Farming characteristics and self-reported health outcomes of Irish farmers.

Background: Irish farmers represent a 'high-risk' group for non-communicable diseases, which, arguably, pose a greater occupational health challenge for farmers. To date, there has been little exploration of the farming characteristics associated with farmers' poor health outcomes. Aims: To examine the relationship between farming and male farmers' self-reported health outcomes and to compare the study findings to national health studies to explore which factors specifically are associated with Irish farmers' poorer health outcomes relative to the general population. Methods: This cross-sectional survey research used self-reported quantitative data on the health outcomes and health behaviours of male farmers from the South-East of Ireland. Data were entered into SPSS and descriptive and binary regression techniques were used for data analysis. Results: There were 314 participants (99% response rate). Age, full-time farming and dairy farming significantly impacted self-reported health outcomes and health behaviours. There was a high prevalence of self-reported arthritis compared with the national average of Irish males. 'Younger' farmers (<45 years) were more likely to engage in harmful health behaviours such as smoking and 'binge-drinking' one or more times per week. Conclusions: This study identified self-reported patterns of risky lifestyle behaviours among particular subgroups of Irish farmers for whom targeted health interventions are warranted. Interventions are particularly important for younger farmers who may see themselves as invincible and impregnable to ill-health.

Stress responses to short-term intensified and reduced training in competitive weightlifters.

We sought to identify and evaluate the tolerance to, and consequences of, short-term variations in training load in competitive weightlifters. Seven international-level lifters performed 1 week of initial training followed by 2 weeks of intensified (INT: +100%, 36.5 ± 11.3 × 10(3) kg/week) and 1 week of subsequently reduced (RED: -25%) training within their annual program. After INT, but not RED, 90 min of weightlifting increased mRNA levels of chemokine (C-C motif) ligand 4 (CCL4), chemokine (C-X-C motif) receptor 4 (CXCR4) and cellular stress-associated DNA-damage-inducible transcript 4 (DDIT4) in peripheral blood mononuclear cells by 40-240%. Resting- and weightlifting-induced changes in plasma protein carbonyls, indicative of oxidative stress, but not pro-inflammatory CCL4 concentrations differed between INT and RED. Symptoms of stress (Daily Analysis of Life Demands of Athletes questionnaire) were reported as worse than normal more frequently during INT and RED than initial training. Global (negative) mood state increased during INT and declined during RED. Maximal snatch (-4.3 ± 3.7%) and vertical jump (-7.2 ± 6.5%), but not clean and jerk, were reduced after INT and restored after RED. Chemokine signaling may thus be part of the stress response to intense weightlifting and short-term reductions in training load support recovery from periodic INT training in weightlifters.

Corticosterone levels of Atlantic puffins vary with breeding stage and sex but are not elevated in poor foraging years.

Corticosterone (CORT) levels in seabirds fluctuate across breeding stages and in different foraging conditions. Here we use a ten-year data set to examine whether CORT levels in Atlantic puffins differ in years with high or low availability of capelin, the preferred forage species. Female puffins had higher CORT levels than males, possibly related to cumulative costs of egg production and higher parental investment. Puffins had higher CORT levels and body mass during pre-breeding than during chick rearing. Yearly mean chick growth rates were higher in years when adults had higher body mass and in years where adults brought chicks a lower percentage of non-fish (invertebrates/larval fish) food. Unlike most results from seabird species with shorter chick-rearing periods, higher CORT levels in puffins were not associated with lower capelin abundance. Puffins may suppress CORT levels to conserve energy in case foraging conditions improve later in the prolonged chick-rearing period. Alternatively, CORT levels may be lowest both when food is very abundant (years not in our sample) or very scarce (e.g., 2009 in this study), and increase when extra foraging effort will increase foraging efficiency (most years in this study). If these data primarily represent years with medium to poor foraging, it is possible that CORT responses to variation in foraging conditions are similar for puffins and other seabirds.

Role for endothelial nitric oxide synthase in nitrite-induced protection against renal ischemia-reperfusion injury in mice.

Nitrite is protective against renal ischemia/reperfusion injury (IRI); an effect due to its reduction to nitric oxide (NO). In addition to other reductase pathways, endothelial NO synthase (eNOS) may also facilitate nitrite reduction in ischemic environments. We investigated the role of eNOS in sodium nitrite (60 microM, 10 ml/kg applied topically 1 min before reperfusion)-induced protection against renal IRI in C57/BL6 wild-type (WT) and eNOS knockout (eNOS KO) mice subjected to bilateral renal ischemia (30 min) and reperfusion (24h). Markers of renal dysfunction (plasma [creatinine] and [urea]), damage (tubular histology) and inflammation (cell recruitment) were elevated following IRI in WT mice; effects significantly reduced following nitrite treatment. Chemiluminescence analysis of cortical and medullary sections of the kidney demonstrated rapid (within 1 min) distribution of nitrite following application. Whilst IRI caused a significant (albeit substantially reduced compared to WT mice) elevation of markers of renal dysfunction and damage in eNOS KO mice, the beneficial effects of nitrite were absent or reduced, respectively. Moreover, nitrite treatment enhanced renal dysfunction in the form of increased plasma [creatinine] in eNOS KO mice. Confirmation of nitrite reductase activity of eNOS was provided by demonstration of nitrite (100 microM)-derived NO production by kidney homogenates of WT mice, that was significantly reduced by L-NMMA. L-NMMA was without effect using kidney homogenates of eNOS KO mice. These results support a role for eNOS in the pathways activated during renal IRI and also identify eNOS as a nitrite reductase in ischemic conditions; activity which in part underlies the protective effects of nitrite.

Mummy of the "Elder Lady" in the tomb of Amenhotep II: Egyptian museum catalog number 61070.

An unidentified female mummy found in a cache of great kings and queens in 1898 in the Valley of the Kings was examined from the viewpoint of Egyptology, x-ray cephalometry, biostatistics, and biochemistry. The result was the identification of Queen Tiye, of the Eighteenth Dynasty, wife of Amenhotep III and mother of Akhenaton.

Genetic structure of Melanotaenia australis at local and regional scales in the east Kimberley, Western Australia.

The Kimberley region of Western Australia possesses a poorly studied freshwater fish fauna with high endemism in an aquatic landscape subject to monsoonal floods and dry season isolation. In the first population genetic study of freshwater fish in this region, the authors tested the effects of geographic barriers on genetic structure at multiple spatial scales in east Kimberley populations of the western rainbowfish, Melanotaenia australis, the most widespread and abundant species in the region. Based on allozyme comparisons, hierarchical analysis of F(ST) revealed increasing genetic subdivision with spatial scale. Minimal genetic structure within creeklines demonstrated that wet season dispersal, rather than dry season isolation, determines genetic structure at small scales. At the scale of sub-catchments, a pattern of isolation by distance along creeklines was evident. Genetic subdivision between adjacent river systems was greater between rivers separated by a plateau than by lowlands. This implies greater connectivity of populations in lowland areas and may explain the greater similarity of the east Kimberly freshwater fish fauna with lowlands to the east than with the more rugged regions to the west. Similarly, greater connectivity between lowland populations may account for the on-average larger distribution of lowland Melanotaeniids.

Granulosa cell survival and proliferation are altered in polycystic ovary syndrome.

CONTEXT: Polycystic ovary syndrome (PCOS) represents the most common endocrine abnormality in women of reproductive age. The cause of PCOS remains largely unknown, but studies suggest an intrinsic ovarian abnormality. OBJECTIVE: The objective of the study was to test our hypothesis that differences in granulosa cell proliferation and apoptosis may underlie abnormalities that affect follicular development. DESIGN: Granulosa cells were prepared from follicular fluid aspirated from 4- to 8-mm follicles of unstimulated ovaries during routine laparoscopy or laparotomy from women with anovulatory PCOS and those with regular ovulatory cycles. SETTING: The study was conducted at a university hospital. PATIENTS: Fourteen women with anovulatory PCOS and nine women with regular ovulatory cycles participated in the study. MAIN OUTCOME MEASURES: Immunocytochemistry on granulosa cells to investigate apoptotic and proliferation rates, together with real-time RT-PCR to analyze gene expression profiles of apoptotic regulators, was measured. RESULTS: Significantly lower apoptotic rates were found in granulosa cells from patients with PCOS, compared with women with regular ovulatory cycles (P=0.004). Lower apoptotic rates were associated with decreased levels of the apoptotic effector caspase-3 (P=0.001) and increased levels of the anti-apoptotic survival factor cellular inhibitor of apoptosis proteins-2 in the PCOS group that were coupled to higher proliferation rates (P=0.032). Gene expression profiling confirmed the immunocytochemical findings. CONCLUSIONS: Our findings indicate that there are significant differences in the rate of cell death and proliferation in granulosa cell populations in PCOS patients. These are associated with decreased expression of apoptotic effectors and increased expression of a cell survival factor. These results provide new insights that may be useful in developing specific therapeutic intervention strategies in PCOS.

Human papillomavirus type 16 E6 gene cooperates with EJ-ras to immortalize primary mouse cells.

Human papillomaviruses (HPVs) are small DNA tumor viruses, a subset of which is closely associated with the development of cervical cancer. The viral E6 and E7 open reading frames encode multifunctional proteins that bind respectively to the p53 protein and to the product of the retinoblastoma tumor-suppressor gene. In this study we demonstrate that the HPV-16 E6 gene cooperates with EJ-ras to immortalize primary cultures of mouse kidney epithelial cells. HPV-16-immortalized cell lines expressing E6 but not E7 contained low levels of wild-type p53 protein. In contrast, those cells immortalized by EJ-ras alone contained elevated p53 protein levels, and were shown to contain a mutation in the gene. These results suggest that activating mutations in the p53 gene can functionally substitute for HPV-16 E6 in transforming primary cells.

E6 proteins from diverse cutaneous HPV types inhibit apoptosis in response to UV damage.

In addition to their role in anogenital cancer, human papillomaviruses (HPVs) are also involved in the development of a range of cutaneous lesions. HPV types 5 and 8 are associated with the development of skin cancers in individuals with Epidermodysplasia verruciformis (EV). A broad spectrum of HPV types are also commonly found in non-melanoma skin cancers in immunocompromised individuals, such as organ transplant recipients. The skin cancers in EV and immunocompromised patients occur predominantly at body sites exposed to ultra violet (UV) radiation, pointing to a key role for UV in their development. Here we show that the E6 protein from a range of cutaneous HPV types effectively inhibits apoptosis in response to UV damage. This occurs in both p53 null and wild type cells and does not require p53 degradation.

Conditional immortalization of primary cells by human papillomavirus type 18 E6 and EJ-ras defines an E6 activity in G0/G1 phase which can be substituted for mutations in p53.

The human papillomavirus (HPV) type 18 E6 gene cooperates with activated Ha-ras to immortalize primary mouse cells in culture. Using a plasmid where HPV18 E6 expression is regulated by the glucocorticoid inducible MMTV LTR, we have generated immortalized cell lines in which the continued expression of E6 was necessary for maintenance of the transformed phenotype. In the absence of exogenously added hormone these cells were found to arrest in G0/G1. Furthermore, we demonstrate that the effects of E6 were essentially p53 independent and therefore define a novel function by which E6 is able to modulate cell proliferation. In addition, when the E6 dependent cells were maintained under conditions of prolonged growth arrest by the removal of E6, revertant cells were isolated which were no longer dependent on E6 expression for continued proliferation. These revertant cells were found to have acquired a mutation in the cellular gene p53, suggesting that certain p53 mutations are dominant over an E6 requirement in this assay.

HPV-16 E7 and adenovirus E1a complex formation with TATA box binding protein is enhanced by casein kinase II phosphorylation.

The major transforming protein of HPV-16 is encoded by the E7 gene. This has been shown to cooperate with EJ-ras in the immortalisation of primary rodent cells and with the viral E6 gene in the immortalisation of primary human keratinocytes. HPV-16 E7 protein has been shown to bind to a number of cellular proteins involved in the control of cell growth; including pRB, p107 and cyclin A. Loss of pRb or p107 binding results in the loss of transforming activity. In this paper we demonstrate that HPV-16 E7 can also complex with the core component of TFIID, the TATA Box Binding Protein (TBP). This interaction is partly dependent upon phosphorylation of the E7 protein by cellular casein kinase II (CKII), since phosphorylation of E7 by CKII increases the affinity with which E7 binds TBP. Similar results are also obtained with the Adenovirus Ela protein, indicating a conservation of function between these two viral oncoproteins. Mutation of the CKII site to two acidic amino acids significantly increases the affinity of E7 for TBP, indicating that the incorporation of two negative charges at this region of E7 is important in regulating the interaction with TBP.

Mutational analysis of HPV-18 E6 identifies domains required for p53 degradation in vitro, abolition of p53 transactivation in vivo and immortalisation of primary BMK cells.

The two major transforming proteins of oncogenic human papillomaviruses are encoded by the E6 and E7 oncogenes. Both viral proteins interact specifically with the products of cellular human tumour suppressor genes; E6 with p53 and E7 with Rb. However, the mechanism of action of E6 is still poorly understood in comparison with that of E7. Although extensive in vitro studies have been done with mutant E6 proteins, very little is known about the activities of E6 in vivo. In this study we have analysed the structure-function relationships of HPV-18 E6 in in vitro analyses and we correlate this with in vivo activity. These studies define a number of domains on the E6 molecule which are involved in the ability of E6 to target p53 for degradation in vitro. This analysis demonstrates that domains previously shown to be important in HPV-16 E6 (Crook et al., 1991; Mietz et al., 1992) are also conserved in HPV-18 and also reconciles the differences between these reports. A series of in vivo studies demonstrate that E6 mediated degradation of p53 in vitro is irrelevant both for cell transformation and for the ability of E6 to abolish p53 transcriptional activation. In addition, we show that at least four distinct regions of the E6 protein are involved in the p53 association in vivo.

Lack of immortalizing activity of a human papillomavirus type 16 variant DNA with a mutation in the E2 gene isolated from normal human cervical keratinocytes.

The oncogenic potential of a human papillomavirus type 16 (HPV16) variant cloned from normal human cervical keratinocytes has been tested in vitro using primary rodent epithelial cells and human cervical keratinocytes. The HPV16 variant was able to extend the lifespan of, but failed to immortalize, human keratinocytes. It could however cooperate with an activated ras oncogene to transform primary rodent cells. Radioimmunoprecipitation assays of the rodent cells showed that they expressed the E7 protein. DNA sequence analysis of the URR/E6/E7 and E5 regions of the HPV16 showed them to be fully functional, but a deletion in the viral E2 open reading frame was detected. This truncated E2 only weakly stimulated transcription of the viral regulatory region. Complementation assays using the HPV16 variant and a full-length E2 enabled the cloned variant to immortalize human cervical keratinocytes with wild-type efficiency. These results suggest that other viral gene products in addition to E6/E7 may play an important role in the in vitro immortalization of cervical keratinocytes in HPV16 and the development of cervical cancer.

Advantages to female rodents of male-induced pregnancy disruptions.

Several, not mutually exclusive, hypotheses have been discussed to account for the advantages of pregnancy disruptions for female rodents. Those hypotheses focusing on differential male behavior to related and unrelated pups may, with additional research, provide the most plausible explanation for the changes throughout pregnancy in the probability that a female will reabsorb a pregnancy when exposed to a new male.

Behavioral interactions increase pregnancy blocking by unfamiliar male meadow voles.

Unfamiliar male meadow voles induce pregnancy disruptions when they are in physical contact with females, but the presence of the female's original mate partially protects her from the blocking effects of an unfamiliar male. This research examines how behavioral interactions affect pregnancy disruptions by testing two hypotheses: a) original males protect females by reducing the aggressive interactions between females and strange males; and b) administration of clonidine, an alpha 2-adrenergic receptor agonist that decreases activity, aggression, and sexual motivation, will decrease the pregnancy-blocking ability of strange males. Strange males were more aggressive when the original sire was absent, indicating that this change in behavior may be related to their greater success in disrupting pregnancy. When injected with clonidine, males were less likely to block pregnancy, and they showed less contact and mating behavior than when they received saline injections. These results indicate that behavioral interactions are important for male-induced pregnancy disruptions in meadow voles.

Postimplantation pregnancy disruptions in meadow voles: relationship to variation in male sexual and aggressive behavior.

Previous research on Microtines indicates that the presence of new males may more effectively produce pregnancy disruptions than do pheromones alone. If the male's presence is important, behavioral differences among males may be related to the occurrence of disruptions. We observed female meadow voles (Microtus pennsylvanicus) interacting with new males twelve days after they had been paired with stud males. Behavioral interactions were recorded for one hour on each of Days 12-14. Timing of parturition and weight gain by Day 12 were used to assess whether a disruption had occurred. Females with disrupted pregnancies were frequently observed mating within an hour of being placed with the new male, whereas females that retained their original pregnancies rarely copulated with the new male. When pregnancies were disrupted, female-new male pairs fought more, but also engaged in more nonaggressive contact than when pregnancies were retained. Pup survival and male attendance of pups were lower when females retained litters, suggesting that females could successfully rear more pups if the original pregnancy was reabsorbed. However, relatively aggressive females paired with nonaggressive new males protected retained litters from new males. New males were tested for aggressive and pup care responses to an unrelated pup on the day before they were placed with the females. Males aggressive to unrelated pups in these tests were also more aggressive to females on Day 12. These data suggest that male aggressiveness may signal females when it would be advantageous to disrupt pregnancy.

Partial mediation of strange-male-induced pregnancy blocks by sexual activity in mice (Mus musculus).

Novel male house mice (Mus musculus) can disrupt early pregnancy in females. Previous research focused on pheromonal rather than behavioral mediation of this phenomenon. In Experiment 1, novel males were housed with females shortly after insemination. Litter production was negatively correlated with the males' sexual activity. Experiment 2 replicated this finding with a larger sample. In Experiment 3, females were exposed to castrated males. Testosterone-treated males completely blocked pregnancy, whereas untreated males did not. In Experiment 4, castrated testosterone-treated males were presented at intervals after insemination. Pregnancy was totally blocked at Days 3 and 4 and mostly blocked at Days 1 and 2 but was less affected at Days 5 and 6. In Experiment 5, females were exposed through a wire-mesh grid to castrated males. Pregnancies occurred in all conditions, even with testosterone-treated males. These data suggest a role for sexual activity in male-induced pregnancy blocks.

Pathologic migration of anterior teeth in patients with moderate to severe periodontitis.

The purpose of this study was to determine the prevalence of pathologic migration of anterior teeth in patients with moderate to severe periodontitis. The correlation between pathologic migration of anterior teeth and attachment loss (AL) was investigated, and an attempt was made to identify the most common early form of pathologic migration. Prevalence of tooth migration was studied in a group of 343 patients with moderate to severe periodontitis before treatment. The presence of pathologic migration was determined from the chief complaint and patient awareness o tooth movement in the last 5 years. Forty-four patients (age range 18 to 69; mean = 48.75) with 75 pairs of migrated and non-migrated teeth were studied further to determine if there is a correlation between severity of periodontal AL and pathologic migration. Migrated teeth were compared to control contralateral teeth that did not have migration. In addition, tooth mobility of the anterior teeth on 36 of the 44 patients was measured using the mobility meter. It was anticipated that tooth mobility would follow the same pattern as AL in relation to pathologic migration. The type and severity of displacement was recorded for each tooth affected by migration. The types of pathologic migration recorded were diastema, extrusion, rotation, facial flaring, and drifting into edentulous spaces. Pathologic migration prevalence was 30.03% +/- 2.5 (103/343 subjects). The mean AL of migrated teeth (4.79 +/- 0.28 mm) was significantly greater (P < 0.0001) than control teeth (3.21 +/- 0.18 mm). The numeric values (called PTV) of migrated teeth (17.6 +/- 1.5) were significantly greater (P < 0.0001) than control teeth (9.4 +/- 1.1). It was difficult to identify a primary form of displacement, as most patients demonstrated a combination of movements. The percentage of the 44 patients who presented with a specific type of movement was: facial flaring (90.9 +/- 4.4%), diastema (88.6 +/- 4.8%), rotation (72.7 +/- 6.8%), extrusion (68.2 +/- 7.1%), and tipping (13.6 +/- 5.2%). The results of this study confirms clinical impressions that periodontal disease destruction of the attachment apparatus plays a major role in the etiology of pathologic migration.

Margaret Clitherow: skeletal identification of an historical figure?

This paper describes the use of physical anthropological methods of analysis in attempting to identify an historical figure in England. The historical background to the examination is detailed and reasons for the belief that the skeletal remains excavated from the site were those of a named person, Margaret Clitherow, are discussed. Analysis of age, sex and manner of death indicated that the remains were not those of Margaret Clitherow.