Population Impact of Sugar-Sweetened Beverages on Dental Caries and Overweight/Obesity in Australian Children.

KNOWLEDGE TRANSFER STATEMENT: The reported findings greatly consolidated evidence of detrimental effects of sugars intake on child oral health and overweight and obesity, some of the most prevalent chronic conditions in children. Evidence on population impact of sugars intake is directly informative to policy makers and the public about the potential impact of population-based programs targeting sugars intake to prevent dental caries and overweight and obesity.

Oral health of community-dwelling older Australian men: the Concord Health and Ageing in Men Project (CHAMP).

BACKGROUND: The Concord Health and Ageing in Men Project (CHAMP) is a cohort study of the health of a representative sample of Australian men aged 70 years and older. The aim of this report is to describe the oral health of these men. METHODS: Oral health was assessed when the men were all aged 78 years or older. Two calibrated examiners conducted a standardized intraoral assessment. Descriptive data were analysed by statistical association tests. Participants were excluded from the collection of some periodontal assessments if they had a medical contraindication. RESULTS: Dental assessments of 614 participants revealed 90 (14.6%) were edentate. Men had a mean of 13.8 missing teeth and 10.3 filled teeth. Dentate participants had a mean of 1.1 teeth with active coronal decay. Those in the low-income group had a higher rate of decayed teeth and lower rate of filled teeth. Thirty-four participants (5.5%) had one or more dental implants, and 66.3% relied on substitute natural teeth for functional occlusion. Of those with full periodontal assessments; 90.9% had sites with pocket depths of 3 mm or more, 96.6% had sites with CAL of 5 mm or more, and 79.7% had three or more sites with GI scores of 2 or more. CONCLUSIONS: There was a high prevalence of periodontal diseases and restorative burden of dentitions, which suggests that greater attention needs to be given to prevention and health maintenance in older Australian men.

Awareness of forensic odontology among dentists in Australia: are they keeping forensically valuable dental records?

BACKGROUND: Forensic odontologists provide an important service to the community by identifying unknown deceased people, allowing both legal outcomes and family closure. Non-visual identification may be achieved by comparison of post-mortem data with ante-mortem dental records provided by oral health practitioners. Success is dependent largely on the accuracy and adequacy of data in the dental records. METHODS: An online self-administered questionnaire evaluated Australian dentists' knowledge and behaviours relevant to forensic odontology. Reported record keeping practices were assessed for detail, legibility, accessibility and retention. Behaviours were classified according to the frequency of response. RESULTS: Dentists reported overall reasonable awareness of the major applications of forensic odontology. Personal information and details of restorative treatment were recorded at high levels, while tooth anomalies, photography, additional patient details and denture marking were recorded inadequately. Legible tooth coding was reported at a high level, while other key legibility practices were recorded inadequately. Few of the behaviours related to retention or to maximize accessibility were recorded at a high level. CONCLUSIONS: Australian dentists have high expectations of the forensic value of their dental records; however, many processes that would enhance the diagnostic, medico-legal and forensic value of dental records are not routinely applied.

New ASCO/CAP guideline recommendations for HER2 testing increase the proportion of reflex in situ hybridization tests and of HER2 positive breast cancers.

Accurate determination of tumour human epidermal growth factor receptor type 2 (HER2) status is critical for optimal treatment of breast cancer. In October 2013, the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) issued joint updated guideline recommendations for HER2 testing in breast cancer, with a revised algorithm for interpretation of immunohistochemistry (IHC) and in situ hybridisation (ISH) results. This study investigates the impact on HER2 IHC categorisation, implication for reflex ISH testing and potential for identification of false negative IHC. HER2 IHC preparations on 251 invasive breast tumours, originally reported according to 2007 guidelines, were re-scored using 2013 guidelines and the diagnostic categories compared. The results of ISH testing on a separate cohort of 32 breast tumours reported as HER2 IHC 2+ following the introduction of the 2013 guidelines, that would have been designated 1+ according to 2007, were reviewed. Application of 2013 guidelines resulted in a decrease in tumours classified as HER2 negative (83/251 vs 144/251) and a comparable increase in those classified as equivocal (2+) (139/251 vs 80/251). Relatively few tumours were re-classified as positive (29/251 vs 27/251). Furthermore, 3/32 breast cancer cases (HER2 IHC 2+ as per 2013 guidelines, 1+ using 2007 guidelines) were HER2 ISH positive. Application of the 2013 guidelines increases the HER2 IHC equivocal (2+) category and requirement for reflex ISH testing. The reduced threshold for ISH testing identifies some patients with HER2 positive breast cancer whose tumours would have been categorised as HER2 negative according to the 2007 guidelines.

Urban-rural differences of gynaecological malignancies in Egypt (1999-2002).

OBJECTIVE: In previous studies, we have shown a three to four times higher urban incidence of breast cancer and estrogen receptor-positive breast cancers in the Gharbiah Province of Egypt. We investigated the urban-rural incidence differences of gynaecologic malignancies (uterine, ovarian and cervical cancers) to explore if they show the same trend that we found for breast cancer. DESIGN: Cancer registry-based incidence comparison. SETTING: Gharbiah population-based cancer registry (GPCR), Tanta, Egypt. SAMPLE: All patients with uterine, ovarian and cervical cancer in GPCR from 1999 to 2002. METHODS: We calculated uterine, ovarian and cervical cancer incidence from 1999 to 2002. For each of the three cancers, we calculated the overall and age-specific rates for the province as a whole, and by urban-rural status, as well as for the eight districts of the province. RESULTS: Incidence of all three cancer sites was higher in urban than in rural areas. Uterine cancer showed the highest urban-rural incidence rate ratio (IRR = 6.07, 95% CI = 4.17, 8.85). Uterine cancer also showed the highest urban incidence in the oldest age group (70+ age category, IRR = 14.39, 95% CI = 4.24, 48.87) and in developed districts (Tanta, IRR = 4.14, 95% CI = 0.41, 42.04). Incidence rates by groups of cancer sites showed an increasing gradient of urban incidence for cancers related to hormonal aetiology, mainly of the breast and uterus (IRR = 4.96, 95% CI = 2.86, 8.61). CONCLUSIONS: The higher urban incidence of uterine cancer, coupled with our previous findings of higher incidence of breast cancer and estrogen receptor positive breast cancer in urban areas in this region, may be suggestive of possible higher exposure to environmental estrogenic compounds, such as xenoestrogens, in urban areas.

A comparison of population-based cancer incidence rates in Israel and Jordan.

Reliable information about comparative cancer incidence in the Middle East has been lacking. The Middle East Cancer Consortium (MECC) has formed a network of population-based registries with standardized basic data. Here the age-adjusted cancer incidences are compared for four populations: Israeli Jews, Israeli non-Jews, Jordanians and the US Surveillance Epidemiology and End Results (SEER) population, for the years 1996-1997 (Israel) and 1996-1998 (other populations). The all-sites rate of cancer is approximately twice as high in Israeli Jews and SEER, compared with Israeli non-Jews and Jordanians. Rates of lung cancer are similar among Israeli Jews and non-Jews and about twice as high as in Jordanians. Childhood leukaemia rates in Jordan are higher than in Israeli Jews, but lower than SEER. Hodgkin lymphoma rates in Israeli non-Jews and Jordanians are similar to SEER, but non-Hodgkin lymphoma rates are lower than SEER. The previous suspicion of higher overall leukaemia and lymphoma rates in Jordan is thus not confirmed.

Modelling muscle motor conformations using low-angle X-ray diffraction.

New results on myosin head organization using analysis of low-angle X-ray diffraction patterns from relaxed insect flight muscle (IFM) from a giant waterbug, building on previous studies of myosin filaments in bony fish skeletal muscle (BFM), show that the information content of such low-angle diffraction patterns is very high despite the 'crystallographically low' resolution limit (65 A) of the spacings of the Bragg diffraction peaks being used. This high information content and high structural sensitivity arises because: (i) the atomic structures of the domains of the myosin head are known from protein crystallography; and (ii) myosin head action appears to consist mainly of pivoting between domains which themselves stay rather constant in structure, thus (iii) the intensity distribution among diffraction peaks in even the low resolution diffraction pattern is highly determined by the high-resolution distribution of atomically modelled domain mass. A single model was selected among 5000+ computer-generated variations as giving the best fit for the 65 reflections recorded within the selected resolution limit of 65 A. Clear evidence for a change in shape of the insect flight muscle myosin motor between the resting (probably like the pre-powerstroke) state and the rigor state (considered to mimic the end-of-powerstroke conformation) has been obtained. This illustrates the power of the low-angle X-ray diffraction method. The implications of these new results about myosin motor action during muscle contraction are discussed.

The use of Lenticules for the process control of enumeration techniques in food and environmental microbiology.

AIMS: Lenticules consist of control-dried plano convex discs in which biologically-active materials are contained within a water-soluble matrix. They can be produced to contain stable numbers of bacteria from 10 cfu lenticule-1 to 108 cfu lenticule-1 with a wide variety of organisms. These experiments were carried out to validate their use as a tool for internal quality control in quantitative microbiology. METHODS AND RESULTS: The Lenticules were used routinely in standard quantitative microbiological procedures across five laboratories. Results showed the materials to be stable, homogeneous and capable of identifying systematic errors. CONCLUSIONS: The Lenticules provide suitable, stable control materials. SIGNIFICANCE AND IMPACT OF THE STUDY: Routine internal quality control of quantitative measurements is greatly improved; the materials are easy to use and enable comparisons between laboratories to be made.

Cancer registration in the Middle East.

This project signals an advance in cancer registration in the Middle East region. While it is too early to declare a major breakthrough, significant strides have been made toward establishing a basis for reliable information on the cancer burden at a population level and future collaborative efforts in cancer epidemiologic research and prevention.

Conformation of the myosin motor during force generation in skeletal muscle.

Myosin motors drive muscle contraction, cytokinesis and cell locomotion, and members of the myosin superfamily have been implicated in an increasingly diverse range of cell functions. Myosin can displace a bound actin filament several nanometers in a single interaction. Crystallographic studies suggest that this 'working stroke' involves bending of the myosin head between its light chain and catalytic domains. Here we used X-ray fiber diffraction to test the crystallographic model and measure the interdomain bending during force generation in an intact single muscle fiber. The observed bending has two components: an elastic distortion and an active rotation that generates force. The average bend of the force-generating myosin heads in a muscle fiber is intermediate between those in crystal structures with different bound nucleotides, and the C-terminus of the head is displaced by 7 nm along the actin filament axis compared with the in vitro conformation seen in the absence of nucleotide.

Myosin rod-packing schemes in vertebrate muscle thick filaments.

Muscle myosin filament backbones are known to be aggregates of long coiled-coil alpha-helical myosin rods, but the packing arrangement is not understood in detail. Here we present new data on fish muscle myosin filaments from low-angle X-ray diffraction and from freeze-fracture, deep-etch electron microscopy which put constraints on the kind of models that might explain all of the observations. In particular, it is known in the case of vertebrate striated muscle thick filaments that the myosin head array in resting muscle is not perfectly helical but contains periodic perturbations. We show by analysis of low-angle X-ray diffraction patterns from resting bony fish muscle that any radial, azimuthal, and axial perturbations of the myosin head origins on the filament surface (due to perturbed myosin rod packing) must all be rather small and that the main perturbations are in the myosin head configurations (i.e., tilts, slews, rotations) on those origins. We provide evidence that the likely arrangement of titin molecules on the myosin filament is with them aligned parallel to the filament long axis, rather than following helical tracks. We also show from freeze-fracture studies of fish muscle that the myosin filament backbone (including titin and other extra proteins) has a radius of about 65-75 A and appears to contain a small (approximately 15-20 A radius) hollow core. Together with previously published evidence showing that the myosin rods are nearly parallel to the thick filament long axis, these results are consistent with the curved crystalline layer model of Squire (J. M. Squire, 1973, J. Mol. Biol. 77, 291-323), and they suggest a general structure for the C-zone part of the thick filament

Myosin crossbridge configurations in equilibrium states of vertebrate skeletal muscle. Heads swing axially or turn upside-down between resting and rigor.

The positions and orientations of the myosin heads in relaxed, active, rigor and S1-labelled fish muscle are being determined by analysis both of electron micrographs and of low-angle X-ray diffraction patterns. The X-ray analysis of resting muscle makes use of the head shape defined from the study of S1 crystals, with variable head configurational parameters being used on each of the three different 3-fold symmetric 14.3 nm-spaced 'crowns' of myosin heads within the 42.9 nm axial repeat of the myosin filaments. Diffraction patterns were stripped using CCP13 fibre diffraction software. Searches and optimisation were carried out using simulated annealing and local refinement procedures to give a 'best fit' relaxed structure with a crystallographic R-factor of about 4%. It had heads oriented all the same way up (i.e. with similar rotations around their own long axes) on the myosin filament, but with a small range of axial tilts. Head configuration in rigor fish muscle is being determined by X-ray diffraction and electron microscopy of normal rigor muscle and of skinned muscle soaked with extrinsic myosin S1. Computed 3-D reconstructions of acto-S1 using X-ray amplitudes and phases from electron microscopy are informative and help to analyse the X-ray diffraction data that extend axially to about 1 nm resolution. An ambiguity is the axial direction of the observed resting myosin head array relative to the known polarity of the actin filaments. One polarity would give little axial displacement (2-3 nm) between opposite ends of the resting and rigor heads, and in this case the heads would need to rotate around their own long axes by about 115 degrees to make a rigor attachment. The other (preferred) filament polarity would provide considerable axial swinging (14-15 nm) between the two states. We are attempting to define the absolute polarity of the resting muscle myosin head array using electron microscopy and image processing either of cryo-sections or of replicas from shadowed, freeze-fractured, rapidly frozen fish muscle fibres.

Myosin head configuration in relaxed fish muscle: resting state myosin heads must swing axially by up to 150 A or turn upside down to reach rigor.

The arrangement and shape of myosin heads in relaxed muscle have been determined by analysis of low-angle X-ray diffraction data from a very highly ordered vertebrate muscle in bony fish. This reveals the arrangement and interactions between the two heads of the same myosin molecule, the shape of the resting myosin head (M.ADP.Pi) assuming a putative hinge between the myosin catalytic domain and the light chain binding-domain, and the way that the actin-binding sites on myosin are arrayed around the actin filaments in the bony fish muscle A-band cell unit. The results are discussed in terms of possible force-generating mechanisms. Changes in myosin head shape or tilt have been implicated in the mechanism of force generation. The myosin head arrangement, including perturbations from perfect helical symmetry, has all heads oriented roughly the same way up (there is only a small range of rotations around the head long axis). X-ray data do not define the absolute polarity of the myosin head array. The resting head rotation is either similar to (65 degrees difference) or opposite to (115 degrees difference) the rotation in the rigor state. If the rotations are similar, probably the more likely possibility, then the average relative axial displacement of the inner and outer ends of the heads from the resting state to rigor is about 140 to 150 A. If (less likely) the resting head rotation is opposite to rigor, then the heads would need to turn over (i.e. rotate about 115 degrees around their own long axes) and the mean relative axial displacement from relaxed to rigor would only be 20 to 30 A.

Translation-targeted therapeutics for viral diseases.

Viruses utilize the protein synthetic machinery of their host. Nonetheless, certain features of the synthesis of viral proteins are distinct from those of host-cell translation. Examples include internal ribosome entry sites in some viral mRNAs and ribosomal frameshifting during production of retroviral proteins. Viruses often inhibit host translation and/or possess mechanisms leading to preferential synthesis of viral proteins. In addition, a participant in the cellular antiviral response is the enzyme PKR (protein kinase, RNA activated), which is involved in the control of cellular translation. Thus, viruses and host cells wage war on the battlefield of translation. The distinctive features of protein synthesis in virally infected cells provide potential targets for therapeutic intervention. Translation-targeted therapeutics have precedence in antibiotics like tetracycline and erythromycin. Means for discovery of translation-targeted therapeutics for viral disease are discussed.

Rev of human immunodeficiency virus and Rex of the human T-cell leukemia virus type I can counteract an mRNA downregulatory element of the transferrin receptor mRNA.

Expression of the structural proteins of the human immunodeficiency virus type 1 (HIV-1), the human T-cell leukemia virus type I (HTLV-I), and of the transferrin receptor (TfR) mRNA depends on posttranscriptional regulatory mechanisms involving both positive and negative elements. In these systems the presence of elements decreasing mRNA expression have been demonstrated. The regulatory proteins (Rev, Rex or iron response element binding protein IRE-BP) antagonize the effects of the downregulatory elements by interacting directly with specific mRNA sites (Rev responsive element, RRE, Rex responsive element, RXRE, or iron responsive elements, IREs) resulting in stabilization and efficient expression of the corresponding mRNAs. To investigate whether this strategy involves common pathways of mRNA utilization, we have studied expression from hybrid mRNAs that contained these previously identified HIV-1 or TfR instability determinants and the binding sites of the regulatory proteins Rev, Rex and/or IRE-BP. Our results demonstrate that only low levels of these hybrid mRNAs accumulate in the absence of the positive regulatory factors Rev, Rex or IRE-BP. The presence of these factors counteracts the effect of heterologous downregulatory elements resulting in increased accumulation of the hybrid mRNAs. However, while Rev or Rex regulation also resulted in efficient protein expression, the IRE-BP only affected mRNA levels without significantly affecting protein expression, suggesting that the pathways of mRNA stabilization/expression are different in these systems.

Equatorial A-band and I-band X-ray diffraction from relaxed and active fish muscle. Further details of myosin crossbridge behaviour.

It has been known for many years that the vertebrate striated muscle A-bands and I-bands both contribute to the observed equatorial X-ray diffraction patterns. Despite this, the observed equatorial patterns, with the exception of the clearly distinct Z-reflection, have often been analysed as coming solely from the A-band, since it has not been possible to separate the observed intensity distribution into individual A-band and I-band contributions. Here we show, for the case of diffraction from the highly ordered muscles in bony fish, that it is possible to separate these contributions to the diffraction patterns from intact muscles and to compute separate electron density maps for the A and I-bands. Difference A-band density maps between resting and active muscles are distinctly altered when the I-band contribution is removed from the observed equatorial intensity. Results from resting and fully active fish muscle A-bands are compared and interpreted in terms of myosin crossbridge movement; the observations are consistent with specific crossbridge labelling of actin filaments, with a strong azimuthal component of crossbridge movement towards actin. From electron microscopy of freeze-substituted fish muscle, it is shown that the I-band X-ray diffraction pattern probably arises mainly from the thin filament arrangement immediately adjacent to the Z-band.