Social defeat stress induces genome-wide 5mC and 5hmC alterations in the mouse brain.

Stress is adverse experience that require constant adaptation to reduce the emotional and physiological burden, or "allostatic load", of an individual. Despite their everyday occurrence, a subpopulation of individuals is more susceptible to stressors, while others remain resilient with unknown molecular signatures. In this study, we investigated the contribution of the DNA modifications, 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), underlying the individual differences in stress susceptibility and resilience. Genome-wide 5mC and 5hmC profiles from 3- and 6-month adult male mice that underwent various durations of social defeat were generated. In 3-month animals, 5mC and 5hmC work in parallel and do not distinguish between stress-susceptible and resilient phenotypes, while in 6-month animals, 5mC and 5hmC show distinct enrichment patterns. Acute stress responses may epigenetically "prime" the animals to either increase or decrease their predisposition to depression susceptibility. In support of this, re-exposure studies reveal that the enduring effects of social defeat affect differential biological processes between susceptible and resilient animals. Finally, the stress-induced 5mC and 5hmC fluctuations across the acute-chronic-longitudinal time course demonstrate that the negative outcomes of chronic stress do not discriminate between susceptible and resilient animals. However, resilience is more associated with neuroprotective processes while susceptibility is linked to neurodegenerative processes. Furthermore, 5mC appears to be responsible for acute stress response, whereas 5hmC may function as a persistent and stable modification in response to stress. Our study broadens the scope of previous research offering a comprehensive analysis of the role of DNA modifications in stress-induced depression.

Two separate outflows in the dual supermassive black hole system NGC 6240.

Theoretical models and numerical simulations have established a framework of galaxy evolution in which galaxies merge and create dual supermassive black holes (with separations of one to ten kiloparsecs), which eventually sink into the centre of the merger remnant, emit gravitational waves and coalesce. The merger also triggers star formation and supermassive black hole growth, and gas outflows regulate the stellar content1-3. Although this theoretical picture is supported by recent observations of starburst-driven and supermassive black hole-driven outflows4-6, it remains unclear how these outflows interact with the interstellar medium. Furthermore, the relative contributions of star formation and black hole activity to galactic feedback remain unknown7-9. Here we report observations of dual outflows in the central region of the prototypical merger NGC 6240. We find a black-hole-driven outflow of [O III] to the northeast and a starburst-driven outflow of Hα to the northwest. The orientations and positions of the outflows allow us to isolate them spatially and study their properties independently. We estimate mass outflow rates of 10 and 75 solar masses per year for the Hα bubble and the [O III] cone, respectively. Their combined mass outflow is comparable to the star formation rate 10 , suggesting that negative feedback on star formation is occurring.

Prostate involvement during sexually transmitted infections as measured by prostate-specific antigen concentration.

BACKGROUND: We investigated prostate involvement during sexually transmitted infections by measuring serum prostate-specific antigen (PSA) as a marker of prostate infection, inflammation, and/or cell damage in young, male US military members. METHODS: We measured PSA before and during infection for 299 chlamydia, 112 gonorrhoea, and 59 non-chlamydial, non-gonococcal urethritis (NCNGU) cases, and 256 controls. RESULTS: Chlamydia and gonorrhoea, but not NCNGU, cases were more likely to have a large rise (40%) in PSA than controls (33.6%, 19.1%, and 8.2% vs 8.8%, P<0.0001, 0.021, and 0.92, respectively). CONCLUSION: Chlamydia and gonorrhoea may infect the prostate of some infected men.

In vitro analyses are not reliable predictors of the plant growth promotion capability of bacteria; a Pseudomonas fluorescens strain that promotes the growth and yield of wheat.

AIMS: In this study, we set out to identify bacteria that can be used to promote the growth of cereals, while concurrently investigating the merits of using a range of such tests to preselect bacteria for glasshouse studies. METHODS AND RESULTS: A panel of 15 strains isolated from the rhizosphere and phyllosphere of cereals was tested for the ability to improve the germination of wheat seeds and for production of a range of factors associated with plant growth promotion. In parallel, all bacteria were tested for their ability to improve biomass and grain yield when applied as a soil amendment in glasshouse trials. CONCLUSIONS: There was no significant correlation between growth promotion potential in the glasshouse and the results of either the phenotypic or the germination tests. Glasshouse tests identified that only one strain, Pseudomonas fluorescens strain MKB37, gave a significant increase in head weight and grain yield. SIGNIFICANCE AND IMPACT OF THE STUDY: While this study has identified a candidate for further field tests, it has also highlighted the fact that the modes of action for plant growth-promoting bacteria (PGPB) are still not fully understood, and that there is no efficient and effective screening method for identifying PGPB by laboratory tests.

Mass immunization programs: principles and standards.

Mass immunization involves delivering immunizations to a large number of people at one or more locations in a short interval of time. Good mass immunization programs apply planning and quality standards that maximize return on resources invested and provide the greatest individual benefits when immunizing many people in a short period of time. These programs can be used to counter contagious outbreaks, adopted as a repeated means of sustained healthcare delivery, or applied where many people move through a specific place in a short interval of time. Relevant quality standards address appropriate facilities and supplies, training of professional and paraprofessional staff, education of potential vaccinees and methods to screen them for contraindications to immunization, safeguards against anaphylaxis and syncope, documentation, safety surveillance, and a quality-improvement program. Successful mass immunization programs require early planning that builds on existing competencies. As the number of available vaccines increases, prioritizing which vaccines to administer during mass campaigns requires consideration of effectiveness, safety, and a cost-benefit equation from both the individual and community perspectives. Mass immunization campaigns aim to maximize the health of a population, but such campaigns need to be customized based on individual contraindications to immunization. Mass immunization programs need to be conducted ethically, with considerations of benefit versus risk and the need for detailed education of healthcare workers and vaccinees.

Carboplatin and vinblastine for the treatment of metastatic transitional cell carcinoma of the urothelial tract.

Many patients with metastatic transitional-cell carcinoma (TCC) are not appropriate candidates for standard cisplatin-based combination, because of inadequate renal function, poor performance status (PS), and other comorbid medical conditions. We have evaluated the efficacy and toxicity of a combination of carboplatin and vinblastine (CV) as a palliative regimen in these patients. The medical records of patients with metastatic TCC, who had been treated with CV at the British Columbia Cancer Agency from 1995 until 1999, were retrospectively reviewed. Treatment consisted of carboplatin (area under the curve = 5) on day 1, and vinblastine (4 mg/m(2)) on days 1 and 8, repeated every 4 weeks. A total of 42 patients were included in this study, of whom 39 had measurable disease. Median age was 73 years. Fifty-two percent of patients had a PS (Eastern Cooperative Oncology Group) of 2 or 3. Node-only disease was present in 26% of patients, bone metastasis in 26%, and liver metastasis in 24%. A total of 119 cycles were administered. Grade IV granulocytopenia occurred in 26% of patients, grade III anemia in 12%, and there were 3 episodes of febrile neutropenia occurring in two patients. The major nonhematologic toxicity was grade III fatigue in 17% of patients. There were no grade IV nonhematologic toxicity or treatment-related deaths. The overall response rate was 33% (13 of 39). Five patients (13%) achieved a complete response and 8 patients (20%) a partial response. The median duration of response was 32 weeks and median overall survival for all patients was 26 weeks. The combination of carboplatin and vinblastine given in this schedule is a feasible, well-tolerated, and active alternative for patients with metastatic TCC unfit for standard chemotherapy.

Perceptions of older people who have experienced physical restraint.

It is well documented that the use of physical restraints on older people has been linked to negative clinical outcomes. However, less is known about the personal perspective of those who have been restrained. This study examines the perceptions of older people who have experienced physical restraints in a rehabilitation ward. A purposive sample was used of 17 male and female patients who were restrained. The patients were interviewed using the Subjective Experience of Being Restrained instrument (Strumpf and Evans, 1988) which is a semi-structured interview schedule. The most commonly used restraint devices included side rails, screw-on tabletops and reclining chairs. The data were analysed using content analysis. The results indicate mixed feelings regarding physical restraints. Patients' impressions of physical restraints included indifference of the devices to their perceived safety value. Overall, a minority of patients (n = 4) had positive feelings about physical restraints as they provided a sense of security to them. However, the negative comments of the patients were more prevalent and their responses were categorized in terms of institutional control, ritualised care, entrapment and discomfort, and possible alternatives.

Relatives' perceptions of side rail use on the older person in hospital.

With an increasing emphasis on improving standards in the care of older people, the use of physical restraints has received growing attention in the nursing literature. Physical restraint use has been likened to abuse as it impedes the movement of a person, encourages dependence on staff and denies autonomy. Side rails (cot sides, bed rails) can be considered as a physical restrain device. The therapeutic use of restraint has not previously been adequately explained. Furthermore, there is a dearth of literature examining the personal experience of physical restraint use. The Family Interview Guide (Strumpf and Evans, 1988) was used to explore perceptions of nine relatives whose family had side rails used during their care in an older person ward. The findings of the study suggest that while families place value on the perceived safety function of side rails, they nonetheless have worries about their use. These pertain to the risk of patient entrapment and possible injury. Patients' relatives associated side rails with ritualized practice in gerontology and make suggestions for the re-design of side rails. The study also highlights the potential for increased family participation in the decision to use side rails.

How lead exposure relates to temporal changes in IQ, violent crime, and unwed pregnancy.

This study compares changes in children's blood lead levels in the United States with subsequent changes in IQ, based on norm comparisons for the Cognitive Abilities Test (CogAT) given to representative national samples of children in 1984 and 1992. The CogAT norm comparisons indicate shifts in IQ levels consistent with the blood lead to IQ relationship reported by an earlier study and population shifts in average blood lead for children under age 6 between 1976 and 1991. The CogAT norm comparisons also support studies indicating that the IQ to blood lead slope may increase at lower blood lead levels. Furthermore, long-term trends in population exposure to gasoline lead were found to be remarkably consistent with subsequent changes in violent crime and unwed pregnancy. Long-term trends in paint and gasoline lead exposure are also strongly associated with subsequent trends in murder rates going back to 1900. The findings on violent crime and unwed pregnancy are consistent with published data describing the relationship between IQ and social behavior. The findings with respect to violent crime are also consistent with studies indicating that children with higher bone lead tend to display more aggressive and delinquent behavior. This analysis demonstrates that widespread exposure to lead is likely to have profound implications for a wide array of socially undesirable outcomes.

Treatment of psoriasis with cyclosporin. Experience at Johannesburg Hospital.

Ten patients with moderate to severe plaque psoriasis were treated with cyclosporin A (CyA) for 2-19 months (mean 12 months). Initial dosages were 2.5 mg/kg/d in 6 patients and 5.0 mg/kg/d in 4. At 3 months the dosage was increased from 2.5 to 5.0 mg/kg/d in 4 patients in accordance with the study protocol. Subsequent dosages were adjusted according to clinical response and side-effects. Treatment was stopped owing to raised serum creatinine levels in 4 patients on the higher dose; levels returned to normal soon after this. The only other important side-effect was hypertension, which developed in 4 patients, in 2 of whom serum creatinine levels were raised. In all patients the psoriasis improved markedly within 2 months but relapsed, either while the dose of CyA was being tapered off or after treatment with the drug was stopped. Relapse was most rapid in patients with severe initial involvement. On a dosage of 2.5 mg/kg/d there was at least 50% clearance of the psoriasis and no evidence of renal side-effects.

Anatomical relationships between sensory afferent arborizations in the cricket cercal system.

The anatomical relationships between sensory afferents within a topographic map in the cricket cercal sensory system were studied using a computer-based reconstruction system developed in our laboratory. Individual identified mechanosensory afferents were characterized physiologically, stained with cobalt, silver intensified, and reconstructed in three dimensions. All reconstructions were scaled to a common standard. The results indicate that there is very little variability in the position or extent of the terminal arborization of identified mechanosensory afferents. The topographic map was divided relatively equally into four regions representing each of the four classes of afferents studied. These regions were discrete but not completely segregated. Approximately 30% of the topographic map contained regions of overlap between two or more classes or afferents.

Dental family stress and coping patterns.

This exploratory study of 28 married male dentists and their families was designed to gain an understanding about the stressors that dentists and their spouses experience, the life events and family strains they incur, the behavioral coping patterns they utilize, and their psychosocial characteristics. The study found that although stable dental families did encounter a significant number of stressors arising from both the dental practice and the family, they maintained their sense of balance through strong family coping skills and family resources. The effect of the dentist's office-related stress was directly felt in the family, especially by the spouse. Strong coping patterns resulted when dentists and spouses maintained a balance of time and responsibility, satisfaction in work and family activity, regular communication, sharing of decision making, good physical health, and the inclusion of an active exercise program within multiple demands on their time.

Active coping strategies. From self-help to psychological counseling.

Everyone must accept a certain measure of responsibility for dealing with personal stresses. This article suggests various active, constructive, self-help strategies. It specifically focuses on the advantages of adopting positive attitudes, maintaining a sense of humor, engaging in a variety of activities, identifying and relabeling stresses, and using multiple, active coping techniques. Demonstrating how professional psychologic counseling may help the individual in effectively dealing with personal problems, the article also defines and delineates counseling. It explains why one should seek professional help, tells how to select a counselor, describes the types of counseling available, advises ways to best utilize the counseling process, and discusses the length and costs of treatments.

Antifertility effects of tetradecyl sodium sulphate in rabbits.

Acrosin and acrosomal hyaluronidase were inhibited by tetradecyl sodium sulphate (TDSS) in vitro at concentrations of less than 10(-4) M. TDSS prevented the removal in vitro of the cumulus oophorus by testicular hyaluronidase and the zona pellucida by acrosin. TDSS had a contraceptive effect in rabbits when administered intravaginally before coitus or released at levels of 1-3 micrograms/day from intrauterine silicone rubber devices.

Parental coping in raising children who have spina bifida cystica.

In this study of 40 married couples who are rising a child with spina bifida cystica, the family stress theory was used to assess family regenerative power and vulnerability to stress. The reserach tested for differences between high and low stress families in the family environment, coping strategies, and severity of the child's problem. When compared with the high stress families, the low stress families appeared to be more cohesive, be better organised, have a more active recreation orientation, be lower in family conflict, utilise more family community relationships, and have children who have less severe physical problems. The practical implications of this study include the potentiality for applied usage of family diagnostic tests, the clinical and research application of the findings on family coping strategies for improved patient outcomes, and the need for additional social-medical research to assess accurately family concerns about health care policies.