Military service and alcohol use: a systematic narrative review.

BACKGROUND: Despite research highlighting the role of alcohol in military life, specifically in relation to mental health and certain combat experiences, there is no synthesised evidence looking at the relationship between military service and alcohol use. AIMS: To synthesize and examine evidence exploring the relationship between military service and alcohol use. METHODS: Six databases were examined across a 10-year period. Papers were included if they involved a military population and focused on alcohol use. From 4046 papers identified, 29 papers were included in the review. RESULTS: Military characteristics and experience were linked to high levels of alcohol use across military populations. Societal and cultural factors also played a role in alcohol use in military populations. Predatory behaviour of alcohol establishments, pressures to conform, an acceptance of alcohol use, and the role of religious services and military affiliated social networks were all considered. Excessive drinking impacted physical and mental health. Those diagnosed with PTSD and associated symptoms appeared to have greater alcohol use. CONCLUSIONS: This review identified certain characteristics and experiences of military service that are associated with higher levels of alcohol use. It is important to identify risk factors for alcohol misuse to develop appropriate policy, targeting prevention.

Influence of ventilation use and occupant behaviour on surface microorganisms in contemporary social housing.

In the context of increasingly airtight homes, there is currently little known about the type and diversity of microorganisms in the home, or factors that could affect their abundance, diversity and nature. In this study, we examined the type and prevalence of cultivable microorganisms at eight different sites in 100 homes of older adults located in Glasgow, Scotland. The microbiological sampling was undertaken alongside a household survey that collated information on household demographics, occupant behaviour, building characteristics, antibiotic use and general health information. Each of the sampled sites revealed its own distinct microbiological character, in both species and number of cultivable microbes. While some potential human pathogens were identified, none were found to be multidrug resistant. We examined whether the variability in bacterial communities could be attributed to differences in building characteristics, occupant behaviour or household factors. Sampled sites furnished specific microbiological characteristics which reflected room function and touch frequency. We found that homes that reported opening windows more often were strongly associated with lower numbers of Gram-negative organisms at indoor sites (p < 0.0001). This work offers one of the first detailed analysis of cultivable microbes in homes of older adults and their relationship with building and occupancy related factors, in a UK context.

Social isolation and loneliness of UK veterans: a Delphi study.

BACKGROUND: Evidence increasingly acknowledges the impact of social isolation and loneliness on the lives of military veterans and the wider Armed Forces Community. AIMS: The study gathered expert consensus to (i) understand if veterans are considered 'unique' in their experiences of social isolation and loneliness; (ii) examine perceived factors leading to social isolation and loneliness of veterans; (iii) identify ways to tackle veterans' social isolation and loneliness. METHODS: This study adopted a three-phase Delphi method. Phase 1 utilized a qualitative approach and Phase 2 and Phase 3 utilized a mixed-methods approach. RESULTS: Several outcomes were identified across the three phases. Transition out of the military was viewed as a period to build emotional resilience and raise awareness of relevant services. It was also concluded that veterans would benefit from integrating into services within the wider community, and that social prescribing services could be a vehicle to link veterans to relevant services. Furthermore, access to, and the content of, programmes was also of importance. CONCLUSIONS: These findings illustrate various important interventional aspects to consider when funding and implementing programmes focussed on tackling social isolation and loneliness.

Scattered radiation during fixation of hip fractures. Is distance alone enough protection?

We measured the scattered radiation received by theatre staff, using high-sensitivity electronic personal dosimeters, during fixation of extracapsular fractures of the neck of the femur by dynamic hip screw. The dose received was correlated with that received by the patient, and the distance from the source of radiation. A scintillation detector and a water-filled model were used to define a map of the dose rate of scattered radiation in a standard operating theatre during surgery. Beyond two metres from the source of radiation, the scattered dose received was consistently low, while within the operating distance that received by staff was significant for both lateral and posteroanterior (PA) projections. The routine use of lead aprons outside the 2 m zone may be unnecessary. Within that zone it is recommended that lead aprons be worn and that thyroid shields are available for the surgeon and nursing assistants.

Essential role for caspase-8 in transcription-independent apoptosis triggered by p53.

p53's dual regulation of arrest versus apoptosis may underlie tumor-selective effects of anti-cancer therapy. p53's apoptotic effect has been suggested to involve both transcription-dependent and -independent mechanisms. It is shown here that caspase-8 is activated early in cells undergoing p53-mediated apoptosis and in S100 cell-free extracts that recapitulate transcription-independent apoptosis. Depletion or inactivation of caspase-8 either in cells or cell-free extracts completely prevents this transcription-independent apoptosis and significantly attenuates overall death induced by wild-type p53. Importantly, caspase-8 activation appears to be independent of FADD, and caspase-8 is found in a novel 600-kDa complex following p53 activation. These findings highlight the roles of both transcription-dependent and -independent apoptosis by p53 and identify an essential role for caspase-8 in the transcription-independent pathway.

Microphthalmia transcription factor. A sensitive and specific melanocyte marker for MelanomaDiagnosis.

Malignant melanomas do not uniformly retain expression of melanocytic gene products-an observation associated with diagnostic dilemmas. Microphthalmia transcription factor (Mitf) is a melanocytic nuclear protein critical for the embryonic development and postnatal viability of melanocytes. It serves as a master regulator in modulating extracellular signals, such as those triggered by alpha-MSH and c-Kit ligand. Because of its central role in melanocyte survival and to assess its potential use as a histopathological marker for melanoma, Mitf expression was examined in histologically confirmed human melanoma specimens. Western blot analysis of melanoma cell lines revealed consistent expression of two Mitf protein isoforms differing by MAP kinase-mediated phosphorylation. In a series of 76 consecutive human melanoma surgical specimens, 100% stained positively for Mitf with a nuclear pattern of reactivity. In a side-by-side comparison, Mitf staining was positive in melanomas that failed to stain for either HMB-45 or S-100, the most common currently used melanoma markers. Of 60 non-melanoma tumors, none displayed nuclear Mitf staining and two displayed cytoplasmic staining. Although Mitf does not distinguish benign from malignant melanocytic lesions, for invasive neoplasms it appears to be a highly sensitive and specific histopathological melanocyte marker for melanoma.

Distinct mathematical behavior of apoptotic versus non-apoptotic tumor cell death.

PURPOSE: The presence or absence of a p53-dependent apoptosis response has previously been shown to greatly influence radiosensitivity in tumor cells. Here, we examine clonogenic survival curves for two genetically related oncogene transformed cell lines differing in the presence or absence of p53 and apoptosis. Solid tumor radiosensitivity patterns have been previously described for these lines. MATERIALS AND METHODS: Oncogene-transformed fibroblasts derived from E1A + Ras transfection of p53-wild-type or p53-null mouse embryonic fibroblasts were plated as single cells and irradiated at increasing radiation doses in single fractions from 1.5 to 11 Gy. Clonogenic cell survival assays were obtained. Survival data are fit to a linear-quadratic relationship: S = e(-alphaD-betaD2). Apoptosis was assessed and quantitated morphologically by staining with the fluorescent nuclear dye DAPI, by TUNEL assay for DNA fragmentation, and by measurement of apoptotic cysteine protease cleavage activity in cytosolic extracts. RESULTS: Whereas radiation triggers massive apoptosis in the presence of p53, it produces no measurable DNA fragmentation, apoptotic cysteine protease cleavage activity, or morphological changes of apoptosis in the cells lacking p53. These contrasting mechanisms of death display dramatically different quantitative behavior: log-survival of apoptotic cells is linearly proportional to dose (S = e(-alphaD)), whereas survival of non-apoptotic (p53 null) is linear-quadratic with a significant quadratic contribution. The surviving fraction at 2 Gy (SF-2) for p53-null cells was 70% verses 12% for p53-intact cells. CONCLUSIONS: In this system, apoptosis appears to exhibit a dominance of single-event which produces a very high alpha/beta ratio, and no significant shoulder; whereas non-apoptotic death in this system exhibits a comparatively small linear component, a low alpha/beta ratio, and a larger shoulder.

Oncogene-dependent regulation of caspase activation by p53 protein in a cell-free system.

The mechanism by which p53 modulates apoptosis in cancer therapy is incompletely understood. Here, cell-free extracts from irradiated tumor cells are described in which endogenous p53 protein is shown to participate in caspase activation. This apoptotic activity is also oncogene-dependent, but independent of transcription in general or the presence of Bax or cytochrome c. A general use for this system is as a cell-free screen for apoptosis modulators. In this way, profound effects of protein kinase A were identified and corroborated in vivo by the protection conferred by cAMP against diverse triggers of p53-dependent apoptosis. This system provides direct biochemical evidence that p53 protein can transduce apoptotic signals through protein-protein interactions and reveals a modulator kinase pathway capable of regulating p53-dependent caspase activation.

DNA bending and the curious case of Fos/Jun.

DNA bending has been implicated as an important regulatory mechanism in several processes involving protein-DNA interactions. Various methods for examining intrinsic and protein-induced DNA bending may lead to different conclusions. For the Fos and Jun transcription factors, this has resulted in controversy over whether these factors significantly bend DNA at all.

Loss of matrix adhesion triggers rapid transformation-selective apoptosis in fibroblasts.

Cell-matrix and cell-cell adhesion are recognized physiological determinants of cell growth and survival. In epithelial and endothelial cell systems, oncogenic transformation has in several cases been shown to confer resistance to apoptosis upon depriving cells of substrate adhesion. We examined the effects of oncogenic transformation in adherent versus adhesion- deprived primary embryonic fibroblasts. Whereas untransformed early passage fibroblasts undergo cell cycle arrest, their Myc/Ras- or E1A/Ras-transformed counterparts rapidly enter apoptosis when placed into suspension. This phenomenon also occurs upon incubation with a soluble, RGD-containing integrin ligand and is blocked by a peptide antagonist to ICE family proteases or by aggregation of cells plated at high density. Loss of wild-type p53 modulates the kinetics but does not abrogate this death pathway. Transformation with activated Src rather than Ras rendered fibroblasts selectively resistant to adhesion-dependent apoptosis, an effect likely related to Src's role in integrin signaling, while simultaneously sensitizing the cells to radiation-induced apoptosis. Thus cell adhesion events regulate transformation-selective apoptosis in fibroblasts and provide potentially important targets for understanding and interfering with tumor cell viability.

Apoptosis in tumorigenesis and cancer therapy.

Apoptosis is a morphologically and biochemically distinct form of cell death which can be triggered by a variety of extracellular agents during both normal development as well as in adult pathological states. Much progress has recently been made in understanding the molecular pathways which regulate this process as well as new intersections between these. A direct interaction between components of the 'executioner'--the ICE-family of cysteine proteases--and the Bcl-2 family of proteins, which modulate a cell's propensity to undergo apoptosis, has recently been demonstrated. New pathways to cell survival, like the PI3-K/Akt signal transduction pathway, are also providing new clues as to the regulation of cell death by growth factors and extracellular matrix for example. The links which exist between apoptosis and cancer research are several. Genetic alterations in components of the apoptosis pathway occur during tumorigenesis and confer resistance to a variety of physiological (oncogene-induced cell death, loss of adhesion, growth under hypoxia) as well as therapeutic (chemotherapy and radiation) death triggers. Similarly, antineoplastic therapies are thought to induce tumor cell apoptosis, and consequently, common mutations in apoptosis-regulatory genes carry a poor prognosis for the patient. A more detailed understanding of the biochemistry of apoptosis and the ways in which it is disabled in tumors will likely reveal new transformation selective death triggers which stimulate cell death in ways independent of components like p53 and increase the therapeutic window of these drugs in the clinics.

Damp housing and asthma: a case-control study.

BACKGROUND: Several epidemiological studies have reported a higher prevalence of respiratory symptoms in subjects living in damp housing, but links with specific respiratory diseases such as asthma have not been satisfactorily established. METHODS: One hundred and two subjects with physician diagnosed asthma and 196 age and sex matched controls were interviewed; 222 (75%) then agreed to have their dwelling surveyed for dampness. The prevalence of both self-reported and observed dampness in the homes of the asthmatic subjects and controls were compared. Both asthma and the severity of the dampness were quantified so that the possibility of a dose-response relationship could be investigated. RESULTS: Asthmatic subjects reported dampness in their current (odds ratio (OR) 1.92, 95% confidence interval (CI) 1.18 to 3.12) and previous (OR 2.11, 95% CI 1.29 to 3.47) dwellings more frequently than control subjects. The surveyor confirmed dampness in 58 of 90 (64%) dwellings of asthmatic subjects compared with 54 of 132 (41%) dwellings of control subjects (OR 2.62, 95% CI 1.50 to 4.55). This association persisted after controlling for socioeconomic and other confounding variables (adjusted OR 3.03, 95% CI 1.65 to 5.57). The severity of asthma was found to correlate statistically with measures of total dampness (r = 0.30, p = 0.006) and mould growth (r = 0.23, p = 0.035) in the dwelling. Patients living in homes with confirmed areas of dampness had greater evidence of airflow obstruction than those living in dry homes (mean difference in forced expiratory volume in one second (FEV1) 10.6%, 95% CI 1.0 to 20.3). CONCLUSIONS: Asthma is associated with living in damp housing and there appears to be a dose-response relationship. Action to improve damp housing conditions may therefore favourably influence asthma morbidity.

The estimation of administered activity of krypton-81m for lung ventilation studies.

Measurement or estimation of the activity of krypton-81m administered to a patient during lung ventilation imaging is difficult, due to the short half-life and continuous delivery via pipework, and no satisfactory method exists. Calculations based on generator activity have the disadvantages that this activity may not be accurately known and that not all activity eluted is inhaled by the patient. The aim of this study was to develop a simple method for estimating the administered activity from the number of counts in each patient image. A formula based on the ratio of counts in 81mKr and technetium-99m lung ventilation and perfusion images was developed and reduced so that administered activity could be directly calculated from the total 81mKr counts, the 99mTc count rate, the administered activity of 99mTc and a constant representing the ratio of counts expected from equal activities of each radioisotope. The formula allows a direct calculation from the image acquisition data following an initial set of experimental work to establish the constant for a particular gamma camera and collimator system.

microphthalmia, a critical factor in melanocyte development, defines a discrete transcription factor family.

The microphthalmia (mi) gene appears essential for pigment cell development and/or survival, based on its mutation in mi mice. It has also been linked to the human disorder Waardenburg Syndrome. The mi gene was recently cloned and predicts a basic/helix-loop-helix/leucine zipper (b-HLH-ZIP) factor with tissue-restricted expression. Here, we show that Mi protein binds DNA as a homo- or heterodimer with TFEB, TFE3, or TFEC, together constituting a new MiT family. Mi can also activate transcription through recognition of the M box, a highly conserved pigmentation gene promoter element, and may thereby determine tissue-specific expression of pigmentation enzymes. Six mi mutations shown recently to cluster in the b-HLH-ZIP region produce surprising and instructive effects on DNA recognition and oligomerization. An alternatively spliced exon located outside of the b-HLH-ZIP region is shown to significantly modulate DNA recognition by the basic domain. These findings suggest that Mi's critical roles in melanocyte survival and pigmentation are mediated by MiT family interactions and transcriptional activities.

Genetic dissection of oligogenic resistance to bacterial wilt in tomato.

To study resistance to bacterial wilt (caused by Pseudomonas solanacearum) in tomato, we analyzed 71 F2 individuals from a cross between a resistant and a susceptible parent with 79 DNA markers. F2 plants were inoculated by two methods: bacteria were injected into shoots of cuttings or poured into soil surrounding wounded roots. Disease responses were scored on a scale of 0 to 5. Statistical comparisons between DNA marker genotypes and disease phenotypes identified three genomic regions correlated with resistance. In plants inoculated through roots, genomic regions on chromosomes 6 and 10 were correlated with resistance. In plants inoculated through shoots, a region on chromosome 7 was significant, as were the regions on chromosomes 6 and 10. The relative impact of resistance loci on disease response differed between shoot and root inoculations. To confirm the existence of a partial resistance gene on chromosome 6, an F2 individual homozygous for the resistant parent's alleles on chromosomes 7 and 10, but heterozygous for markers on chromosome 6, was selfed. Analysis of the F3 progeny confirmed that a partial resistance locus was located on chromosome 6, very close to CT184. The presence of a partial resistance locus on chromosome 10 was similarly confirmed by analysis of progeny of another F2 plant chosen on the basis of its marker phenotype.

Tectonics and evolution of venus.

The global tectonics of Venus differs significantly from that of Earth, most markedly in that the surface is covered predominately by gently rolling terrain; there apparently are no features like ocean rises; the gravity is positively correlated with topography at all wavelengths; and the few highlands are estimated to be supported or compensated at a depth of approximately 100 kilometers. The surface of Venus appears to be covered mainly by an ancient crust, the high surface temperature making subduction difficult. It seems likely that well over 1 billion years ago water was destabilized at the surface and, soon after, plate tectonics ceased. The highlands appear to be actively supported, presumably as manifestations of long-enduring hot spots.

Venus: preliminary topographic and surface imaging results from the pioneer orbiter.

Three large Venus surface features, identified previously in images obtained from Earth-based radar observations, are shown by the Pioneer Venus radar mapper to be elevated 5 to 10 kilometers above the surrounding terrain. Two of these features, one bright and the other dark, lie adjacent to each other astride the 65 degrees N parallel between longitudes 310 degrees E and 10 degrees E. The combined region forms a huge tectonically uplifted plateau, surmounted by radar-bright ridges that may have either a volcanic or tectonic origin. The third feature, located at 30 degrees N, 283 degrees E, is radar-bright and may consist of volcanic material extruded along a fault zone. A first radar-scattering image, compiled from data obtained by the mapper in its imaging mode, shows a region north of the equator; several circular depressions seen in this area may result from meteoritic impact.