Cervical Cancer Control, Priorities and New Directions

Cervical cancer is caused by infection with a range of high risk oncogenic human papillomavirus (HPV) types, and it is now accepted that >99% of cervical cancer is initiated by HPV infection. The estimated lifetime risk of cervical cancer is nevertheless relatively low (less than I in 20 for most community based studies). Although sensitivity and specificity of the available diagnostic techniques are suboptimal, Screening for persistent HPV infection is effective in reducing the incidence of cervical cancer. Infection can be detected by molecular techniques or by cytological examination of exfoliated cervical cells. Persistent infection is the single best predictor of risk of cervical cancer.(1) The latest findings of HPV and cervical cancer research need to be widely disseminated to the scientific and medical societies that are updating screening and management protocols, public health professionals, and to women and clinicians. This report reviews current evidence, clinical implications and directions for further research in the prevention, control and management of cervical cancer. We report the conclusions of the Experts' Meeting at the EUROGIN 2003 conference. (C) 2003 Wiley-Liss, Inc.

The ins and outs of transcriptional control: nucleocytoplasmic shuttling in development and disease

Recent findings relating to SOX transcription factors indicate that defects in organogenesis can be caused not only by impairment of the biochemical properties of transcription factors but also, in some cases, by deficient nuclear import. In addition, experimentally interfering with the nuclear export signals of some SOX factors has now been found to cause developmental defects. Controlling the balance of nuclear import and export might be a common means by which transcription factor activity can be regulated during development, and defects in these processes might underlie a broader spectrum of inherited developmental disorders.

Borrowing from models of motor control to translate cognitive processes: Evidence for hypokinetic-hyperkinetic linguistic homologues?

In relation to motor control, the basal ganglia have been implicated in both the scaling and focusing of movement. Hypokinetic and hyperkinetic movement disorders manifest as a consequence of overshooting and undershooting GPi (globus pallidus internus) activity thresholds, respectively. Recently, models of motor control have been borrowed to translate cognitive processes relating to the overshooting and undershooting of GPi activity, including attention and executive function. Linguistic correlates, however, are yet to be extrapolated in sufficient detail. The aims of the present investigation were to: (1) characterise cognitive-linguistic processes within hypokinetic and hyperkinetic neural systems, as defined by motor disturbances; (2) investigate the impact of surgically-induced GPi lesions upon language abilities. Two Parkinsonian cases with opposing motor symptoms (akinetic versus dystonic/dyskinetic) served as experimental subjects in this research. Assessments were conducted both prior to as well as 3 and 12 months following bilateral posteroventral pallidotomy (PVP). Reliable changes in performance (i.e. both improvements and decrements) were typically restricted to tasks demanding complex linguistic operations across subjects. Hyperkinetic motor symptoms were associated with an initial overall improvement in complex language function as a consequence of bilateral PVP, which diminished over time, suggesting a decrescendo effect relative to surgical beneficence. In contrast, hypokinetic symptoms were associated with a more stable longitudinal linguistic profile, albeit defined by higher proportions of reliable decline versus improvement in postoperative assessment scores. The above findings endorsed the integration of the GPi within cognitive mechanisms involved in the arbitration of complex language functions. In relation to models of motor control, 'focusing' was postulated to represent the neural processes underpinning lexical-semantic manipulation, and 'scaling' the potential allocation of cognitive resources during the mediation of high-level linguistic tasks. (c) 2005 Elsevier Ltd. All rights reserved.

Integrated versus non-integrated management and care for clients with co-occurring mental health and substance use disorders: a qualitative systematic review of randomised controlled trials

The purpose of this paper is to conduct a qualitative review of randomised controlled trials in relation to the treatment of adults with co-occurring mental health and substance use disorder (MH/SUD). In particular, integrated approaches are compared with non-integrated approaches to treatment. Ten articles were identified for inclusion in the review. The findings are equivocal with regard to the superior efficacy of integrated approaches to treatment, although the many limitations of the studies need to be considered in our understanding of this finding. Clearly, this is an extremely challenging client group to engage and maintain in intervention research, and the complexity and variability of the problems render control particularly difficult. The lack of available evidence to support the superiority of integration is discussed in relation to these challenges. Much remains to be investigated with regard to integrated management and care for people with co-occurring and MH/SUD, particularly for specific combinations of dual diagnosis and giving consideration to the level of inter-relatedness between the disorders. (C) 2004 Elsevier Ltd. All rights reserved.

Control of hypersonic turbulent skin friction by boundary-layer combustion of hydrogen

Shvab-Zeldovich coupling of flow variables has been used to extend Van Driest's theory of turbulent boundary-layer skin friction to include injection and combustion of hydrogen in the boundary layer. The resulting theory is used to make predictions of skin friction and heat transfer that are found to be consistent with experimental and numerical results. Using the theory to extrapolate to larger downstream distances at the same experimental conditions, it is found that the reduction in skin-friction drag with hydrogen mixing and combustion is three times that with mixing alone. In application to flow on a flat plate at mainstream velocities of 2, 4, and 6 knits, and Reynolds numbers from 3 X 10(6) to 1 x 10(8), injection and combustion of hydrogen yielded values of skin-friction drag that were less than one-half of the no-injection skin-friction drag, together with a net reduction in heat transfer when the combustion heat release in air was less than the stagnation enthalpy. The mass efficiency of hydrogen injection, as measured by effective specific impulse values, was approximately 2000 s.

Hypothalamic control of bone formation: Distinct actions of leptin and Y2 receptor pathways

Leptin and Y2 receptors on hypothalamic NPY neurons mediate leptin effects on energy homeostasis; however, their interaction in modulating osteoblast activity is not established. Here, direct testing of this possibility indicates distinct mechanisms of action for leptin anti-osteogenic and Y2(-/-) anabolic pathways in modulating bone formation. Introduction: Central enhancement of bone formation by hypothalamic neurons is observed in leptin-deficient oblob and Y2 receptor null mice. Similar elevation in central neuropeptide Y (NPY) expression and effects on osteoblast activity in these two models suggest a shared pathway between leptin and Y2 receptors in the central control of bone physiology. The aim of this study was to test whether the leptin and Y2 receptor pathways regulate bone by the same or distinct mechanisms. Materials and Methods: The interaction of concomitant leptin and Y2 receptor deficiency in controlling bone was examined in Y2(-/-) oblob double mutant mice, to determine whether leptin and Y2 receptor deficiency have additive effects. Interaction between leptin excess and Y2 receptor deletion was examined using recombinant adeno-associated viral vector overproduction of NPY (AAV-NPY) to produce weight gain and thus leptin excess in adult Y2(-/-) mice. Cancellous bone volume and bone cell function were assessed. Results: Osteoblast activity was comparably elevated in oblob, Y2(-/-), and Y2(-/-) oblob mice. However, greater bone resorption in oblob and Y2(-/-) oblob mice reduced cancellous bone volume compared with Y2(-/-). Both wildtype and Y2(-/-) AAV-NPY mice exhibited marked elevation of white adipose tissue accumulation and hence leptin expression, thereby reducing osteoblast activity. Despite this anti-osteogenic leptin effect in the obese AAV-NPY model, osteoblast activity in Y2(-/-) AAV-NPY mice remained significantly greater than in wildtype AAV-NPY mice. Conclusions: This study suggests that NPY is not a key regulator of the leptin-dependent osteoblast activity, because both the leptin-deficient stimulation of bone formation and the excess leptin inhibition of bone formation can occur in the presence of high hypothalamic NPY. The Y2(-/-) pathway acts consistently to stimulate bone formation; in contrast, leptin continues to suppress bone formation as circulating levels increase. As a result, they act increasingly in opposition as obesity becomes more marked. Thus, in the absence of leptin, the cancellous bone response to loss of Y2 receptor and leptin activity can not be distinguished. However, as leptin levels increase to physiological levels, distinct signaling pathways are revealed.

Changes in head and neck position have a greater effect on elbow joint position sense in people with whiplash-associated disorders

Background: It has been shown that perception of elbow joint position is affected by changes in head and neck position. Further, people with whiplash-associated disorders (WAD) present with deficits in upper limb coordination and movement. Objectives: This study is aimed to determine whether the effect of changes in head position on elbow joint position error (JPE) is more pronounced in people with WAD, and to determine whether this is related to the participant's pain and anxiety levels. Methods: Nine people with chronic and disabling WAD and 11 healthy people participated in this experiment. The ability to reproduce a position at the elbow joint was assessed after changes in the position of the head and neck to 30 degrees, and with the head in the midline. Pain was monitored in WAD participants. Results: Absolute elbow JPE with the head in neutral was not different between WAD and control participants (P = 0.5). Changes in the head and neck position increased absolute elbow JPE in the WAD group (P < 0.05), but did not affect elbow JPE in the control group (P = 0.4). There was a connection between pain during testing and the effect of changes in head position on elbow JPE (P < 0.05). Discussion: Elbow JPE is affected by movement of the head and neck, with smaller angles of neck rotation in people with WAD than in healthy individuals. This observation may explain deficits in upper limb coordination in people with WAD, which may be due to the presence of pain or reduced range of motion in this population.

Disorders of breathing and continence have a stronger association with back pain than obesity and physical activity

Although obesity and physical activity have been argued to predict back pain, these factors are also related to incontinence and breathing difficulties. Breathing and continence mechanisms may interfere with the physiology of spinal control, and may provide a link to back pain. The aim of this study was to establish the association between back pain and disorders of continence and respiration in women. We conducted a cross-sectional analysis of self-report, postal survey data from the Australian Longitudinal Study on Women's Health. We used multinomial logistic regression to model four levels of back pain in relation to both the traditional risk factors of body mass index and activity level, and the potential risk factors of incontinence, breathing difficulties, and allergy. A total of 38 050 women were included from three age-cohorts. When incontinence and breathing difficulties were considered, obesity and physical activity were not consistently associated with back pain. In contrast, odds ratios (OR) for often having back pain were higher for women often having incontinence compared to women without incontinence (OR were 2.5, 2.3 and 2.3 for young, mid-age! and older women, respectively). Similarly, mid-aged and older women had higher odds of having back pain often when they experienced breathing difficulties often compared to women with no breathing problems (OR of 2.0 and 1.9, respectively). Unlike obesity and physical activity, disorders of continence and respiration were strongly related to frequent back pain. This relationship may be explained by physiological limitations of co-ordination of postural, respiratory and continence functions of trunk muscles.

Pre-term delivery and periodontal disease: a case-control study from Croatia

Aim: The aim of this report was to assess the strength and influence of periodontitis as a possible risk factor for pre-term birth (PTB) in a cohort of 81 primiparous Croatian mothers aged 18-39 years. Methods: PTB cases (n=17; mean age 25 +/- 2.9 years; age range 20-33 years) were defined as spontaneous delivery after less than 37 completed weeks of gestation that were followed by spontaneous labour or spontaneous rupture of membranes. Controls (full-time births) were normal births at or after 37 weeks of gestation (n=64; mean age 25 +/- 2.9 years; age range 19-39 years). Information on known risk factors and obstetric factors included the current pregnancy history, maternal age at delivery, pre-natal care, nutritional status, tobacco use, alcohol use, genitourinary infections, vaginosis, gestational age, and birth weight. Full-mouth periodontal examination was performed on all mothers within 2 days of delivery. Results: PTB cases had significantly worse periodontal status than controls (p=0.008). Multivariate logistic regression model, after controlling for other risk factors, demonstrated that periodontal disease is a significant independent risk factor for PTB, with an adjusted odds ratio of 8.13 for the PTB group (95% confidence interval 2.73-45.9). Conclusion: Periodontal disease represents a strong, independent, and clinically significant risk factor for PTB in the studied cohort. There are strong indicators that periodontal therapy should form a part of preventive prenatal care in Croatia.

Molecular control of cell type diversity in the developing spinal cord

1, During embryonic development, a diverse array of neurons and glia are generated at specific positions along the dorsoventral and rostro-caudal axes of the spinal cord from a common pool of precursor cells. 2. This cell type diversity can be distinguished by the spatially and temporally coordinated expression of several transcription factors that are also linked to cell type specification at a very early stage of spinal cord development. 3, Recent studies have started to uncover that the generation of cell type diversity in the developing spinal cord. Moreover, distinct cell types in the spinal cord appear to be determined by the spatially and temporally coordinated expression of transcription factors. 4. The expression of these factors also appears to be controlled by gradients of factors expressed by ventral and dorsal midline cells, namely Sonic hedgehog and members of the transforming growth factor-beta family. 5, Changes in the competence of precursor cells and local cell interactions may also play important roles in cell type specification within the developing spinal cord.

A pathology of the animal spirits - the clinical neurology of Thomas Willis (1621-1675) Part I - Background, and disorders of intrinsically normal animal spirits

Thomas Willis (1621-1675), author of the classical work Cerebri Anatome (1664), was arguably the father of the modem era of neurology. As compared with his neuroanatomy, relatively little attention has been paid to Willis' clinical neurology, as described in his Pathologiae Cerebri (1667) and Do Anima Brutorum (1672), where he gave a structured account of disease of the nervous system as it was known in his day. His account was largely derived from personal observations and not from traditional authorities and was based around his concept of the animal spirits, a fictitious entity in many ways analogous to the present day idea of the nerve impulse. This concept allowed him to develop a pathology of the animal spirits which embraced the whole content of the clinical neurology and psychiatry of his times. The anatomical and physiological background to Willis! concepts of animal spirit dysfunction, and those disorders he regarded as due to disturbed function of intrinsically normal animal spirits (mainly headache, disorders of consciousness, apoplexy and palsy) are dealt with in the present paper. The disorders he attributed to inherently abnormal animal spirits are considered in a second part of the paper. (C) 2002 Elsevier Science Ltd. All eights reserved.