Nursing shortages: let's be flexible

The following paper is a report outlining a significant work pattern change in an acute cardiac ward at a large Brisbane-based private hospital. The nursing staff expressed the desire for more flexible rostering and the opportunity to work 12-hour shifts. After agreement was reached between the hospital, the union and the Industrial Relations Board, guidelines were put in place and a Flexible Rostering System was proposed and trialed. An 80% consensus of staff was required both to proceed with the trial and to implement any permanent changes. Initially, the trial was conducted for three months and extended to six months. The shifts trialed were between four and 12 hours in length with varied starting and finishing times. The Flexible Rostering System was evaluated using feedback from staff surveys and the results of a staff vote. In addition, patient feedback, incident reports, financial and managerial evaluation of staff costs, hours per patient day utilised, sick leave, and the use of permanent staff for voluntary extra shifts were also monitored. The outcome of the trial was positive with over 80% of staff voting to implement the Flexible Rostering System permanently. A significant reduction in sick leave of 41% and improved retention of skilled registered nursing staff was noted. There was no increase in the number of incident reports or patient complaints. Both patients and nurses commented on the improved continuity of care. Salaries and wages were within budget. Staff surveys showed positive feedback such as increased morale, increased flexibility with rosters, decreased fatigue levels, improved patient assessment on night duty and an increase in number of days off. In conclusion, the Flexible Rostering System has been accepted as a positive change for staff and is cost effective for the hospital. In light of nursing shortages, the outcome of this trial cannot be ignored.     

Neurological deficits and glycosphingolipid accumulation in saposin B deficient mice

Saposin B derives from the multi-functional precursor, prosaposin, and functions as an activity enhancer for several glycosphingolipid (GSL) hydrolases. Mutations in saposin B present in humans with phenotypes resembling metachromatic leukodystrophy. To gain insight into saposin B's physiological functions, a specific deficiency was created in mice by a knock-in mutation of an essential cysteine in exon 7 of the prosaposin locus. No saposin B protein was detected in the homozygotes (B-/-) mice, whereas prosaposin, and saposins A, C and D were at normal levels. B-/- mice exhibited slowly progressive neuromotor deterioration and minor head tremor by 15 months. Excess hydroxy and non-hydroxy fatty acid sulfatide levels were present in brain and kidney. Alcian blue positive (sulfatide) storage cells were found in the brain, spinal cord and kidney. Ultrastructural analyses showed lamellar inclusion material in the kidney, sciatic nerve, brain and spinal cord tissues. Lactosylceramide (LacCer) and globotriaosylceramide (TriCer) were increased in various tissues of B-/- mice supporting the in vivo role of saposin B in the degradation of these lipids. CD68 positive microglial cells and activated GFAP positive astrocytes showed a proinflammatory response in the brains of B-/- mice. These findings delineate the roles of saposin B for the in vivo degradation of several GSLs and its primary function in maintenance of CNS function. B-/- provide a useful model for understanding the contributions of this saposin to GSL metabolism and homeostasis.     

The pancreatic ductal epithelium serves as a potential pool of progenitor cells

Abstract:  With the increasing success of islet transplantation, β-cell replacement therapy has had renewed interest. To make such a therapy available to more than a few of the thousands of patients with diabetes, new sources of insulin-producing cells must become readily available. The most promising sources are stem cells, whether embryonic or adult stem cells. Clearly identifiable adult pancreatic stem cells have yet to be characterized. Although considerable evidence suggests their possibility, recent lineage-tracing experiments challenge their existence. Even in light of these lineage-tracing experiments, we suggest that evidence for neogenesis or new islet formation after birth remains strong. Our work has suggested that the pancreatic duct epithelium itself serves as a pool for progenitors for both islet and acinar tissues after birth and into adulthood and, thus, that the duct epithelium can be considered 'facultative stem cells'. We will develop our case for this hypothesis in this perspective.     

Assessing depressive symptoms in persons who die of suicide in mainland China

BACKGROUND: The potential insensitivity to depression of translated diagnostic instruments makes it difficult to assess the relationship of depressive symptoms to suicide in non-Western cultures. METHODS: Addition of culturally sensitive probes and other modifications were made to the depression section of the Chinese version of the SCID; the standard SCID probes and the expanded-probes are separately used to assess each symptom of depression, the resultant diagnoses and the overall severity of depression. This modified SCID was included in the psychological autopsy interviews with family members and, separately, close associates of 887 suicides and 721 non-suicidal decedents from 23 regions of mainland China. RESULTS: Compared to the standard interview, the expanded-probe method increased reported prevalence of major depressive episode among suicide decedents from 26.4% (234/887) to 40.2% (357/887) and for other deaths from 1.0% (7/721) to 2.1% (15/701). The additional 131 cases identified using the expanded-probe method had substantial social impairment and a greatly elevated risk of suicide compared to those with no depressive symptoms (OR=37.0, 95% CI=17.6-77.6). Inter-observer reliability for major depressive episode between the two independent interviews was greater for the expanded probe method (ICC=0.77 vs. 0.67, P<0.001). For both interview methods there was a strong dose-response relationship between suicide risk and the number and severity of depressive symptoms. LIMITATIONS: This study uses proxy informants to obtain information about the psychological status of deceased subjects; the value of this expanded-probe method for the diagnosis of depression in non-Western cultures needs to be confirmed with living subjects. CONCLUSIONS: Adding culture-appropriate probes about depressive symptoms to standardized diagnostic instruments identifies many Chinese subjects with unrecognized depression. Dimensional measures of depressive symptoms are more powerful predictors of suicide risk than categorical diagnoses.     

Correlative BOLD MR imaging of stages of synovitis in a rabbit model of antigen-induced arthritis

Background

Because of the ability of blood-oxygen-level-dependent (BOLD) MRI to assess blood oxygenation changes within the microvasculature, this technique holds potential for evaluating early perisynovial changes in inflammatory arthritis.

Objective

To evaluate the feasibility of BOLD MRI to detect interval perisynovial changes in knees of rabbits with inflammatory arthritis.

Materials and methods

Rabbit knees were injected with albumin (n?=?9) or saline (n?=?6) intra-articularly, or were not injected (control knees, n?=?9). Except for two rabbits (albumin-injected, n?=?2 knees; saline-injected, n?=?2 knees) that unexpectedly died on days 7 and 21 of the experiment, respectively, all other animals were scanned with BOLD MRI on days 0, 1, 7, 14, 21 and 28 after induction of arthritis. T2*-weighted gradient-echo MRI was performed during alternate 30?s of normoxia/hyperoxia. BOLD MRI measurements were compared with clinical, laboratory and histological markers.

Results

Percentage of activated voxels was significantly greater in albumin-injected knees than in contralateral saline-injected knees (P?=?0.04). For albumin-injected knees (P?P?=?0.009), the percentage of activated BOLD voxels varied over time. A quadratic curve for on-and-off BOLD difference was delineated for albumin- and saline-injected knees over time (albumin-injected, P?=?0.047; saline-injected, P?=?0.009). A trend toward a significant difference in synovial histological scores between albumin-injected and saline-injected knees was noted only for acute scores (P?=?0.07).

Conclusion

As a proof of concept, BOLD MRI can depict perisynovial changes during progression of experimental arthritis.     

Palmitate-TLR4 signaling regulates the histone demethylase,JMJD3, in macrophages and impairs diabetic wound healing

Chronic macrophage inflammation is a hallmark of type 2 diabetes (T2D) and linked to the development of secondary diabetic complications. T2D is characterized by excess concentrations of saturated fatty acids (SFA) that activate innate immune inflammatory responses, however, mechanism(s) by which SFAs control inflammation is unknown. Using monocyte-macrophages isolated from human blood and murine models, we demonstrate that palmitate (C16:0), the most abundant circulating SFA in T2D, increases expression of the histone demethylase, Jmjd3. Upregulation of Jmjd3 results in removal of the repressive histone methylation (H3K27me3) mark on NFκB-mediated inflammatory gene promoters driving macrophage-mediated inflammation. We identify that the effects of palmitate are fatty acid specific, as laurate (C12:0) does not regulate Jmjd3 and the associated inflammatory profile. Further, palmitate-induced Jmjd3 expression is controlled via TLR4/MyD88-dependent signaling mechanism, where genetic depletion of TLR4 (Tlr4^−/−) or MyD88 (MyD88^−/−) negated the palmitate-induced changes in Jmjd3 and downstream NFκB-induced inflammation. Pharmacological inhibition of Jmjd3 using a small molecule inhibitor (GSK-J4) reduced macrophage inflammation and improved diabetic wound healing. Together, we conclude that palmitate contributes to the chronic Jmjd3-mediated activation of macrophages in diabetic peripheral tissue and a histone demethylase inhibitor-based therapy may represent a novel treatment for nonhealing diabetic wounds.     

Inflammation, ageing and cancer

Cancer is generally recognized as an age-related disease. In fact, incidence and mortality rates of most human cancers increase consistently with age up to 90 years, but they plateau and decline thereafter. A low-grade systemic inflammation characterizes ageing and this pro-inflammatory status underlies biological mechanisms responsible for age-related inflammatory diseases. On the other hand, clinical and epidemiological studies show a strong association between chronic infection, inflammation and cancer and indicate that even in tumours not directly linked to pathogens, the microenvironment is characterized by the presence of a smouldering inflammation, fuelled primarily by stromal leukocytes. In this review, we have briefly mentioned inflammatory mediators involved in cancer although we decided to choose the ones which show a strict association with ageing and longevity. Inflammation is necessary to manage with damaging agents and is crucial for survival. But, in our opinion, the pro-inflammatory status of ageing might be one of the mechanisms which relate cancer to ageing. The most appropriate inflammatory genes have been selected to survive and to reproduce. Paradoxically, inflammatory age-related diseases (including cancer) are the marks of the same evolutionistic trait. Centenarians are characterized by a higher frequency of genetic markers associated with better control of inflammation. The reduced capacity of centenarians to mount inflammatory responses appears to exert a protective effect towards the development of those age-related pathologies having a strong inflammatory pathogenetic component, including cancer. All in all, centenarians seem to carry a genetic background with a peculiar resistance to cancer which is also an anti-inflammatory profile.     

Cautions on the Use of Multiple Imputation When Selecting Between Latent Categorical versus Continuous Models for Psychological Constructs

Clinical psychology researchers studying adolescents and young adults long have been interested in characterizing the latent categorical (classes/profiles) versus continuous (factors) nature of psychological syndromes. To inform this debate, researchers sometimes compare the fit of finite mixture versus factor analysis models to symptom data. This study explains and evaluates how missing data handling methods can impact results of this important model fit comparison. Via simulation, we assess three missing data-handling methods previously recommended to researchers fitting these models: multiple imputation using a saturated multivariate normal imputation model, multiple imputation using a hypothesized model, or full information maximum likelihood using the EM algorithm (FIML-EM). Results show that, under certain conditions, the method used to handle missing data can interfere with clinical psychologists' ability to accurately discriminate latent classes from continua. For instance, certain imputation methods increase the chance of selecting latent continua when latent classes truly exist. FIML-EM performed best overall. Recommendations for practice are discussed.