Towards a computational reconstruction of the electrodynamics of premature and full term human labour

We apply virtual tissue engineering to the full term human uterus with a view to reconstruction of the spatiotemporal patterns of electrical activity of the myometrium that control mechanical activity via intracellular calcium. The three-dimensional geometry of the gravid uterus has been reconstructed from segmented in vivo magnetic resonance imaging as well as ex vivo diffusion tensor magnetic resonance imaging to resolve fine scale tissue architecture. A late-pregnancy uterine smooth muscle cell model is constructed and bursting analysed using continuation algorithms. These cell models are incorporated into partial differential equation models for tissue synchronisation and propagation. The ultimate objective is to develop a quantitative and predictive understanding of the mechanisms that initiate and regulate labour.     

Using a graph of the abnormal predictive value versus the positive predictive value for the determination of outlier laboratories in the National Health Service cervical screening programme

R.G. Blanks Using a graph of the abnormal predictive value versus the positive predictive value for the determination of outlier laboratories in the National Health Service cervical screening programme. Objective: The positive predictive value (PPV) for the detection of cervical intraepithelial neoplasia (CIN) grade 2 or worse of referral to colposcopy from moderate dyskaryosis or worse (equivalent to high‐grade squamous intraepithelial lesion or worse) is a standard performance measure in the National Health Service cervical screening programme. The current target is to examine ‘outlier’ laboratories with PPVs outside the 10th–90th percentile, which automatically identifies 20% of laboratories for further investigation. A more targeted method of identifying outliers may be more useful. Methods: A similar measure to the PPV, the abnormal predictive value (APV), can be defined as the predictive value for CIN2 or worse for referrals from borderline (includes atypical squamous and glandular cells) and mild dyskaryosis (equivalent to low‐grade squamous intraepithelial lesion) combined. A scatter plot of the APV versus the PPV can be produced (the APV‐PPV diagram). Three kinds of ‘outlier’ can be defined on the diagram to help determine laboratories with unusual data. These are termed a true outlier value (TOV) or an extreme value (EV) for either PPV or APV, or a residual extreme value (REV) from the APV‐PPV best line of fit. Results: Using annual return information for 2007/8 from 124 laboratories, two were defined as having EVs for PPV (both had a relatively low PPV of 62%). For APV, four laboratories were considered to have EVs of 34%, 34%, 34% and 4% and one was considered to be a TO with an APV of 45%. Five were identified as REV laboratories, although three of these were also identified as having extreme or outlier values, leaving two that had not been identified by the other methods. A total of eight (6%) laboratories were therefore identified as meriting further investigation using this methodology. Conclusions: The method proposed could be a useful alternative to the current method of identifying outliers. Slide exchange studies between the identified laboratories, particularly those at opposing ends of the diagram, or other further investigations of such laboratories, may be instructive in understanding why such variation occurs, and could therefore potentially, lead to improvements in the national programme.     

Herbal medicine use in the districts of Nakapiripirit, Pallisa, Kanungu, and Mukono in Uganda

ABSTRACT: BACKGROUND: Traditional medicine (TM) occupies a special place in the management of diseases in Uganda. Not with standing the many people relying on TM, indigenous knowledge (IK) related to TM is getting steadily eroded. To slow down this loss it is necessary to document and conserve as much of the knowledge as possible. This study was conducted to document the IK relevant to traditional medicine in the districts of Mukono, Nakapiripirit, Kanungu and Pallisa, in Uganda. METHODS: An ethnobotanical survey was conducted between October 2008 and February 2009 using techniques of key informant interviews and household interviews. RESULTS: The common diseases and conditions in the four districts include malaria, cough, headache, diarrhea, abdominal pain, flu, backache and eye diseases. Respondents stated that when they fall sick they self medicate using plant medicines or consult western-trained medicine practitioners. Self medication using herbal medicines was reported mostly by respondents of Nakapiripirit and Mukono. Respondents have knowledge to treat 78 ailments using herbal medicines. 44 species, mentioned by three or more respondents have been prioritized. The most frequently used part in herbal medicines is the leaf, followed by the stem and root. People sometime use animal parts, soil, salt and water from a grass roof, in traditional medicines. Herbal medicines are stored for short periods of time in bottles. The knowledge to treat ailments is acquired from parents and grandparents. Respondents' age and tribe appears to have a significant influence on knowledge of herbal medicine, while gender does not. CONCLUSION: This survey has indicated that IK associated with TM stills exists and that TM is still important in Uganda because many people use it as a first line of health care when they fall sick. Age and tribe influence the level of IK associated with herbal medicine, but gender does not.     

Characterization of the tissue‐level Ca2+ signals in spontaneously contracting human myometrium

In the labouring uterus, millions of myocytes forming the complex geometrical structure of myometrium contract in synchrony to increase intrauterine pressure, dilate the cervix and eventually expel the foetus through the birth canal. The mechanisms underlying the precise coordination of contractions in human myometrium are not completely understood. In the present study, we have characterized the spatio‐temporal properties of tissue‐level [Ca²⁺]_i transients in thin slices of intact human myometrium. We found that the waveform of [Ca²⁺]_i transients and isotonic contractions recorded from thin slices was similar to the waveform of isometric contractions recorded from the larger strips in traditional organ bath experiments, suggesting that the spatio‐temporal information obtained from thin slices is representative of the whole tissue. By comparing the time course of [Ca²⁺]_i transients in individual cells to that recorded from the bundles of myocytes we found that the majority of myocytes produce rapidly propagating long‐lasting [Ca²⁺]_i transients accompanied by contractions. We also found a small number of cells showing desynchronized [Ca²⁺]_i oscillations that did not trigger contractions. The [Ca²⁺]_i oscillations in these cells were insensitive to nifedipine, but readily inhibited by the T‐type Ca²⁺ channel inhibitor NNC55‐0396. In conclusion, our data suggest that the spread of [Ca²⁺]_i signals in human myometrium is achieved via propagation of long‐lasting action potentials. The propagation was fast when action potentials propagated along bundles of myocytes and slower when propagating between the bundles of uterine myocytes.     

Treatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients

Background

Bone marrow stromal cell antigen 2 (BST-2) is a cellular factor that restricts the egress of viruses such as human immunodeficiency virus (HIV-1) from the surface of infected cells, preventing infection of new cells. BST-2 is variably expressed in most cell types, and its expression is enhanced by cytokines such as type I interferon alpha (IFN-??). In this present study, we used the beta-retrovirus, mouse mammary tumor virus (MMTV) as a model to examine the role of mouse BST-2 in host infection in vivo.

Results

By using RNA interference, we show that loss of BST-2 enhances MMTV replication in cultured mammary tumor cells and in vivo. In cultured cells, BST-2 inhibits virus accumulation in the culture medium, and co-localizes at the cell surface with virus structural proteins. Furthermore, both scanning electron micrograph (SEM) and transmission electron micrograph (TEM) show that MMTV accumulates on the surface of IFN??-stimulated cells.

Conclusions

Our data provide evidence that BST-2 restricts MMTV release from naturally infected cells and that BST-2 is an antiviral factor in vivo.     

ABC3 Part II: a review of the new criteria for evaluating cervical cytology in England

R.G. Blanks
ABC3 Part II: a review of the new criteria for evaluating cervical cytology in England The new Achievable Standards, Benchmarks for Reporting, and Criteria for Evaluating Cervical Cytopathology, 3rd edn (ABC3) includes radical changes in the criteria for evaluating cervical cytology. First, they include a new mission statement ‘the objective of cervical screening is to reduce cervical cancer incidence and mortality by screening with a high sensitivity for the detection of CIN2 or worse, whilst maintaining a high specificity’. Second, the original four performance measurement criteria where laboratories were examined further if they were below the 10th or above the 90th percentile has been changed to three and laboratories are only mandatorily examined if they fall below the 5th or above the 95th percentile. The old criteria related to the percentage of samples that were inadequate, the percentage of all adequate samples reported as moderate dyskaryosis or worse (equivalent to high‐grade squamous intraepithelial lesion or cancer), the percentage of adequate samples reported as mild dyskaryosis or borderline (equivalent to low‐grade squamous intraepithelial lesion or atypical squamous/glandular cells) and the positive predictive value. The new criteria are percentage of inadequate samples, positive predictive value and a new measure termed referral value. These changes mean that far fewer laboratories will require mandatory examination. Third, a raft of optional performance measures have been introduced to help laboratories examine their annual statistical return to the Department of Health in comparison with other laboratories. These measures have been designed to produce a more uniform national programme, and to help laboratories decide whether they are maximizing the benefit of screening while minimizing the harm, which is the goal of all screening programmes. This review examines in detail the new criteria and explains in more detail some of the thinking behind them.     

Lack of association between glucocorticoid use and presence of the metabolic syndrome in patients with rheumatoid arthritis: a cross-sectional study

Lupus nephritis is a major contributor to morbidity and mortality in systemic lupus erythematosus, but little is known about the pathogenic processes that underlie the progressive decay in renal function. A common finding in lupus nephritis is thickening of glomerular basement membranes associated with immune complex deposition. It has been speculated that alterations in the synthesis or degradation of membrane components might contribute to such changes, and thereby to initiation and progression of nephritis through facilitation of immune complex deposition. Matrix metalloproteinases (MMPs) are enzymes that are intimately involved in the turnover of major glomerular basement membrane constituents, including collagen IV and laminins. Alterations in the expression and activity of MMPs have been described in a number of renal diseases, suggesting their relevance to the pathogenesis of various glomerulopathies. The same is true for their natural inhibitors, the tissue inhibitor of metalloproteinase family. Recent data from our group have identified an increase in proteolytic activity within the glomerulus coinciding with the development of proteinuria in the mouse model of systemic lupus erythematosus. (NXB × NZW)F₁ Here we review current understanding of MMP/tissue inhibitor of metalloproteinase function within the kidney, and discuss their possible involvement in the development and progression of lupus nephritis.     

赤红壤早稻田甲烷排放通量及其影响因素

用封闭箱法对广东省赤红壤早稻田CH4排放通量进行了观测。结果表明,CH4排放有明显的季节变化规律,3个排放高峰分别出现在水稻分蘖末期、孕穗抽穗期和乳熟期,平均通量为5.7mg.m-2.h-1。在测定期内,CH4排放与5和10cm土壤温度呈显著正相关,与土壤Eh呈显著负相关,与土壤pH值、水层深浅相关不明显。