Salivary characteristics and dental caries experience in remote Indigenous children in Australia: a cross-sectional study.

BACKGROUND: While associations between salivary characteristics and dental caries have been well studied, we are not aware of this being assessed in a remote Indigenous child population, where lifestyles may be different from urban children. Our aim was to assess associations between caries experience and putative biomarkers in saliva, accounting for oral hygiene and dietary habits. METHODS: Children attending schools in an Indigenous community in remote north Queensland, Australia were invited to an oral examination by qualified and calibrated examiners. Salivary flow rate, pH, buffering capacity and loads of mutans streptococci (MS), lactobacilli (LB) and yeasts were determined. Also, data on tooth brushing frequency and soft drinks consumption were obtained via a questionnaire. Caries experience was recorded by the International Caries Detection and Assessment System (ICDAS-II), and quantified as decayed, missing and filled surfaces. Relationships between the salivary variables and the cumulative caries experience (dmfs+DMFS) in the deciduous and permanent dentitions were examined by multivariate analyses to control the effect of confounders. RESULTS: The mean cumulative decayed (DS + ds), missing (MS + ms) and filled (FS + fs) surfaces were 3.64 (SD: 4.97), 1.08 (4.38) and 0.79 (1.84) respectively. Higher salivary MS and LB counts, low tooth brushing frequency and daily soft drink consumption were significantly related to greater caries experience. Caries experience was about twice in those with ≥10^5 CFU/ml saliva counts of MS (mean = 6.33, SD: 8.40 vs 3.11, 5.77) and LB (7.03, 7.49 vs 4.41, 8.00). In the fully-adjusted multivariate model, caries experience in those with higher counts of MS and LB were 51 and 52% more than those with lower counts. CONCLUSIONS: As with studies in other populations, childhood salivary counts of MS and LB were significantly associated with greater caries experience in this remote Indigenous community. To address the serious burden of oral disease, we are researching ways to promote a healthy oral environment by encouraging good dietary habits, and emphasising the importance of daily tooth brushing with a fluoridated toothpaste. Our ongoing longitudinal studies will indicate the success of measures employed to reduce the counts of bacteria closely associated with cariogenesis and their impact on caries increment. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ANZCTR ), No: ACTRN12615000693527; date of registration: 3rd July 2015.

Hereditary colorectal cancer registries in Canada: report from the Colorectal Cancer Association of Canada consensus meeting; Montreal, Quebec; October 28, 2011.

At a consensus meeting held in Montreal, October 28, 2011, a multidisciplinary group of Canadian experts in the fields of genetics, gastroenterology, surgery, oncology, pathology, and health care services participated in presentation and discussion sessions for the purpose of developing consensus statements pertaining to the development and maintenance of hereditary colorectal cancer registries in Canada. Five statements were approved by all participants.

Nonsimultaneous chains and dominos in kidney- paired donation-revisited.

Since 2008, kidney exchange in America has grown in part from the incorporation of nondirected donors in transplant chains rather than simple exchanges. It is controversial whether these chains should be performed simultaneously 'domino-paired donation', (DPD) or nonsimultaneously 'nonsimultaneous extended altruistic donor, chains (NEAD). NEAD chains create 'bridge donors' whose incompatible recipients receive kidneys before the bridge donor donates, and so risk reneging by bridge donors, but offer the opportunity to create more transplants by overcoming logistical barriers inherent in simultaneous chains. Gentry et al. simulated whether DPD or NEAD chains would produce more transplants when chain segment length was limited to three transplants, and reported that DPD performed at least as well as NEAD chains. As this finding contrasts with the experience of several groups involved in kidney-paired donation, we performed simulations that allowed for longer chain segments and used actual patient data from the Alliance for Paired Donation. When chain segments of 4-6 transplants are allowed in the simulations, NEAD chains produce more transplants than DPD. Our simulations showed not only more transplants as chain length increased, but also that NEAD chains produced more transplants for highly sensitized and blood type O recipients.

Family history as a predictor of uptake of cancer preventive procedures by women with a BRCA1 or BRCA2 mutation.

Women with a BRCA1 or BRCA2 mutation are at an elevated risk of developing breast and ovarian cancer; however, it is unclear to what extent family history influences the uptake of cancer prevention options. Women with a BRCA1/2 mutation completed a follow-up questionnaire that assessed uptake of cancer preventive options. The pedigree of each woman was reviewed, and information was recorded on cancers diagnosed in relatives. Five hundred and seventeen women were included in the study. Women with a sister with breast cancer were more likely to have a prophylactic mastectomy than those without a sister with breast cancer [odds ratios (OR) = 2.4, p = 0.003]. Uptake of prophylactic mastectomy was significantly lower in women with a mother with ovarian cancer compared with those whose mother did not have ovarian cancer (OR = 0.4, p = 0.01). Having a mother or sister with ovarian cancer significantly predicted the uptake of prophylactic oophorectomy (OR = 1.6, p = 0.04). Women with a BRCA2 mutation were less likely to have a prophylactic oophorectomy than those with a BRCA1 mutation (OR = 0.49, p = 0.0004). Among women with a BRCA1 or BRCA2 mutation, family history predicts the uptake of prophylactic mastectomy and prophylactic oophorectomy.

Apoptosis: A Functional Paradigm for Programmed Plant Cell Death Induced by a Host-Selective Phytotoxin and Invoked during Development.

The host-selective AAL toxins secreted by Alternaria alternata f sp lycopersici are primary chemical determinants in the Alternaria stem canker disease of tomato. The AAL toxins are members of a new class of sphinganine analog mycotoxins that cause cell death in both animals and plants. Here, we report detection of stereotypic hallmarks of apoptosis during cell death induced by these toxins in tomato. DNA ladders were observed during cell death in toxin-treated tomato protoplasts and leaflets. The intensity of the DNA ladders was enhanced by Ca2+ and inhibited by Zn2+. The progressive delineation of fragmented DNA into distinct bodies, coincident with the appearance of DNA ladders, also was observed during death of toxin-treated tomato protoplasts. In situ analysis of cells dying during development in both onion root caps and tomato leaf tracheary elements revealed DNA fragmentation localized to the dying cells as well as the additional formation of apoptotic-like bodies in sloughing root cap cells. We conclude that the fundamental elements of apoptosis, as characterized in animals, are conserved in plants. The apoptotic process may be expressed during some developmental transitions and is the functional process by which symptomatic lesions are formed in the Alternaria stem canker disease of tomato. Sphinganine analog mycotoxins may be used to characterize further signaling pathways leading to apoptosis in plants.

Psychophysiological correlates of the inter-individual variability of head movement control in seated humans.

We recently conducted experiments where 24 seated participants were subjected (with eyes closed) to small amplitude, high-jerk impulses of linear acceleration. Responses were distributed as a continuum between two extremes. The "stiff" participants showed little movement of the head relative to the trunk, whereas the "floppy" participants showed a large head rotation in the direction opposite the sled movement. We hypothesized that the stiff behavior resulted from the spontaneous use of an imagined visual frame of reference and undertook this larger-scale study to test that idea. The distribution along the "stiff-floppy" continuum was compared with the scores on psychophysiological tests measuring vividness of imagery, visual field-dependence and motion sickness susceptibility. Multivariate regression analysis revealed that the "stiffness" of individuals was loosely, but significantly related to the vividness of their imagery. However, "stiffness" was not linked to visual field-dependence or motion sickness susceptibility. Even if it explains only 20% of the variance of the data, the increase of "stiffness" with vividness of imagery fits our hypothesis. With eyes closed, stiff people may use imagined external visual cues to stabilize their head and trunk. Floppy people, who are poorer imagers, may rely more on "egocentric", proprioceptive and vestibular inputs.

Programmed cell death in plant disease: the purpose and promise of cellular suicide.

The interaction of pathogens with plants leads to a disruption in cellular homeostasis, often leading to cell death, in both compatible and incompatible relationships. The mechanistic basis of this cellular disruption and consequent death is complex and poorly characterized, but it is established that host responses to pathogens are dependent on gene expression, involve signal transduction, and require energy. Recent data suggest that in animals, a genetically regulated, signal transduction-dependent programmed cell death process, commonly referred to as apoptosis, is conserved over a wide range of phyla. The basic function of apoptosis is to direct the selective elimination of certain cells during development, but it also is a master template that is involved in host responses to many pathogens. Programmed cell death in plants, while widely observed, has not been studied extensively at either the biochemical or genetic level. Current data suggest that activation or suppression of programmed cell death may underlie diseases in plants as it does in animals. This review describes some of the fundamental characteristics of apoptosis in animals and points to a number of connections to programmed cell death in plants that may lead to both a better understanding of disease processes and novel strategies for engineering disease resistance in plants.

Mycotoxins reveal connections between plants and animals in apoptosis and ceramide signaling.

Plants undergo programmed cell death during development and disease in contexts that are functionally analogous to apoptosis in animals. Recent studies involving plant cell death induced by mycotoxins, pathogens and lethal mutations along with the cell-autonomous death during development now point to several conserved connections to apoptosis in animals. Morphological markers indicative of apoptosis recently reported in plants include TUNEL positive cells, DNA ladders, Ca2+-activated nucleosomal DNA cleavage, and formation of apoptotic-like bodies that occur in some but not all situations involving ordered cell death. In parallel studies with animal and plant cells treated with sphinganine analog mycotoxins our results indicate that the induction and inhibition of death may be mediated by ceramide-linked signaling systems. The presence and significance of ceramide-linked second messenger systems is well documented in animals but is virtually unknown in plants. Further research will discern the manner in which the important function of programmed cell death is conserved as well as diverged between the two kingdoms.

Germline E-cadherin mutations in hereditary diffuse gastric cancer: assessment of 42 new families and review of genetic screening criteria.

BACKGROUND: Mutations in the E-cadherin (CDH1) gene are a well documented cause of hereditary diffuse gastric cancer (HDGC). Development of evidence based guidelines for CDH1 screening for HDGC have been complicated by its rarity, variable penetrance, and lack of founder mutations. METHODS: Forty three new gastric cancer (GC) families were ascertained from multiple sources. In 42 of these families at least one gastric cancer was pathologically confirmed to be a diffuse gastric cancer (DGC); the other family had intestinal type gastric cancers. Screening of the entire coding region of the CDH1 gene and all intron/exon boundaries was performed by bi-directional sequencing. RESULTS: Novel mutations were found in 13 of the 42 DGC families (31% overall). Twelve of these mutations occur among the 25 families with multiple cases of gastric cancer and with pathologic confirmation of diffuse gastric cancer phenotype in at least one individual under the age of 50 years. The mutations found include small insertions and deletions, splice site mutations, and three non-conservative amino acid substitutions (A298T, W409R, and R732Q). All three missense mutations conferred loss of E-cadherin function in in vitro assays. Multiple cases of breast cancers including pathologically confirmed lobular breast cancers were observed both in mutation positive and negative families. CONCLUSION: Germline truncating CDH1 mutations are found in 48% of families with multiple cases of gastric cancer and at least one documented case of DGC in an individual under 50 years of age. We recommend that these criteria be used for selecting families for CDH1 mutational analysis.

Alzheimer's disease: interaction of apolipoprotein E genotype, family history of dementia, gender, education, ethnicity, and age of onset.

We evaluated 197 patients with predominantly late-onset Alzheimer's disease (AD) who belonged to several ethnic groups and analyzed the relationship of age of onset of AD to the presence or absence of several risk factors in this entire group of patients. The apolipoprotein E (apoE) epsilon 4 allele frequency, which was 29% in all patients (compared with the reported population mean of 13.7%, p < 0.001, did not vary significantly between ethnic groups but declined significantly with increasing age. The apoE epsilon 2 allele frequency was 3%, compared with the reported population mean of 7.4% (p = 0.001). The frequency of a positive family history of dementia in first-degree relatives (FH +) (overall 45%) did not vary significantly between ethnic groups. ApoE epsilon 4-positive (epsilon 4+) patients tended to have a higher FH + rate (58%) than apoE epsilon 4-negative (epsilon 4-) patients (40%) (p = 0.02). When the potential risk factors of gender, education, FH+ status, and epsilon 4+ status were examined together in a multiple linear-regression analysis, FH+ and epsilon 4+ status (but not gender or education) were significant (they were both associated with an earlier age of onset of AD). In a post-hoc analysis, we found a reduced age of onset in women, but not men, who were both FH + and epsilon 4+. Additionally, those probands who were epsilon 4+ were more likely to inherit the disease from their mothers than their fathers. The mechanism by which epsilon 4+ and FH+ status operate as risk factors may be by their effect on the age of onset of AD.

A dose-response analysis of the beneficial effects of the ACTH-(4-9) analogue, Org 2766, on behavioural recovery following unilateral labyrinthectomy in guinea-pig.

1. After removal of the peripheral vestibular receptors in one inner ear (unilateral labyrinthectomy, UL), oculo-motor and postural symptoms occur but disappear over time in a process of recovery known as vestibular compensation. 2. ACTH-(4-10), a fragment of the adrenocorticotrophic hormone (ACTH) molecule, which is devoid of corticotrophic activity, has been shown to enhance vestibular compensation. The present study investigated the effect of the ACTH-(4-9) analogue, Org 2766, on vestibular compensation in guinea-pig. Org 2766 is reported to be more potent behaviourally than ACTH-(4-10). 3. After UL, Org 2766 was delivered via an osmotic minipump implanted s.c. to 30 animals randomly assigned to one of five conditions: 1, 5, 10, 20 or 40 nmol kg-1 Org 2766, every 4 h for 52 h post-UL. Although infusion was continuous, in the present study the doses are expressed as nmol per 4 h in order to compare the results to a previous study in which animals received a discrete dose of ACTH-(4-10) at the end of each 4 h period. All animals were compared to saline controls (n = 6). 4. Three symptoms of UL, spontaneous ocular nystagmus, roll head tilt and yaw head tilt, were measured every 4 h for 52 h, beginning at 10 h post-UL. 5. Rates of infusion of 1, 5 and 10 nmol kg-1 accelerated spontaneous nystagmus compensation; 20 nmol kg-1 produced a significant decrease in the frequency of spontaneous nystagmus, as well as accelerating its compensation; 40 nmol kg-1 had no significant effect on spontaneous nystagmus compensation. 6. In comparison to the effects of Org 2766 on spontaneous nystagmus compensation, Org 2766 had little effect on the compensation of the postural symptoms, yaw head tilt and roll head tilt. Only 5 and 40 nmol kg-1 produced a significant change in postural compensation, and this was a reduction in the rate of roll head tilt compensation.7. At the optimal infusion rate of 20 nmol kg-1 every 4 h, Org 2766 produced a similar effect on spontaneous nystagmus compensation to that of ACTH-(4-10). However, Org 2766 was effective in accelerating spontaneous nystagmus compensation at much smaller doses per 4 h period than ACTH-(4-10). Org 2766 did not have the same effect on. postural compensation as it had on the compensation of spontaneous nystagmus.

Myelodysplasia and leukemia syndrome with monosomy 7: a genetic perspective.

Acquired monosomy 7 is a frequent finding in myelodysplastic syndromes, including acute myelogenous leukemia. A subset of these patients has been described with an apparently distinct condition: myelodysplasia and leukemia syndrome with monosomy 7 (MLSM7). We report 2 brothers, 3 and 5 years of age, with MLSM7 and review other reports of familial occurrence. Genetic factors appear to be important in the cause of MLSM7, but the reported families do not fit neatly into any monogenic pattern. Recognition of the frequently familial nature of this condition requires hematological evaluation and genetic counseling for the families of patients with MLSM7.

Large kindred with Ehlers-Danlos syndrome type IV due to a point mutation (G571S) in the COL3A1 gene of type III procollagen: low risk of pregnancy complications and unexpected longevity in some affected relatives.

Ehlers-Danlos syndrome (EDS) type IV is an autosomal dominant connective tissue disorder. Early morbidity and mortality results from rupture of vessels and internal organs. A large kindred with EDS type IV was studied clinically, and the biochemical defects and underlying mutation in the COL3A1 gene that encodes the chains of type III procollagen were identified. A G-->A transition results in a single amino acid substitution, G571S, in the triple helical domain of the products of one COL3A1 allele. Although the clinical findings seen on examination are characteristic of EDS type IV, longevity is longer than that seen in many families and there is less pregnancy-associated morbidity or mortality than in some families. This suggests that some clinical aspects of EDS type IV may be related to the nature of the mutation and its effect on the behavior of the protein.

Phrenic involvement in Charcot-Marie-Tooth disease. A pathologic documentation.

A 69-year-old woman diagnosed as having Charcot-Marie-Tooth disease (CMT) for 30 years' duration died of respiratory failure secondary to diaphragmatic weakness. At autopsy, identical neuropathic changes were found in phrenic and other affected somatic peripheral nerves. We conclude that the phrenic nerve may be involved by the neuropathy of at least some forms of CMT.

Life-threatening status asthmaticus at 12.5 weeks' gestation. Report of a normal pregnancy outcome.

A 26-year-old woman had a life-threatening attack of status asthmaticus at 12.5 weeks of pregnancy. Subsequently, an apparently normal male infant was born at full-term.

Comparison of the effects of adrenocorticotropic hormone fragment 4-10 (ACTH(4-10)) and [D-Phe7]ACTH(4-10) on the compensation of spontaneous nystagmus in guinea pig.

Following unilateral labyrinthectomy (UL), spontaneous nystagmus (SN) was measured in guinea pigs which received i.m. injections of 100 or 400 µg/kg ACTH(4-10) or 800 µg/kg [D-Phe7]ACTH(4-10), every 4 h for 48 h post-UL. The results were compared to those from a previous study, conducted under identical conditions, in which guinea pigs received similar injections of 200 µg/kg ACTH(4-10) or 0.1 ml/kg saline. ACTH(4-10) significantly accelerated the rate of compensation of SN at 100, 200, and 400 µg/kg doses, although the average effects were larger for the 200 µg/kg condition. [D-Phe7]ACTH(4-10) significantly increased the frequency of SN following UL compared to saline-treated animals; however, it also accelerated the rate of SN compensation. These results indicate that the acceleration of SN compensation in guinea pig by ACTH(4-10) follows an inverted U-shaped dose-response curve and that [D-Phe7]ACTH(4-10) increases the frequency of SN.

Evidence that short ACTH fragments enhance vestibular compensation via direct action on the ipsilateral vestibular nucleus.

The aim of the present study was to determine whether administration of the synthetic ACTH-(4-9) analogue, Org 2766, directly into the ipsilateral vestibular nucleus complex (VNC), would enhance vestibular compensation following unilateral labyrinthectomy (UL). Either artificial cerebrospinal fluid (ACSF; n = 4) or Org 2766 (0.67 nmol kg-1 every 4 h for 52 h; n = 4), was administered directly into the VNC via a stainless steel cannula connected to an osmotic minipump implanted s.c. Three symptoms of UL, spontaneous ocular nystagmus (SN), roll head tilt (RHT) and yaw head tilt (YHT), were measured at 10, 20, 25, 30, 40, 45 and 50 h post-UL. Org 2766 produced a significant decrease in the frequency of SN and accelerated its compensation. Org 2766 had no significant effect on either the compensation of RHT or YHT. This result suggests that vestibular compensation is enhanced by short ACTH fragments as a result of direct action on the ipsilateral VNC itself.

Electrophysiological evidence for vestibular activation of the guinea pig hippocampus.

Vestibular information modulates hippocampal activity for spatial processing and place cell firing. However, evidence of a purely vestibular stimulus modulating hippocampal activity is confounded as most studies use stimuli containing somatosensory and visual components. In the present study, high-frequency electrical stimulation of specific vestibular sensory regions of the right labyrinth in anaesthetized guinea pigs induced an evoked field potential in the hippocampal formation bilaterally with a latency of about 40 ms following stimulation onset. Field potentials localized in the hippocampal formation occurred with stimulus current parameters that were too small to produce eye movements. This provides direct electrophysiological evidence of vestibular input to the hippocampus.

Semicircular canal occlusion causes permanent VOR changes.

We measured the guinea pig horizontal vestibulo-ocular reflex (hVOR) to high acceleration impulsive head rotations following a unilateral lateral semicircular canal (LSCC) occlusion. We found a significant hVOR deficit for rotations toward the side of the occluded LSCC and this deficit did not show systematic changes over 3 months. We considered the LSCC nerve was still functional as shown by the normal appearance of the crista of the LSCC ampulla and also electrical stimulation of the LSCC. We conclude that the VOR during angular acceleration in response to high acceleration shows no adaptive plasticity following a unilateral LSCC occlusion.

Surgical safaris with the East Africa Flying Doctor Service.

A few hundred small mission and government hospitals serve the 20 million people who live in rural East Africa. The physician-patient ratio is 1:25,000. Surgical support to many of these hospitals is provided through the East Africa Flying Doctor Service of the African Medical and Research Foundation. Small aircraft that are coordinated by a wide radio network bring surgical capability to a maximum number of patients in this area of 1,300,000 sq km (500,00 sq miles). The clinical problems, differential diagnoses, operative decisions, risk, and complications of surgical care all have a distinctly African quality. The working conditions and variety and magnitude of problems provide a stimulating challenge. Surgical safaris are a catalyst for gaining acceptance of modern scientific methods by Africa's tradition-oriented tribesmen.