ABSTRACT
Changes in frequency and severity of heat waves due to climate change pose a considerable challenge to livestock production systems. Although it is well known that heat stress reduces feed intake in cattle, effects of heat stress vary between animal genotypes and climatic conditions and are context specific. To derive a generic global prediction that accounts for the effects of heat stress across genotypes, management and environments, we conducted a systematic literature review and a meta-analysis to assess the relationship between dry matter intake (DMI) and the temperature-humidity index (THI), two reliable variables for the measurement of feed intake and heat stress in cattle, respectively. We analysed this relationship accounting for covariation in countries, breeds, lactation stage and parity, as well as the efficacy of various physical cooling interventions. Our findings show a significant negative correlation (r = - 0.82) between THI and DMI, with DMI reduced by 0.45 kg/day for every unit increase in THI. Although differences in the DMI-THI relationship between lactating and non-lactating cows were not significant, effects of THI on DMI varied between lactation stages. Physical cooling interventions (e.g. provision of animal shade or shelter) significantly alleviated heat stress and became increasingly important after THI 68, suggesting that this THI value could be viewed as a threshold for which cooling should be provided. Passive cooling (shading) was more effective at alleviating heat stress compared with active cooling interventions (sprinklers). Our results provide a high-level global equation for THI-DMI across studies, allowing next-users to predict effects of heat stress across environments and animal genotypes.
Subject(s)
Lactation , Milk , Animals , Cattle , Female , Heat-Shock Response , Hot Temperature , Humidity , Pregnancy , TemperatureABSTRACT
Humans spend a considerable portion of their lives engaged in 'stimulus-independent thoughts' (SIT), or mental activity that occurs independently of input from the immediate external environment. Although such SITs are, by definition, different from thoughts that are driven by stimuli in one's external environment (i.e. stimulus-dependent thoughts; SDTs), at times, the phenomenology of these two types of thought appears to be deceptively similar. But how similar are they? We address this question by comparing the content of two types of SIT (dreaming and waking SITs) with the content of SDTs. In this 7 day, smartphone-based experience-sampling procedure, participants were intermittently probed during the day and night to indicate whether their current thoughts were stimulus dependent or stimulus independent. They then responded to content-based items indexing the qualitative aspects of their experience (e.g. My thoughts were jumping from topic to topic). Results indicate substantial distinctiveness between these three types of thought: significant differences between at least two of the three mental states were found across every measured variable. Implications are discussed. This article is part of the theme issue 'Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation'.
Subject(s)
Attention/physiology , Dreams/physiology , Ecological Momentary Assessment , Female , Humans , Male , Young AdultABSTRACT
BACKGROUND: Police are exposed to a wide range of stressors and this is especially true in developing countries such as Jamaica. Exposure to psychosocial stressors and use of maladaptive coping styles can result in mental ill-health. AIMS: To examine the relationship between work characteristics, coping and mental health in Jamaican police officers and to test whether work characteristics are indirectly associated with mental health outcomes through perceived job stress and job satisfaction. METHODS: Police officers from the Jamaican police force completed a questionnaire using a cross-sectional design. We analysed the data using hierarchical regression. RESULTS: The study group consisted of 134 police officers; the response rate was 94%. Negative work characteristics, lower levels of positive work factors and work support and emotion-focused coping styles were associated with increased levels of depression (F(8, 125) = 7.465, P < 0.001). Subjective feelings of anxiety were positively associated with negative work characteristics and emotion-focused coping (F(8, 125) = 7.586, P < 0.001). The relationship between work characteristics and mental health outcomes was mediated by perceived stress. Job satisfaction mediated the relationship between positive work characteristics and depression. CONCLUSIONS: Stress management and intervention programmes should address modifiable work conditions, monitor stress levels and reduce maladaptive coping.
Subject(s)
Adaptation, Psychological , Depression/etiology , Mental Health , Occupational Exposure/adverse effects , Police/psychology , Stress, Psychological/etiology , Work/psychology , Adult , Anxiety/etiology , Cross-Sectional Studies , Depressive Disorder/etiology , Female , Humans , Jamaica , Job Satisfaction , Male , Occupational Diseases/etiology , Occupational Diseases/psychology , Surveys and QuestionnairesABSTRACT
ACCESSIBLE SUMMARY: What is known on the subject? Stress can impact students on mental health nurse training. This can have implications at the individual level (e.g. their own mental health) and at the level of the organization (e.g. sickness absence and attrition). What this paper adds to existing knowledge? We interviewed 12 mental health nursing students regarding the stress they experienced during training. Participants described how the academic demands can at times be unbearable during clinical placements. There were also issues with 'being a student' on some placements, with participants describing negative attitudes towards them from staff. The younger participants reported feeling overwhelmed on their initial placements and described some of the main challenges of mental health work for them. Raising concerns about the quality of care on wards was also described as particularly challenging for the students. What are the implications for practice? This paper can be useful to help training providers support mental health nursing students. Recommendations include reducing academic demands during clinical placements and extending and promoting existing support services beyond normal 9 am-5 pm working hours, even if these services are limited. Younger students could be better supported by being allocated to the more well-resourced placements in the early stages of their training. Raising awareness among staff of the tasks students can and cannot perform can help improve staff/student relations. Finally, students should be educated about the issues around raising concerns on placements to help the government's drive for a more open and transparent National Health Service (NHS). INTRODUCTION: Previous studies investigating stress in nursing students focus on general nursing students or adopt quantitative measures. PURPOSE OF STUDY: A qualitative study focusing specifically on mental health nursing students is required. METHOD: One-to-one interviews were carried out with mental health nursing students (n = 12). Data were thematically analysed. RESULTS: Participants reported unreasonable demands during clinical blocks, and described how control/support is lowest on placements with staff shortages. Negative attitudes towards students from staff and related issues were also discussed. Younger participants described struggling with mental health work during the early stages of training. DISCUSSION: Training providers should strive to provide adequate support to students to help them manage stress during training. Implications for practice Academic demands should be reasonable during clinical blocks and support services outside normal working hours should be available for students, even if these are limited in scope. Greater consideration to the allocation of placements for younger students in the mental health branch could be helpful. Furthermore, staff on placements should be aware of the tasks students can and cannot perform, to help improve staff/student relations. Educating students on the issues of raising concerns can help the government's drive for a more open and transparent National Health Service (NHS).
Subject(s)
Education, Nursing, Baccalaureate , Psychiatric Nursing/education , Stress, Psychological/psychology , Students, Nursing/psychology , Adult , Female , Humans , Interview, Psychological , Male , Nursing Education Research , Qualitative Research , Young AdultABSTRACT
AIMS: Among people with diabetes, 10-25% will experience a foot ulcer. Research has shown that supplementation with arginine, glutamine and ß-hydroxy-ß-methylbutyrate may improve wound repair. This study tested whether such supplementation would improve healing of foot ulcers in persons with diabetes. METHODS: Along with standard of care, 270 subjects received, in a double-blinded fashion, (twice per day) either arginine, glutamine and ß-hydroxy-ß-methylbutyrate or a control drink for 16 weeks. The proportion of subjects with total wound closure and time to complete healing was assessed. In a post-hoc analysis, the interaction of serum albumin or limb perfusion, as measured by ankle-brachial index, and supplementation on healing was investigated. RESULTS: Overall, there were no group differences in wound closure or time to wound healing at week 16. However, in subjects with an albumin level of ≤ 40 g/l and/or an ankle-brachial index of < 1.0, a significantly greater proportion of subjects in the arginine, glutamine and ß-hydroxy-ß-methylbutyrate group healed at week 16 compared with control subjects (P = 0.03 and 0.008, respectively). Those with low albumin or decreased limb perfusion in the supplementation group were 1.70 (95% CI 1.04-2.79) and 1.66 (95% CI 1.15-2.38) times more likely to heal. CONCLUSIONS: While no differences in healing were identified with supplementation in non-ischaemic patients or those with normal albumin, addition of arginine, glutamine and ß-hydroxy-ß-methylbutyrate as an adjunct to standard of care may improve healing of diabetic foot ulcers in patients with risk of poor limb perfusion and/or low albumin levels. Further investigation involving arginine, glutamine and ß-hydroxy-ß-methylbutyrate in these high-risk subgroups might prove clinically valuable.
Subject(s)
Arginine/administration & dosage , Diabetic Foot/physiopathology , Dietary Supplements , Glutamine/administration & dosage , Valerates/administration & dosage , Wound Healing , Adult , Aged , Aged, 80 and over , Ankle Brachial Index , Diabetic Foot/diet therapy , Double-Blind Method , Female , Humans , Male , Middle Aged , Prospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Having initially reported on the overall level of stress in Her Majesty's Coastguard (HMCG), in a second study we found that a combined (negative) effects approach to stress was better able to identify the associated psychosocial risk factors than by using the well-documented Effort-Reward Imbalance (ERI) or Job Demand-Control Support (JDCS) models alone. Using the same combined effects method, this study now examines the negative health and wellbeing outcomes associated with the level of high stress found in this occupational group. MATERIAL AND METHODS: Participants included 282 coastguards. A range of known stress outcomes were measured including: mental and physical health, accidents, risk taking, effects of memory, lifestyle, and job satisfaction. RESULTS: Significant associations were found with: anxiety, depression, number of sick days, perception that illness was caused or made worse by work, number of symptoms, medicines taken, insomnia, ability to maintain a desired body weight or take planned exercise and find time to relax and wind down, time spent on hobbies or interests, the impact of job on family life/family life on job, and job satisfaction. CONCLUSIONS: Sixteen negative outcomes were significantly associated with the combined effects approach, compared with 15 using ERI or 10 using JDCS alone. Results clearly demonstrated the harmful effects of stress in maritime related roles, other than those of seafarers and suggest that further research in this area would be useful. Further studies on the more flexible stress model, which allows for the examination of both established and new combinations of risk factors and associated outcomes, would also be beneficial.
Subject(s)
Adaptation, Psychological , Occupational Exposure , Occupational Health , Ships , Stress, Psychological/complications , Adult , Analysis of Variance , Confidence Intervals , Female , Humans , Job Satisfaction , Male , Models, Psychological , Psychometrics , Risk Factors , Statistics as Topic , Stress, Psychological/epidemiology , Stress, Psychological/psychology , Surveys and Questionnaires , United States/epidemiologyABSTRACT
Previous research has indicated that chewing gum enhances reported alertness, but has variable effects on attention. Demand characteristics may explain these effects. The current study investigated the effects of gum and demand characteristics on attention and reported mood over time. Participants completed measures of mood and attention, with and without chewing gum. To manipulate demand characteristics, they were told that the hypothesised effect of gum was either positive or negative, or no hypothesis was mentioned. Attitudes towards gum were assessed pre- and post-manipulation. Gum increased reported alertness; this effect was only significant for positive and neutral demand characteristics. Vigilance accuracy was reduced for chewing gum, but only in the fourth minute of the task, and gum reduced focussed attention accuracy, but only for the first 64 trials. Demand characteristics did not moderate time-on-task effects. Gum improved selective attention. A positive effect on response organisation was observed; this was significant when demand characteristics and pre-test attitudes to gum were both negative. The results suggest that demand characteristics moderate effects on self-reported alertness and response organisation, but cannot explain time-on-task effects or variable main effects on other aspects of attention.
Subject(s)
Affect/physiology , Attention/physiology , Chewing Gum , Reaction Time , Adolescent , Female , Humans , Male , Self Report , Young AdultABSTRACT
RATIONALE: Chewing gum has been shown to reliably increase subjective alertness whereas the effects on attention are more variable. It has been suggested that chewing gum only enhances attention when the person has been performing a task for some time. OBJECTIVES: The current research aimed to investigate if time-on-task trends enhancing effects of chewing gum could be observed in alertness and attention during and following chewing. METHODS: Study 1 used tests of reported mood, including reported mood, and tests of attention (categoric search, focussed attention, simple reaction time, and vigilance). These tasks were performed shortly after the start of chewing. Study 2 examined effects of previous and current chewing on reported alertness and the attention tests. RESULTS: Study 1 showed that chewing gum increased reported alertness and hedonic tone and improved performance on the categoric search task. Chewing gum maintained reported alertness across sessions in study 2. In the first experimental session of study 2 gum improved categoric search performance, and during the second session gum broadened focus of attention and quickened vigilance reaction time. This effect on vigilance reaction time was moderated by time-on-task, with an initial negative effect being replaced by a positive effect. DISCUSSION: The results confirm the robust effect of chewing gum on reported alertness and show that changes in the effects of chewing gum on attention require further investigation. Future research may also determine underlying mechanisms for an alerting effect.
Subject(s)
Arousal/physiology , Attention/physiology , Chewing Gum , Mastication/physiology , Adult , Affect/physiology , Female , Humans , Male , Reaction Time/physiology , Task Performance and Analysis , Time FactorsABSTRACT
OBJECTIVES: This study investigated the relationships between job characteristics and coping in predicting levels of anxiety and depression in nurses. The study was based on current theories of occupational stress, and predictors included job demands, social support, decision authority and skill discretion control, effort, over-commitment, rewards, and ways of coping. It was predicted that job demands, extrinsic effort, over-commitment, and negative coping behaviours would be positively associated with depression and anxiety, and social support, rewards, decision authority, skill discretion control, and positive coping would be negatively associated with depression and anxiety. METHODS: Participants were 870 nurses, who responded to a bulk mail sent randomly to 4,000 nurses from the south of England. RESULTS: The results showed that job demands, extrinsic effort, and over-commitment were associated with higher levels of anxiety and depression. Social support, rewards, and skill discretion were negatively associated with mental health problems. Few interactions were found between the variables. Coping behaviours significantly added to the explanation of variance in anxiety and depression outcomes, over and above the use of demand-control-support, and effort-reward factors alone. CONCLUSION: The results from the study demonstrated the importance of coping factors in work-stress research, in accordance with the multi-factorial premise of transactional stress models. It is argued that multi-factor research is needed to help develop effective organizational interventions.
Subject(s)
Employment/psychology , Mental Disorders/epidemiology , Mental Disorders/psychology , Nurses/psychology , Nurses/statistics & numerical data , Stress, Psychological/epidemiology , Stress, Psychological/psychology , Adaptation, Psychological , Adult , Employment/statistics & numerical data , England/epidemiology , Female , Humans , Job Description , Job Satisfaction , Male , Mental Health/statistics & numerical data , Social Support , Surveys and Questionnaires , Workload/psychology , Workplace/psychologyABSTRACT
BACKGROUND. As a previously unresearched occupational group, the overall aim of this research was to establish the prevalence of stress and associated outcomes in Her Majesty's Coastguard (HMCG). MATERIAL AND METHODS. Data were collected from 282 coastguards by paper questionnaire and compared with general UK working population data from the Bristol Stress and Health at Work Study (SHAW) and the Psychosocial Working Conditions Survey (PWC), 2009. RESULTS. The level of high stress reported in HMCG (11%) was significantly lower than the comparison data (17%). The level of depression found was significantly higher. CONCLUSIONS. HMCG had lower levels of stress than the general UK working population, due, in part to high levels of social support. Data suggests HMCG worthy of study for both negative effects of stress and stress reduction elsewhere.
Subject(s)
Health Status , Military Personnel/statistics & numerical data , Occupational Diseases/epidemiology , Occupational Health/statistics & numerical data , Ships , Stress, Psychological/epidemiology , Adult , Comorbidity , Humans , Job Satisfaction , Male , Occupational Diseases/diagnosis , Stress, Psychological/diagnosis , Surveys and Questionnaires , United Kingdom , Young AdultSubject(s)
Fatigue , Motion Pictures , Occupational Diseases , Occupational Health , Ships , Humans , Naval Medicine , Work Schedule Tolerance , WorkloadABSTRACT
BACKGROUND: To determine the extent to which work-related stress in Her Majesty's Coastguard (HMCG) could be accounted for by the Effort-Reward Imbalance (ERI) and Job Demand-Control- -Support (JDCS) stress models. MATERIAL AND METHODS: Participants included a total of 282 coastguards. Data on risk factors were collected via questionnaire, within the wider context of the UK HSE Management Standards framework for stress reduction. Analyses included an examination of each model and its association with stress and mental health outcomes, as well as their impact in combination with the range of other risk factors measured. RESULTS: Significant predictors of stress included ERI, organisation change, and exposure to physical agents (noise). Anxiety was predicted by ERI, noise, and bullying, and depression by ERI, bullying, noise, training, and role conflict/ambiguity. CONCLUSIONS: For this occupational group, the main source of high stress, anxiety, and depression was ERI. These results raise implications for the use and interpretation of data when using these models, as well as for HSE Management Standards, which are biased towards JDCS. Results from this and other studies also suggest further research is required into the benefits of a more flexible model or framework, which can examine both established and new combinations of risk factors.
Subject(s)
Military Personnel/psychology , Occupational Diseases/psychology , Occupational Exposure/adverse effects , Ships , Stress, Psychological/complications , Travel Medicine/statistics & numerical data , Adaptation, Psychological , Analysis of Variance , Anxiety/epidemiology , Depression/epidemiology , Female , Humans , Male , Military Personnel/statistics & numerical data , Occupational Diseases/epidemiology , Oceans and Seas , Prevalence , Psychometrics , Risk Assessment , Risk Factors , Social Support , Surveys and Questionnaires , United Kingdom/epidemiology , Workplace/psychologyABSTRACT
BACKGROUND: Much recent work extending the field of job characteristics to include positive aspects of work makes the implicit assumption that the absence of negative work characteristics is equivalent to the presence of positive work characteristics. AIMS: To consider the effect sizes seen at different ends of job characteristic dimensions and to compare the impact of the presence and absence of job characteristics in association with mental health and well-being outcomes. METHODS: Data from 8755 workers were analysed to compare the impacts of the presence or absence of job characteristics (job demand, extrinsic effort and social support) in associations with both positive (job satisfaction) and negative (work-related stress) outcome measures. RESULTS: Comparable presence and absence impacts were apparent for extrinsic effort in association with work-related stress. However, in the association between job demand and work-related stress, the presence of high levels of job demand had a significantly greater impact than the absence of high levels of job demand; while in the association between social support and job satisfaction, the absence of high levels of social support had a significantly greater impact than the presence of high levels of social support. CONCLUSIONS: It is not always appropriate to assume that the absence of negative aspects of the work environment is equivalent to the presence of positive aspects.
Subject(s)
Employment/psychology , Mental Health , Stress, Psychological/etiology , Work/psychology , Workload/psychology , Data Interpretation, Statistical , Female , Health Status , Health Surveys , Humans , Job Satisfaction , Male , Social Support , Stress, Psychological/epidemiology , United Kingdom/epidemiology , Work/statistics & numerical data , Workplace/organization & administration , Workplace/psychologyABSTRACT
OBJECTIVE: To determine the effect of sleeping position on the lung function of prematurely born infants when post term, whether any effect was similar to that before discharge from the neonatal unit, and if it differed according to bronchopulmonary (BPD) status. DESIGN: Prospective study. SETTING: Tertiary neonatal unit. PATIENTS: Twenty infants, median gestational age 30 weeks (range 25-32); 10 had BPD. INTERVENTIONS: Before neonatal unit discharge (median age 36 weeks postmenstrual age (PMA)) and when post term, infants were studied prone and supine, each position maintained for 3 h. MAIN OUTCOME MEASURES: Oxygen saturation was monitored continuously and, at the end of each 3 h period, functional residual capacity (FRC) and compliance (CRS) and resistance (RRS) of the respiratory system were measured. RESULTS: At a median of 36 weeks PMA and 6 weeks later (post term), respectively, oxygen saturation (98% vs 96%, p = 0.001; 98% vs 97%, p = 0.011), FRC (26 vs 24 ml/kg, p<0.0001; 35 vs 31 ml/kg, p = 0.001) and CRS (3.0 vs 2.4 ml/cm H(2)O, p = 0.034; 3.7 vs 2.5 ml/cm H(2)O, p = 0.015) were higher in the prone than the supine position. In the prone position, both BPD and non-BPD infants had significantly greater FRCs on both occasions and oxygen saturation at 36 weeks PMA, but oxygen saturation was significantly better post term only in non-BPD infants. Twelve infants had superior oxygen saturation and 17 superior FRCs in the prone compared with the supine position at both 36 weeks PMA and post term. CONCLUSIONS: These results suggest that lung function impairment does not explain why prematurely born infants are at increased risk of sudden infant death syndrome in the prone compared with the supine position.
Subject(s)
Infant, Premature/physiology , Lung/physiology , Oxygen/metabolism , Sleep/physiology , Sudden Infant Death/etiology , Female , Functional Residual Capacity/physiology , Humans , Infant, Newborn , Infant, Premature/blood , Male , Oximetry , Prone Position/physiology , Prospective Studies , Respiratory Function Tests , Sudden Infant Death/blood , Supine Position/physiologyABSTRACT
Myc and transforming growth factor-beta (TGFbeta) signaling are mutually antagonistic, that is Myc suppresses the activation of TGFbeta-induced genes, whereas TGFbeta represses c-myc transcription. Here, we report a positive role for Myc in the TGFbeta response, consisting in the induction of an epithelial-to-mesenchymal transition (EMT) and the activation of the EMT-associated gene Snail. Knockdown of either Myc or the TGFbeta effectors SMAD3/4 in epithelial cells eliminated Snail induction by TGFbeta. Both Myc and SMAD complexes targeted the Snail promoter in vivo, DNA binding occurring in a mutually independent manner. Myc was bound prior to TGFbeta treatment, and was required for rapid Snail activation upon SMAD binding induced by TGFbeta. On the other hand, c-myc downregulation by TGFbeta was a slower event, occurring after Snail induction. The response of Snail to another cytokine, hepatocyte growth factor (HGF), also depended on Myc and SMAD4. Thus, contrary to their antagonistic effects on Cip1 and INK4b, Myc and SMADs cooperate in signal-dependent activation of Snail in epithelial cells. Although Myc also targeted the Snail promoter in serum-stimulated fibroblasts, it was dispensable for its activation in these conditions, further illustrating that the action of Myc in transcriptional regulation is context-dependent. Our findings suggest that Myc and TGFbeta signaling may cooperate in promoting EMT and metastasis in carcinomas.
Subject(s)
Epithelial Cells/metabolism , Mesoderm/metabolism , Proto-Oncogene Proteins c-myc/physiology , Transcription Factors/genetics , Transforming Growth Factor beta/metabolism , Animals , Cells, Cultured , Chromatin Immunoprecipitation , Humans , Immunoblotting , Mammary Glands, Animal/cytology , Mammary Glands, Animal/metabolism , Mesoderm/cytology , Mice , RNA, Small Interfering/pharmacology , Smad2 Protein/antagonists & inhibitors , Smad2 Protein/genetics , Smad2 Protein/metabolism , Smad3 Protein/antagonists & inhibitors , Smad3 Protein/genetics , Smad3 Protein/metabolism , Smad4 Protein/antagonists & inhibitors , Smad4 Protein/genetics , Smad4 Protein/metabolism , Snail Family Transcription Factors , Transcription Factors/metabolism , Transcription, Genetic , Transforming Growth Factor beta/geneticsABSTRACT
N'-ethyl-N'-nitrosourea (ENU) is a powerful germline mutagen used in conjunction with phenotype-driven screens to generate novel mouse mutants. ENU also induces genetic lesions in somatic cells and dosage requires optimization between maximum germline mutation rate versus induced sterility and tumourigenesis that compromise the welfare and fecundity of the ENU-treated males. Here, we present our experience with BALB/cAnNCrl and C57BL/6J mice in terms of the pathology induced by ENU and its impact on breeding. In both mouse strains, morbidity and mortality rises with ENU dose. In more than 75% of C57BL/6J males, morbidity and mortality were attributable to the development of malignant T-lymphoblastic lymphoma. Approximately 50% of ENU-treated BALB/cAnNCrl males develop early malignant T-lymphoblastic lymphoma, but the cohort that survives develops late-onset lung carcinoma. Within strains, the latency of these clinically important tumour(s) was not dosage-dependent, but the proportion of mice developing tumours and consequently removed from the breeding programme increased with ENU dosage. The median number of offspring per ENU-treated C57BL/6J male in standard matings with C3H/HeH females decreased with increasing dosage. The two most important underlying causes for lower male fecundity were increased infertility in the highest dosage group and reduced numbers of litters born to the remaining fertile C57BL/6J males due to a higher incidence of morbidity. These findings have allowed us to refine breeding strategy. To maximize the number of offspring from each ENU-treated male, we now rotate productive males between two cages to expose them to more females. This optimizes the number of mutation carrying offspring while reducing the number of ENU-treated males that must be generated.
Subject(s)
Animal Husbandry/methods , Ethylnitrosourea/toxicity , Fertility/drug effects , Mice, Inbred Strains , Mutagenesis , Mutagens/toxicity , Age Factors , Animal Welfare , Animals , Case-Control Studies , Dose-Response Relationship, Drug , Ethylnitrosourea/administration & dosage , Female , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mutagens/administration & dosage , Neoplasms, Experimental/chemically induced , Neoplasms, Experimental/pathology , Retrospective StudiesABSTRACT
The RhD protein which is the RHD gene product and a major component of the Rh blood group system carries the strongest blood group immunogen, the D-antigen. This antigen is absent in a significant minority of the human population (RhD-negatives) due to RHD deletion or alternation. The origin and persistence of this RhD polymorphism is an old evolutionary enigma. Before the advent of modern medicine, the carriers of the rarer allele (e.g. RhD-negative women in the population of RhD-positives or RhD-positive men in the population of RhD-negatives) were at a disadvantage as some of their children (RhD-positive children born to pre-immunized RhD-negative mothers) were at a higher risk of foetal or newborn death or health impairment from haemolytic disease. Therefore, the RhD-polymorphism should be unstable, unless the disadvantage of carriers of the locally less abundant allele is counterbalanced by, for example, higher viability of the heterozygotes. Here we demonstrated for the first time that among Toxoplasma-free subjects the RhD-negative men had faster reaction times than Rh-positive subjects and showed that heterozygous men with both the RhD plus and RhD minus alleles were protected against prolongation of reaction times caused by infection with the common protozoan parasite Toxoplasma gondii. Our results suggest that the balancing selection favouring heterozygotes could explain the origin and stability of the RhD polymorphism. Moreover, an unequal prevalence of toxoplasmosis in different countries could explain pronounced differences in frequencies of RhD-negative phenotype in geographically distinct populations.
Subject(s)
Blood Donors , Polymorphism, Genetic , Reaction Time , Rh-Hr Blood-Group System/genetics , Toxoplasma/pathogenicity , Toxoplasmosis/prevention & control , Adult , Animals , Antibodies, Protozoan/blood , Evolution, Molecular , Female , Heterozygote , Humans , Male , Military Personnel , Psychomotor Performance , Reaction Time/physiology , Rh-Hr Blood-Group System/analysis , Rh-Hr Blood-Group System/blood , Selection, Genetic , Toxoplasma/immunology , Toxoplasmosis/parasitologyABSTRACT
BACKGROUND: The mainstays of treatment for pulmonary disease caused by opportunist mycobacteria are rifampicin (R) and ethambutol (E). The role of macrolides, quinolones and immunotherapy with Mycobacterium vaccae is not clear. A trial was undertaken to compare clarithromycin (Clari) and ciprofloxacin (Cipro) as third drugs added to [corrected] 2 years of treatment with R and E for pulmonary disease caused by M avium-intracellulare (MAC), M malmoense and M xenopi (REClari and RECipro). An optional comparison of immunotherapy with M vaccae vs no immunotherapy was also performed. METHODS: Progress was monitored annually during the 2 years of treatment and for 3 years thereafter. If the patient was not improving at 1 year the regimen was supplemented by the addition of the drug not received in the original allocation of treatment. RESULTS: 371 patients (186 REClari, 185 RECipro) entered the study (170 MAC, 167 M malmoense, 34 M xenopi). All-cause mortality was high for both groups (44% REClari, 43% RECipro); for MAC it was higher with REClari than with RECipro (48% vs 29%) but for M malmoense (42% vs 56%) and M xenopi (29% vs 47%) it was higher with RECipro (p = 0.006). 3% died from their mycobacterial disease (REClari = RECipro). At the end of treatment, 4% of REClari and 10% of RECipro patients still had positive cultures. Among those with negative cultures at the end of treatment, 6% of the REClari group and 4% of the RECipro group had relapsed. At 5 years 30% of the REClari group were known to have completed treatment as allocated and to be alive and cured compared with 21% of the RECipro group (p = 0.04), but this difference was principally due to those with M malmoense (REClari 38%, RECipro 20%). Patients with MAC or M xenopi were more likely to have a poor outcome than those with M malmoense (p = 0.004), with no difference between REClari and RECipro. Overall, 20% in each group were unable to tolerate the regimen allocated, Cipro being associated with more unwanted effects than Clari (16% vs 9%, p = 0.05). No significant differences in outcomes were found between M vaccae-treated patients and those not treated with M vaccae immunotherapy. CONCLUSION: Considering all three species together, there were no differences in outcome between the REClari and RECipro groups. Immunotherapy did not improve outcome. New therapies, optimised management of co-morbid conditions and a more holistic approach must be explored in the hope of improving outcome.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Antitubercular Agents/therapeutic use , Immunotherapy/methods , Opportunistic Infections/therapy , Tuberculosis, Pulmonary/therapy , Adolescent , Adult , Aged , Ciprofloxacin/therapeutic use , Clarithromycin/therapeutic use , Drug Therapy, Combination , Ethambutol/therapeutic use , Female , Humans , Male , Middle Aged , Opportunistic Infections/mortality , Rifampin/therapeutic use , Tuberculosis, Pulmonary/mortalityABSTRACT
AIMS: There is considerable overlap between the histological features of sebaceoma and basal cell carcinoma (BCC). The distinction between these two tumours is important due to the often more locally aggressive nature of BCC and the association of sebaceoma with the Muir-Torre syndrome. The aim of this study was to describe the immunohistochemical reactivity of the cells in sebaceoma to Ber-EP4 and epithelial membrane antigen (EMA) and investigate the utility of this panel to differentiate sebaceoma from basal cell carcinoma. METHODS AND RESULTS: Immunohistochemistry of 25 sebaceomas for Ber-EP4 and EMA revealed unequivocal negative expression of Ber-EP4 in 24 of 25 sebaceomas. A single case exhibited focal weak Ber-EP4 staining, predominantly in mature sebocytes and in < 10% of the tumour cells. EMA was not expressed in the germinative cells of sebaceoma, but was expressed strongly in approximately 50% of mature sebocytes in all cases and highlighted the cytoplasmic vacuoles. We reviewed the immunoreactivity of 51 cases of nodular BCCs and found moderate or strong BerEP4 expression in all cases with never less than 20% of the tumour staining. Expression of EMA was uncommon in BCC (moderate or strong in 8%) and was confined to keratotic or squamoid areas. CONCLUSION: The use of Ber-EP4 in combination with EMA, both widely used immunomarkers in histopathology, is a helpful aid in distinguishing sebaceoma from nodular BCC.
Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Basal Cell/metabolism , Mucin-1/metabolism , Neoplasms, Adnexal and Skin Appendage/metabolism , Skin Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Biopsy , Carcinoma, Basal Cell/diagnosis , Carcinoma, Basal Cell/pathology , Diagnosis, Differential , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Mucin-1/genetics , Neoplasms, Adnexal and Skin Appendage/diagnosis , Neoplasms, Adnexal and Skin Appendage/pathology , Sebaceous Glands/metabolism , Sebaceous Glands/pathology , Skin Neoplasms/diagnosis , Skin Neoplasms/pathologyABSTRACT
Although patients diagnosed with melanoma of = 1.00 mm thickness have a relatively good cure rate, the prognosis for patients with locally advanced and metastatic melanoma is grave. The discovery of new and effective therapies for this disease depends in large part on molecular studies that will resolve why advanced-stage melanoma is refractory to conventional chemotherapy and radiation therapy. To identify genes that have important functions in advanced-stage melanomas, in particular, in melanoma-infiltrated lymph nodes, which are not well characterized at the molecular level, we generated a LongSAGE library from a melanoma-positive lymph node, and subjected melanoma-infiltrated lymph nodes to protein expression profiling. The data document that the molecular signature of melanoma, which has spread to regional lymph nodes, is very similar to the molecular signature of primary melanomas. Equally important, we provide evidence that the ubiquitin-conjugating enzyme, Ubc9, is expressed at high levels in melanoma-positive lymph nodes, and that it plays a crucial role in preventing advanced-stage melanomas from undergoing chemotherapy-induced apoptosis.