Decoding Natural Grasping Behaviors: Insights into MRCP Source Features and Coupling Dynamics.
The effective decoding of natural grasping behaviors is crucial for the natural control of neural prosthetics. This study aims to investigate the decoding performance of movement-related cortical potential (MRCP) source features between complex grasping actions and explore the temporal and frequency differences in inter-muscular and cortical-muscular coupling strength during movement. Based on the human grasping taxonomy and their frequency, five natural grasping motions-medium wrap, adducted thumb, adduction grip, tip pinch, and writing tripod-were chosen. We collected 64-channel electroencephalogram (EEG) and 5-channel surface electromyogram (sEMG) data from 17 healthy participants, and projected six EEG frequency bands into source space for further analysis. Results from multi-classification and binary classification demonstrated that MRCP source features could not only distinguish between power grasp and precision grasp, but also detect subtle action differences such as thumb adduction and abduction during the execution phase. Besides, we found that during natural reach-and-grasp movement, the coupling strength from cortical to muscle is lower than that from muscle to cortical, except in the hold phase of γ frequency band. Furthermore, a 12-Hz peak of inter-muscular coupling strength was found in movement execution, which might be related to movement planning and execution. We believe that this research will enhance our comprehension of the control and feedback mechanisms of human hand grasping and contributes to a natural and intuitive control for brain-computer interface.


Nursing diagnosis risk for bleeding as an indicator of quality of care for patient safety.
To describe the implantation of a care quality indicator associated to the nursing diagnosis of patients at high risk of bleeding, based on the alarming results of prothrombin time (PT), partially activated thromboplastin time (aPTT) and platelets. Retrospective experience report of multidisciplinary actions developed in a university hospital. The stages of the study involved team meetings, search for effective communication strategies and creation of a new indicator of quality of care. The indicator was called "Compliance of Nursing Diagnosis Risk for bleeding", monitored monthly since June 2016. The technical file includes the characteristics and attributes of the indicator. Based on the analyzes of the indicator, action plans are established for its qualification. The implementation of the quality of care indicator associated to the nursing diagnosis improved the communication process, the monitoring and the nursing care to patients at risk of bleeding.


The association between physical health and delusional-like experiences: a general population study.
Delusional-like experiences (DLE) are prevalent in the community. Recent community based studies have found that DLE are more common in those with depression and anxiety disorders, and in those with subclinical symptoms of depression and anxiety. Chronic physical disorders are associated with comorbid depression and anxiety; however, there is a lack of evidence about the association of DLE with common physical conditions. The aim of this study was to explore associations between the common physical disorders and DLE using a large population sample. Subjects were drawn from the Australian National Survey of Mental Health and Wellbeing 2007, a national household survey of 8841 residents aged between 16 and 85 years. The presence of DLE, selected common physical disorders and symptoms were assessed using a modified World Mental Health Composite International Diagnostic Interview (CIDI) schedule. We examined the relationship between DLE, and physical health-related variables using logistic regression, with adjustments for potential confounding factors. Of the 8771, 776 (8.4%) subjects positively endorsed one or more DLE. Of the six physical disorders examined, only diabetes and arthritis were significantly associated with the endorsement of DLE. Of the seven broad physical symptoms explored, only hearing problems were consistently associated with DLE. Delusional-like experiences are common in the Australian community, and are associated with selected chronic physical disorders and with impaired hearing. The direction of causality between these variables warrants closer research scrutiny.


Long-term back pain after a single-level discectomy for radiculopathy: incidence and health care cost analysis.
The most common spinal procedure performed in the US is lumbar discectomy for disc herniation. Longterm disc degeneration and height loss occur in many patients after lumbar discectomy. The incidence of mechanical back pain following discectomy varies widely in the literature, and its associated health care costs are unknown. The authors set out to determine the incidence of and the health care costs associated with mechanical back pain attributed to segmental degeneration or instability at the level of a prior discectomy performed at their institution. The authors retrospectively reviewed the data for 111 patients who underwent primary, single-level lumbar hemilaminotomy and discectomy for radiculopathy. All diagnostic modalities, conservative therapies, and operative treatments used for the management of postdisectomy back pain were recorded. Institutional billing and accounting records were reviewed to determine the billed costs of all diagnostic and therapeutic measures. At a mean follow-up of 37.3 months after primary discectomy, 75 patients (68%) experienced minimal to no back pain, 26 (23%) had moderate back pain requiring conservative treatment only, and 10 (9%) suffered severe back pain that required a subsequent fusion surgery at the site of the primary discectomy. The mean cost per patient for conservative treatment alone was $4696. The mean cost per patient for operative treatment was $42,554. The estimated cost of treatment for mechanical back pain associated with postoperative same-level degeneration or instability was $493,383 per 100 cases of first-time, single-level lumbar discectomy ($4934 per primary discectomy). Postoperative mechanical back pain associated with same-level degeneration is not uncommon in patients undergoing single-level lumbar discectomy and is associated with substantial health care costs.


Targeting thymidylate synthase in colorectal cancer: critical re-evaluation and emerging therapeutic role of raltitrexed.
5-fluorouracil continues to be the cornerstone of treatment for colorectal cancer. Although fluoropyrimidines are generally considered as well-tolerated drugs, severe toxicities can be a major clinical problem, and the recommended prolonged infusion of 5-fluorouracil provokes discomfort in patients. Raltitrexed (Tomudex), a quinazoline analogue of folinic acid, is a selective and direct thymidylate synthase (TS) inhibitor with a convenient 3-weekly schedule of administration. In this review, through critical insight into the mechanism of action and main clinical experiences, the authors suggest the necessity to reconsider raltitrexed as a valuable anticancer drug and as a suitable option for colorectal cancer. The authors highlight its emerging therapeutic role in clinical practice for patients with fluoropyrimidine-induced cardiotoxicity or a significant history of cardiac disease. This review discusses if TS could still be a relevant target for colorectal cancer in the era of molecular therapy and if raltitrexed should still be considered a drug with a life-threatening toxicity. Furthermore, this review discusses the principal combination clinical experiences of raltitrexed and its emerging therapeutic role in clinical practice as a suitable option for colorectal cancer patients with fluoropyrimidine-induced cardiotoxicity or a significant history of cardiac disease.


Cross-linked small-molecule capsules with excitation wavelength-dependent photoluminescence and high loading capacity: design, synthesis and application in imaging-guided drug delivery.
The cross-linked small-molecule micelles (cSMs) have found applications in many fields but their low loading capacity and non-fluorescence property hindered their further development. Herein, water-soluble organic nanoparticles were applied as templates to "stretch" the hydrophobic core of cSMs and photo-cross-linking was employed to supply photoluminescence. The resulting cross-linked small-molecule capsules (cSCs) not only reserve the superior properties of cSMs of accurate monomer, easy functionalization and robust stability, but also achieve high drug loading capacity and excitation wavelength-dependent fluorescence, where the drug loading contents (DLCs) for various hydrophobic drugs were more than 30-fold higher than that of cSMs, and the maximum quantum yield could be as high as 12.0%. Featuring these superiorities, the cSCs hold promising potential in many fields and an example of doxorubicin-loaded cSCs (DOX@cSCs) for multichannel imaging-guided drug delivery is shown in this work.


Use of x-ray-computed tomography as an aid in localization of adrenal masses in the dog.
Four dogs with clinical evidence of hyperadrenocorticism were evaluated by use of x-ray-computed tomography (CT). Adrenal masses were identified accurately and localized. Unilateral adrenal masses were diagnosed accurately in dogs 1, 2, and 3 and were removed surgically via a paracostal retroperitoneal approach to the adrenal gland. Using CT and IV contrast medium, the adrenal mass in dog 3 also was accurately diagnosed as being highly vascular. The histopathologic diagnosis was adrenal adenoma in dogs 1, 2, and 3. In dog 4, the CT-roentgen diagnosis was asymmetric bilateral adrenal enlargement. Necropsy examination of dog 4 indicated moderate enlargement of the left adrenal gland and severe enlargement of the right adrenal gland. Results of microscopic examination indicated chronic inflammation of the left adrenal gland and adenocarcinoma of the right adrenal gland. Use of CT facilitated localization of adrenal masses and fulfilled the needs of a localizing technique. A unilateral mass can be removed surgically via a limited exposure, retroperitoneal incision on the affected side of the animal instead of removal via abdominal laparotomy, which is more invasive. Advantages of CT can reduce the needs of other imaging modalities for the localization of adrenal masses.


Current concepts in the management of paratesticular rhabdomyosarcoma.
Paratesticular rhabdomyosarcoma is a rare malignant disease most commonly seen in infants and children. In contrast with rhabdomyosarcomas in sites other than the genitourinary tract, paratesticular rhabdomyosarcomas tend to metastasize via a lymphatic route. This influences the therapeutic approach in which surgery, chemotherapy and, in selected cases, radiation therapy play an essential role. On hand of 7 of our own patients, uniformly treated at one institution, a review of the current approach of paratesticular rhabdomyosarcomas with excellent therapeutic results is given.


Benzo(a)pyrene-induced alterations in growth-related gene expression and signaling in precision-cut adult rat liver and kidney slices.
Benzo(a)pyrene (BaP) and related aromatic hydrocarbons are suspected carcinogens; however, the molecular basis underlying tumorigenesis remains unclear. To identify acute molecular targets of BaP within the liver and kidney, precision-cut slices harvested from naive, adult female Sprague-Dawley rats were challenged with BaP (0.3-30 microM) for 0.5 to 24 h. BaP did not elicit cytotoxicity, as assessed by intracellular K+ and ATP content and histological evaluation over the 24-h period. To determine if molecular signaling pathways were maintained in precision-cut slices, induction of the aryl hydrocarbon receptor (AhR) pathway was assessed following BaP challenge. Induction of cytochrome P450IA1 (P450IA1) mRNA and protein expression was observed in both liver and kidney slices. c-fos and c-Ha-ras gene expression was enhanced in liver, but not kidney, slices by BaP. c-jun mRNA levels were decreased in liver and kidney slices, although the effect was earlier (0.5 h) in liver slices compared to kidney slices. BaP increased the DNA binding of nuclear proteins to the AP-1 consensus recognition element in liver, but decreased DNA binding in kidney slices. In contrast, DNA binding of NF-kappa B was not affected by BaP in either liver or kidney slices. These results suggest that acute BaP challenge is associated with altered expression of several growth-related genes and AP-1 signaling and establish precision-cut slices as a useful in vitro system to investigate the molecular basis of BaP-induced tumorigenesis, including organ-specific differences.


Rapid determination of the amount of cetylpyridinium chloride bound by bacteria.
A modification of the Colowick and Womack procedure for measuring ligand binding by macromolecules is described for drug binding by bacteria. This technique is based on the determination of drug concentration in the dialysate from a bacteria-drug mixture at equilibrium. The dialysis cell of the original procedure was replaced by a Minibeaker (Bio-Rad), which has a larger membrane surface area, and the dialysate was continuously monitored with a spectrophotometer equipped with a flow cell. With this system, only 3 min was required to determine the amount of cetylpyridinium chloride bound by Escherichia coli K-12 strain P678. Possible applications of the technique are discussed.


The National Cancer Institute ALMANAC: A Comprehensive Screening Resource for the Detection of Anticancer Drug Pairs with Enhanced Therapeutic Activity.
To date, over 100 small-molecule oncology drugs have been approved by the FDA. Because of the inherent heterogeneity of tumors, these small molecules are often administered in combination to prevent emergence of resistant cell subpopulations. Therefore, new combination strategies to overcome drug resistance in patients with advanced cancer are needed. In this study, we performed a systematic evaluation of the therapeutic activity of over 5,000 pairs of FDA-approved cancer drugs against a panel of 60 well-characterized human tumor cell lines (NCI-60) to uncover combinations with greater than additive growth-inhibitory activity. Screening results were compiled into a database, termed the NCI-ALMANAC (A Large Matrix of Anti-Neoplastic Agent Combinations), publicly available at https://dtp.cancer.gov/ncialmanac Subsequent in vivo experiments in mouse xenograft models of human cancer confirmed combinations with greater than single-agent efficacy. Concomitant detection of mechanistic biomarkers for these combinations in vivo supported the initiation of two phase I clinical trials at the NCI to evaluate clofarabine with bortezomib and nilotinib with paclitaxel in patients with advanced cancer. Consequently, the hypothesis-generating NCI-ALMANAC web-based resource has demonstrated value in identifying promising combinations of approved drugs with potent anticancer activity for further mechanistic study and translation to clinical trials. Cancer Res; 77(13); 3564-76. ©2017 AACR.


Venous thromboembolism and escitalopram.
Selective serotonin reuptake inhibitors (SSRIs) are currently used as a first-line treatment for depression, as they have a favorable side-effect profile. Escitalopram, a new SSRI, is also well-tolerated and serious side effects are rarely associated with its use. There have been several reports that SSRIs might increase bleeding tendency in some patients by affecting platelet function. However, to our knowledge, there have been no reports about their relation to thrombosis. In this brief report, we present a case of venous thromboembolism associated with escitalopram in a patient with psychotic depression without any major risk factors for thrombosis. SSRIs might have a dual effect on platelet function. The immediate and early effect of SSRI use on platelets might be an increase be an in tendency for thrombosis, whereas the late effect after repeated dosing might be an increase in tendency to bleed, as suggested by previous literature.


Reported changes in the sexual behavior of men at risk for AIDS, San Francisco, 1982-84--the AIDS Behavioral Research Project.
We surveyed 454 men in November 1983 and in May 1984 regarding their sexual practices during the month before the survey. In the 1983 survey, we also asked for reports about sexual behavior during the same month 1 year prior to the survey. The sample consisted of men recruited as they left bath-houses and bars, men who had not used bars or baths for meeting sexual partners for 2 months prior to the November 1983 survey, and men in committed primary relationships with another man. We found substantial changes in reported sexual behavior with persons other than a primary partner. The average number of male partners declined from 6.3 in November 1982 to 3.9 in May 1984. Receptive anal intercourse without condom declined from 1.9 to 0.7, oral-anal contact declined from 1.1 to 0.3, and swallowing semen declined from 2.8 to 0.7 in terms of the number of times that the respondent engaged in the act in the last month. These same changes did not occur in relation to sex with a primary partner. Only one variable, namely, increased length of time since the first homosexual experience, distinguished persons maintaining few sexual partners from those increasing the number of sexual partners from November 1983 to May 1984. Four variables distinguished those retaining high numbers of sexual partners from those lowering the number of sexual partners, namely, ability to remember a visual image of AIDS deterioration, age, relationship status, and length of time since first homosexual experience.


Prolonged luteal lifespan and pseudopregnancy in Asian elephants (Elephas maximus).
Pseudopregnancy is a physiological occurrence in mammals which have copulation induced ovulation, but is rarely described in spontaneous ovulating species. In this study, three cases of prolonged luteal lifespan are reported in non-pregnant Asian elephants (Elephas maximus). Case 1 was a 25-year-old female that had produced three calves previously; Case 2 was a nulliparous and 32-year-old at the start of the pseudopregnancy episode; and Case 3 occurred in a 49-year-old nulliparous elephant. Serum progesterone metabolite concentrations remained elevated for 10 months in Case 1. Urinary progestagens were high for >16 months in Case 2 and for five months in Case 3. In Case 1, multiple persistent corpora lutea were visualized monthly by ultrasonography. In all three cases, uterine leiomyoma were present and progestagen concentrations decreased spontaneously. In Case 1, the elephant became pregnant 3 years later, whilst with Case 2, the female resumed estrous cycling normally, and for the Case 3 female, there was continuation with another prolonged luteal phase before ovarian function was purposely suppressed. These examples indicate that persistently elevated progestagen concentrations may not always be indicative of pregnancy in elephants. The reasons for prolonged luteal lifespan are not understood, although serum prolactin concentrations quantified in the Case 1 female were elevated compared to values from previous reports and two other herd mates. Furthermore, all three elephants had varying degrees of uterine pathologies. It is believed that the resulting damage to the endometrium may have led to a reaction similar to implantation, which includes prolactin secretion. Prolactin may exert luteotropic properties and is thought to initiate luteal rescue during pregnancy in elephants.


Changes in environmental tobacco smoke exposure: the Beaver Dam experience.
Environmental tobacco smoke (ETS) exposure has been associated with adverse health outcomes. Our goal was to determine if ETS exposure changed between 1998-2000 and 2003-2005 among participants in the population-based Epidemiology of Hearing Loss Study. ETS exposure was ascertained using a cotinine-validated questionnaire at the 5-year (1998-2000) and 10-year follow-up examinations (2003-2005). Non-smoking participants with data from both visits were included (n=1898; ages 53-96 years at 5-yr follow-up). McNemar's test was used to test differences in ETS exposure overall and in 3 settings: home, work, and social settings. Generalized estimating equations (GEE) were used for multivariate logistic regression models of exposure. The proportion of nonsmokers with no or little ETS exposure increased from 80% to 88% (P< 0.0001). The percent living in a home with no indoor smokers increased from 94% to 97% (P<0.0001). The percent reporting no exposure at work increased from 91% to 95% (P<0.0001). The percent reporting the lowest frequency of social exposure increased from 65% to 77% (P<0.0001). In the GEE model, age was inversely associated with overall ETS exposure (Odds Ratio [OR] per 5 yr= 0.87, 95% CI= 0.81, 0.94), as was education (OR for college vs < high school=0.25, 95% CI=0.16, 0.37), female gender (ORI= 0.41, 95% CI= 0.33, 0.51), and later examination period (OR =0.62, 95% CI= 0.53, 0.73); current employment was positively associated with exposure (OR=1.44, 95% CI=1.14, 1.83). Between the late 1990s and the mid-2000s, ETS exposure in older adults decreased. Decreasing exposures suggest there may be future declines in ETS-related adverse health outcomes.


Efficient algorithms for training the parameters of hidden Markov models using stochastic expectation maximization (EM) training and Viterbi training.
Hidden Markov models are widely employed by numerous bioinformatics programs used today. Applications range widely from comparative gene prediction to time-series analyses of micro-array data. The parameters of the underlying models need to be adjusted for specific data sets, for example the genome of a particular species, in order to maximize the prediction accuracy. Computationally efficient algorithms for parameter training are thus key to maximizing the usability of a wide range of bioinformatics applications. We introduce two computationally efficient training algorithms, one for Viterbi training and one for stochastic expectation maximization (EM) training, which render the memory requirements independent of the sequence length. Unlike the existing algorithms for Viterbi and stochastic EM training which require a two-step procedure, our two new algorithms require only one step and scan the input sequence in only one direction. We also implement these two new algorithms and the already published linear-memory algorithm for EM training into the hidden Markov model compiler HMM-CONVERTER and examine their respective practical merits for three small example models. Bioinformatics applications employing hidden Markov models can use the two algorithms in order to make Viterbi training and stochastic EM training more computationally efficient. Using these algorithms, parameter training can thus be attempted for more complex models and longer training sequences. The two new algorithms have the added advantage of being easier to implement than the corresponding default algorithms for Viterbi training and stochastic EM training.


The relationship between delta-aminolaevulinate synthetase induction and the concentration of cytochrome P-450 and catalase in rat liver.
The porphyrinogenic drug 2-allyl-2-isopropylacetamide causes the degradation of microsomal cytochrome P-450 and inhibits the synthesis of catalase in rat liver. The inhibition of catalase synthesis follows the induction of delta-aminolaevulinate synthetase and the consequent overproduction of haem. The allylisopropylacetamide-mediated breakdown of cytochrome P-450 is a rapid event and has a reciprocal relationship to the pattern of delta-aminolaevulinate synthetase induction. Breakdown of cytochrome P-450 appears to be one of the conditions leading to the ;derepression' of delta-aminolaevulinate synthetase.


To swim or not to swim: A population-level model of Xenopus tadpole decision making and locomotor behaviour.
We present a detailed computational model of interacting neuronal populations that mimic the hatchling Xenopus tadpole nervous system. The model includes four sensory pathways, integrators of sensory information, and a central pattern generator (CPG) network. Sensory pathways of different modalities receive inputs from an "environment"; these inputs are then processed and integrated to select the most appropriate locomotor action. The CPG populations execute the selected action, generating output in motor neuron populations. Thus, the model describes a detailed and biologically plausible chain of information processing from external signals to sensors, sensory pathways, integration and decision-making, action selection and execution and finally, generation of appropriate motor activity and behaviour. We show how the model produces appropriate behaviours in response to a selected scenario, which consists of a sequence of "environmental" signals. These behaviours might be relatively complex due to noisy sensory pathways and the possibility of spontaneous actions.


Spinal cord gliomas and hydrocephalus: utility of neuroendoscopy.
The aim of this study is to report on the role of neuroendoscopy during the management of hydrocephalus that led to the diagnosis of intracranial tumoral dissemination and the subsequent finding of a spinal cord glioma. We present two children each with an intramedullary astrocytoma that presented initially with hydrocephalus without spinal cord symptoms. In both cases leptomeningeal gliomatous dissemination was asserted during routine endoscopy for the management of hydrocephalus. The diagnosis of a cervical and a lower thoracic intramedullary tumor was made soon after on magnetic resonance imaging. Spinal cord MRI with contrast should be considered initially in selected cases of hydrocephalus without evident diagnosis. The intraoperative diagnosis of gliomatous dissemination and secondary hydrocephalus due to unrecognized spinal cord gliomas was possible, in our experience, with the routine use of the neuroendoscope.


Sid2p, a spindle pole body kinase that regulates the onset of cytokinesis.
The fission yeast Schizosaccharomyces pombe divides by medial fission through the use of an actomyosin contractile ring. Precisely at the end of anaphase, the ring begins to constrict and the septum forms. Proper coordination of cell division with mitosis is crucial to ensure proper segregation of chromosomes to daughter cells. The Sid2p kinase is one of several proteins that function as part of a novel signaling pathway required for initiation of medial ring constriction and septation. Here, we show that Sid2p is a component of the spindle pole body at all stages of the cell cycle and localizes transiently to the cell division site during medial ring constriction and septation. A medial ring and an intact microtubule cytoskeleton are required for the localization of Sid2p to the division site. We have established an in vitro assay for measuring Sid2p kinase activity, and found that Sid2p kinase activity peaks during medial ring constriction and septation. Both Sid2p localization to the division site and activity depend on the function of all of the other septation initiation genes: cdc7, cdc11, cdc14, sid1, spg1, and sid4. Thus, Sid2p, a component of the spindle pole body, by virtue of its transient localization to the division site, appears to determine the timing of ring constriction and septum delivery in response to activating signals from other Sid gene products.


Concepts of dementia prevention in the health promotion among older adults: A narrative review.
The number of older adults with dementia is predicted to markedly increase in the coming decades. A person suffers from dementia every 3 seconds globally, and one out of every 7 people suffers from dementia in Taiwan. The purpose of this narrative review is to integrate existing concepts of dementia prevention into health promotion and improve older adults' quality of life. This narrative review was performed using the PubMed database by searching for basic research and systematic reviews on dementia prevention and health promotion among older adults. We established a framework for dementia prevention and health promotion with regard to the physical, mental, spiritual, and social health aspects. We identified the following strategies related to older adults towards dementia prevention and health promotion in follows: Physical health promotion: cognitive activities, physical activities, body mass index, balanced diet, rainbow diet, Mediterranean diet, dietary approaches to stop hypertension diet, mind diet, no smoking and drinking, avoiding the "three highs" (i.e., hyperglycemia, hyperlipidemia, and hypertension), and head trauma; Mental health promotion: Positive thinking, Brief Symptom Rating Scale (BSRS-5), depression scale, and ascertained dementia 8 questionnaire (AD8) screening; Spiritual health promotion: religious beliefs, spiritual music, meditative activities, mindfulness, yoga, Qi-gong, Tai-chi, and Baduanjin; and Social health promotion: A supportive family system, socialization, social support, social networks, social interaction, and social participation. The conclusion of this narrative review was to integrate the concepts of dementia prevention and health promotion among older adults.


Revolutionizing Tuberculosis Treatment: Uncovering New Drugs and Breakthrough Inhibitors to Combat Drug-Resistant Mycobacterium tuberculosis.
Tuberculosis (TB) is a global health threat that causes significant mortality. This review explores chemotherapeutics that target essential processes in Mycobacterium tuberculosis, such as DNA replication, protein synthesis, cell wall formation, energy metabolism, and proteolysis. We emphasize the need for new drugs to treat drug-resistant strains and shorten the treatment duration. Emerging targets and promising inhibitors were identified by examining the intricate biology of TB. This review provides an overview of recent developments in the search for anti-TB drugs with a focus on newly validated targets and inhibitors. We aimed to contribute to efforts to combat TB and improve therapeutic outcomes.


Congenital canine myasthenia gravis: II. Acetylcholine receptor metabolism.
Acetylcholine receptor (AChR) metabolism was studied in muscle from juvenile and adult dogs with congenital myasthenia gravis (CMG) and their unaffected littermates. Although the amount of AChR in the junctional region of innervated CMG muscle fibers was 25% of normal, or less, denervation of CMG fibers resulted in the appearance of AChR in extrajunctional membranes at as high a concentration as in denervated normal fibers. The rate of degradation of junctional AChR in CMG fibers explanted to organ culture did not differ significantly from normal. In monolayer cultures derived from enzyme-dissociated CMG muscle, myotubes of normal morphology developed, and the synthesis and degradation of AChR did not differ from normal. Addition of sera from dogs with the acquired autoimmune form of MG accelerated the degradation of AChR on cultured myotubes, but CMG dog sera were without effect. These data suggest that the low junctional membrane density of AChR in CMG does not reflect a primary inability of muscle to synthesize AChR, nor an accelerated degradation of AChR in the postsynaptic membrane, but rather a low insertion rate of AChR in the postsynaptic membrane.


Study on the applicability of pressurized physically activated carbon as an adsorbent in adsorption heat pumps.
Activated carbon is a suitable adsorbent for adsorption heat pumps (AHPs) with ethanol refrigerants. Although chemically activated carbon with highly developed pore structures exhibits good ethanol adsorption, the associated high production costs inhibit its practical application as an AHP adsorbent. Moreover, although physical activation can produce inexpensive activated carbon, the limited pore development limits the ethanol uptake. Recently, we developed a pressurized physical activation method that can produce activated carbon with a well-developed pore structure and characteristic pore size distribution. In this study, we investigated the applicability of the pressurized physically activated carbon as an adsorbent in activated carbon-ethanol AHP systems. Because of the large number of pressurization-induced pores of appropriate size, the pressurized physically activated carbon showed effective ethanol uptake comparable with that of chemically activated carbon on a weight basis. Furthermore, on a volume basis, the pressurized physically activated carbon, with a high bulk density, showed much higher effective ethanol uptake than chemically activated carbon. These results confirm the potential of the pressurized physically activated carbon as a relatively inexpensive high-performance adsorbent for AHP systems with ethanol refrigerants.


New treatments for allergen immunotherapy.
Allergen-specific immunotherapy (SIT) represents the only curative and specific way for the treatment of allergic diseases, which have reached a pandemic dimension in industrial countries affecting up to 20-30% of the population. Although applied for 100 years to cure allergy, SIT still faces several problems related to side effects and limited efficacy. Currently, allergen-SIT is performed with vaccines based on allergen extracts that can cause severe, often life threatening, anaphylactic reactions as well as new IgE sensitization to other allergens present in the extract. Low patient adherence and high costs due to long duration (3 to 5 years) of treatment have been commonly reported. Several strategies have been developed to tackle these issues and it became possible to produce recombinant allergen-SIT vaccines with reduced allergenic activity.


PTEN in Lung Cancer: Dealing with the Problem, Building on New Knowledge and Turning the Game Around.
Lung cancer is the most common malignancy and cause of cancer deaths worldwide, owing to the dismal prognosis for most affected patients. Phosphatase and tensin homolog deleted in chromosome 10 (PTEN) acts as a powerful tumor suppressor gene and even partial reduction of its levels increases cancer susceptibility. While the most validated anti-oncogenic duty of PTEN is the negative regulation of the PI3K/mTOR/Akt oncogenic signaling pathway, further tumor suppressor functions, such as chromosomal integrity and DNA repair have been reported. PTEN protein loss is a frequent event in lung cancer, but genetic alterations are not equally detected. It has been demonstrated that its expression is regulated at multiple genetic and epigenetic levels and deeper delineation of these mechanisms might provide fertile ground for upgrading lung cancer therapeutics. Today, PTEN expression is usually determined by immunohistochemistry and low protein levels have been associated with decreased survival in lung cancer. Moreover, available data involve PTEN mutations and loss of activity with resistance to targeted treatments and immunotherapy. This review discusses the current knowledge about PTEN status in lung cancer, highlighting the prevalence of its alterations in the disease, the regulatory mechanisms and the implications of PTEN on available treatment options.


Mistranslation-associated perturbations of proteostasis do not promote accumulation of amyloid beta and plaque deposition in aged mouse brain.
A common perception in age-related neurodegenerative diseases posits that a decline in proteostasis is key to the accumulation of neuropathogenic proteins, such as amyloid beta (Aβ), and the development of sporadic Alzheimer's disease (AD). To experimentally challenge the role of protein homeostasis in the accumulation of Alzheimer's associated protein Aβ and levels of associated Tau phosphorylation, we disturbed proteostasis in single APP knock-in mouse models of AD building upon Rps9 D95N, a recently identified mammalian ram mutation which confers heightened levels of error-prone translation together with an increased propensity for random protein aggregation and which is associated with accelerated aging. We crossed the Rps9 D95N mutation into knock-in mice expressing humanized Aβ with different combinations of pathogenic mutations (wild-type, NL, NL-F, NL-G-F) causing a stepwise and quantifiable allele-dependent increase in the development of Aβ accumulation, levels of phosphorylated Tau, and neuropathology. Surprisingly, the misfolding-prone environment of the Rps9 D95N ram mutation did not affect Aβ accumulation and plaque formation, nor the level of phosphorylated Tau in any of the humanized APP knock-in lines. Our findings indicate that a misfolding-prone environment induced by error-prone translation with its inherent perturbations in protein homeostasis has little impact on the accumulation of pathogenic Aβ, plaque formation and associated phosphorylated Tau.


Management of multicellular senescence and oxidative stress.
Progressively sophisticated understanding of cellular and molecular processes that contribute to age-related physical deterioration is being gained from ongoing research into cancer, chronic inflammatory syndromes and other serious disorders that increase with age. Particularly valuable insight has resulted from characterization of how senescent cells affect the tissues in which they form in ways that decrease an organism's overall viability. Increasingly, the underlying pathophysiology of ageing is recognized as a consequence of oxidative damage. This leads to hyperactivity of cell growth pathways, prominently including mTOR (mammalian target of rapamycin), that contribute to a build-up in cells of toxic aggregates such as progerin (a mutant nuclear cytoskeletal protein), lipofuscin and other cellular debris, triggering formation of senescent cellular phenotypes, which interact destructively with surrounding tissue. Indeed, senescent cell ablation dramatically inhibits physical deterioration in progeroid (age-accelerated) mice. This review explores ways in which oxidative stress creates ageing-associated cellular damage and triggers induction of the cell death/survival programs' apoptosis, necrosis, autophagy and 'necroapoptophagy'. The concept of 'necroapoptophagy' is presented here as a strategy for varying tissue oxidative stress intensity in ways that induce differential activation of death versus survival programs, resulting in enhanced and sustained representation of healthy functional cells. These strategies are discussed in the context of specialized mesenchymal stromal cells with the potential to synergize with telocytes in stabilizing engrafted progenitor cells, thereby extending periods of healthy life. Information and concepts are summarized in a hypothetical approach to suppressing whole-organism senescence, with methods drawn from emerging understandings of ageing, gained from Cnidarians (jellyfish, corals and anemones) that undergo a unique form of cellular regeneration, potentially conferring open-ended lifespans.


[Bach transcription factors regulate hematopoietic stem/progenitor cell differentiation in response to environmental changes].
Differentiation of hematopoietic stem/progenitor cells should be tightly regulated depending on the environmental changes to maintain homeostasis. For example, erythropoiesis repression and myelopoiesis induction are widely recognized as infectious/inflammatory conditions. Transcription factors are expected to play significant roles in achieving such alterations. However, the precise mechanism by which the differentiation trajectory shift is controlled under environmental changes has not fully been elucidated. In this study, we showed that Bach transcription factors organize the erythro-myeloid differentiation in hematopoietic stem/progenitor cells in response to the environmental changes. Under the steady state, Bach transcription factors support erythroid differentiation and repress myeloid differentiation by regulating the expression of their target genes. In contrast, the functions of Bach transcription factors were repressed, which induced myelopoiesis and repressed erythropoiesis, under emergency conditions, such as infection/inflammation. Competitive roles of Bach transcription factors and C/EBP, the key regulator of myelopoiesis, might be important for tuning erythro-myeloid differentiation trajectory and its shift in response to infection/inflammation. Disfunction of Bach transcription factors was considered to be related to anemia in chronic inflammation and myelodysplastic syndromes. In addition, considering previous findings, Bach2 might possess important roles in the conditioning of the hematopoietic system for subsequent emergency conditions.


Long-term effects of enalapril monotherapy and enalapril/hydrochlorothiazide combination therapy on blood pressure, renal function, and body fluid composition.
Enalapril, a potent long-acting angiotensin-converting enzyme inhibitor, was prescribed either alone (n = 9) or in combination (n = 20) with hydrochlorothiazide for 96 weeks in essential hypertensive subjects. Blood pressure was well controlled following both monotherapy or combination therapy. Plasma renin activity was stimulated in all subjects; plasma aldosterone concentration was stimulated only in subjects receiving combination therapy. Glomerular filtration rate (assessed by inulin clearance) was unchanged in subjects with initial clearances greater than 80 ml/min/1.73 m2 but was significantly improved (55%) following either form of therapy in subjects with initial clearances less than or equal to 80 ml/min/1.73 m2. Neither monotherapy nor combination therapy adversely affected 24-hour urinary protein excretion, sodium excretion, or body fluid composition. These results suggest that enalapril, either alone or in combination with hydrochlorothiazide, is effective therapy for mild to moderate hypertension. There are no adverse effect on renal function; indeed, enalapril has the capability of improving renal function in those subjects whose renal function was initially impaired from long-standing hypertension.


Accurate assessment of the strain energy in a protein-bound drug using QM/MM X-ray refinement and converged quantum chemistry.
An ongoing question regarding the energetics of protein-ligand binding has been; what is the strain energy that a ligand pays (if any) when binding to its protein target? The traditional method to estimate strain energy uses force fields to calculate the energy difference between the ligand bound conformation and its nearest local minimum/global minimum on the gas-phase or aqueous phase potential energy surface. This makes the implicit assumption that the underlying force field as well as the reference crystal structure is accurate. Herein, we use ibuprofen as a test case and compare MMFF and ab initio QM methods to identify the local and global minimum conformations. Nine low energy conformations were identified with HF/6-31G* geometry optimization in vacuo. We also obtained highly accurate relative energies for ibuprofen's conformational energy surface based on M06/aug-cc-pVXZ (X = D and T), MP2/aug-cc-pVXZ (X = D and T) and the MP2/CBS method (with and without solvent corrections). Moreover, we curate and re-refine the ibuprofen-protein complex (PDB 2BXG) using QM/MM X-ray refinement approaches (HF/6-31G* was the QM method and the MM model was the AMBER force field ff99sb), which were compared with the low energy conformers to calculate the strain energy. The result indicates that there was an 88% reduction in ibuprofen conformation strain using the QM/MM refined structure versus the original PDB ibuprofen conformations. Furthermore, our results indicate that, due to its inherent limitations in estimating electrostatic interactions, force fields are not suitable to gauge strain energy for charged drug molecules like ibuprofen. The present work offers a carefully validated conformational potential energy surface for a drug molecule as well as a reliable QM/MM re-refined X-ray structure that can be used to test current structure-based drug design approaches.


Clara-cell hyperplasia after quartz and coal-dust instillation in rat lung.
Bronchiolo-alveolar hyperplasia of type II cells in rat lungs after particle exposure is a well-known preneoplastic lesion. The Clara cell, stem cell of the bronchiolar epithelium and the main carrier of cytochrome P-450 isoenzyme system in the lung, has barely been evaluated with regard to this effect. The aim of this study was to examine Clara-cell hyperplasia after particle exposure and to characterize cell proliferation and its normal function. Female Wistar rats were intratracheally instilled with coal dust samples of variable quartz content, quartz (DQ12), titanium dioxide, or saline solution containing 0.5% Tween 80. After 126-129 wk, all coal mine dust- and quartz-exposed animals developed Clara-cell hyperplasia: up to 0.48% of the total lung area, which was significantly increased compared to titanium dioxide (p <.05) and control (p <.03) animals. Proliferation and hyperplasia of bronchiolar Clara cells by coal dusts was independent of their quartz content. The lack of proliferating cell nuclear antigen staining in most of the hyperplastic Clara cells suggests that following damage of alveolar epithelial cells, Clara cells migrate in and remodulate the alveolar epithelium. After the migration they keep their function in the xenobiotic metabolism, as shown by expansion of CYP2E1 active Clara cells. The minor development of Clara-cell hyperplasia in titanium dioxide-treated rats indicates that this is not a general particle effect, and is possibly due to its lower toxicity to epithelial cells.


[Maternal and perinatal morbidities associated to advanced age in pregnant women].
Women in advanced maternal age (older than 35 years of age) are at higher risk of obstetric complications and adverse perinatal outcomes than younger women. To know the maternal and perinatal morbidities associated to advanced age in pregnant women. Analytical cross-sectional study. Women with resolution of pregnancy in the medical unit were included and distributed in two groups: group 1, advanced age, ≥ 35 years, and group 2, < 35 years. Clinical data, maternal and perinatal morbidities of the newborn (NB) were collected from the medical record. We included 240 patients, 120 per group; a significant association of advanced maternal age with maternal morbidities such as diseases prior to pregnancy was demonstrated (p < 0.0001), including diabetes mellitus during pregnancy (p = 0.002), hypertensive disease of pregnancy (p = 0.0001), pregnancy resolution by cesarean section (p = 0.04), obstetric hemorrhage (p = 0.0002), prenatal control with < 5 consultations (p = 0.008), as well as those with perinatal morbidities of the NB: preterm gestational age (p = 0.001), intrauterine growth retardation (p = 0.01), low weight for gestational age (p = 0.001) and admission of the NB to the neonatal intensive care unit (p = 0.007); with multivariate analysis, an association of advanced maternal age with diabetes mellitus, hypertensive disease of pregnancy and obstetric hemorrhage was observed (R2 = 0.9884; p < 0.0001). The maternal and perinatal morbidities are associated with advanced age in pregnant women.


Root phenotyping: from component trait in the lab to breeding.
In the last decade cheaper and faster sequencing methods have resulted in an enormous increase in genomic data. High throughput genotyping, genotyping by sequencing and genomic breeding are becoming a standard in plant breeding. As a result, the collection of phenotypic data is increasingly becoming a limiting factor in plant breeding. Genetic studies on root traits are being hampered by the complexity of these traits and the inaccessibility of the rhizosphere. With an increasing interest in phenotyping, breeders and scientists try to overcome these limitations, resulting in impressive developments in automated phenotyping platforms. Recently, many such platforms have been thoroughly described, yet their efficiency to increase genetic gain often remains undiscussed. This efficiency depends on the heritability of the phenotyped traits as well as the correlation of these traits with agronomically relevant breeding targets. This review provides an overview of the latest developments in root phenotyping and describes the environmental and genetic factors influencing root phenotype and heritability. It also intends to give direction to future phenotyping and breeding strategies for optimizing root system functioning. A quantitative framework to determine the efficiency of phenotyping platforms for genetic gain is described. By increasing heritability, managing effects caused by interactions between genotype and environment and by quantifying the genetic relation between traits phenotyped in platforms and ultimate breeding targets, phenotyping platforms can be utilized to their maximum potential.


Prediction of poorer prognosis by infection with antibiotic-resistant gram-positive cocci than by infection with antibiotic-sensitive strains.
Surgical patients with antibiotic-resistant gram-positive coccal (GPC) infections have a poorer prognosis than those with antibiotic-sensitive GPC infections, and colonization with resistant GPC predisposes to the development of resistant GPC infections. All infections among surgical patients from December 1, 1996, to December 1, 1998, were followed up prospectively. Patients with antibiotic-sensitive and antibiotic-resistant GPC infections were compared. Cohorts were also subdivided on the basis of GPC species, colonization status, and immunosuppression. The surgical wards and intensive care units of a tertiary care, university hospital. In-hospital mortality, inhospital mortality during antibiotic therapy, length of stay, and length of stay from the time of initiation of antibiotics to discharge. Antibiotic-resistant GPC infection compared ki4th antibiotic-sensitive GPC infection was associated with a higher mortality and previous colonization rate (25.8% and 31.0% vs 17.6% and 8.8%, respectively; P = .04 and P<.001, respectively) and a markedly longer length of stay (55.0 +/- 3.3 vs 31.0 +/- 2.0 days; P<.001). Length of stay and treatment to discharge times were longer after resistant Staphylococcus aureus infections than after resistant Staphylococcus epidermidis infections. The mortality and length of stay of patients with gentamicin-resistant or vancomycin-resistant enterococcal infections were equivalently higher than those with antibiotic-sensitive enterococcal infections. Transplant recipients with resistant enterococcal infection had the highest mortality (41.9%). Surgical patients who develop antibiotic-resistant GPC infections have a significantly higher mortality rate, longer length of stay, and longer treatment to discharge time than patients with antibiotic-sensitive GPC infections. Colonization with resistant GPC predisposes to resistant GPC infection. Gentamicin-resistant enterococcus appears to be as virulent as vancomycin-resistant enterococcus.


Sun's procedure of total arch replacement using a tetrafurcated graft with stented elephant trunk implantation: analysis of early outcome in 398 patients with acute type A aortic dissection.
Acute type A aortic dissection (AAAD) remains one of the most lethal conditions requiring surgical repair, and is associated with a high rate of postoperative mortality and morbidity. Despite the satisfactory clinical outcomes achieved with the frozen elephant trunk technique so far, controversies still exist regarding the use of this aggressive approach in patients with AAAD. In this study, we seek to analyze the early outcomes of the Sun's procedure, which is an approach integrating total arch replacement using a 4-branched graft with implantation of a special stented graft in the descending aorta, and identify the risk factors for postoperative mortality and morbidity of the Sun's procedure in patients with AAAD. Clinical data of 398 consecutive AAAD patients undergoing the Sun's procedure were analyzed. The associations between 20 preoperative and intraoperative variables and early mortality were assessed by univariate and multivariate analysis. Early mortality occurred in 31 patients (7.8%, 31/398), with leading causes including multi-organ failure in 16 patients (51.6%), permanent neurologic deficit in 6 (19.4%), and low cardiac output syndrome in 4 (12.9%). Permanent neurologic deficit and spinal cord injury occurred, each in 10 patients (2.5%, 10/398). Five significant risk factors for early mortality were identified with multivariate analysis: preexisting cerebrovascular disease [relative risk (RR) 14.76; P<0.001], acute heart failure (RR 18.18; P=0.001), spinal cord malperfusion (RR 60.13; P<0.002), visceral malperfusion (RR 30.25; P<0.001) and cardiopulmonary bypass time >190 minutes (RR 3.62; P=0.007). The Sun's procedure has generated a relatively lower mortality rate in 398 patients with AAAD. Patients with preexisting cerebrovascular disease, acute heart failure, spinal cord malperfusion, visceral malperfusion and long cardiopulmonary bypass time are at a higher risk of early mortality.


Sr65: a widely effective gene for stem rust resistance in wheat.
Sr65 in chromosome 1A of Indian wheat landrace Hango-2 is a potentially useful all-stage resistance gene that currently protects wheat from stem rust in Australia, India, Africa and Europe. Stem rust, caused by Puccinia graminis f. sp. tritici (Pgt), threatened global wheat production with the appearance of widely virulent races that included TTKSK and TTRTF. Indian landrace Hango-2 showed resistance to Pgt races in India and Australia. Screening of a Hango-2/Avocet 'S' (AvS) recombinant inbred line population identified two stem rust resistance genes, a novel gene (temporarily named as SrH2) from Hango-2 and Sr26 from AvS. A mapping population segregating for SrH2 alone was developed from two recombinant lines. SrH2 was mapped on the short arm of chromosome 1A, where it was flanked by KASP markers KASP_7944 (proximal) and KASP_12147 (distal). SrH2 was delimited to an interval of 1.8-2.3 Mb on chromosome arm 1AS. The failure to detect candidate genes through MutRenSeq and comparative genomic analysis with the pan-genome dataset indicated the necessity to generate a Hango-2 specific assembly for detecting the gene sequence linked with SrH2 resistance. MutRenSeq however enabled identification of SrH2-linked KASP marker sunCS_265. Markers KASP_12147 and sunCS_265 showed 92% and 85% polymorphism among an Australian cereal cultivar diversity panel and can be used for marker-assisted selection of SrH2 in breeding programs. The effectiveness of SrH2 against Pgt races from Europe, Africa, India, and Australia makes it a valuable resource for breeding stem rust-resistant wheat cultivars. Since no wheat-derived gene was previously located in chromosome arm 1AS, SrH2 represents a new locus and named as SR65.


Microarray-based detection of mannose-binding lectin 2 (MBL2) polymorphisms in a routine clinical setting.
The assessment of allelic variants in the human mannose-binding lectin 2 (MBL2) gene is of great clinical importance in newborns or immune-suppressed patients at high risk for a variety of infections. Here, we present a study on the genotyping accuracy of a DNA microarray-based on-chip PCR method suited for the detection of five different polymorphisms in the MBL2 gene. We tested 153 genomic DNA samples, prepared from archival blood spots on Guthrie cards, for the presence of allelic variants in the human MBL2 gene by the on-chip PCR method and compared the obtained results of three variants to standard DNA capillary sequencing. The genotyping power of the described assay was readily comparable to DNA sequencing (453/459 correct genotype calls in 153 DNA samples; 98.7% accuracy), mainly due to intrinsic technical benefits of microarrays such as high number of test replicates and automated data analysis. This study demonstrates, for the first time, the accuracy and reliability of a microarray-based on-chip PCR genotyping assay for measuring allelic variants in a routine clinical setting.


Coronary artery bypass grafting supported with intracardiac microaxial pumps versus normothermic cardiopulmonary bypass: a prospective randomized trial.
To analyze the difference in coronary artery bypass grafting (CABG) performed with normothermic cardiopulmonary bypass (CPB) and CABG supported with the intracardiac microaxial pump (ICP, Impella, Aachen, Germany). A prospective randomized study was conducted in seven centers. The study population consists of 199 patients undergoing isolated primary CABG (CPB group 94 patients, ICP group 105 patients). Both groups are equal in demographic variables, number of bypasses performed, and Euroscore predicted mortality. We analyzed clinical outcome, myocardial enzymes and blood parameters of hemolysis, organ function and inflammatory response. Seventeen patients (16%), randomized in the ICP group, were switched to the CPB group. This was due to the inability to position the right side catheter adequately (n=8), to a pump failure (n=1) or to the perioperative decision that beating heart surgery is technically not possible (n=8). There was no significant difference between the two study arms regarding the pump assistance time (CPB 67.1+/-22.9 min; ICP 67.7+/-30.3 min; P=0.88861), the number of grafts (CPB 2.4+/-0.7; ICP 2.3+/-0.8) and the number of grafts to the back wall (CFX; both groups n=37). There is no significant difference in clinical outcome, evolution of myocardial enzymes, indices of organ function and hemolysis. There is a reduced inflammatory response in the ICP group as indicated in the postoperative release of granulocyte elastase (CPB 259+/-195; ICP 150+/-126 microg/l; P<0.00001) and complement C3 (CPB 0.73+/-0.2; ICP 0.65+/-0.2g/l; P=0.008). The intracardiac pump for the right heart is difficult to introduce. As a consequence the right side pump underwent design modifications. There were no differences in clinical outcome between both groups. The inflammatory response is significantly reduced in the ICP group.


Effects of chicken anemia virus on macrophage function in chickens.
One-day-old chicks were inoculated intramuscularly with chicken anemia virus (CAV). Four birds were killed at 7, 14, 21, 28, and 42 days postinoculation (PI), and macrophages were recovered from spleen and bone-marrow suspensions. These were tested for interleukin-1 (IL-1) production, Fc receptor expression, phagocytosis, and bactericidal activity. Macrophages recovered from uninoculated chickens at the same sample times, and exposed to CAV in vitro, were also tested. IL-1 production, Fc receptor expression, phagocytosis, and bactericidal activity were significantly lower in all macrophage cultures from CAV-inoculated chickens, and in cultures exposed to the virus in vitro, than in uninfected controls.


Sub-Saharan Africa descendents in Rio de Janeiro (Brazil): population and mutational data for 12 Y-STR loci.
A male sample of 135 African descendents from the Rio de Janeiro population were typed for the 12 Y-chromosome short tandem repeat (STR) loci included in the PowerPlex Y System. A high haplotype diversity was observed (0.9971), with 91% of haplotypes being unique, demonstrating the usefulness and informative power of this Y-STR set in male lineage identification. Samples with shared haplotypes were additionally typed with the Yfiler kit, which includes five extra markers. The haplotype diversity when using the 17-Yfiler loci increased to (0.9998) with 97% unique haplotypes. The same set of Y-STRs was also typed in 135 father/son pairs and three single-step mutations were observed: one at DYS19 and two at DYS385. Genetic distance analysis showed highly significant differences in all pairwise comparisons between this sample of African descendents and the general population from Rio de Janeiro, as well as with Iberian and African samples from Portugal, Mozambique, Angola and Equatorial Guinea. Comparisons with samples from other regions in Brazil showed that heterogeneity does exist, indicating that a Y-haplotype database for the whole country should take into account the population sub-structure. Moreover, a strong European influence was detected, and thus, a Y-chromosome STR profile proves a rather poor indicator for the ethnic origin of an individual in Rio de Janeiro.


Cancer-related circulating and tumor-associated neutrophils - subtypes, sources and function.
In recent years, the role of neutrophils in cancer biology has been a matter of increasing interest. Many patients with advanced cancer show high levels of neutrophilia, tumor neutrophils are connected to dismal prognosis, and the neutrophil-to-lymphocyte ratio has been introduced as a significant prognostic factor for survival in many types of cancer. Neutrophils constitute an important portion of the infiltrating immune cells in the tumor microenvironment, but controversy has long surrounded the function of these cells in the context of cancer. Multiple evidences have shown that neutrophils recruited to the tumor can acquire either protumor or antitumor function. These findings have led to the identification of multiple and heterogeneous neutrophil subsets in the tumor and circulation. In addition, tumor-associated neutrophils (TANs) were shown to demonstrate functional plasticity, driven by multiple factors present in the tumor microenvironment. In this review, we examine the current knowledge on cancer-related circulating neutrophils, their source and the function of the different subtypes, both mature and immature. We then discuss the pro vs antitumor nature of TANs in cancer, their functional plasticity and the mechanisms that regulate neutrophil recruitment and polarization. Although the vast majority of the knowledge on neutrophils in cancer comes from murine studies, recent work has been done on human cancer-related neutrophils. In the final paragraphs, we expand on the current knowledge regarding the role of neutrophils in human cancer and examine the question whether cancer-related neutrophils (circulating or intratumoral) could be a new possible target for cancer immunotherapy.


Using agent based modeling to assess the effect of increased Bus Rapid Transit system infrastructure on walking for transportation.
The effect of transport infrastructure on walking is of interest to researchers because it provides an opportunity, from the public policy point of view, to increase physical activity (PA). We use an agent based model (ABM) to examine the effect of transport infrastructure on walking. Particular relevance is given to assess the effect of the growth of the Bus Rapid Transit (BRT) system in Bogotá on walking. In the ABM agents are assigned a home, work location, and socioeconomic status (SES) based on which they are assigned income for transportation. Individuals must decide between the available modes of transport (i.e., car, taxi, bus, BRT, and walking) as the means of reaching their destination, based on resources and needed travel time. We calibrated the model based on Bogota's 2011 mobility survey. The ABM results are consistent with previous empirical findings, increasing BRT access does indeed increase the number of minutes that individuals walk for transportation, although this effect also depends on the availability of other transport modes. The model indicates a saturation process: as more BRT lanes are added, the increment in minutes walking becomes smaller, and eventually the walking time decreases. Our findings on the potential contribution of the expansion of the BRT system to walking for transportation suggest that ABMs may prove helpful in designing policies to continue promoting walking.


Synthesis of abnormal immunoglobulins by hybridomas from autoimmune "viable motheaten" mutant mice.
Secretory defects in abnormal plasma cells, called Mott cells, that appear in lymphoid tissues of spontaneously autoimmune, "viable motheaten" (mev/mev) mice lead to deposition of immunoglobulin in RER-bound vesicles. Such vesicles have been termed Russel bodies. Cells with Russel bodies can also be observed rarely in normal animals, usually as a result of extreme antigenic loads or pathologic states. To understand why these abnormal cells appear commonly in mev/mev mice, we have established a panel of hybridomas that contain Russell bodies. Using immunochemical analysis and immunoelectron microscopy, we have characterized the secretory defects. Although these hybridoma cells synthesize a normal size heavy chain and it associates with light chain, the Russell bodies have many characteristics of inclusion bodies, which commonly appear in cells synthesizing mutant proteins and often are associated with incompletely or abnormally folded proteins. Pulse-chase experiments showed that immunoglobulins synthesized by these hybridomas accumulate rapidly into insoluble complexes and have an intracellular half life approximately 10 time greater than normal immunoglobulins. The defect affected only the immunoglobulin derived from the mev/mev mice and did not affect the secretion of normal immunoglobulin produced by an IgG1-secreting fusion partner. In addition to accumulating intracellular immunoglobulins, many mutant cell lines also secreted immunoglobulin. Endoglycosidase H digestion was used to determine the state of processing of the N-linked carbohydrates on the immunoglobulin molecules. This analysis demonstrated that the N-linked carbohydrates on the secreted immunoglobulin were resistant to endoglycosidase H digestion, indicating that they were processed normally. The insoluble IgM molecules were sensitive to endoglycosidase H, which is consistent with their localization to the RER. We propose several models by which these abnormal immunoglobulin-secreting cells commonly appear in this autoimmune mutant mouse.


Duodenal ulcer-related antigens from Helicobacter pylori: immunoproteome and protein microarray approaches.
Helicobacter pylori is an important risk factor of duodenal ulcer (DU). Although many virulence factors of H. pylori have been identified, few have been reported to show an association with the pathogenesis of DU. The aims of this study were to identify H. pylori antigens showing a high seropositivity in DU and to develop a platform for rapid and easy diagnosis for DU. Because DU and gastric cancer (GC) are considered clinical divergent gastroduodenal diseases, we compared two-dimensional immunoblots of an acid-glycine extract of an H. pylori strain from a patient with DU probed with serum samples from 10 patients with DU and 10 with GC to identify DU-related antigens. Of the 11 proteins that were strongly recognized by serum IgG from DU patients, translation elongation factor EF-G (FusA), catalase (KatA), and urease alpha subunit (UreA) were identified as DU-related antigens, showing a higher seropositivity in DU samples (n = 124) than in GC samples (n = 95) (FusA, 70.2 versus 45.3%; KatA, 50.8 versus 41.1%; UreA, 44.4 versus 27.4%). In addition, we found that the use of multiple antigens improved the discrimination between patients with DU and those with GC as the odds ratios increased from 1.82 (95% confidence interval (CI), 0.79-4.21; p = 0.1607) for seropositivity for FusA, KatA, or UreA alone to 4.95 (95% CI, 2.05-12.0; p = 0.0004) for two of the three antigens and to 5.71 (95% CI, 1.86-17.6; p = 0.0024) for all three antigens. Moreover a protein array containing the three DU-related antigens was developed to test the idea of using multiple biomarkers in diagnosis. We conclude that FusA, KatA, and UreA are DU-related antigens of H. pylori, and the combination of these on a protein array provided a rapid and convenient method for detecting serum antibody patterns of DU patients.


Preliminary Analysis of MicroRNAs Expression Profiling in MC3T3-E1 Cells Exposed to Fluoride.
Overexposure to fluoride from environmental sources can cause serious public health problems. Disrupted osteoblast function and impaired bone formation were found to be associated with excessive fluoride exposure. A massive analysis of microRNAs (miRNAs) was used to figure out the possible pathways in which fluoride affects osteoblast function. MC3T3-E1 cells were treated with 8 mg/L of fluorine for 7 days. Total RNA of cells was extracted, and their integrity and purity were tested. RNA samples were analyzed by using miRNA array, including miRNA labeling, hybridization, scanning, and expression data analysis to compare the profiling of miRNA expression between control and fluoride-treated group. Transcriptome analysis console and enrichment analysis calculated by miRSystem were used to predict target genes and collect miRNAs pathway maps. Forty-five upregulated and 31 downregulated miRNAs expression were found in the fluoride-treated group, and most of the verified miRNAs were mature. The KEGG pathway enrichment analysis searched out 36 pathways that scored more than 0.1. These pathways mainly included intracellular signaling, cytokines, metabolism, and cytoskeleton-related pathways. Among them, the Wnt, insulin, TGF-beta, hedgehog, VEGF, and notch pathways in osteoblasts were those mainly affected by fluoride treatment. These results have shown a number of higher level systemic pathways activated by overexposure of fluoride in osteoblastic cells and verified that fluoride affected the molecular crosstalk in the osteoblasts.


Effect of biotin treatment on hepatic gene expression in streptozotocin-induced diabetic rats.
Biotin functions as a coenzyme for four carboxylases involved in energy metabolism in mammals. Besides these classical functions, biotin has novel functions in the cellular processes via the modulation of gene expression. In this study, we examined the alteration of gene expression by biotin administration in the liver of streptozotocin (STZ)-induced diabetic rats. In comparison with the control, the mRNA levels of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase were significantly reduced and glucokinase mRNA was increased 3 h after the administration of biotin or insulin. The expression of hepatocyte nuclear factor 4alpha, one of the transcription factors responsible for gluconeogenic gene expression, was decreased by biotin at both mRNA and protein levels. In addition, forkhead box O1 and sterol regulatory element-binding protein 1c mRNA expression that was enhanced by the insulin treatment was inversely decreased by biotin. These results indicate that biotin repressed the gluconeogenic genes and their transcription factors via a pathway independent of insulin-signaling and could improve the diabetic condition.


Effect of water-to-bean ratio on the contents and compositions of isoflavones in tofu.
The present study investigated the changes of the bioavailable isoflavones, including daidzin, genistin, daidzein, and genistein, during the making of tofu. The amount of extracted daidzin and genistin in soy milk increased with increasing water-to-bean ratios from 5 to 9 and reached the maximum level at the ratios of 9-11. On the other hand, the amount of extracted free isoflavones (daidzein and genistein) was not affected by the water-to-bean ratio at the range of 5-11, and their extracted amounts in soy milk were 2-4-fold those in raw soybean. It is suggested that these free isoflavones are mainly derived from daidzin, genistin, malonyldaidzin, and malonylgenistin through enzymatic hydrolysis during the making of soy milk. Tofu made with water-to-bean ratios of 9:1 and 10:1 had the maximal retentions of daidzin and genistin, which were due to the fine homogeneous network microstructure that is supposed to be more effectively retained through hydrophilic interaction with protein. On the contrary, the retained amount of free isoflavones decreased significantly as the water-to-bean ratio increased from 7 to 11, due to their weakening hydrophobic interaction with protein. In this study it was found that the homogeneous microstructure of tofu improved the retention of hydrophilic daidzin and genistin and that the increased amount of drained water does not significantly reduce their retention in the final tofu products as generally imagined.


Preparation and characterization of intravaginal vardenafil suppositories targeting a complementary treatment to boost in vitro fertilization process.
Vaginal route has been recently considered as a potential route for systemic delivery of drugs with poor oral bioavailability. Vardenafil (VDF) is a relatively new phosphodiesterase-5 inhibitor that exhibits a limited oral bioavailability (≈15%) due to extensive first-pass metabolism. In this study, we attempted to enhance the systemic bioavailability of VDF via its formulation within vaginal suppositories. Witepsol H15 and Suppocire NA50 were adopted as lipophilic suppository bases while polyethylene glycol 4000/400 and glycerogelatin were used as hydrophilic suppository bases. The effect of different base types and/or the incorporation of bioadhesive polymer on in vitro release of VDF were evaluated. The in vivo fate and organ biodistribution of VDF following intravaginal (IVG) administration were also investigated. VDF release from water-soluble bases was higher than that from lipophilic bases. The incorporation of bioadhesive polymers, such as Na alginate, remarkably sustained drug release from suppository base. The organ biodistribution study showed a higher Cmax (32 times) and AUC0-4h (20 times) of VDF in uterus following IVG administration of conventional suppositories, compared to oral administration of VDF suspension. In addition, cyclic guanosine monophosphate (cGMP) serum levels, used as an indicator of the in vivo activity of VDF, in animals were higher following IVG administration rather than oral administration. This study suggests that IVG administration of VDF might represent a potential alternative to oral route with superior therapeutic benefits especially when targeting the uterus.


Stiffness gradients in vascular bundles of the palm Washingtonia robusta.
Palms can grow at sites exposed to high winds experiencing large dynamic wind and gust loads. Their stems represent a system of stiff fibrous elements embedded in the soft parenchymatous tissue. The proper design of the interface of the stiffening elements and the parenchyma is crucial for the functioning of the stem. The strategy of the palm to compromise between stiff fibre caps and the soft parenchymatous tissue may serve as a model system for avoiding stress discontinuities in inhomogeneous and anisotropic fibre-reinforced composite materials. We investigated the mechanical, structural and biochemical properties of the fibre caps of the palm Washingtonia robusta at different levels of hierarchy with high spatial resolution. A gradual decrease in stiffness across the fibre cap towards the surrounding parenchymatous tissue was observed. Structural adaptations at the tissue level were found in terms of changes in cell cross sections and cell wall thickness. At the cell wall level, gradients across the fibre cap were found in the degree of orientation of the microfibrils and in the lignin level and composition. The impact of these structural variations in the local material stiffness distribution is discussed.


Actions of NAD+ on renal brush border transport of phosphate in vivo and in vitro.
Previous studies showed that an increase in NAD+ content in renal cortex in vivo was accompanied by specific inhibition of Na+-dependent inorganic phosphate (Pi) transport across the renal brush border membrane (BBM). Further, in vitro addition of NAD+ to isolated renal BBM vesicles specifically inhibited Na+ gradient-dependent transport of Pi. The present study examined some aspects of the mechanism of this inhibition by NAD+ in vitro and in vivo. When NAD+ was increased in vivo by nicotinamide injection, the apparent Vmax was decreased, but the apparent Km was not different, indicating apparent noncompetitive inhibition. In the presence of 0.3 mM NAD+ added in vitro, the apparent Km for Na+-dependent Pi transport by BBM vesicles was increased, whereas the apparent Vmax was unchanged, indicating apparent competitive inhibition. These changes in apparent Km and apparent Vmax were identical when Pi uptake was measured either at 30-s or at 5-s (the initial rate) incubation times. Inhibition of Pi transport by BBM vesicles in vitro was due primarily to the action of intact added NAD+, although there may be some contribution by isotope dilution due to Pi released from NAD+ by enzymatic hydrolysis. Although in vitro inhibition of Pi transport by added NAD+ was reversed by washing the BBM, the inhibition due to increased NAD+ in vivo persisted after extensive washing of the isolated BBM. The specificity of the inhibitory effect of NAD+ in vivo was indicated by the finding that changes in renal cortical content of ATP or Pi, evoked by loading with glycerol or fructose, did not change BBM transport of Pi.(ABSTRACT TRUNCATED AT 250 WORDS)


Linking symbiont community structures in a model arbuscular mycorrhizal system.
• The influence of plant communities on symbiotic arbuscular mycorrhizal fungal (AMF) communities is difficult to study in situ as both symbionts are strongly influenced by some of the same soil and environmental conditions, and thus we have a poor understanding of the potential links in community composition and structure between host and fungal communities. • AMF were characterized in colonized roots of thermal soil Mimulus guttatus in both isolated plants supporting AMF for only a few months of the growing season and plants growing in mixed plant communities composed of annual and perennial hosts. Cluster and discriminant analysis were used to compare competing models based on either communities or soil conditions. • Mimulus guttatus in adjacent contrasting plant community situations harbored distinct AMF communities with few fungal taxa occurring in both community types. Isolated plants harbored communities of fewer fungal taxa with lower diversity than plants in mixed communities. Host community type was more indicative than pH of AMF community structure. • Our results support an inherent relationship between host plant and AMF community structures, although pH-based models were also statistically supported.


Differential expression of cancer associated proteins in breast milk based on age at first full term pregnancy.
First full term pregnancy (FFTP) completed at a young age has been linked to low long term breast cancer risk, whereas late FFTP pregnancy age confers high long term risk, compared to nulliparity. Our hypothesis was that proteins linked to breast cancer would be differentially expressed in human milk collected at three time points during lactation based on age at FFTP. We analyzed breast milk from 72 lactating women. Samples were collected within 10 days of the onset of lactation (baseline-BL), two months after lactation started and during breast weaning (W). We measured 16 proteins (11 kallikreins (KLKs), basic fibroblast growth factor, YKL-40, neutrophil gelatinase-associated lipocalin and transforming growth factor (TGF) β-1 and -2) associated with breast cancer, most known to be secreted into milk. During lactation there was a significant change in the expression of 14 proteins in women < 26 years old and 9 proteins in women > = 26 at FFTP. The most significant (p < .001) changes from BL to W in women divided by FFTP age (< 26 vs. > = 26) were in KLK3,6, 8, and TGFβ2 in women < 26; and KLK6, 8, and TGFβ2 in women > = 26. There was a significant increase (p = .022) in KLK8 expression from BL to W depending on FFTP age. Examination of DNA methylation in the promoter region of KLK6 revealed high levels of methylation that did not explain the observed changes in protein levels. On the other hand, KLK6 and TGFβ1 expression were significantly associated (r2 = .43, p = .0050). The expression profile of milk proteins linked to breast cancer is influenced by age at FFTP. These proteins may play a role in future cancer risk.


α-((4-Cyanobenzoyl)oxy)-ω-methyl poly(ethylene glycol): a new stabilizer for silver nanoparticles.
The article describes the synthesis and properties of α-((4-cyanobenzoyl)oxy)-ω-methyl poly(ethylene glycol), the first poly(ethylene glycol) stabilizer for metal nanoparticles that is based on a cyano rather than a thiol or thiolate anchor group. The silver particles used to evaluate the effectiveness of the new stabilizer typically have a bimodal size distribution with hydrodynamic diameters of ca. 13 and ca. 79 nm. Polymer stability was evaluated as a function of the pH value both for the free stabilizer and for the polymers bound to the surface of the silver nanoparticles using 1H NMR spectroscopy and zeta potential measurements. The polymer shows a high stability between pH 3 and 9. At pH 12 and higher the polymer coating is degraded over time suggesting that α-((4-cyanobenzoyl)oxy)-ω-methyl poly(ethylene glycol) is a good stabilizer for metal nanoparticles in aqueous media unless very high pH conditions are present in the system. The study thus demonstrates that cyano groups can be viable alternatives to the more conventional thiol/thiolate anchors.


Ketoconazole in the prevention of candidiasis in patients with cancer. A prospective, randomized, controlled, double-blind study.
A prospective, randomized, controlled, double-blind study was performed between 1982 and 1985 to assess the ability of ketoconazole to prevent fungal infections in selected patients with cancer. Fifty-six patients receiving induction chemotherapy for acute leukemia, autologous bone marrow transplant for refractory nonhematopoietic malignant neoplasms, multidrug chemotherapy for malignant lymphoma, or corticosteroids for brain metastases were randomized to receive either oral ketoconazole, 400 mg/d, or placebo and observed until leukopenia resolved or corticosteroid therapy was stopped. Oral candidiasis developed in eight (28%) of 29 patients receiving placebo compared with none of 27 receiving ketoconazole. However, ketoconazole failed to prevent Candida esophagitis and vulvovaginitis in two patients and one patient, respectively. Furthermore, prophylactic use of ketoconazole did not significantly alter the total number of hospital days, febrile days, or antibiotic days or the requirement for amphotericin B in patients with acute leukemia and autologous bone marrow transplant. Since oral candidiasis can be successfully managed by several different treatment modalities when it does occur, we do not think that the routine prophylactic use of ketoconazole is justified.


Predicting and preventing postconcussive problems in paediatrics (5P) study: protocol for a prospective multicentre clinical prediction rule derivation study in children with concussion.
Persistent postconcussive symptoms (PCSs) is the persistence of somatic, cognitive, physical, psychological and/or behavioural changes lasting more than 1 month following concussion. Persistent concussion impacts the quality of life through impaired cognition, memory and attention affecting school performance, mood and social engagement. No large epidemiological studies have determined the true prevalence of persistent concussion symptoms. Validated, easy-to-use prognosticators do not exist for clinicians to identify children at highest risk. The goal of Predicting and Preventing Postconcussive Problems in Pediatrics study is to derive a clinical prediction rule for the development of persistent postconcussion symptoms in children and adolescents presenting to emergency department following acute head injury. This study is a prospective, multicentre cohort study across nine academic Canadian paediatric emergency departments. We will recruit the largest prospective epidemiological cohort of children with concussion. Eligible children will be followed using Post-Concussion Symptom Inventory, a validated tool in children as young as 5 years. Patients will follow-up at 1, 2, 4, 8 and 12 weeks postinjury. The main outcome will be the presence/absence of PCSs defined as three or more persistent concussion symptoms 1 month following the injury. 1792 patients provide adequate power to derive a clinical decision rule using multivariate analyses to find predictor variables sensitive for detecting cases of persistent postconcussion symptoms. Results of this large prospective study will enable clinicians to identify children at highest risk, optimise treatment and provide families with realistic and appropriate anticipatory guidance. Ethics has been obtained through the Children's Hospital of Eastern Ontario Research Ethics Board. Results will be disseminated at international conferences and in four manuscripts to peer-reviewed journals. This study is registered at Clinicaltrials.gov through the US National Institute of Health/National Library of Medicine (NCT01873287; http://clinicaltrials.gov/ct2/show/NCT01873287).


In vitro recordings from area postrema neurons demonstrate responsiveness to adrenomedullin.
Adrenomedullin (ADM) is a recently discovered 52-amino acid peptide that exerts potent vasodilatory effects in the periphery and influences the control of body fluid balance when injected centrally. In this study extracellular single-unit recordings were obtained from 94 AP neurons in rat brain slices. Bath application of ADM (10(-7) M) excited 47% (32 of 68) of cells tested, and these effects were found to be dose dependent from 10(-7) to 10(-9) M. Excitation was maintained during synaptic blockade in a low-Ca2+ artificial cerebrospinal fluid solution, demonstrating direct actions of ADM on these neurons. The remaining cells were either unaffected (n = 25) or inhibited (n = 11) by ADM. ADM (10(-7) M) also influenced the spontaneous activity of 9 (7 inhibited, 2 excited) of 16 neurons located in the nucleus tractus solitarii (NTS). However, these effects could be eliminated during synaptic blockade, suggesting indirect actions of the peptide on NTS neurons. These data demonstrate that a specific population of CNS neurons within the AP are directly influenced by ADM and suggest that ADM may exert its effects on the central control of fluid balance through direct actions at this circumventricular organ.


Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity.
We investigated the contributions of the structural proteins of severe acute respiratory syndrome (SARS) coronavirus (CoV) to protective immunity by expressing them individually and in combinations from a recombinant parainfluenza virus (PIV) type 3 vector called BHPIV3. This vector provided direct immunization of the respiratory tract, the major site of SARS transmission, replication, and disease. The BHPIV3/SARS recombinants were evaluated for immunogenicity and protective efficacy in hamsters, which support a high level of pulmonary SARS-CoV replication. A single intranasal administration of BHPIV3 expressing the SARS-CoV spike protein (S) induced a high titer of SARS-CoV-neutralizing serum antibodies, only 2-fold less than that induced by SARS-CoV infection. The expression of S with the two other putative virion envelope proteins, the matrix M and small envelope E proteins, did not augment the neutralizing antibody response. In absence of S, expression of M and E or the nucleocapsid protein N did not induce a detectable serum SARS-CoV-neutralizing antibody response. Immunization with BHPIV3 expressing S provided complete protection against SARS-CoV challenge in the lower respiratory tract and partial protection in the upper respiratory tract. This was augmented slightly by coexpression with M and E. Expression of M, E, or N in the absence of S did not confer detectable protection. These results identify S among the structural proteins as the only significant SARS-CoV neutralization antigen and protective antigen and show that a single mucosal immunization is highly protective in an experimental animal that supports efficient replication of SARS-CoV.


Infants' and adults' looking behavior does not indicate perceptual distraction for constrained modelled actions - An eye-tracking study.
When observing a novel action, infants pay attention to the model's constraints when deciding whether to imitate this action or not. Gergely et al. (2002) found that more 14-month-olds copied a model's use of her head to operate a lamp when she used her head while her hands were free than when she had to use this means because it was the only means available to her (i.e., her hands were occupied). The perceptional distraction account (Beisert et al., 2012) claims that differences between conditions in terms of the amount of attention infants paid to the modeled action caused the differences in infants' performance between conditions. In order to investigate this assumption we presented 14-month-olds (N=34) with an eye-tracking paradigm and analyzed their looking behavior when observing the head-touch demonstration in the two original conditions. Subsequently, they had the chance to operate the apparatus themselves, and we measured their imitative responses. In order to explore the perceptional processes taking place in this paradigm in adulthood, we also presented adults (N=31) with the same task. Apart from the fact that we did not replicate the findings in imitation with our participants, the eye-tracking results do not support the perceptional distraction account: infants did not statistically differ - not even tendentially - in their amount of looking at the modeled action in both conditions. Adults also did not statistically differ in their looking at the relevant action components. However, both groups predominantly observed the relevant head action. Consequently, infants and adults do not seem to attend differently to constrained and unconstrained modelled actions.


A polarization-sensitive light field imager for multi-channel angular spectroscopy of light scattering in biological tissues.
Angular spectroscopy of light scattering can be used for quantitative analysis of cellular and subcellular properties, and thus promises a noninvasive methodology for in vivo assessment cellular integrity to complement in vitro histological examination. Spatial information is essential for accurate identification of localized abnormalities. However, conventional angular spectroscopy systems only provide single-channel measurement, which suffers from poor spatial resolution or requires time-consuming scanning over extended area. The purpose of this study was to develop a multi-channel angular spectroscopy for light field imaging in biological tissues. A microlens array (MLA) (8×8) based light field imager for 64-channel angular spectroscopy was developed. A pair of crossed polarizers was employed for polarization-sensitive recording to enable quantitative measurement at high signal specificity and sensitivity. The polarization-sensitive light field imager enables rapid measurement of multiple sampling volumes simultaneously at 18 μm spatial-resolution and 3° angular-resolution. Comparative light field imaging and electrophysiological examination of freshly isolated and physiologically deteriorated lobster leg nerves have been conducted. Two-dimensional (2D) polarization-sensitive scattering patterns of the fresh nerves were highly elliptical, while they gradually lost the ellipticity and became rotationally symmetric (i.e., circular) as the nerves physiologically deteriorated due to repeated electrical stimulations. Characterized parameters, i.e., the ellipticity and the scattering intensity, rendered spatially various characteristics such as different values and deteriorating rates. The polarization-sensitive light field imager is able to provide multi-channel angular spectroscopy of light scattering with both spatial and angular resolutions. The light scattering properties of nerves are highly dependent on the orientation of nerves and their physiological status. Further development of polarization-sensitive multi-channel angular spectroscopy may promise a methodology for rapid and reliable identification of localized abnormalities in biological tissues.