The Schizosaccharomyces pomberfc3 + gene encodes a homologue of the human hRFC36 and Saccharomyces cerevisiae Rfc3 subunits of replication factor C

In the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe replication factor C (RF-C) plays key roles both in chromosomal DNA replication and in DNA replication checkpoint function. At the replication fork, the five-subunit RF-C complex functions to load the trimeric polymerase accessory factor PCNA onto DNA. PCNA then acts as a sliding clamp, tethering Pol δ to the DNA to maximise its processivity. Here we describe the cloning of the S. pomberfc3 ⁺ gene, encoding a homologue of the S. cerevisiae Rfc3 and human hRFC36 proteins. The 1026 bp rfc3 ⁺ ORF is interrupted by five introns, ranging in size from 49 to 165 bp. The spliced ORF is predicted to encode a 342 amino-acid protein that is approximately 50% identical at the amino acid sequence level to the S. cerevisiae Rfc3 and human hRFC36 proteins. As expected, S. pomberfc3 ⁺ is an essential gene, with rfc3Δ cells being defective for DNA replication. Loss of rfc3 ⁺ function can be rescued by heterologous expression of either the S. cerevisiae Rfc3 or human hRFC36 proteins in S. pombe. Received: 15 October 1999     

Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice

CD4⁺ T cells in the mouse can be subdivided into two fractionsbased on the level of expression of the CD45RB determinant.Previous studies have shown that these subsets are functionallydistinct. We have further characterized the properties of thesesubpopulations in vivo by injecting them into C. B-17 scid mice.The animals restored with the CD45RB^highCD4⁺ T cell populationdeveloped a lethal wasting disease with severe mononuclear cellinfiltrates into the colon and elevated levels of IFN- mRNA.In contrast, animals restored with the reciprocal CD45RB^lowsubset or with unfractionated CD4⁺ T cells did not develop thewasting or colitis. Importantly, the co-transfer of the CD45RB^lowpopulation with the CD45RB^high population prevented the wastingdisease and colitis. These data indicate that important regulatoryinteractions occur between the CD45RB^high and CD45RB^lowCD4⁺T cell subsets and that disruption of this mechanism has fatalconsequences.     

Implementing a Stratified Vocational Advice Intervention for People on Sick Leave with Musculoskeletal Disorders: A Multimethod Process Evaluation

Journal of Occupational Rehabilitation - Purpose To perform a process evaluation of a stratified vocational advice intervention (SVAI), delivered by physiotherapists in primary care, for people on...     

Puumala Virus Infection in Family,Switzerland

We report 3 cases of Puumala virus infection in a family in Switzerland in January 2019. Clinical manifestations of the infection ranged from mild influenza-like illness to fatal disease. This cluster illustrates the wide range of clinical manifestations of Old World hantavirus infections and the challenge of diagnosing travel-related hemorrhagic fevers.     

The implementation of an infection control bundle within a Total Care Burns Unit

AimTo evaluate the impact of the implementation of a best practice infection prevention and control bundle on healthcare associated burn wound infections in a paediatric burns unit.BackgroundBurn patients are vulnerable to infection. For this patient population, infection is associated with increased morbidity and mortality, thereby representing a significant challenge for burns clinicians who care for them.MethodsAn interrupted time series was used to compare healthcare associated burn wound infections in paediatric burn patients before and after implementation of an infection prevention and control bundle. Prospective surveillance of healthcare associated burn wound infections was conducted from 2012 to 2014. Other potential healthcare associated infection rates were also reviewed over the study period, including urinary tract infections, pneumonia, upper respiratory tract infections and sepsis. An infection prevention and control bundle developed in collaboration between the paediatric burn unit and infection control clinicians was implemented in 2013 in addition to previous standard practice.ResultsDuring the study period a total of 626 patients were admitted to the paediatric burns unit. Healthcare associated burn wound infections reduced from 34 in 2012 to 0 in 2014 following the implementation of the infection prevention and control bundle. Pneumonia and sepsis also reduced to 0 in 2013 and 2014, however one upper respiratory tract infection occurred in 2013 and urinary tract infections persisted in 2013.ConclusionThe implementation of an infection prevention and control bundle was effective in reducing healthcare associated burn wound infections, pneumonia and sepsis within our paediatric burns unit. Urinary tract infections remain a challenge for future improvement.     

Decreased neuroplasticity in minor burn injury survivors compared to non-injured adults: A pilot study in burn injury survivors aged 45 years and older

ObjectiveNeuroplasticity is the capacity of the brain to change or adapt with experience: brain changes occur with use, disuse, and injury. Repetitive transcranial magnetic stimulation (rTMS) can be used to induce neuroplasticity in the human brain. Here, we examined rTMS-induced neuroplasticity in the primary motor cortex in burns survivors and controls without injury, and whether neuroplasticity is associated with functional recovery in burns survivors.MethodsSixteen burn injury survivors (total body surface area of burn injury <15%) and 13 non-injured control participants were tested. Repetitive TMS (specifically, spaced continuous theta-burst stimulation[cTBS]) was applied to induce neuroplasticity 6 and 12 weeks after injury in burn survivors and in two sessions separated by 6 weeks in controls. Motor evoked potentials (MEPs) elicited by single-pulse TMS were measured before and after rTMS to measure neuroplasticity. Burns survivors completed a functional assessment 12 weeks after injury.ResultsNon-injured controls showed decreased MEP amplitude 15?30 min after spaced cTBS in both experimental sessions. Burn survivors showed a smaller change in MEP amplitude after spaced cTBS compared to controls 6 weeks after burn injury but no difference compared to controls 12 weeks after burn injury. In burn survivors, there was a significant positive association between general health outcome (Short-Form Health Survey) and the change in MEP amplitude after spaced cTBS 12 weeks after injury (r=.73, p = .01).ConclusionsThe current findings suggest that burn survivors have a reduced capacity for neuroplasticity early in the recovery period (6 weeks after injury), which normalizes later in the recovery period (12 weeks after injury). Furthermore, the results provide preliminary evidence to suggest that burn survivors with normalized neuroplasticity 12 weeks after injury recover faster after burn injury.     

The impact of a Housing First intervention and health-related risk factors on incarceration among people with experiences of homelessness and mental illness in Canada

ObjectiveTo examine the effect of a Housing First (HF) intervention and health-related risk factors on incarceration among adults with experiences of homelessness and mental illness.MethodsParticipants (N = 508) were recruited at the Toronto site of the At Home/Chez Soi study. The outcome was incarceration in Ontario from 2009 to 2014. Exposures were intervention group (HF vs. treatment as usual), Axis I mental health diagnoses, emergency department (ED) visit, and history of traumatic brain injury (TBI). Logistic regression was used to examine the association between exposures and incarceration.ResultsOf 508 participants, 220 (43.3%) were incarcerated at least once during the study period. Among those incarcerated, 81.9% were male, 52.7% had been diagnosed with alcohol dependence/abuse, 60.9% had been diagnosed with substance dependence/abuse, 65.1% reported having visited an ED within the last 6 months, and 66.4% had a history of TBI. After adjusting for demographic covariates, substance dependence/abuse (aOR: 2.06; 95% CI: 1.40, 3.03), alcohol dependence/abuse (aOR: 1.52, 95% CI: 1.04, 2.22), ED visit (aOR: 1.54; 95% CI: 1.02, 2.32), and history of TBI (aOR: 2.60; 95% CI: 1.75, 3.85) were associated with incarceration. We found no significant effect of the HF intervention on incarceration outcome (aOR: 1.08; 95% CI: 0.76, 1.55).ConclusionsAmong adults with experiences of homelessness and severe mental illness, those with substance and alcohol dependence/abuse disorders, history of TBI, and recent ED visits were at increased odds of incarceration. Strategies are needed to prevent and reduce incarceration for this population, including treatment of mental illness in the community.Supplementary InformationThe online version of this article (10.17269/s41997-020-00433-z) contains supplementary material, which is available to authorized users.     

Factors influencing routine cognitive impairment screening in older at-risk drinkers: Findings from a qualitative study in the United Kingdom

Cognitive Impairment (CI) screening is recommended for those engaged in harmful levels of alcohol use. However, there is a lack of evidence on implementation. This paper explores the barriers and facilitators to CI screening experienced across a service specifically for older drinkers. The findings draw on data gathered as part of an evaluation of a multilevel programme to reduce alcohol-related harm in adults aged 50 and over in five demonstration areas across the United Kingdom. It is based on qualitative interviews and focus groups with 14 service providers and 22 service users. Findings are presented thematically under the section headings: acceptability of screening, interpretation and making sense of screening and treatment options. It is suggested that engagement with CI screening is most likely when its fit with agency culture and its purpose is clear; where service providers have the technical skills to administer and discuss the results of screening with service users; and where those undertaking screening have had the opportunity to reflect on their own experience of being screened. Engagement with CI screening is also most likely where specific intervention pathways and engagement practices can be accessed to respond to assessed need.     

Pharmacokinetics and pharmacodynamics of prolonged oral etoposide in women with metastatic breast cancer

The pharmacokinetics and pharmacodynamics of prolonged oral etoposide chemotherapy were investigated in 15 women with metastatic breast cancer who received oral etoposide 100 mg as a single daily dose for up to 15 days. There was considerable interpatient variability in the day 1 pharmacokinetic parameters: area under the plasma concentration time curve (AUC) (0–24 h) 1.95±0.87 mg/ml per min (mean ± SD), apparent oral clearance 60.9±21.7 ml/min per 1.73 m², peak plasma concentration 5.6±2.5 g/ml, time to peak concentration 73±35 min and half-life 220±83 min. However, intrapatient variability in systemic exposure to etoposide was much less with repeated doses. The intrapatient coefficient of variation (CV) of AUC for day 8 relative to day 1 was 20% and for day 15 relative to day 1 was 15%, compared to the day 1 interpatient CV of 45%. Neutropenia was the principal toxicity. Day 1 pharmacokinetic parameters were related to the percentage decrease in absolute neutrophil count using the sigmoidal E_max equation. A good fit was found between day 1 AUC and neutrophil toxicity (R ²=0.77). All patients who had a day 1 AUC>2.0 mg/ml per min had WHO grade III or IV neutropenia. The predictive performance of the models for neutrophil toxicity was better for AUC (percentage mean predictive error 5%, percentage root mean square error 18.1%) than apparent oral clearance, peak plasma concentration, or daily dose (mg/m²). A limited sampling strategy was developed to predict AUC using a linear regression model incorporating a patient effect. Data sets were divided into training and test sets. The AUC could be estimated using a model utilizing plasma etoposide concentration at only two time points, 4 h and 6 h after oral dosing (R ²=98.9%). The equation AUC_pr=–0.376+0.631×C_4h+0.336×C_6h was validated on the test set with a relative mean predictive error of –0.88% and relative root mean square error of 6.4%. These results suggest monitoring of AUC to predict subsequent myelosuppression as a strategy for future trials with oral etoposide.Division of Haematology and Medical Oncology, Peter MacCallum Cancer Institute, Locked Bag 1, A'Beckett St, Melbourne 3000, Australia