Exploring correlations between the breast density of the women of Papua New Guinea and breast cancer risk factors.

INTRODUCTION: Papua New Guinea (PNG), has experienced an increase in breast cancer incidence correlating to the westernisation of the country. Increased breast density is known to increase breast cancer risk. This study investigates if there are any factors unique to the women of PNG that may impact breast density and breast cancer risk. METHOD: A survey was undertaken of 1,161 women who had undergone mammographic imaging at the Pacific International Hospital (PIH). Results were correlated with the five Tabár mammographic parenchymal patterns (TP), recorded for each woman and geographical location, parity, breast size, occupation, marital and menstrual status, smoking and alcohol consumption, hormone replacement therapy (HRT), and exercise. Statistical analysis was undertaken using chi-square test, Fisher's exact test and Odds Ratio (OR). RESULTS: Relationships were identified between TP and parity (p < 0.001), marital status (p < 0.001), smoking (p < 0.001), alcohol intake (p = 0.029) and HRT (p = 0.029). There was no evidence of a relationship between pattern type and geographical location (p = 0.290), breast size (p = 0.592), occupation (p = 0.724), menstruation (p = 0.866) or exercise (p = 0.290). Married women, OR = 0.4004, CI 95% (0.2873-0.5579) and those with higher parity, OR 0.5034, CI 95% (0.3693-0.6862) were half as likely to have increased breast density reducing risk. CONCLUSION: There was no clear relationship across almost all data. Factors associated with increased breast density in PNG included parity, marital status, smoking, alcohol, and HRT use were evidenced in this snapshot of PNG women. Breast cancer risk was shown to be reduced for married women and those with increased parity.

Temperature and soil moisture control microbial community composition in an arctic-alpine ecosystem along elevational and micro-topographic gradients.

Microbial communities in arctic-alpine soils show biogeographic patterns related to elevation, but the effect of fine-scale heterogeneity and possibly related temperature and soil moisture regimes remains unclear. We collected soil samples from different micro-topographic positions and elevational levels in two mountain regions of the Scandes, Central Norway. Microbial community composition was characterized by 16S rRNA gene amplicon sequencing and was dependent on micro-topography and elevation. Underlying environmental drivers were identified by integration of microbial community data with a comprehensive set of site-specific long-term recorded temperature and soil moisture data. Partial least square regression analysis allowed the description of ecological response patterns and the identification of the important environmental drivers for each taxonomic group. This demonstrated for the first time that taxa responding to elevation were indeed most strongly defined by temperature, rather than by other environmental factors. Micro-topography affected taxa were primarily controlled by temperature and soil moisture. In general, 5-year datasets had higher explanatory power than 1-year datasets, indicating that the microbial community composition is dependent on long-term developments of near-ground temperature and soil moisture regimes and possesses a certain resilience, which is in agreement with an often observed delayed response in global warming studies in arctic-alpine regions.

Mammographic parenchymal pattern and breast cancer risk profile of Papua New Guinean women - A baseline study of the screening population.

INTRODUCTION: The aim of this research is to evidence for the first time the breast density of Papua New Guinean (PNG) women as described by mammographic parenchymal patterns (MPPs) and profile breast cancer risk; to examine the relationship of age and MPPs. METHODS: A retrospective analysis of 1161 screening mammograms of women who had undergone imaging at the Pacific International Hospital (PIH) was undertaken. Mammograms were classified into one of five Tabár MPPs; age was recorded in years. Descriptive analysis of the data for pattern distribution and a chi-square test, to test for relationships between age and pattern type were undertaken. RESULTS: The majority (51.42%) of women had Pattern I breasts; Pattern II (30.58%), Pattern III (4.31%), Pattern IV (7.24%), and Pattern V (6.46%). The mean age was 38.8 with a range of 30-80 years; there were no obvious differences in mean age across the categories of patterns. A chi-square test reported no evidence of a relationship between age and pattern type (p-value = 0.504). Pattern V differed from other patterns, with proportionally more women aged over 50 and less aged in their 40s. CONCLUSION: This study sets a baseline for future studies of the MPPs of PNG women, and demonstrated that in this snapshot of PNG women, there is no unique distribution of MPPs and no increased risk of breast cancer based on breast density profile. This result does not help to explain the high incidence of breast cancer in PNG. A more comprehensive study of the PNG screening population is required to validate this study.

The NOX1/4 inhibitor GKT136901 as selective and direct scavenger of peroxynitrite.

NADPH oxidases (NOX), catalyzing the reduction of molecular oxygen to form the superoxide radical anion (•O2⁻) and hydrogen peroxide (H2O2), are involved in several pathological conditions, such as stroke, diabetes, atherosclerosis, but also in chronic neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, or multiple sclerosis. GKT136901 is a novel NOX-1/4 inhibitor with potential application in the areas of diabetic nephropathy, stroke, or neurodegeneration. In the present study, we investigated additional pharmacological activities of the compound with respect to direct free radical scavenging. GKT136901 did not interact with nitric oxide (•NO), •O2⁻, or hydroxyl radicals (•OH), but it acted as selective scavenger of peroxynitrite (PON) already in the submicromolar concentration range. Alpha synuclein (ASYN) is a protein involved in the pathogenesis of Parkinson's disease and a known target for PON-dependent tyrosine nitration. Submicromolar concentrations of GKT136901 prevented tyrosine nitration and di-tyrosine-dependent dimer formation of ASYN by PON as indicated by Western blot and mass spectrometric analysis. GKT136901 itself was degraded when exposed to PON. In a human neuronal cell model, GKT136901 prevented both the depletion of reduced intracellular glutathione, and the degeneration of neurites when present during PON treatment of the cells. When GKT136901 was applied after PON treatment, no protective effect was observed, thus excluding an impact of GKT136901 on cellular death/survival pathways. In summary, selective scavenging of PON is an additional pharmacological property of the NOX-1/4 inhibitor GKT136901, and this may add to the efficiency of the drug in several disease models.

Delayed inhibition of Nogo-A does not alter injury-induced axonal sprouting but enhances recovery of cognitive function following experimental traumatic brain injury in rats.

Traumatic brain injury causes long-term neurological motor and cognitive deficits, often with limited recovery. The inability of CNS axons to regenerate following traumatic brain injury may be due, in part, to inhibitory molecules associated with myelin. One of these myelin-associated proteins, Nogo-A, inhibits neurite outgrowth in vitro, and inhibition of Nogo-A in vivo enhances axonal outgrowth and sprouting and improves outcome following experimental CNS insults. However, the involvement of Nogo-A in the neurobehavioral deficits observed in experimental traumatic brain injury remains unknown and was evaluated in the present study using the 11C7 monoclonal antibody against Nogo-A. Anesthetized, male Sprague-Dawley rats were subjected to either lateral fluid percussion brain injury of moderate severity (2.5-2.6 atm) or sham injury. Beginning 24 h post-injury, monoclonal antibody 11C7 (n=17 injured, n=6 shams included) or control Ab (IgG) (n=16 injured, n=5 shams included) was infused at a rate of 5 microl/h over 14 days into the ipsilateral ventricle using osmotic minipumps connected to an implanted cannula. Rats were assessed up to 4 weeks post-injury using tests for neurological motor function (composite neuroscore, and sensorimotor test of adhesive paper removal) and, at 4 weeks, cognition was assessed using the Morris water maze. Hippocampal CA3 pyramidal neuron damage and corticospinal tract sprouting, using an anterograde tracer (biotinylated dextran amine), were also evaluated. Brain injury significantly increased sprouting from the uninjured corticospinal tract but treatment with monoclonal antibody 11C7 did not further increase the extent of sprouting nor did it alter the extent of CA3 cell damage. Animals treated with 11C7 showed no improvement in neurologic motor deficits but did show significantly improved cognitive function at 4 weeks post-injury when compared with brain-injured, IgG-treated animals. To our knowledge, the present findings are the first to suggest that (1) traumatic brain injury induces axonal sprouting in the corticospinal tract and this sprouting may be independent of myelin-associated inhibitory factors and (2) that post-traumatic inhibition of Nogo-A may promote cognitive recovery unrelated to sprouting in the corticospinal tract or neuroprotective effects on hippocampal cell loss following experimental traumatic brain injury.

Novel restraint system for neuroendocrine studies of socially living common marmoset monkeys.

We describe a novel soft jacket and sling-harness restraint that permits species-typical postures for small-bodied primates, such as the common marmoset (Callithrix jacchus), during long-term (>6 h), continuous restraint. The restraint system is straightforward to use and manipulate, it is easily repaired, and the materials used are readily available. The soft jacket allows for increased versatility and longevity, and the sling-harness provides for greater movement and much longer duration of continuous restraint (up to 3 days) compared to a previously described, more conventional chair restraint for small-bodied primates. The new restraint system prevents the normal diurnal decrease in plasma cortisol levels across the daylight hours; however, it does not disrupt ovulatory cycles. Unlike the previously available techniques, therefore, this new restraint system is applicable to many neurobiological and neuroendocrine studies involving small-bodied, non-human primates and is especially suited to investigations requiring the maintenance of relationships within social groups.

Structure and specific expression of a Nicotiana sylvestris putative amino-acid transporter gene in mature and in vitro germinating pollen.

We report here the structure and expression analysis of a Nicotiana sylvestris gene, called nsaap1, coding for a protein which shows significant identity to the members of the Arabidopsis thaliana amino acid permease family. The nsaap1 gene is expressed exclusively in binucleate pollen. Its transcripts begin to accumulate after first pollen mitosis and dramatically increase in mature pollen shortly before anthesis and during in vitro pollen germination. The nsaap1 5'-flanking region contains long regions homologous to the promoter region of the tobacco pollen specific eIF-4A8 translation factor. Our results support the occurrence of an amino acid remobilization in binucleate pollen. The nsaap1 gene could play a role in exchanges between the vegetative and the generative pollen cells.

[A Trojan horse in nursing? Nursing diagnosis and its theoretical context]. / Ein Trojanisches Pferd in der Pflege? Pflegediagnosen und ihr theoretisches Umfeld.

Nursing diagnosis and their theoretical context. The necessity of developing and using nursing diagnoses is indisputable. In the process of the professionalisation of nursing they constitute a fundamental aspect of nursing science. However, if nursing diagnoses are not to harm nursing, they must be developed with care. One difficulty will be to translate the theoretical framework in its abstract form into realisable elements in practice. For this purpose the nursing related terminology must be unambiguous and understandable. Nursing must seek the discussion with allied sciences. Nurses must develop their cognitive skills to ensure a valid use of nursing diagnoses. The areas common with other occupational groups in the treatment process have to be classified and their contents have to be determined. This is a challenge to colleagues in all areas of work and indifferent functions to participate in this development. It is also a challenge to nursing science itself.

Effects of anti-microtubule agents on Paramecium cell culture growth.

Since there are no systematic studies available on the effects of anti-microtubule agents on ciliated protozoa, we screened a wide variety of such compounds for their effects on the growth of Paramecium tetraurelia cell cultures. Compounds tested include agents of widely different chemical composition and with reported effects on widely different cell types. We can differentiate between different drug effects: (a) Rotenone is the only agent without any recognisable effect, (b) Another group of compounds (including colchicine) requires very high concentrations, as compared to higher animal cells, i.e., rather close to a cytotoxic level; this group also includes tubulozole (unexpectedly without any difference between the cis- and the trans-stereoisomer). (c) A third group of drugs inhibits cell culture growth without any lethal effects (benzimidazoles, nocodazole, parbendazole; the [anti-]fungal antibiotic, griseofulvin; the herbicide, trifluralin). (d) Finally a group of agents are active in a concentration range also reported for plants (the herbicide, APM) or for higher animal cells (including the microtubule stabiliser, taxol) or for both (vinblastine, vincristine, triethyl lead), although they are cytotoxic at higher concentrations (like compounds of group [b]). Therefore, in particular compounds of group (c) and possibly of group (d) might be considered further on for a more detailed analysis of a possibly genuine anti-microtubular effect in Paramecium cells. Of particular interest may be nocodazole, parbendazole and trifluralin, since they can inhibit cell culture growth (over 24 h tested) in relatively low concentrations (comparable to other cell types) without any impairment of cell viability.

Secretory organelle docking at the cell membrane of Paramecium cells: dedocking and synchronized redocking of trichocysts.

We present the first evidence that secretory organelle docking at the cell membrane can be reversed in vivo. In nondischarge (nd) mutants of Paramecium tetraurelia all trichocysts can be detached from the cell surface within 2-3 h by different means, including cytochalasin B (but not D), high cell density, or Ca2+ ionophores. Considering the well-established ultrastructural differences between nd and wild-type (wt) cells, one can conclude that trichocyst docking at the cell periphery involves two docking sites (I, II): Site I ties the organelles to the epiplasm, and site II is the connection to the cell membrane at the fusogenic zone (expressed only in wt cells); both sites are close to the cell surface and only 150 nm apart. When the trigger for detachment of cortically docked trichocysts (high cell density, cytochalasin B) is relieved, trichocysts are synchronously reattached at the cell membrane, within 40-50 min, with a rate of 20-40 organelles/min, which far exceeds spontaneous docking rates. This is therefore also the first report on synchronization of secretory organelle docking. It is shown by radioactive leucine labeling that the same organelles are redocked, because trichocyst biogenesis is minimal under the conditions of de/redocking used. Surprisingly not only redocking but also detachment of trichocysts from the cell surface can be abolished by inhibitors of protein synthesis. Since Ca2+ ionophores mimic the effects of other conditions sufficient to detach trichocysts from the cell surface, we assume that a protein-dependent mechanism sensitive to Ca2+ (or other ions in exchange) may operate in trichocyst detachment. The precise mechanism involved in attachment or detachment of trichocysts remains to be elucidated.

Antihypertensive thiadiazoles. 1. Synthesis of some 2-aryl-5-hydrazino-1,3,4-thiadiazoles with vasodilator activity.

Some 2-aryl-5-hydrazino-1,3,4-thiadiazoles have been synthesized and screened for antihypertensive activity. In general, compounds with a 2-substituted phenyl ring had higher activity than their 3- or 4-substituted counterparts or those containing heteroaryl groups. The 2-methylphenyl and 2-ethylphenyl derivatives 7 and 18 were the most potent members of the series. Preliminary studies indicated that the hypotensive action of these compounds was due to a direct relaxant effect on vascular smooth muscle.

Antihypertensive thiadiazoles. 2. Vasodilator activity of some 2-aryl-5-guanidino-1,3,4-thiadiazoles.

Some 2-aryl-5-guanidino-(or N-substituted guanidino)-1,3,4-thiadiazoles and closely related analogues were found to lower blood pressure in metacorticoid (DOCA) hypertensive rats. In the unsubstituted guanidines that exhibited low toxicity, optimum activity resulted when the aryl group was a 2-methylphenyl ring (11). Modifications to the guanidine group did not increase antihypertensive activity, but, in the 2-methylphenyl series, the N-n-butyl- and N-(2-methoxyethyl)guanidines (63 and 78) and the related iminoimidazolidine 93 were of comparable activity to that of the unsubstituted guanidine 11. The iminoimidazolidine 93 showed a somewhat longer duration of action than the guanidine derivatives. Preliminary studies in a pithed rat preparation indicated that these thiadiazole derivatives (11, 63, and 93) lowered blood pressure by a direct relaxant effect on vascular smooth muscle.

[Holter ECG monitoring during peridural anesthesia with bupivacaine 0.75%]. / Holter-EKG-Uberwachung bei Periduralanaesthesie mit Bupivacain 0.75%.

Electrocardiographic monitoring was undertaken in thirteen women and seven men before, during, and after epidural anaesthesia with bupivacaine 0.75%. The average surveying time lasted 18:28 h. Bupivacaine 0.75% was given in a dose of 1.5 mg/kg body weight (n = 8) and 2 mg/kg body weight (n = 12). Eleven patients (8 female/3 male) = 55% showed VES of category I of the LOWN-classification. Three subjects (3 female) suffered VES before and after injection of bupivacaine 0.75%. Five patients (3 female/2 male) showed VES before and three (2 female/1 male) only after epidural blockade. Serious arrhythmias or other signs of toxic actions on the myocardium were not registered.

Synchronous exocytosis in Paramecium cells. VI. Ultrastructural analysis of membrane resealing and retrieval.

After the synchronous induction of exocytosis of secretory organelles (trichocysts) in Paramecium tetraurelia cells the process of membrane resealing and retrieval could be followed under synchronous conditions. The characteristic aggregates of membrane intercalated particles (MIPs) contained within the freeze-fractured cell membrane (rings and rosettes) and trichocyst membranes (annulus MIPs), in addition to collar striations on the top of trichocyst membranes, served as endogenous ultrastructural markers. This allowed us to follow the re-arrangement of membrane constituents during and after exocytosis with high temporal and spatial precision. Membrane specificity is maintained to a considerable extent (approximately 99.5%), as judged from the rare occurrence of aberrant resealing (according to freeze-fracture data) and from the rather minute shift of glycocalyx components (according to electron staining experiments) during normal membrane resealing. Coated pits are not involved in membrane retrieval (155 ghosts analysed); since the membrane regions involved in exocytotic fusion are backed by apposed materials, probably proteins, this may restrain membrane constituents from intermixing. Another factor for maintaining membrane specificity is the fact that resealing of the exocytotic opening occurs much more rapidly than in most other systems. The retrieval operates with a half-life of 3 (strain 7S) to 9 min (K401); the involvement of cortical microtubules in the retrieval can be largely excluded, since only two microtubules (of unidentified origin) were seen to approach ghost structures in 4074 cases analysed during this period of intense ghost retrieval. Phalloidin microinjected at a dose that blocked all cytoplasmic streaming (before synchronous exocytosis was induced) did not abolish membrane resealing and retrieval, which, therefore, may be passive processes.

Synchronous exocytosis in Paramecium cells. V. Ultrastructural adaptation phenomena during re-insertion of secretory organelles.

We used aminoethyldextran (AED) as a secretagogue for the simultaneous exocytosis of a great proportion of secretory organelles (trichocysts) from Paramecium tetraurelia cells and we applied freeze-fracturing and ultrathin sectioning for a quantitative analysis of the re-arrangement of ultrastructural details within the cell membrane during re-insertion of new trichocysts. Characteristic arrangements of membrane-intercalated particles (MIPs) occur over trichocyst docking sites: 300 nm large double rings of MIPs and a MIP rosette in the middle. Empty sites, displaying a compressed ring ("parenthesis") without a rosette, are expanded to full size rings when a trichocyst is docked. We obtained a first hint on the possible existence of a short lived (approximately 5 min) adaptation stage, represented by rings without a rosette. This could mean that docking of a trichocyst would induce the assembly of rosette MIPs over a newly docked trichocyst. The reformation of rosettes is paralleled by an increasing number of extrudable trichocysts which underscores the causal role of rosette MIPs in exocytosis performance. New trichocysts are inserted at the old predetermined sites after removal of ghosts and formation of a "plug" as a receptor-type structure. The number of non-docked, free trichocysts in the cytoplasm is only slightly changed, indicating a continuous synthesis and docking rate (approximately 2-3 organelles per min). Since in strain 7S ghosts are removed within approximately 10 min and docking goes on over 9 h, there occur many empty docking sites in the time period in between, with a maximum of approximately 1 h after AED triggering, thus providing a unique situation for further experiments.