobically on the dicarboxylic acids of the citric acid cycle. Such mutants have normal uptake of dicarboxylic acids and functional enzymes of the citric acid cycle and the aerobic respiratory chain. The ability of S. typhimurium to grow on succinate, fumarate, and malate is dependent on the state of modification in position 37 of those tRNAs normally having ms2io6A37 and is not due to a second cellular function of tRNA (ms2io6A37)hydroxylase, the miaE gene product. We suggest that S. typhimurium senses the hydroxylation status of the isopentenyl group of the tRNA and will grow on succinate, fumarate, or malate only if the isopentenyl group is hydroxylated.


Does concomitant bacteraemia hide the fungi in blood cultures? An in vitro study.
Introduction. Polymicrobial infections including yeasts and bacteria are not rare and patients with polymicrobial bloodstream infection have higher early and overall case fatality rates. The diagnosis of invasive fungal and bacterial infections is mainly based on blood culture.Aim. The aim was to reveal the effect of concomitant bacteraemia on the detection of fungi from blood cultures in the presence of polymicrobial bloodstream infections involving Candida and non-Candida fungi and to show the superiority of blood culture bottles including selective fungal media in such situations.Methodology. Twenty-four polymicrobial bloodstream infection models - involving one fungus and one bacterium - were constituted by using clinical blood culture isolates (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Candida glabrata, Fusarium solani and Trichosporon asahii). The Plus Aerobic/F (PAF) and Mycosis IC/F (MICF) culture bottles were used with the BACTEC 9240 device. After a bottle signalled positive, direct microscopic examination and subcultures on agar plates were performed.Results. All of fungi that were inoculated alone and in combination were detected by both direct microscopic examination and subcultures on agar plates from MICF bottles, whereas direct microscopic examination only revealed the bacterial agents from PAF bottles including combinations. Furthermore, fungal growth was hidden by bacterial growth on blood agar subcultures from PAF bottles including combinations of F. solani, C. glabrata or T. asahii with bacteria.Conclusion. Blood culture bottles including selective fungal media that can allow selective growth of fungi and earlier detection of some species should be preferred in addition to non-selective blood culture bottles, especially in specific patient populations. Further, the use of selective agar plates such as inhibitory mould agar may contribute to the solution of this problem in clinical laboratories.


[Quantitative determination of the soluble O antigen of Salmonella serogroup B and of specific antibodies in different classes by using immunoenzyme analysis].
The results of measurements of S. typhimurium O-antigen and specific IgA-, IgG- and IgM-antibodies in 115 serum samples from patients with salmonellosis induced by group B salmonellae are analyzed. As determined in this study, the concentrations of IgA-antibodies ranged 0-15 micrograms/ml, the minimal diagnostically significant value being 3.6 micrograms/ml; the concentrations of IgG-antibodies ranged 0-13 micrograms/ml, the minimal diagnostically significant value being 1.3 micrograms/ml; and the concentrations of IgM-antibodies ranged 0-50 microgram/ml, the minimal diagnostically significant value being 5.0 micrograms/ml. The minimal diagnostically significant concentration of O-antigen, determined in selected serum samples obtained from healthy donors, was 0.1 microgram/ml. There is a significant correlation between the concentrations of IgA-, IgG- and IgM-antibodies, but the concentrations of these antibodies do not correlate with the concentration of soluble O-antigen. The study showed that the simultaneous determination of S. typhimurium O-antigen and specific antibodies in the material under test significantly enhances the effectiveness of the serodiagnosis of the disease.


Biomaterial design strategies to address obstacles in craniomaxillofacial bone repair.
Biomaterial design to repair craniomaxillofacial defects has largely focused on promoting bone regeneration, while there are many additional factors that influence this process. The bone microenvironment is complex, with various mechanical property differences between cortical and cancellous bone, a unique porous architecture, and multiple cell types that must maintain homeostasis. This complex environment includes a vascular architecture to deliver cells and nutrients, osteoblasts which form new bone, osteoclasts which resorb excess bone, and upon injury, inflammatory cells and bacteria which can lead to failure to repair. To create biomaterials able to regenerate these large missing portions of bone on par with autograft materials, design of these materials must include methods to overcome multiple obstacles to effective, efficient bone regeneration. These obstacles include infection and biofilm formation on the biomaterial surface, fibrous tissue formation resulting from ill-fitting implants or persistent inflammation, non-bone tissue formation such as cartilage from improper biomaterial signals to cells, and voids in bone infill or lengthy implant degradation times. Novel biomaterial designs may provide approaches to effectively induce osteogenesis and new bone formation, include design motifs that facilitate surgical handling, intraoperative modification and promote conformal fitting within complex defect geometries, induce a pro-healing immune response, and prevent bacterial infection. In this review, we discuss the bone injury microenvironment and methods of biomaterial design to overcome these obstacles, which if unaddressed, may result in failure of the implant to regenerate host bone.