Evidence for vagal sensory neural involvement in influenza pathogenesis and disease.

Influenza A virus (IAV) is a common respiratory pathogen and a global cause of significant and often severe morbidity. Although inflammatory immune responses to IAV infections are well described, little is known about how neuroimmune processes contribute to IAV pathogenesis. In the present study, we employed surgical, genetic, and pharmacological approaches to manipulate pulmonary vagal sensory neuron innervation and activity in the lungs to explore potential crosstalk between pulmonary sensory neurons and immune processes. Intranasal inoculation of mice with H1N1 strains of IAV resulted in stereotypical antiviral lung inflammation and tissue pathology, changes in breathing, loss of body weight and other clinical signs of severe IAV disease. Unilateral cervical vagotomy and genetic ablation of pulmonary vagal sensory neurons had a moderate effect on the pulmonary inflammation induced by IAV infection, but significantly worsened clinical disease presentation. Inhibition of pulmonary vagal sensory neuron activity via inhalation of the charged sodium channel blocker, QX-314, resulted in a moderate decrease in lung pathology, but again this was accompanied by a paradoxical worsening of clinical signs. Notably, vagal sensory ganglia neuroinflammation was induced by IAV infection and this was significantly potentiated by QX-314 administration. This vagal ganglia hyperinflammation was characterized by alterations in IAV-induced host defense gene expression, increased neuropeptide gene and protein expression, and an increase in the number of inflammatory cells present within the ganglia. These data suggest that pulmonary vagal sensory neurons play a role in the regulation of the inflammatory process during IAV infection and suggest that vagal neuroinflammation may be an important contributor to IAV pathogenesis and clinical presentation. Targeting these pathways could offer therapeutic opportunities to treat IAV-induced morbidity and mortality.

The swan genome and transcriptome, it is not all black and white.

BACKGROUND: The Australian black swan (Cygnus atratus) is an iconic species with contrasting plumage to that of the closely related northern hemisphere white swans. The relative geographic isolation of the black swan may have resulted in a limited immune repertoire and increased susceptibility to infectious diseases, notably infectious diseases from which Australia has been largely shielded. Unlike mallard ducks and the mute swan (Cygnus olor), the black swan is extremely sensitive to highly pathogenic avian influenza. Understanding this susceptibility has been impaired by the absence of any available swan genome and transcriptome information. RESULTS: Here, we generate the first chromosome-length black and mute swan genomes annotated with transcriptome data, all using long-read based pipelines generated for vertebrate species. We use these genomes and transcriptomes to show that unlike other wild waterfowl, black swans lack an expanded immune gene repertoire, lack a key viral pattern-recognition receptor in endothelial cells and mount a poorly controlled inflammatory response to highly pathogenic avian influenza. We also implicate genetic differences in SLC45A2 gene in the iconic plumage of the black swan. CONCLUSION: Together, these data suggest that the immune system of the black swan is such that should any avian viral infection become established in its native habitat, the black swan would be in a significant peril.

Anabolic-Androgenic Steroid Misuse: Mechanisms, Patterns of Misuse, User Typology, and Adverse Effects.

Anabolic-androgenic steroids (AAS) encompass a broad group of natural and synthetic androgens. AAS misuse is highly prevalent on a global scale, with the lifetime prevalence of AAS misuse in males being estimated to be around 6%, with 15 to 25% of male gym attendees using it at any one time. AAS are associated with sudden cardiac death, neuropsychiatric manifestations, and infertility. The average AAS user is unlikely to voluntarily declare their usage to a physician, with around 1 in 10 actively engaging in unsafe injection techniques. The aim of this paper is to review the current evidence base on AAS with emphasis on mechanisms of action, adverse effects, and user profiles that are most likely to engage in AAS misuse. This paper also reviews terminologies and uses methods specific to the AAS user community.

A delicate balancing act: immunity and immunopathology in human H7N9 influenza virus infections.

PURPOSE OF REVIEW: A delicate balance exists between a protective and detrimental immune response to an invading viral pathogen. Here, we review the latest advancements in our understanding of immunity and immunopathology during H7N9 influenza A virus (IAV) infections and its relevance to disease management and diagnosis. RECENT FINDINGS: Recent studies have highlighted the role of specific leukocytes in the pathogenesis of H7N9 IAV infections and potential diagnostic role that host cytokine profiles can play in forecasting disease severity. Furthermore, alterations in diet have emerged as a possible preventive measure for severe IAV infections. SUMMARY: The recent emergence and continued evolution of H7N9 IAVs have emphasized the threat that these avian viruses pose to human health. Understanding the role of the host immune response in both disease protection and pathogenesis is an essential first step in the creation of novel therapeutic and preventive measures for H7N9 IAV infections.

Hypothesis concerning embodied calendars: A case study of number form, color spreading, and taste-color synaesthesia.

We propose a hypothesis concerning the neural basis of the mental 'calendar' we all carry around in our brains, based on observations we made on a 25year old 'projector synaesthete', EA, who displays some novel and instructive features. In addition to her grapheme-color synaesthesia, she has a circular 'calendar line', laid out vividly in front of her in the horizontal plane with December 31st passing through the middle of her chest and other months arranged in clockwise sequence ending with December on her right (July was 3 feet in front of her). Her access to episodic memories felt, subjectively, as if it was facilitated by her calendar line. Intriguingly, if she turned her sideways to look to the right, the calendar remained 'stuck to the chest' - meaning that it was body centered rather than head centered. Even more surprising is how, when she rotated her head rightward, the left portion of her calendar became "fuzzy", and memories of February and March became less accessible; a striking example of embodied cognition - memories gated by information from neural networks representing the activity of neck muscles. We postulate that the human calendar is mediated by connections between the angular gyrus and hippocampal place and time cells-via the inferior longitudinal fasciculus. Other aspects of EA's synaesthesia were also explored. The colors evoked by graphemes spread outside the grapheme itself, but the spread could be blocked by real as well as illusory contours. These interactions might be mediated by cells signaling illusory contours (in V2) and color/texture sensitive cells in (V4). Tastes also evoked colors, but, intriguingly, the colors were experienced inside her mouth rather than out there in the world. We discuss the deeper implications of these findings for understanding the nature of quale, and the manner in which the self anchors itself in space and time.

The placebo effect and homeopathy.

BACKGROUND: Like other forms of medicine, including Complementary and Alternative Medicine (CAM), homeopathy elicits expectations in patients. The physician-patient relationship, personal and comprehensive treatment and lack of adverse effects are elements in creating positive expectations. Other elements may be associated with negative expectations. METHODS: We conducted a systematic literature review on placebo and nocebo effects in acupuncture and homeopathy using Medline. RESULTS: Findings on the psychophysiological and neuromediating mechanisms of the placebo-nocebo phenomenon are reviewed. Studies of these effects reveal how expectations and unconscious conditioning can be measured by imaging and EEG methods. They result in significant, non-specific therapeutic effects, which may confuse the evaluation of the specific therapeutic effects treatment, hampering selection of the simillimum. CONCLUSIONS: Directions for future research on non-specific therapeutic effects of homeopathy to improve clinical practice and clinical research are discussed.

Myofascial compartments of the hand in relation to compartment syndrome: a cadaveric study.

BACKGROUND: Acute compartment syndrome of the hand is an emergency requiring prompt surgical decompression. This cadaveric study aims to identify the myofascial compartments of the hand by detailed dissection and direct visualization, to provide an accurate anatomical basis for surgical decompression. METHODS: Fourteen fresh-frozen cadaveric hands were dissected. The findings were recorded by still digital photography. RESULTS: There was no well-defined tough fascia overlying the thenar muscles, the hypothenar muscles, or the adductor pollicis. Areolar tissue was present between the individual thenar and hypothenar muscles. A distinct band of fascia was noted over the entire length of the ulnar three dorsal interosseous muscles. A band of fascia was noted over the distal portion of the palmar interossei but not over the proximal aspect. The above findings were found in all 14 specimens. A layer of loose areolar tissue was noted over the dorsal aspect of the first web space in eight specimens, whereas a distinct band of fascia was noted overlying the first dorsal interosseous muscle in the remaining six. CONCLUSIONS: This study has shown that no distinct tough fascia surrounded any of the intrinsic muscles of the hand completely. The thin filmy fascia partially encasing some of the muscles is unlikely to contribute to development of compartment syndrome. It is postulated that the unyielding overlying skin may serve as a constricting layer in addition to the fascia and contribute to raised intracompartmental pressures.

Evaluation of chromatin condensation in human spermatozoa: a flow cytometric assay using acridine orange staining.

The quality of sperm chromatin is an important factor in fertilization and is especially critical where one spermatozoon is artificially selected for fertilizing an egg (as in intracytoplasmic sperm injection). In this study, flow cytometry after staining of human spermatozoa with Acridine Orange was used to study chromatin structure. A method is described for estimating the percentage of cells in a human sperm sample that have completed epididymal maturation in regard to chromatin condensation. Of the 121 samples of the semen that were examined, nine contained a higher percentage of hypocondensed spermatozoa and six samples contained elevated amounts of hypercondensed spermatozoa. In addition to aberrancies in chromatin condensation other defects showed up as satellite populations of spermatozoa with higher than normal ratios of red/green fluorescence after Acridine Orange staining. Such defects were found in 15 semen samples. The use of swim-up and Percoll gradient centrifugation methods was shown to improve the percentage of spermatozoa with normal chromatin structure in some samples with poor initial quality.

Inhibition of bacterial growth in vitro by human ejaculate seminal plasma fraction 1 and its possible practical use in male infertility phenomenon.

PURPOSE: The in vitro bacteriostatic effect on bacteria by a fraction of human ejaculate (HuSePl-Fr1) was studied. METHOD: As bacterial indicators, Pseudomonas aeruginosa (Pa), total coliforms (Tc), fecal coliforms (Fc), Escherichia coli (Ec), and Staphylococcus aureus (Sa) were used. These bacterial strains are known as agents that cause urinary and sexually transmitted infections (STI). RESULTS: Preliminary results suggest that HuSePl-Fr1 has a significant in vitro bacteriostatic effect on Pa and Sa at 42 degrees C. In addition, Pa was inhibited at 37 degrees C after 48 hr incubation. The remaining bacterial indicators were not affected. CONCLUSION: The results indicate a possible protective role of HuSePl-Fr1 in treatment of infertile men due to genital infections.

Multiple malignancies in immunocompetent patients.

We have reported two patients with multiple primary cancers in the presence of normal tests of cellular immune function, including normal natural killer cell activity. Immunodeficiency has been associated with an increased incidence of neoplastic disorders, but the resulting malignancies are unique, consisting of non-Hodgkin's lymphomas and a limited number of carcinomas. Immunosuppressive therapy and AIDS have been associated with aggressive sarcomas. Immunocompetence is of major importance against certain tumors. On the other hand, in spite of the limitations of the clinical evaluation of immunologic function, immunocompetence is insufficient to protect against neoplasia.

Relationship of blood groups and bladder cancer. A retrospective study.

A retrospective study to evaluate the relationship of blood groups of 96 patients with transitional cell carcinoma of the bladder in Israeli population, reports that patients with blood group O had higher grade tumors and higher recurrence rates than the other blood groups, without a difference in the mortality rates.

Immunosuppressant material in human seminal fluid. Inhibition of blast transformation and of NK activity by seminal fluid patients of a male infertility clinic.

Human seminal plasma from normal or patients with abnormal parameters of the ejaculates contains an inhibitory material that expresses potent in vitro inhibitory activity on PHA-M-induced blast transformation and NK activity. Using the test of inhibition of NK activity, the semen samples from individuals with higher concentrations of fructose had higher inhibitory activity. The results described herein suggest that inhibitory activity for blast transformation may be present in the prostatic fluid while the NK inhibition aspects are correlated with the vesicle-marker (fructose). Inhibition of the immune responses by human seminal plasma of the effector functions indicates the interesting implication that soluble factors may indirectly protect against or promote human autoimmune infertility disease.

Effect of the inhibitory material from male genital tract on natural killing activities.

A male inhibitory material (HuSePl-Frl) was separated from normal human seminal plasma by gel filtration on Sephadex G-100. This material has high avidity for cell membranes of human red blood cells (RBC). In vitro, PHA-M-induced blast transformation of human lymphocytes is inhibited by small quantities of HuSePl-Frl. This inhibition was also evident when RBC coated with HuSePl-Frl is added to mitogen stimulated lymphocytes in cultures. Small quantities of HuSePl-Frl are inhibitory to natural killer (NK) cell activation. The modulating role of the HuSePl-Frl in preventing the spermatozoal rejection during fertilization is discussed.

Successful long-term immunotherapy for human seminal plasma anaphylaxis.

Anaphylactic sensitivity to her husband's seminal fluid occurred in a 46-year-old woman six weeks after a hysterectomy. Her husband was azoospermic as a result of an elective vasectomy. A pooled sample of his seminal fluid was used for skin and laboratory tests. Fractionating (Sephadex G100) chromatography was also performed on his seminal fluid. The patient showed positive intracutaneous skin tests to his unfractionated seminal plasma and a Sephadex G100 fraction designated No. 3. This fraction was also passively transferable to a nonallergic volunteer and it stimulated histamine release from the patient's leukocytes. The dose-response effects of this fraction compared with unfractionated seminal plasma in these assays showed greater bioactivity. After informed consent was obtained, the patient was immunized to fraction 3 in a classic desensitization protocol. Two weeks after the final dose of immunotherapy, intercourse was performed without condoms in a medical facility and under the supervision of a physician. No adverse symptoms were experienced by the patient on this occasion. Regular and frequent sexual activity is required to maintain her tolerant state.

In vitro studies in reproductive immunology: 4. Mechanisms of immune response control in human male genital tract.

Fractionation of human seminal plasma by high-speed centrifugation and by gel filtration on Sephadex G-100 produces a high molecular weight component which displays immunosuppressive characteristics. Both materials inhibit mitogen-induced blast transformation of normal human peripheral monocytes, the component isolated by gel filtration being more effective in this regard. Prior treatment with trypsin of the inhibitory material isolated by centrifugation virtually abolishes its inhibitory potency suggesting that an intact protein is essential for biological function. The results also suggest that suppression of the mitogen-induced blast transformation response of cultured monocytes, T- and B-cells can be reversed by the addition of freshly isolated T- or B-cells. The relevance of these experimental observations to problems of human infertility is discussed.