bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying Vulnerable Pathways in Mycobacterium tuberculosis by Using a Knockdown Approach
Authors: Carroll Paul , Faray-Kele Marie-Claire , Parish Tanya 
Published: June 2011

ABSTRACT

We constructed recombinant strains of
Mycobacterium tuberculosis
in which expression of specific genes was downregulated to identify vulnerable drug targets. Growth phenotypes in macrophages and culture were used to rank targets: the
dprE1
,
clpP1
, and
fadD32
operons were the best targets and
glnA1
,
glnE
,
pknL
,
regX3
, and
senX3
were poor targets.
Modulation of Morphogenesis in Candida albicans by Various Small Molecules
Authors: Shareck Julie , Belhumeur Pierre 
Published: June 2011

ABSTRACT

The pathogenic yeast
Candida albicans
, a member of the mucosal microbiota, is responsible for a large spectrum of infections, ranging from benign thrush and vulvovaginitis in both healthy and immunocompromised individuals to severe, life-threatening infections in immunocompromised patients. A striking feature of
C. albicans
is its ability to grow as budding yeast and as filamentous forms, including hyphae and pseudohyphae. The yeast-to-hypha transition contributes to the overall virulence of
C. albicans
and may even constitute a target for the development of antifungal drugs. Indeed, impairing morphogenesis in
C. albicans
has been shown to be a means to treat candidiasis. Additionally, a large number of small molecules such as farnesol, fatty acids, rapamycin, geldanamycin, histone deacetylase inhibitors, and cell cycle inhibitors have been reported to modulate the yeast-to-hypha transition in
C. albicans
. In this minireview, we take a look at molecules that modulate morphogenesis in this pathogenic yeast. When possible, we address experimental findings regarding their mechanisms of action and their therapeutic potential. We discuss whether or not modulating morphogenesis constitutes a strategy to treat
Candida
infections.
Structure-Guided Investigation of Lipopolysaccharide O-Antigen Chain Length Regulators Reveals Regions Critical for Modal Length Control
Authors: Kalynych Sergei , Ruan Xiang , Valvano Miguel A. , Cygler Miroslaw 
Published: June 2011

ABSTRACT

The O-antigen component of the lipopolysaccharide (LPS) represents a population of polysaccharide molecules with nonrandom (modal) chain length distribution. The number of the repeat O units in each individual O-antigen polymer depends on the Wzz chain length regulator, an inner membrane protein belonging to the polysaccharide copolymerase (PCP) family. Different Wzz proteins confer vastly different ranges of modal lengths (4 to >100 repeat units), despite having remarkably conserved structural folds. The molecular mechanism responsible for the selective preference for a certain number of O units is unknown. Guided by the three-dimensional structures of PCPs, we constructed a panel of chimeric molecules containing parts of two closely related Wzz proteins from
Salmonella enterica
and
Shigella flexneri
which confer different O-antigen chain length distributions. Analysis of the O-antigen length distribution imparted by each chimera revealed the region spanning amino acids 67 to 95 (region 67 to 95), region 200 to 255, and region 269 to 274 as primarily affecting the length distribution. We also showed that there is no synergy between these regions. In particular, region 269 to 274 also influenced chain length distribution mediated by two distantly related PCPs, WzzB and FepE. Furthermore, from the 3 regions uncovered in this study, region 269 to 274 appeared to be critical for the stability of the oligomeric form of Wzz, as determined by cross-linking experiments. Together, our data suggest that chain length determination depends on regions that likely contribute to stabilize a supramolecular complex.
Recognition of DNA by the Helix-Turn-Helix Global Regulatory Protein Lrp Is Modulated by the Amino Terminus
Authors: Hart Benjamin R. , Mishra Pankaj K. , Lintner Robert E. , Hinerman Jennifer M. , Herr Andrew B. , Blumenthal Robert M. 
Published: June 2011

ABSTRACT

The AsnC/Lrp family of regulatory proteins links bacterial and archaeal transcription patterns to metabolism. In
Escherichia coli
, Lrp regulates approximately 400 genes, over 200 of them directly. In earlier studies,
lrp
genes from
Vibrio cholerae
,
Proteus mirabilis
, and
E. coli
were introduced into the same
E. coli
background and yielded overlapping but significantly different regulons. These differences were seen despite amino acid sequence identities of 92% (
Vibrio
) and 98% (
Proteus
) to
E. coli
Lrp, including complete conservation of the helix-turn-helix motifs. The N-terminal region contains many of the sequence differences among these Lrp orthologs, which led us to investigate its role in Lrp function. Through the generation of hybrid proteins, we found that the N-terminal diversity is responsible for some of the differences between orthologs in terms of DNA binding (as revealed by mobility shift assays) and multimerization (as revealed by gel filtration, dynamic light scattering, and analytical ultracentrifugation). These observations indicate that the N-terminal tail plays a significant role in modulating Lrp function, similar to what is seen for a number of other regulatory proteins.
The Campylobacter jejuni Transcriptional Regulator Cj1556 Plays a Role in the Oxidative and Aerobic Stress Response and Is Important for Bacterial SurvivalIn Vivo
Authors: Gundogdu Ozan , Mills Dominic C. , Elmi Abdi , Martin Melissa J. , Wren Brendan W. , Dorrell Nick 
Published: June 2011

ABSTRACTCampylobacter jejuniis the leading bacterial cause of human gastroenteritis worldwide. Despite stringent microaerobic growth requirements,C. jejuniis ubiquitous in the aerobic environment and so must possess regulatory systems to sense and adapt to external stimuli, such as oxidative and aerobic (O2) stress. Reannotation of theC. jejuniNCTC11168 genome sequence identified Cj1556 (originally annotated as a hypothetical protein) as a MarR family transcriptional regulator, and further analysis indicated a potential role in regulating the oxidative stress response. AC. jejuni11168HCj1556mutant exhibited increased sensitivity to oxidative and aerobic stress, decreased ability for intracellular survival in Caco-2 human intestinal epithelial cells and J774A.1 mouse macrophages, and a reduction in virulence in theGalleria mellonellainfection model. Microarray analysis of gene expression changes in theCj1556mutant indicated negative autoregulation ofCj1556expression and downregulation of genes associated with oxidative and aerobic stress responses, such askatA,perR, andhspR. Electrophoretic mobility shift assays confirmed the binding of recombinant Cj1556 to the promoter region upstream of theCj1556gene.cprS, which encodes a sensor kinase involved in regulation of biofilm formation, was also upregulated in theCj1556mutant, and subsequent studies showed that the mutant had a reduced ability to form biofilms. This study identified a novelC. jejunitranscriptional regulator, Cj1556, that is involved in oxidative and aerobic stress responses and is important for the survival ofC. jejuniin the natural environment andin vivo.
Advance care planning in life limiting illness
Authors: Judez J , Vivancos L , Antunez C , Quesada M , Novoa A , Feito L , Ogando B 
Published: May 2011

In the Spanish advance care planning (ACP) Program ‘KAYRÓS- Helping Conversations’, inspired in Respecting Choices philosophy, we developed an innovative cluster research, NEURO-KAYRÓS, applied to two neurodegenerative diseases with contrasting trajectories: early Alzheimer's Disease (AD)-grant research project for clinical research ACP implementation in dyads (patient-surrogate)- and Amyotrophic Lateral Sclerosis (ALS)- stem cell non-commercial research grant clinical trial with clinical psychology follow-up. We monitor the ACP dyadic (patient-surrogate) interview with tools, combining quantitative with qualitative approaches, that allow us to gain insight in the process of living (and planning) with a threatening neurodegenerative illness/hoping for the best/preparing for the worst. Quantitative tools for: ACP knowledge; trends of preferences for goals of treatment in different potential (or experienced) losses during illness trajectory; congruence with surrogate; critical milestones marking transitions. Qualitative tools: discussion groups and in-depth interview.AD and ALS although share some common features, leaning towards dependency, vary significantly in some key notes regarding both with the perception of the illness trajectory (related to patient's own biography) and, along it, with the potential support received from the ACP process.Initial lessons from the first 6 months of the ongoing 2 year project.Illness trajectory (perception AD vs ALS): (slow) cognitive versus (fast) physical decline; advanced versus middle-age; slow versus fast adaptation (subject, carers & environment); role of substituted decision.ACP Process: in clinical versus research (clinical trial) setting; from ignorance to gratitude if initial anxiety and/or threat are overcome by a system that shows that cares and stands, come what may.
Sustainable ACP in aged care facilities with dedicated time and funding
Authors: Neale D , Mann J 
Published: May 2011

Barwon Health is Victoria's largest regional health service. Alan David Lodge (ADL) is an Aged Care Facility providing high level care for approximately 105 residents.Advance care planning (ACP) is included in the goals of care for residents at ADL but had not been fully implemented due to staff limitations, in particular the availability of time, for trained staff to facilitate the ACP process. The Respecting Patient Choices (RPC) program at Barwon Health provided funding for a dedicated 4 h per week over a 6-month period to allow staff that had previously completed RPC training/workshops to facilitate ACP at ADL.RPC program provided education sessions and support for staff and this together with dedicated time to facilitate the process, produced a significant increase in participation of residents and families in ACP through consultation with familiar staff whereby there is an established rapport.It was anticipated that improved quality of care for residents and a reduction in the incidence of family/staff conflict would result by ensuring medical treatment and personal wishes were known prior to a health crisis. The potential improvement in resource allocation through reduced acute admissions, dislocation and medical interventions was also highly probable but not measurable during the project period.Overall there was a marked increase in ACP uptake and the outcomes of the project demonstrated that with a moderate amount of dedicated funding and allocated hours a sustainable model for ACP in aged care facilities is achievable.
Deaths in older adults in England
Authors: Verne J , Ruth K , Pring A 
Published: May 2011

We will present key results from the report, ‘Deaths in Older Adults in England' produced by the South West Public Health Observatory on behalf of the National End of Life Care Intelligence Network. This report describes differences in place and cause of death in older people and is part of work to provide information and evidence to support the End of Life Care Strategy.The report analysed deaths in people aged 75 and over registered in England in 2006–2008 (source: ONS mortality data). There were differences in underlying cause of death and place of death according to age and sex. In people aged 75 and over, a higher proportion of deaths in females were from pneumonia (organism unspecified), stroke and dementia compared with males. Deaths from senility and dementia were more common with increasing age. In people aged 75 and over, a greater proportion of males than females died in hospital or in their own residence, while a lower proportion of males than females died in nursing homes and old people's homes.It is important to consider the implications of these findings when planning end of life care services as two-thirds of deaths in England are in people aged 75 and over and, in the future, the proportion of deaths in the oldest age groups are expected to increase further.
Difference is opinion regarding end-of-life between older patients and their family, a Thai perspective
Authors: Kajornkijaroen A , Srinonprasert V , Kornbongkotmart S , Praditsuwan R 
Published: May 2011

Making decision for the love ones toward the end-of-life is a sensitive and complex task. Having established advance care plan is rarely occurred in Eastern culture. The discordance among patients and decision makers has been documented in literature but never been explored in Thailand. We conducted a survey among geriatric patients using 5-category likert scale, 13-situation-based questionnaire. We also enquired the families to rate how they believed what older patients would have thought regarding issues in end-of-life care.Elderly and their families demonstrated fairly similar attitude for most of the items inquired. However, significant higher proportion of patients wished not to be a burden to their families and not to prolong suffers when chance of survival is slim.Of note, only 45.2% of patients wished to pass away at home while 70% of family believed that older patients would have wanted to die at home. Factor associated with agreeing to die at home were age less than 75, having education more than 4 years and being single with OR of 2.93 (1.39 to 6.16; p=0.005), 2.76 (1.30 to 5.87; p=0.009) and 2.78 (1.33 to 5.83; p=0.007),respectively
The survey of opinions regarding good death for geriatric patients from the perspectives of geriatric patients and physicians
Authors: Kornbongkotmas S , Srinonprasert V , Kajornkitjaroen A , Praditsuwan R 
Published: May 2011

Nowadays growing concern over providing the best possible end-of-life care for geriatric patients has been raised worldwide. It is not uncommon that different perspectives of patients, families and caring physicians may result in unwanted suffering of dying patients. Learning the differences might lead to appropriate interventions and bring about better quality of care for older patients toward the end of life.We conducted a survey on older patients and physicians at a university hospital inThailand. We elicited opinions on end-of-life care by applying 5-category likert scale, 13-situation-based questionnaire. Older people were asked to rate their agreement with those items while physicians were enquired to rate their opinions on what they believed older people would have thought. We also enquired participants to rank the most important aspects concerning good death.Nearly 90% of physicians believed that older people would wish to be involved in decision-making and completing unfinished business while only 70% elderly really did. Being mentally aware was rated by older patients at much higher proportion than physicians. More importantly, one-fourth of older patient did not wish to die at home while only 6% of physician believed so. The only factor associated with not willing to pass away at home among these two groups after adjusted in multivariate analysis was sex. When it came to ranking the most important aspect, older patients place it on not to prolong suffering while this was not ranked on the top-three items by physicians.
‘Futility’ – let's put it out of its misery
Authors: Saul P 
Published: May 2011

Though still on life support, George improved when his infected leg was amputated above the knee. But his wife, Annette, pleaded with the surgeon to withdraw intensive care treatment. George had made her promise that she would never let him have an amputation.But who has the authority to make this choice? The surgeon believed it was the best medical practice to continue (as treatment was not ‘futile’), but George very clearly had a preference, and Annette a responsibility to promote it.The concept of futility was introduced into this discussion to help resolve this dilemma (which rapidly became a dispute), and, as often happens, failed to produce a resolution.The notion of futility has been dissected in countless law courts, medical journals and standard textbooks of medical ethics for a generation. But much of the discussion has, ironically, proved futile and numbers of publications in this area is rapidly falling. I suggest that futility, as originally conceived in a medical setting, is no longer a valid concept, and, like euthanasia, is a term better abandoned than further debated.I suggest that, as in debates about ‘best interests’ (another term looking for a definition), all discussion eventually returns to what the patient or family might have seen as important. The very basis of futility, originally conceived as a medical judgement based on probabilities, has disappeared.I contend that we abandon the term, and instead invest in fair and transparent processes that maximise authentic and justifiable decisions.
Investigation on the use of advance directives for patients attending a hospital in Japan
Authors: Miura H , Nishikawa M , Nakashima K , Hong Y J , Detering K , Jones D , Silvester W 
Published: May 2011

BackgroundIn Japan, living wills and advance directives (AD) are not commonly used, and there is no system or law to support the decision making of patients. Furthermore, there is no available law about the withdrawal of life-sustaining treatments or appointment of a medical attorney. Thus, medical staff must deal with ethical dilemmas related to medical decision making in end-stage disease.AimTo investigate the use of AD for patients attending a hospital of the National Centre for Geriatrics and Gerontology for treatment from May, 2008.MethodsWe examined the contents described in ADs and assessed the trend of the wishes.ResultsTo date 127 people (67 female, average age 74.6) have participated. Many have respiratory diseases (26 people) and malignant disorders (21 people). Most people wished to nominate an attorney but only one had a medical attorney, 111 people did not wish for resuscitation. More than 90% did not wish for life-sustaining treatment (respirator, or tube feeding), whereas the wish for intravenous feeding was relatively high (32.3%). As for the place of death, 62 people wished to die in hospital and the least preferred place was at home (11 people).ConclusionWe found that many Japanese, during their end-of-life care, want to die in hospital while receiving some kind of treatment such as intravenous feeding. The construction of the system to support the decision making of the patients is an urgent problem in Japan.
Advance Care Planning (PEACE) for care home residents in an acute hospital setting: impact on ongoing advance care planning and readmissions
Authors: Hayes N , Kalsi T , Steves C , Martin F , Evans J , Schiff R , Briant L 
Published: May 2011

PEACE (Proactive Elderly Advance CarE) is an advance care planning (ACP) developed at two acute hospital sites in London, UK, for care home (nursing) residents prior to discharge. Patient's preferences are documented, or in the cases of mental incapacity, best interests decisions are made, to give clinical advice and escalation decisions for future medical care. The document is sent on transfer back to nursing homes, as agreed with GPs and care homes.At Site 1, 20 patients were discharged with PEACE and 80% (N=16/20) were followed up at 2 weeks after transfer. 69% (N=11/16) of PEACE documents were in place in the nursing notes. ACPs had further been developed from PEACE in 73% (N=8/11). None of these residents were readmitted to the discharging hospital to date. However, of those residents whose ACPs were not further developed, 37.5% (N=3/8) were readmitted inappropriately (palliative plans), and 25% (N=2/8) were readmitted appropriately as judged by their original PEACE document in 3 months.At Site 2, 12/37 patients discharged over 4 months were sent with a PEACE document. 25% (N=3/12) of patients with a PEACE document were readmitted within 6 months, only 8% (N=1/12) inappropriately. 56% (N=14/25) of nursing home residents discharged without PEACE in the same period were readmitted.Our findings suggest that PEACE may reduce inappropriate readmissions. The results also suggest that PEACE is useful in supporting further ACP after transfer to care homes.
Variations in hospital death
Authors: Osinowo A , Pring A , Verne J 
Published: May 2011

BackgroundDeath largely occurs in old age and there are large variations in the proportion of hospital deaths by Local Authorities (LAs) in England. In the period between 2007 and 2009 deaths occurring in hospital ranged between 43% and 75% with about 12% of LAs having less than 50% hospital deaths. Funnel plots are powerful tools that can be adapted for use in showing and understanding the variations in hospital deaths in English LAs.AimTo explore variations in proportion of hospital deaths in LAs by age of population.MethodsAge specific mortality data relating to place of death were extracted from ONS mortality files for years 2007–2009. Hospital deaths as a proportion of all deaths in LAs were calculated and funnel plots were used to study variations by population size and by age.ResultsThe proportions of LA deaths in hospital are overdispersed, with more LAs lying outside the control limits of the funnel plot than would be expected if the size of a LA were the only factor predicting hospital death. Factors such as social deprivation, demographics and local End of Life (EOL) care service configuration contribute to the overdispersion for example, some LAs provide specialist palliative care services within hospitals while others provide this service elsewhere. EOL care in less well organised LAs may result in people near the EOL being unnecessarily admitted to die in hospital.ConclusionsPlace to place comparison of hospital deaths reveals stack differences which must be understood to ensure equality of care.
Religious affiliation on end-of-life decisions in intensive care units
Authors: Kleanthous E 
Published: May 2011

ObjectiveEnd of life is frequently enforced in intensive care units in several countries. Recent surveys have shown that medical practices for end of life vary between countries among health care professionals. Religious affiliation has been included among other factors such as culture, attitudes of health care professionals, legislation, illness, quality of life and others. The determination and the affiliation of religion in end of life decisions in intensive care units is the objective of this review study. In addition in this review we are presenting the conventions and opinions of major religions regarding end of life care and decisions in intensive care units.DesignFor this review CINAHL, Pubmed and Medline were searched under the keywords ‘religion’, ‘end of life’ and ‘intensive care units’.ResultsThere are several different opinions among health care professionals in the issue of religion which influence end of life decisions in intensive care units. Health care professionals must understand patients' and families' religion and culture in order to provide better end of life care in patients. Furthermore, understanding religious affiliation will enhance communication among health care professionals with patients and families. Religious affiliation may support the development of guidelines for end of life practices.