Low dose influenza virus challenge in the ferret leads to increased virus shedding and greater sensitivity to oseltamivir

Ferrets are widely used to study human influenza virus infection. Their airway physiology and cell receptor distribution makes them ideal for the analysis of pathogenesis and virus transmission, and for testing the efficacy of anti-influenza interventions and vaccines. The 2009 pandemic influenza virus (H1N1pdm09) induces mild to moderate respiratory disease in infected ferrets, following inoculation with 106 plaque-forming units (pfu) of virus. We have demonstrated that reducing the challenge dose to 102 pfu delays the onset of clinical signs by 1 day, and results in a modest reduction in clinical signs, and a less rapid nasal cavity innate immune response. There was also a delay in virus production in the upper respiratory tract, this was up to 9-fold greater and virus shedding was prolonged. Progression of infection to the lower respiratory tract was not noticeably delayed by the reduction in virus challenge. A dose of 104 pfu gave an infection that was intermediate between those of the 106 pfu and 102 pfu doses. To address the hypothesis that using a more authentic low challenge dose would facilitate a more sensitive model for antiviral efficacy, we used the well-known neuraminidase inhibitor, oseltamivir. Oseltamivir-treated and untreated ferrets were challenged with high (106 pfu) and low (102 pfu) doses of influenza H1N1pdm09 virus. The low dose treated ferrets showed significant delays in innate immune response and virus shedding, delayed onset of pathological changes in the nasal cavity, and reduced pathological changes and viral RNA load in the lung, relative to untreated ferrets. Importantly, these observations were not seen in treated animals when the high dose challenge was used. In summary, low dose challenge gives a disease that more closely parallels the disease parameters of human influenza infection, and provides an improved pre-clinical model for the assessment of influenza therapeutics, and potentially, influenza vaccines

Concepts of Human Physiology in Ayurveda

‘Human Physiology’, or the study of functional aspects of human body, is designated by the term ‘Śarīra Vicaya’ in Ayurvedic literature. The word ‘Vicaya’ means the special or detailed knowledge. Detailed knowledge of normal human body i.e., ‘Śarīra’, is considered helpful in understanding the factors influencing the health. Though most of the\ud basic concepts of human physiology explained in Ayurveda are strikingly similar to the concepts of modern physiology, some concepts like ‘Ātmā’, ‘Manas’ and ‘Prakrti’ are unique\ud to Ayurveda. Understanding of Physiology in Ayurveda should start with the understanding of innumerable minute individual living units called ‘Śarīra Paramānus’ or ‘Anu Srotāmsi’. These units are now known as cells. A group of such functionally and structurally similar units is called a ‘Dhātu’. These ‘Dhātus’ are almost equivalent to the tissues. Seven such ‘Dhātus’ have been enumerated. Similarly, the individual systems in the body have been\ud designated by the term ‘Sthūla Srotāmsi’ and thirteen such ‘Srotāmsi’ have been described by Caraka. ‘Annavaha Stotas’, for example, stands equivalent to the digestive system and ‘Rasavaha Srotas’ to the cardio vascular system. Apart from these, the functioning of individual systems has also been described in a considerably detailed manner. Cardiovascular system as a closed circuit, role of liver in the functioning of hemopoietic system, functional significance of brain in the neural mechanisms, basics of digestion and metabolism and basics of immunity ‐ are some such topics worth mentioning. Theory of ‘Tridosha’ is another important theory of physiology. This represents the various reciprocally\ud functioning homeostatic mechanisms at various levels of organization. The state of equilibrium among these ‘Doshas’ is responsible for maintenance of health. Three ‘Doshas’ –\ud i.e., ‘Vāta’, ‘Pitta’ and ‘Kapha’ in general, represent neural, endocrine and immune mechanisms respectively and form the basis of neuro‐ immuno‐ endocrinology

Street slang and schizophrenia

We report the case of a 26 year old streetwise young postman who presented with a six month history of reduced occupational and social function, low mood, and lack of motivation. He complained of feeling less sociable and less interested in his friends and of being clumsy and finding it harder to think. He was otherwise fit and healthy, with no physical abnormalities, neurological signs, or objective cognitive impairments. There was no history of a recent stressor that might have precipitated his symptoms. He was referred to a specialist service for patients in the prodromal phase of psychotic illness for further assessment after he had seen his general practitioner and the local community mental health team. The differential diagnosis at this stage was depression, the prodrome of schizophrenia, or no formal clinical disorder. His premorbid occupational and social function had been good. There was no history of abnormal . social, language, and motor development and he left school with two A levels. After three years of service at the post office he had been promoted to a supervisory role. He had a good relationship with his family and had six or so good friends. There has been a number of previous heterosexual relationships, although none in the past year. Aside from smoking cannabis on two occasions when he was 19, there was no history of illicit substance use. Detailed and repeated assessment of his mental state found a normal affect, no delusions, hallucinations, or catatonia, and no cognitive dysfunction. His speech, however, was peppered with what seemed (to his middle class and older psychiatrist) to be an unusual use of words, although he said they were street slang (table).Go It was thus unclear whether he was displaying subtle signs of formal thought disorder (manifest as disorganised speech, including the use of unusual words or phrases, and neologisms) or using a "street" argot. This was a crucial diagnostic distinction as thought disorder is a feature of psychotic illnesses and can indicate a diagnosis of schizophrenia. We sought to verify his explanations using an online dictionary of slang (urbandictionary.com). To our surprise, many of the words he used were listed and the definitions accorded with those he gave (see table). We further investigated whether his speech showed evidence of thought disorder by examining recordings of his speech as he described a series of ambiguous pictures from the thematic apperception test, a procedure that elicits thought disordered speech. His speech was transcribed and rated with the thought and language index, a standardised scale for assessing thought disorder. Slang used in a linguistically appropriate way is not scored as abnormal on this scale. His score was 5.25, primarily reflecting a mild loosening of associations. For example, he described a picture of a boat on a lake thus: "There’s a boat and a tree. There seems to be a reflection. There are no beds, and I wonder why there are no beds. There’s a breeze going through the branches of the tree." His score was outside the normal range (mean for normal controls 0.88, SD 1.15) and indicates subtle thought disorder, equivalent to that evident in remitted patients with schizophrenia (mean in remitted patients 3.89, SD 2.56) but lower than that in patients with formal thought disorder (mean 27.4, SD 8.3). Over the following year his social and occupational functioning deteriorated further, and he developed frank formal thought disorder as well as grandiose and persecutory delusions to the extent that he met DSM-IV criteria for schizophrenia. His speech was assessed as before, and the thought and language index score had increased to 11.75. This mainly reflected abnormalities on items comprising "positive" thought disorder, particularly the use of neologisms such as "chronocolising" and non-sequiturs. To our knowledge this is the first case report to describe difficulties in distinguishing "street" argots from formal thought disorder. It is perhaps not surprising that slang can complicate the assessment of disorganised speech as psychotic illnesses usually develop in young adults, whereas the assessing clinician is often from an older generation (and different sociocultural background) less familiar with contemporary urban slang. Online resources offer a means of distinguishing street argot from neologisms or a peculiar use of words, and linguistic rating scales may be a useful adjunct to clinical assessment when thought disorder is subtle. Differentiating thought disorder from slang can be especially difficult in the context of "prodromal" signs of psychosis, when speech abnormalities, if present, are usually subtle. Nevertheless, accurate speech assessment is important as subtle thought disorder can, as in this case, predate the subsequent onset of schizophrenia, and early detection and treatment of psychosis might be associated with a better long term clinical outcome

When the Sun Prickles Your Nose: An EEG Study Identifying Neural Bases of Photic Sneezing

BACKGROUND: Exposure to bright light such as sunlight elicits a sneeze or prickling sensation in about one of every four individuals. This study presents the first scientific examination of this phenomenon, called 'the photic sneeze reflex'. METHODOLOGY AND PRINCIPAL FINDINGS: In the present experiment, 'photic sneezers' and controls were exposed to a standard checkerboard stimulus (block 1) and bright flashing lights (block 2) while their EEG (electro-encephalogram) was recorded. Remarkably, we found a generally enhanced excitability of the visual cortex (mainly in the cuneus) to visual stimuli in 'photic sneezers' compared with control subjects. In addition, a stronger prickling sensation in the nose of photic sneezers was found to be associated with activation in the insula and stronger activation in the secondary somatosensory cortex. CONCLUSION: We propose that the photic sneeze phenomenon might be the consequence of higher sensitivity to visual stimuli in the visual cortex and of co-activation of somatosensory areas. The 'photic sneeze reflex' is therefore not a classical reflex that occurs only at a brainstem or spinal cord level but, in stark contrast to many theories, involves also specific cortical areas

Evaluation of Occupational Hazards of Workers Working in Vital Tea Factory Tehsil Haroonabad District Bahawalnagar-Pakistan

Background: Occupational health aims at prevention of disease and maintenance of the highest degree of physical, mental and social well-being of workers in all occupations. Occupational health hazards refer to the potential risks to health and safety of workers at their workplaces. Tea factory workers are susceptible to a number of hazards due to physical, biological, mechanical, chemical and psychosocial factors. The present study tries to examine the occupational health hazards faced by the tea factory workers of Vital Tea Factory Tehsil Haroonabad, District Bahawalnagar.Objectives of study: To assess the occupational hazards of the workers working at Vital Tea Factory and to make recommendations for better occupational safety and health measures for workers of the factory. Material & Methods: It was a cross-sectional descriptive study. The place of study was factory workers of Vital Tea Factory, Tehsil Haroonabad, District Bahawalnagar. 63 respondents working in tea factory and they were included in the study and questions were asked to assess the occupational hazards to which the workers are exposed.Results: Results showed that most of the workers of the factory were educated. Only 4 (6.3%) sustained accidental injuries. Among them, finger cut was seen in three respondents and one sustained laceration to finger. With tea dust, 16 (25.4%) workers suffered cough while only 9.5% suffered cough and sneezing. Headache was seen in 10 (15.9%) individuals and tinnitus in only 3 (4.8%). With humidity and increased temperature, 12 (19%) suffered body aches, 3 (4.8%) faced heat cramps. All basic facilities like adequate lighting, fencing around machines, ventilated rooms, food and catering and proper sanitation were provided.Conclusion: This study was conducted to explore health hazards posed to tea factory workers. Tea industry is not a high risk industry as is evident that majority of respondents did not get job related illnesses. It was a pleasant sign that this particular factory is located outside of residential areas of city. Keywords: Occupational Hazards, Injury, Tea Factory Workers. Type of paper: Original Research Article

Effect of voicing and articulation manner on aerosol particle emission during human speech.

Previously, we demonstrated a strong correlation between the amplitude of human speech and the emission rate of micron-scale expiratory aerosol particles, which are believed to play a role in respiratory disease transmission. To further those findings, here we systematically investigate the effect of different 'phones' (the basic sound units of speech) on the emission of particles from the human respiratory tract during speech. We measured the respiratory particle emission rates of 56 healthy human volunteers voicing specific phones, both in isolation and in the context of a standard spoken text. We found that certain phones are associated with significantly higher particle production; for example, the vowel /i/ ("need," "sea") produces more particles than /ɑ/ ("saw," "hot") or /u/ ("blue," "mood"), while disyllabic words including voiced plosive consonants (e.g., /d/, /b/, /g/) yield more particles than words with voiceless fricatives (e.g., /s/, /h/, /f/). These trends for discrete phones and words were corroborated by the time-resolved particle emission rates as volunteers read aloud from a standard text passage that incorporates a broad range of the phones present in spoken English. Our measurements showed that particle emission rates were positively correlated with the vowel content of a phrase; conversely, particle emission decreased during phrases with a high fraction of voiceless fricatives. Our particle emission data is broadly consistent with prior measurements of the egressive airflow rate associated with the vocalization of various phones that differ in voicing and articulation. These results suggest that airborne transmission of respiratory pathogens via speech aerosol particles could be modulated by specific phonetic characteristics of the language spoken by a given human population, along with other, more frequently considered epidemiological variables

Divergent functions for airway epithelial matrix metalloproteinase 7 and retinoic acid in experimental asthma.

The innate immune response of airway epithelial cells to airborne allergens initiates the development of T cell responses that are central to allergic inflammation. Although proteinase allergens induce the expression of interleukin 25, we show here that epithelial matrix metalloproteinase 7 (MMP7) was expressed during asthma and was required for the maximum activity of interleukin 25 in promoting the differentiation of T helper type 2 cells. Allergen-challenged Mmp7(-/-) mice had less airway hyper-reactivity and production of allergic inflammatory cytokines and higher expression of retinal dehydrogenase 1. Inhibition of retinal dehydrogenase 1 restored the asthma phenotype of Mmp7(-/-) mice and inhibited the responses of lung regulatory T cells, whereas exogenous administration of retinoic acid attenuated the asthma phenotype. Thus, MMP7 coordinates allergic lung inflammation by activating interleukin 25 while simultaneously inhibiting retinoid-dependent development of regulatory T cells

Rhinitis in the geriatric population

The current geriatric population in the United States accounts for approximately 12% of the total population and is projected to reach nearly 20% (71.5 million people) by 2030[1]. With this expansion of the number of older adults, physicians will face the common complaint of rhinitis with increasing frequency. Nasal symptoms pose a significant burden on the health of older people and require attention to improve quality of life. Several mechanisms likely underlie the pathogenesis of rhinitis in these patients, including inflammatory conditions and the influence of aging on nasal physiology, with the potential for interaction between the two. Various treatments have been proposed to manage this condition; however, more work is needed to enhance our understanding of the pathophysiology of the various forms of geriatric rhinitis and to develop more effective therapies for this important patient population

Traditional Chinese Medicine ZHENG Identification Provides a Novel Stratification Approach in Patients with Allergic Rhinitis

Background. We aimed to apply the ZHENG identification to provide an easy and useful tool to stratify the patients with allergic rhinitis (AR) through exploring the correlation between the quantified scores of AR symptoms and the TCM ZHENGs. Methods. A total of 114 AR patients were enrolled in this observational study. All participants received the examinations of anterior rhinoscopy and acoustic rhinometry. Their blood samples were collected for measurement of total serum immunoglobulin E (IgE), blood eosinophil count (Eos), and serum eosinophil cationic protein (ECP). They also received two questionnaire to assess the severity scores of AR symptoms and quantified TCM ZHENG scores. Multiple linear regression analysis was used to determine explanatory factors for the score of AR manifestations. Results. IgE and ECP level, duration of AR, the 2 derived TCMZHENG scores of “Yin-Xu − Yang-Xu”, and “Qi-Xu + Blood-Xu” were 5 explanatory variables to predict the severity scores of AR symptoms. The patients who had higher scores of “Yin-Xu − Yang-Xu” or “Qi-Xu + Blood-Xu” tended to manifest as “sneezer and runner” or “blockers,” respectively. Conclusions. The TCM ZHENG scores correlated with the severity scores of AR symptoms and provided an easy and useful tool to stratify the AR patients