Aims: To determine the mechanisms of killing of Bacillus subtilis spores by ethanol or strong acid or alkali. Methods and Results: Killing of B. subtilis spores by ethanol or strong acid or alkali ...was not through DNA damage and the spore coats did not protect spores against these agents. Spores treated with ethanol or acid released their dipicolinic acid (DPA) in parallel with spore killing and the core wet density of ethanol- or acid-killed spores fell to a value close to that for untreated spores lacking DPA. The core regions of spores killed by these two agents were stained by nucleic acid stains that do not penetrate into the core of untreated spores and acid-killed spores appeared to have ruptured. Spores killed by these two agents also did not germinate in nutrient and nonnutrient germinants and were not recovered by lysozyme treatment. Spores killed by alkali did not lose their DPA, did not exhibit a decrease in their core wet density and their cores were not stained by nucleic acid stains. Alkali-killed spores released their DPA upon initiation of spore germination, but did not initiate metabolism and degraded their cortex very poorly. However, spores apparently killed by alkali were recovered by lysozyme treatment. Conclusions: The data suggest that spore killing by ethanol and strong acid involves the disruption of a spore permeability barrier, while spore killing by strong alkali is due to the inactivation of spore cortex lytic enzymes. Significance and Impact of the Study: The results provide further information on the mechanisms of spore killing by various chemicals.
Aims: To determine the effect of sporulation temperature on Bacillus subtilis spore resistance and spore composition. Methods and Results: Bacillus subtilis spores prepared at temperatures from 22 to ...48 degrees C had identical amounts of dipicolinic acid and small, acid-soluble proteins but the core water content was lower in spores prepared at higher temperatures. As expected from this latter finding, spores prepared at higher temperatures were more resistant to wet heat than were spores prepared at lower temperatures. Spores prepared at higher temperatures were also more resistant to hydrogen peroxide, Betadine, formaldehyde, glutaraldehyde and a superoxidized water, Sterilox. However, spores prepared at high and low temperatures exhibited nearly identical resistance to u.v. radiation and dry heat. The cortex peptidoglycan in spores prepared at different temperatures showed very little difference in structure with only a small, albeit significant, increase in the percentage of muramic acid with a crosslink in spores prepared at higher temperatures. In contrast, there were readily detectable differences in the levels of coat proteins in spores prepared at different temperatures and the levels of at least one coat protein, CotA, fell significantly as the sporulation temperature increased. However, this latter change was not due to a reduction in cotA gene expression at higher temperatures. Conclusions: The temperature of sporulation affects a number of spore properties, including resistance to many different stress factors, and also results in significant alterations in the spore coat and cortex composition. Significance and Impact of the Study: The precise conditions for the formation of B. subtilis spores have a large effect on many spore properties.
The frequency, preventability, severity, root causes, and projected costs of adverse drug events (ADEs) occurring after or causing admission to a four-hospital integrated academic health network were ...studied. The sample included all admissions during a 53-day study period. Events were identified through daily record review of a random patient sample, computerized flags, and self-reporting. A case review committee validated the occurrence, classification, and root causes of the events. Additional length of stay and costs associated with ADEs were analyzed by using a case-control, multiple linear regression model. The estimated ADE rate during hospitalization was 4.2 events per 100 admissions, with a cost of $2162 per ADE. In addition, 3.2% of admissions were caused by ADEs, with an associated cost of $6685 per event. Fifteen percent of hospital ADEs and 76% of ADEs causing admission were judged preventable. The annual cost to the organization for events occurring during hospitalization was $1.7 million, and the cost of preventable ADEs was $260,000, while the projected costs of preventable ADEs causing admission were $3.8 million. The rate of admissions to the mental health center caused by ADEs was higher than for other settings at 13.6%, with a cost of preventable ADEs of $1.3 million. Patient noncompliance was judged to be the cause of the 69% of the ADEs causing admission. Seventy-one percent of the serious medication errors occurred at the prescribing stage of the medication-use process. ADEs were frequent, costly, and often preventable and resulted in many admissions to a mental health center.
Advance Directives are written documents, which are used for people to notify their preference for a future situation when they are unable to give their consent. In psychiatry, psychiatric advance ...directives (PADs) can be used for patients with chronic psychotic disorders such as schizophrenia, or a bipolar disorder. PADs give the patient an opportunity to state wishes in advance about his/her treatment when he/she is in an acute state of illness. PADs were initially developed as a way for patients to defend themselves against the power of the psychiatrists, but are likely to become a useful tool in psychiatric care. PADs may contain information about medication, non pharmaceutical devices, and the name of a proxy decision maker. The main objective is to reduce the number of compulsory hospitalisations.
This article is a qualitative review which carries out a state-of-the-art on the use of PADs for people with chronic psychotic disorders and defines suggestions to include this intervention in the French psychiatric context.
We used the keywords psychiatric advance directives, crisis card, Ulysse directives, joint crisis plan (JCP) in the MEDLINE database to propose a qualitative review. We selected original clinical studies about the use of PADs for people with psychotic disorders.
We included 36 articles. The qualitative analysis identified seven main themes: different types of PADs, effectiveness of PADs, practical use of PADs, patient's views, clinician's views, economical aspects, and legal aspects. The content of the PADs is consistent with psychiatric standard care in nearly all cases, regarding medical instructions, pre-emergency interventions, non-hospital alternatives and non-medical personal care. Patients use their PADs to describe prodromal symptoms of relapse and to suggest a treatment and a hospitalisation in advance. PADs are not used to refuse all treatments. Patients show a strong interest in creating a directive and a high level of satisfaction when using it. They feel they have more control over their mental health problem and are more respected and valued as a person. Thirty-six to fifty-three percent of clinicians had positive opinions regarding PADs. They valued the increase of the patient's autonomy and the prevention of relapse, but were concerned about difficulties for accessing the documents, and about the lack of training of the medical teams. Clinicians also feared the pressure of relatives or partners on treatment decisions. The qualitative analysis revealed the specific benefit of the JCP, a particular type of PADs negotiated with the medical team, on the reduction of the general number of admissions. We can identify practical problems such as the lack of accessibility to PADs in emergency situations, and the clinician's reluctance to use PADs. The only economical evaluation showed a non-significant decrease in total costs.
PADs are used in a few countries, although their benefits in terms of patient's perceptions and compulsory admissions are promising. The JCP proposes a specific clinical approach based on therapeutic alliance. Its creation also involves the clinician, family members and a neutral mediator in a negotiated process. The JCP is likely to be the most efficient PAD model in reducing compulsory admissions. The use of the JCP appears to be relevant in the context of the new French legislation, establishing outpatient commitment orders and could be an effective way to improve the relationships with patients.
Abstract
Purpose
To review the incidence of clinically significant pulmonary toxicity following total body irradiation (TBI) as a part of the conditioning regimen for acute lymphoblastic leukaemia ...(ALL) patients undergoing bone marrow transplantation (BMT) at The Ottawa Hospital Cancer Centre.
Methods
This is a retrospective review of ALL patients who received TBI in The Ottawa Hospital Bone Marrow Transplant Program (TOH-BMT) as part of their conditioning regimen from 1991 to 2011 inclusive. The patients were treated using a locally developed translating-couch irradiation technique. We have analysed all available data for the first 100 days following TBI to determine the incidence of radiation-induced pulmonary toxicities.
Results
Of the total 622 patients undergoing TBI during the specified period, 88 had ALL. Median age at BMT was 30 years and the conditioning regimens varied. A total of 74 (84%) patients received 12 Gy/6 F/BID of TBI. A total of 55 (63%) patients have died, 32 (36%) within the 1st year after BMT. In the 1st year, pulmonary events were reported for 24 (27%) patients, and the follow-up notes were unavailable for seven (8%). Pulmonary toxicities were reported as the cause of death for six patients, five (6%) within the 1st year. It is estimated that the total number of deaths in the 1st year possibly attributed to radiation-induced lung injury was four (4·5%). Eight (9%) patients had symptoms suggestive of non-lethal grade 2–3 radiation-induced pneumonitis.
Conclusions
TBI continues to be an important component of the conditioning regimen for ALL patients undergoing BMT, and the incidence of radiation-induced pulmonary injury, using our technique and lung dose, is comparable to the published literature.
Attempts to inactivate an essential gene in the protozoan parasite Leishmania have often led to the generation of extra copies of the wild-type alleles of the gene. In experiments with Leishmania ...tarentolae set up to disrupt the gene encoding the J-binding protein 1 (JBP1), a protein binding to the unusual base β-d-glucosyl-hydroxymethyluracil (J) of Leishmania, we obtained JBP1 mutants containing linear DNA elements (amplicons) of ∼100 kb. These amplicons consist of a long inverted repeat with telomeric repeats at both ends and contain either the two different targeting cassettes used to inactivate JBP1, or one cassette and one JBP1 gene. Each long repeat within the linear amplicons corresponds to sequences covering the JBP1 locus, starting at the telomeres upstream of JBP1 and ending in a ∼220 bp sequence repeated in an inverted (palindromic) orientation downstream of the JBP1 locus. We propose that these amplicons have arisen by a template switch inside a DNA replication fork involving the inverted DNA repeats and helped by the gene targeting.
Killing of wild-type spores of Bacillus subtilis with formaldehyde also caused significant mutagenesis; spores (termed alpha-beta-) lacking the two major alpha/beta-type small, acid-soluble spore ...proteins (SASP) were more sensitive to both formaldehyde killing and mutagenesis. A recA mutation sensitized both wild-type and alpha-beta- spores to formaldehyde treatment, which caused significant expression of a recA-lacZ fusion when the treated spores germinated. Formaldehyde also caused protein-DNA cross-linking in both wild-type and alpha-beta- spores. These results indicate that: (i) formaldehyde kills B. subtilis spores at least in part by DNA damage and (b) alpha/beta-type SASP protect against spore killing by formaldehyde, presumably by protecting spore DNA.
Hypothesis A suicide attempt is an major event that creates harm on both family and close relatives, that can be measured in terms of traumatic stress and medico-economic impact (costs). Each year, ...3.750.000 French people are concerned by a suicide attempt of a relative (or close person). Subjects Male or female, older than 16, being a relative of a suicide attempter (i.e. living in the same house as the suicide attempter). 171 families were included (171 suicide attempters and 171 « family informants »). These subjects were compared to IRDES datas on French population (Institute of Research and Documentation on Health Economy ; sample of 20.000 subjects, representing 95% of the French families). All subjects were reassessed by phone at 3 month and 1 year. Results 80% of the relatives declare “being fine” at 1 year; the 20% that declare being “not so well” are important to qualify, the sooner after the suicide attempt. An explicative model trying to evaluate the risk of being “not so well” at 1 year is possible ; this model is highly represented by the psychotraumatic impact of the confrontation with the suicide attempt. On the economic plan, we can observe a great stability in healthcare contacts at 1 year (hospitalizations, GP or Specialists contacts, other kind of care contact…), contrasting with a big increase in medication use (× 2.37 in comparison with IRDES population); all the medication types being concerned, psychotropic and others. The question of a self-medication partly unconscious is raised.
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