bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethanol Effect on BK Channels is Modulated by Magnesium
Authors: Marrero Héctor G. , Treistman Steven N. , Lemos José R.
Published: September 2015

Background

Alcoholics have been reported to have reduced levels of magnesium in both their extracellular and intracellular compartments. Calcium‐dependent potassium channels (BK) are known to be one of ethanol (EtOH)’s better known molecular targets.

Methods

Using outside‐out patches from hippocampal neuronal cultures, we examined the consequences of altered intracellular Mg2+ on the effects that EtOH has on BK channels.

Results

We find that the effect of EtOH is bimodally influenced by the Mg2+ concentration on the cytoplasmic side. More specifically, when internal Mg2+ concentrations are ≤200 μM, EtOH decreases BK activity, whereas it increases activity when Mg2+ is at 1 mM. Similar results are obtained when using patches from HEK cells expressing only the α‐subunit of BK. When patches are made with the actin destabilizer cytochalasin D present on the cytoplasmic side, the potentiation caused by EtOH becomes independent of the Mg2+ concentration. Furthermore, in the presence of the actin stabilizer phalloidin, EtOH causes inhibition even at Mg2+ concentrations of 1 mM.

Conclusions

Internal Mg2+ can modulate the EtOH effects on BK channels only when there is an intact, internal actin interaction with the channel, as is found at synapses. We propose that the EtOH‐induced decrease in cytoplasmic Mg2+ observed in frequent/chronic drinkers would decrease EtOH's actions on synaptic (e.g., actin‐bound) BK channels, producing a form of molecular tolerance.
Stimulating immune responses to fight cancer: Basic biology and mechanisms
Authors: O'Byrne Kenneth
Published: September 2015

Chronic inflammation is now recognized as a major cause of malignant disease. In concert with various mechanisms (including DNA instability), hypoxia and activation of inflammatory bioactive lipid pathways and pro‐inflammatory cytokines open the doorway to malignant transformation and proliferation, angiogenesis, and metastasis in many cancers. A balance between stimulatory and inhibitory signals regulates the immune response to cancer. These include inhibitory checkpoints that modulate the extent and duration of the immune response and may be activated by tumor cells. This contributes to immune resistance, especially against tumor antigen‐specific T‐cells. Targeting these checkpoints is an evolving approach to cancer immunotherapy, designed to foster an immune response. The current focus of these trials is on the programmed cell death protein 1 (PD‐1) receptor and its ligands (PD‐L1, PD‐L2) and cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4). Researchers have developed anti‐PD‐1 and anti‐PDL‐1 antibodies that interfere with the ligands and receptor and allow the tumor cell to be recognized and attacked by tumor‐infiltrating T‐cells. These are currently being studied in lung cancer. Likewise, CTLA‐4 inhibitors, which have had success treating advanced melanoma, are being studied in lung cancer with encouraging results.
The Unbounded Self: Peak Experiences and Border Crossings in Southern Indiana
Authors: Carspecken Lucinda
Published: September 2015

In early visits to Lothlorien—which is a loosely Pagan community of environmentalists in Indiana—I was confounded by attempts to categorize either the place or the people. As one of the founders said, “I tend to run from labels so I don't know what I am. It's safer that way.” In this paper I explore four members’ narratives about the emotional high points in their lives, where they often cross the usual boundaries of self and other. At the same time the subjectivity at the core of these experiences is something that is felt and that cannot be dismissed as a discursive construct. Through these narratives I attempt to understand selfhood as a process—experientially inescapable but essentially in flux. I see a strong case for anthropologists moving beyond an overly neat, overly dichotomized view of “Western” and “non‐Western” senses of self.
Shareholder Primacy and Deontology
Authors: von Kriegstein Hasko
Published: September 2015

This article argues that shareholder primacy cannot be defended on the grounds that there is something special about the position of shareholders that grounds a right to preferential treatment on part of management. The notions of property and contract, traditionally thought to ground such a right, are now widely recognized as incapable of playing that role. This leaves shareholder theorists with two options. They can either abandon the project of arguing for their view on broadly deontological grounds and try to advance consequentialist arguments instead or they can search for other morally relevant properties that could ground shareholder rights. The most sustained argument in the latter vein is Marcoux's attempt to show that the vulnerability of shareholders mandates that managers are their fiduciaries. I show that this argument leads to the unacceptable conclusion that it would be unethical for corporations to make incomplete contracts with nonshareholding stakeholders.
Telomerase reverse transcriptase moonlights: Therapeutic targets beyond telomerase
Authors: Maida Yoshiko , Masutomi Kenkichi
Published: September 2015

Telomeres, the repetitive sequences at chromosomal ends, protect intact chromosomes. Telomeres progressively shorten through successive rounds of cell divisions, and critically shortened telomeres trigger senescence and apoptosis. The enzyme that elongates telomeres and maintains their structure is known as telomerase. The catalytic subunit of this enzyme (telomerase reverse transcriptase [TERT]) is expressed at a high level in malignant cells, but at a very low level in normal cells. Although telomerase activity was long believed to be the only function of TERT, emerging evidence indicates that TERT plays roles beyond telomeres. For example, TERT contributes to stem cell maintenance and cell reprogramming processes in a manner independent of its canonical function. Even some types of splice variants that lack the telomerase catalytic domains exhibit the functions in a manner that does not depend on telomerase activity. We recently demonstrated that the RNA‐dependent RNA polymerase (RdRP) activity of TERT is involved in regulation of gene silencing and heterochromatic transcription. Moreover, TERT RdRP activity is mediated by a newly identified complex, distinct from the authentic telomerase complex, that plays a role in cancer stem cells in a telomere maintenance independent manner. TERT has attracted interest as a molecular target for anticancer treatment, but previous efforts aimed at developing novel therapeutic strategies focused only on the canonical function of TERT. However, accumulating evidence about the non‐canonical functions of TERT led us to speculate that the functions other than telomerase might be therapeutic targets as well. In this review, we discuss the non‐canonical functions of TERT and their potential applications for anticancer treatment.
The Role of Mediators in the Development of Longitudinal Mathematics Achievement Associations
Authors: Watts Tyler W. , Duncan Greg J. , Chen Meichu , Claessens Amy , Davis‐Kean Pamela E. , Duckworth Kathryn , Engel Mimi , Siegler Robert , Susperreguy Maria I.
Published: September 2015

Despite research demonstrating a strong association between early and later mathematics achievement, few studies have investigated mediators of this association. Using longitudinal data (n = 1,362), this study tested the extent to which mathematics self‐concepts, school placement, executive functioning, and proficiency in fractions and division account for the association between mathematics achievement in first grade and at age 15. As hypothesized, a strong longitudinal association between first‐grade and adolescent mathematics achievement was present (β = .36) even after controlling for a host of background characteristics, including cognitive skills and reading ability. The mediators accounted for 39% of this association, with mathematics self‐concept, gifted and talented placement, and knowledge of fractions and division serving as significant mediators.
The Development of Early Profiles of Temperament: Characterization, Continuity, and Etiology
Authors: Beekman Charles , Neiderhiser Jenae M. , Buss Kristin A. , Loken Eric , Moore Ginger A. , Leve Leslie D. , Ganiban Jody M. , Shaw Daniel S. , Reiss David
Published: September 2015

This study used a data‐driven, person‐centered approach to examine the characterization, continuity, and etiology of child temperament from infancy to toddlerhood. Data from 561 families who participated in an ongoing prospective adoption study, the Early Growth and Development Study, were used to estimate latent profiles of temperament at 9, 18, and 27 months. Results indicated that four profiles of temperament best fit the data at all three points of assessment. The characterization of profiles was stable over time, while membership in profiles changed across age. Facets of adoptive parent and birth mother personality were predictive of children's profile membership at each age, providing preliminary evidence for specific environmental and genetic influences on patterns of temperament development from infancy to toddlerhood.
Effects of intermission and resumption of long‐term testosterone replacement therapy on body weight and metabolic parameters in hypogonadal in middle‐aged and elderly men
Authors: Yassin Aksam , Almehmadi Yousef , Saad Farid , Doros Gheorghe , Gooren Louis
Published: September 2015

Objective

In addition to primary and secondary (‘classical’) hypogonadism, hypogonadism occurring in middle‐aged and elderly men has been recognized. There is evidence that restoring T levels to normal improves body weight, serum lipids and glucose levels.

Design

Observational registry study.

Patients

Two hundred and sixty‐two hypogonadal, middle‐aged and elderly, men received testosterone replacement treatment (TRT). After having been on TRT for a mean duration of 65·5 months, TRT was temporarily intermitted in 147 patients for a mean of 16·9 months (Group I) due to cost reimbursement issues and in seven men due to prostate cancer. All these men resumed TRT for a mean period of 14·5 months. Of the cohort, 115 men were treated continuously (designated as Group C). To compare on‐treatment to off‐treatment periods, three periods of equal duration were defined: pre‐intermission (on TRT), during intermission (off TRT) and post‐intermission (on TRT after resumption of TRT). For proper comparison, the same periods were analysed for those patients who continued TRT throughout (Group C).

Measurements

Variables of body weight, glucose metabolism, lipids, blood pressure and C‐reactive protein (CRP).

Results

In Group C there was a continuous improvement of body weight, serum lipids, glucose, HbA1c, blood pressure and CRP. In Group I there was a similar initial improvement which was reversed upon intermission of T administration but which appeared again when T treatment was reinstated.

Conclusions

Our observation indicates that T administration improves body weight and metabolic factors in men with hypogonadism but withdrawal of T reverses these beneficial effects to appear again when TRT is resumed.
Do As I Say and Not As I Think: Parent Socialisation of Lie‐Telling Behaviour
Authors: Lavoie Jennifer , Leduc Karissa , Crossman Angela M. , Talwar Victoria
Published: September 2015

This study explored parent (N = 146) perspectives about situations in which they think it is acceptable to lie, how this corresponds to how they socialise their children about lie‐telling and their children's actual behaviour. Results indicated the methods parents report using to teach their children about the acceptability of lie‐telling are consistent with what they report teaching their children about lie‐telling overall. Also, the frequency of lies that children told (N = 88) to protect themselves from psychological distress or conflict differed between those who were taught that lying is sometimes acceptable versus those taught it is never acceptable.
Elderly patients have more infectious complications following laparoscopic colorectal cancer surgery
Authors: Kvasnovsky C. L. , Adams K. , Sideris M. , Laycock J. , Haji A. K. , Haq A. , Nunoo‐Mensah J. , Papagrigoriadis S.
Published: September 2015

Aim

Elderly patients may be at higher risk of postoperative complications, particularly infective, than younger patients.

Method

We prospectively followed 163 consecutive patients undergoing elective laparoscopic resection for cancer. We compared patients < 65, 65–80 and > 80 years of age at the time of surgery.

Results

Seventy (42.9%) patients had no complication; 93 (57.1%) had at least one complication following surgery and in 20 (12.3%) this was major. There was no difference in major complications between the groups (P = 0.47). Patients over 65 years of age were more likely to have a complication of any severity [< 65 years, 39.3%; 65–80 years, 69.3%; and > 80 years, 63.0% (P = 0.002)]. The frequency of gastrointestinal complications (30.1%) was similar in the groups (P = 0.29), as was wound infection (25.2%) (P = 0.65). There was an increase in the frequency of infectious complications, especially chest infection, with age, from 14.8% in patients < 65 years, to 22.7% in patients 65–80 years, to 44.4% in patients > 80 years (P = 0.01). Multivariate analysis showed no increase in overall complications in elderly patients, but Stage II or Stage III cancer (OR = 2.59, P = 0.04) and increasing body mass index (BMI) (OR = 1.07 for each unit increase in BMI, P = 0.04) were related to complications. Age remained the only predictor of an infective complication on multivariate analysis. Patients > 80 years of age had 4.21 times the OR of an infective complication (P = 0.03).

Conclusion

Older patients are more susceptible to infective complications postoperatively, particularly chest complications. Surgeons should alter their practice to reduce morbidity, such as adopting protocols requiring early physiotherapy.
EFFECTS OF THE SUNDAY SHOPPING RESTRICTION IN KOREA
Authors: Choi Yun Jeong , Jeong Jinook
Published: September 2015

We examine the effectiveness of Korea's Sunday superstore shopping regulation, whose purpose is to protect small‐ and medium‐sized retailers as well as traditional markets. Applying a two‐way random‐effects regression model to the daily sales data of four megastores and four super supermarkets, we find the net sales decrease of superstores is on average 5.61% of daily sales after taking into account sales increases due to consumers' switching to weekdays. Only about 17%–19% of the reduced superstore sales are transferred to traditional markets. Based on these estimates, the compensating variation per year is predicted to be 2.4–2.5 trillion Korean won (around US $2.1–2.2 billion). (JEL L51, L88)
Overhearers Use Addressee Backchannels in Dialog Comprehension
Authors: Tolins Jackson , Fox Tree Jean E.
Published: September 2015

Observing others in conversation is a common format for comprehending language, yet little work has been done to understand dialog comprehension. We tested whether overhearers use addressee backchannels as predictive cues for how to integrate information across speaker turns during comprehension of spontaneously produced collaborative narration. In Experiment 1, words that followed specific backchannels (e.g.,really,oh) were recognized more slowly than words that followed either generic backchannels (e.g.,uh huh,mhm) or pauses. In Experiment 2, we found that when the turn after the backchannel was a continuation of the narrative, specific backchannels prompted the fastest verification of prior information. When the turn after was an elaboration, they prompted the slowest, indicating that overhearers took specific backchannels as cues to integrate preceding talk with subsequent talk. These findings demonstrate that overhearers capitalize on the predictive relationship between backchannels and the development of speakers’ talk, coordinating information across conversational roles.
Alcohol use–sickness absence association and the moderating role of gender and socioeconomic status: A literature review
Authors: Schou Line , Moan Inger Synnøve
Published: September 2015

Issues

How strong is the available empirical evidence for an association between alcohol use and sickness absence? Does type of measures influence the association, and is the association moderated by gender and socioeconomic status?

Approach

We designed a search strategy to find all studies on the alcohol use–sickness absence association using individual‐level data, published in peer‐reviewed journals from 1980 onwards. The quality of the associations was evaluated, giving a score of 0–4 points.

Key Findings

Our inclusion criteria were met by 27 papers containing 28 separate studies, testing 48 associations. There is empirical evidence for an association between alcohol use and both long‐ and short‐term absence. High‐quality associations were statistically significant in 100% of the cases. Among low–medium‐quality associations, alcohol was less consistently related to long‐term than to short‐term absence (significant in 25% and 100% of the cases, respectively). Second, the association did not vary systematically across measures of alcohol use. Third, the association applies to both genders and in all socioeconomic strata, but in some instances more strongly in lower socioeconomic strata.

Implications

Preventive strategies have to be targeted at all drinking employees, but more research into group differences for example across gender, socioeconomics, occupations and age, could prove valuable. More longitudinal studies are needed to explore causal mechanisms.

Conclusion

The alcohol use–sickness absence association is well founded in research. The association may be moderated by gender and socioeconomics, but more research is needed to draw firm conclusions on this issue. [Schou L, Moan IS. The alcohol use: Sickness absence association and the moderating role of gender and socioeconomic status: A literature review. Drug Alcohol Rev 2016;35:158–69]
Symptomatic treatment of children with anti‐NMDAR encephalitis
Authors: Mohammad Shekeeb S , Jones Hannah , Hong Martin , Nosadini Margherita , Sharpe Cynthia , Pillai Sekhar C , Brilot Fabienne , Dale Russell C
Published: September 2015

Aim

We performed the first study on the perceived benefit and adverse effects of symptomatic management in children with anti‐N‐methyl‐d‐aspartate receptor (NMDAR) encephalitis.

Method

A retrospective chart review was undertaken at two tertiary paediatric hospitals in Australia and New Zealand. We included 27 children (12 males, 15 females; mean age at admission 7y 1mo) with anti‐NMDAR antibodies in serum or cerebrospinal fluid with a typical clinical syndrome.

Results

Only two out of 27 patients were white, whereas 16 out of 27 patients were from the Pacific Islands/New Zealand Maori. The mean duration of admission was 69 days (10–224d) and 48% of patients (13/27) needed treatment in an intensive care setting. A mean of eight medications per patient was used for symptomatic management. Symptoms treated were agitation (n=25), seizures (n=24), movement disorders (n=23), sleep disruption (n=17), psychiatric symptoms (n=10), and dysautonomia (n=four). The medications used included five different benzodiazepines (n=25), seven anticonvulsants (n=25), eight sedatives and sleep medications (n=23), five antipsychotics (n=12), and five medications for movement disorders (n=10). Sedative and sleep medications other than benzodiazepines were the most effective, with a mean benefit of 67.4% per medication and a mean adverse effect‐benefit ratio of 0.04 per medication. Antipsychotic drugs were used for a short duration (median 9d), and had the poorest mean benefit per medication of 35.4% and an adverse effect‐benefit ratio of 2.0 per medication.

Interpretation

Long‐acting benzodiazepines, anticonvulsants, and clonidine can treat multiple symptoms. Patients with anti‐NMDAR encephalitis appear vulnerable to antipsychotic‐related adverse effects. Pacific Islanders appear to have a vulnerability to anti‐NMDAR encephalitis in our region.
Declining prevalence of cerebral palsy in Europe: good news?
Authors: Smithers‐Sheedy Hayley
Published: September 2015

This commentary is on the original article by Sellier et al. on pages 85–92 of this issue.
Less is sometimes less: the effectiveness of Mellow Parenting is uncertain
Authors: Schuengel Carlo
Published: September 2015

This commentary is on the systematic review by MacBeth et al. on
pages 1119–1128 of this issue.
Shift in responsibilities in diabetes care: the Nurse‐Driven Diabetes In‐Hospital Treatment protocol (N‐DIABIT)
Authors: Manders I. G. , Stoecklein K. , Lubach C. H. C. , Bijl‐Oeldrich J. , Nanayakkara P. W. B. , Rauwerda J. A. , Kramer M. H. H. , Eekhoff E. M. W.
Published: September 2015

Aims

To investigate the feasibility, safety and efficacy of the Nurse‐Driven Diabetes In‐Hospital Treatment protocol (N‐DIABIT), which consists of nurse‐driven correctional therapy, in addition to physician‐guided basal therapy, and is carried out by trained ward nurses.

Methods

Data on 210 patients with diabetes consecutively admitted in the 5‐month period after the introduction of N‐DIABIT (intervention group) were compared with the retrospectively collected data on 200 consecutive patients with diabetes admitted in the 5‐month period before N‐DIABIT was introduced (control group). Additional per‐protocol analyses were performed in patients in whom mean patient‐based protocol adherence was ≥ 70% (intervention subgroup, n = 173 vs. control subgroup, n = 196).

Results

There was no difference between the intervention and the control group in mean blood glucose levels (8.9 ± 0.1 and 9.1 ± 0.2 mmol/l, respectively; P = 0.38), consecutive hyperglycaemic (blood glucose ≥ 10.0 mmol/l) episodes; P = 0.15), admission duration (P = 0.79), mean number of blood glucose measurements (P = 0.21) and incidence of severe hypoglycaemia (P = 0.29). Per‐protocol analyses showed significant reductions in mean blood glucose levels and consecutive hypoglycaemia and hyperglycaemia in the intervention compared with the control group.

Conclusions

Implementation of N‐DIABIT by trained ward nurses in non‐intensive care unit diabetes care is feasible, safe and non‐inferior to physician‐driven care alone. High protocol adherence was associated with improved glycaemic control.
Rev‐erbα and the circadian transcriptional regulation of metabolism
Authors: Gerhart‐Hines Z. , Lazar M. A.
Published: September 2015

The circadian clock orchestrates the co‐ordinated rhythmicity of numerous metabolic pathways to anticipate daily and seasonal changes in energy demand. This vital physiological function is controlled by a set of individual clock components that are present in each cell of the body, and regulate each other as well as clock output genes. A key factor is the nuclear receptor, Rev‐erbα, a transcriptional repressor which functions not only as a clock component but also as a modulator of metabolic programming in an array of tissues. This review explores the role of Rev‐erbα in mediating this crosstalk between circadian rhythm and tissue‐specific biological networks and its relevance to organismal physiology.
Plasticity of circadian clocks and consequences for metabolism
Authors: Coomans C. P. , Lucassen E. A. , Kooijman S. , Fifel K. , Deboer T. , Rensen P. C. N. , Michel S. , Meijer J. H.
Published: September 2015

The increased prevalence of metabolic disorders and obesity in modern society, together with the widespread use of artificial light at night, have led researchers to investigate whether altered patterns of light exposure contribute to metabolic disorders. This article discusses the experimental evidence that perturbed environmental cycles induce rhythm disorders in the circadian system, thus leading to metabolic disorders. This notion is generally supported by animal studies. Distorted environmental cycles, including continuous exposure to light, affect the neuronal organization of the central circadian pacemaker in the suprachiasmatic nucleus (SCN), its waveform and amplitude of the rhythm in electrical activity. Moreover, repeated exposure to a shifted light cycle or the application of dim light at night are environmental cues that cause a change in SCN function. The effects on the SCN waveform are the result of changes in synchronization among the SCN's neuronal cell population, which lead consistently to metabolic disturbances. Furthermore, we discuss the effects of sleep deprivation and the time of feeding on metabolism, as these factors are associated with exposure to disturbed environmental cycles. Finally, we suggest that these experimental studies reveal a causal relationship between the rhythm disorders and the metabolic disorders observed in epidemiological studies performed in humans.
Keeping circadian time with hormones
Authors: Challet E.
Published: September 2015

Daily variations of metabolism, physiology and behaviour are controlled by a network of coupled circadian clocks, comprising a master clock in the suprachiasmatic nuclei of the hypothalamus and a multitude of secondary clocks in the brain and peripheral organs. Light cues synchronize the master clock that conveys temporal cues to other body clocks via neuronal and hormonal signals. Feeding at unusual times can reset the phase of most peripheral clocks. While the neuroendocrine aspect of circadian regulation has been underappreciated, this review aims at showing that the role of hormonal rhythms as internal time‐givers is the rule rather than the exception. Adrenal glucocorticoids, pineal melatonin and adipocyte‐derived leptin participate in internal synchronization (coupling) within the multi‐oscillatory network. Furthermore, pancreatic insulin is involved in food synchronization of peripheral clocks, while stomach ghrelin provides temporal signals modulating behavioural anticipation of mealtime. Circadian desynchronization induced by shift work or chronic jet lag has harmful effects on metabolic regulation, thus favouring diabetes and obesity. Circadian deregulation of hormonal rhythms may participate in internal desynchronization and associated increase in metabolic risks. Conversely, adequate timing of endocrine therapies can promote phase‐adjustment of the master clock (e.g. via melatonin agonists) and peripheral clocks (e.g. via glucocorticoid agonists).
Skeletal muscle functions around the clock
Authors: Mayeuf‐Louchart A. , Staels B. , Duez H.
Published: September 2015

In mammals, the central clock localized in the central nervous system imposes a circadian rhythmicity to all organs. This is achieved thanks to a well‐conserved molecular clockwork, involving interactions between several transcription factors, whose pace is conveyed to peripheral tissues through neuronal and humoral signals. The molecular clock plays a key role in the control of numerous physiological processes and takes part in the regulation of metabolism and energy balance. Skeletal muscle is one of the peripheral organs whose function is under the control of the molecular clock. However, although skeletal muscle metabolism and performances display circadian rhythmicity, the role of the molecular clock in the skeletal muscle has remained unappreciated for years. Peripheral organs such as skeletal muscle, and the liver, among others, can be desynchronized from the central clock by external stimuli, such as feeding or exercise, which impose a new rhythm at the organism level. In this review, we discuss our current understanding of the clock in skeletal muscle circadian physiology, focusing on the control of myogenesis and skeletal muscle metabolism.
Transcriptional control of circadian metabolic rhythms in the liver
Authors: Li S. , Lin J. D.
Published: September 2015

Diurnal metabolic rhythms add an important temporal dimension to metabolic homeostasis in mammals. Although it remains a challenge to untangle the intricate networks of crosstalk among the body clock, nutrient signalling and tissue metabolism, there is little doubt that the rhythmic nature of nutrient and energy metabolism is a central aspect of metabolic physiology. Disruption of the synchrony between clock and metabolism has been causally linked to diverse pathophysiological states. As such, restoring the rhythmicity of body physiology and therapeutic targeting directed at specific time windows during the day may have important implications in human health and medicine. In this review, we summarize recent findings on the integration of hepatic glucose metabolism and the body clock through a regulatory network centred on the PPARγ coactivator 1 (PGC‐1) transcriptional coactivators. In addition, we discuss the transcriptional mechanisms underlying circadian control of the autophagy gene programme and autophagy in the liver.
The islet circadian clock: entrainment mechanisms, function and role in glucose homeostasis
Authors: Rakshit K. , Qian J. , Colwell C. S. , Matveyenko A. V.
Published: September 2015

Circadian regulation of glucose homeostasis and insulin secretion has long been appreciated as an important feature of metabolic control in humans. Circadian disruption is becoming increasingly prevalent in today's society and is likely responsible in part for the considerable rise in type 2 diabetes (T2DM) and metabolic syndrome worldwide. Thus, understanding molecular mechanisms driving the inter‐relationship between circadian disruption and T2DM is important in context of disease prevention and therapeutics. In this regard, the goal of this article is to highlight the role of the circadian system, and islet circadian clocks in particular, as potential regulators of β‐cell function and survival. To date, studies have shown that islet clocks respond to changes in feeding patterns, and regulate a multitude of critical cellular processes in insulin secreting β‐cells (e.g. insulin exocytosis, mitochondrial function and response to oxidative stress). Subsequently, either genetic or environmental disruption of normal islet clock performance compromises β‐cell function and leads to loss of glycaemic control. Future work is warranted to further unravel the role of circadian clocks in human islet function in health and contributions to pathogenesis of T2DM.
Mind the gap: Multiple events and lengthy delays before presentation with a “first seizure”
Authors: Firkin Anna L. , Marco David J. T. , Saya Sibel , Newton Mark R. , O'Brien Terence J. , Berkovic Samuel F. , McIntosh Anne M.
Published: September 2015

Objective

Up to half of patients assessed for suspected new‐onset epileptic seizures report previous undiagnosed events. This suggests that delay to timely and expert assessment is a major issue. Very little is known about the degree of delay or nature of the undiagnosed events, impacting on our understanding of new‐onset epilepsy. In this study we aimed to examine events that occur before presentation, as well as the extent and risk factors for delay to assessment.

Method

Included in this retrospective study were 220 patients diagnosed at the First Seizure Clinic (Austin Health, Australia) between 2003 and 2006 with an epileptic index seizure. Patients with a prior diagnosis of epileptic seizures were excluded. Chart review was undertaken, including detailed interviews conducted by an epileptologist at first assessment. Logistic regression assessed risk factors for delay from first event to presentation, including event characteristics, socioeconomic disadvantage, employment, and distance to medical facility.

Results

Forty‐one percent (n = 90) of patients had one or more event before their index seizure. Of these, 50% had multiple or more than five prior events and 28% experienced one or more convulsive event before the index seizure. Of the total 220 patients, 36% had delayed presentation >4 weeks, 21% delayed >6 months, and 14% delayed >2 years. First events without convulsions or features likely to disrupt behaviour were strongly associated with delay (p = <0.001). Relative socioeconomic disadvantage was also associated with delay to presentation (p = 0.04).

Significance

Our findings suggest a gap in early diagnosis and care in a sizable proportion of new‐onset cases, despite a “first world” urban environment and the availability of free basic medical care. Delay appears particularly likely when events are nonconvulsive or low‐impact, suggesting that these seizure types may be underrepresented in studies of new‐onset epilepsy. This has implications for our understanding of the incidence, evolution, impact, and treatment response of new‐onset epilepsy.
The Effectiveness of Couple and Individual Relationship Education: Distress as a Moderator
Authors: Carlson Ryan G. , Rappleyea Damon L. , Daire Andrew P. , Harris Steven M. , Liu Xiaofeng
Published: September 2015

Current literature yields mixed results about the effectiveness of relationship education (RE) with low‐income participants and those who experience a high level of individual or relational distress. Scholars have called for research that examines whether initial levels of distress act as a moderator of RE outcomes. To test whether initial levels of relationship and/or individual distress moderate the effectiveness of RE, this study used two samples, one of couples who received couple‐oriented relationship education with their partner (n = 192 couples) and one of individuals in a relationship who received individual‐oriented RE by themselves (n = 60 individuals). We delivered RE in a community‐based setting serving primarily low‐income participants. For those attending with a partner, there was a significant interaction between gender, initial distress, and time. Findings indicate that women who were relationally distressed before RE reported the largest pre‐postgains. Those who attended an individual‐oriented RE program reported significant decreases in individual distress from pre to post, but no significant relationship gains. Findings also suggest that initial levels of distress did not moderate the effectiveness of individual‐oriented RE.
Conventional treatment, Hall Technique or immediate pulpotomy for carious primary molars: a cost‐effectiveness analysis
Authors: Schwendicke F. , Stolpe M. , Innes N.
Published: September 2015

Aim

To compare the cost‐effectiveness of three strategies for treating primary molars with cavitated carious lesions and sensible (vital), asymptomatic pulps.

Methodology

Conventional excavation and restoration, Hall Technique (caries sealing using a preformed crown), and pulpotomy were compared. As the latter would not be applied to all teeth in clinical reality, decision‐making under perfect information was modelled, with teeth at‐risk for pulpal complications receiving immediate pulpotomy, whilst all others were treated conventionally. A Markov model was constructed and transition probabilities derived from randomized trials and systematic reviews. A carious molar in a 5‐year‐old child was followed until exfoliation. Cost‐effectiveness was assessed within the German healthcare system using a public‐payer perspective. Monte Carlo microsimulations were performed to evaluate the primary outcome, costs (in Euros) per year of tooth retention.

Results

Conventional treatment was least effective and more expensive than the Hall Technique. Risk‐based pulpotomy was more costly, but also more effective than alternatives. Overall, the Hall Technique was most cost‐effective (9.77 Euros year−1), followed by pulpotomy (11.75 Euros year−1) and conventional treatment (13.31 Euros year−1). For payers willing to invest >59 Euros per additional year of tooth retention, risk‐based pulpotomy was most cost‐effective. Providing pulpotomy to all teeth was not cost‐effective.

Conclusions

The Hall Technique was most cost‐effective, whilst conventional treatment was least effective and more costly. Performing pulpotomy for molars at‐risk of pulpal complications might be effective, but was more expensive than alternatives. Moreover, accurately predicting such pulpal complications is currently not possible. Risk‐based decision‐making does not necessarily reduce costs.
Developing a nurse‐led urodynamics clinic
Authors: Townsend Jacinta
Published: September 2015

Nurse‐led clinics in primary and secondary care settings have been widely acclaimed as a positive step towards improving access to investigation and specialist advice, and offering a solution towards limited clinician resource. Many nurse‐led clinics have been traditionally heavily protocoled, but with the evolution of advanced senior nursing roles corresponding role expansion within the multidisciplinary team has occurred. The development of procedural nurse‐led clinics such as urodynamics is not well published. The interpretation and application of published clinical guidelines into practice can present challenges, particularly if consensus has not been found. The proposal of a new clinic requires a vision and commitment from stakeholders to develop and support the implementation of nurse‐led clinics, which have traditionally sat within the realm of medicine. The decision was made to develop this clinic, so a tailored training package that included formal theoretical training, clinical mentorship and supervision and reflective practice was devised. This approach has been documented as central to good urodynamic practice and is based upon published recommended best practice. The successful implementation has provided our patient population faster access to urodynamics procedures, reducing time to treatment based upon the findings and has freed up over 50 appointment slots per annum, for Urologists to see other patients. With a robust training package and clinical support nurse‐led clinics can have a positive impact not only upon health care delivery but also provide the opportunity for professional development and increased job satisfaction.
Physical activity attitudes and preferences among inpatient adults with mental illness
Authors: Fraser Sarah J. , Chapman Justin J. , Brown Wendy J. , Whiteford Harvey A. , Burton Nicola W.
Published: September 2015

The life expectancy of adults with mental illness is worse than that of the general population and is largely due to poor physical health status. Physical activity has been consistently recommended for the prevention and management of many chronic physical health conditions and can also have benefits for mental health. This cross sectional study assessed the attitudes towards and preferences for physical activity among inpatient adults with mental illness, and differences by distress and gender. Self‐report questionnaires were completed by 101 patients. Findings indicated that inpatient adults with mental illness are interested in doing physical activity while in hospital, primarily to maintain good physical health and improve emotional wellbeing. Fewer than half of participants agreed that physical activity has benefits for serious mental illness. Participants indicated a preference for walking and physical activity that can be done alone, at a fixed time and with a set routine and format. Major barriers were fatigue and lack of motivation. Females were more likely than males to prefer activities done with others of the same gender (P = 0.001) and at the same level of ability (P < 0.001). There were no significant differences by level of distress. These findings can inform physical activity intervention programming in hospital settings, which may contribute to decreasing the chronic disease burden and improve the psychological wellbeing in adults with mental illness.
Erasing Drug Memories Through the Disruption of Memory Reconsolidation: A Review of Glutamatergic Mechanisms
Authors: Dennis Torry S. , Perrotti Linda I.
Published: September 2015

Over the past decade, a growing body of research has sought to investigate how the pharmacological disruption of memory reconsolidation can degrade or erase memories. Much of this research has focused specifically on disrupting memories that are considered bad or maladaptive for the ultimate purpose of translation to a human population. While most of the research was pioneered in fear memory, recent studies have focused on degrading drug‐cued memories in the context of addiction. Essentially, this research seeks to disrupt cues as predictors of reward or drug availability. A core component of this reconsolidation process is glutamate signaling. An overall review of the literature suggests that disruption of glutamate signaling under reconsolidation parameters is sufficient to erase drug‐related memories. This review will focus on specific studies that examine the glutamatergic mechanisms of reconsolidation disruption in the context of drug addiction.
Nonvacuum Solution Synthesis of (Ag,Cu)(In,Ga)Se2 Absorbers for Applications in Thin‐Film Solar Cells
Authors: Wu Jyun‐Jie , Yang Che‐Yuan , Sung Jen‐Cheng , Lu Chung‐Hsin
Published: September 2015

The effects of selenization temperatures on the phase formation and the photovoltaic properties of silver‐ion‐doped Cu(In,Ga)Se2 (ACIGS) films were investigated. Cu2−xSe phase coexisted with CuInSe2 phase in the films as the selenization temperature was relatively low. Increasing the selenization temperatures promoted the formation of the chalcopyrite phase and increased the grain size. Upon increasing the selenization temperature to 600°C, single‐phased ACIGS films with a grain size of 2.1–2.2 μm were successfully synthesized. The incorporation of Ag+ and Ga3+ ions into CuInSe2 during the phase formation of ACIGS elevated the band gaps of the films, thereby improving the open‐circuit voltage (Voc) of the solar cells. The grain growth on raising the selenization temperatures also elevated the short‐circuit current (Jsc) values owing to the suppression of the electron‐hole recombination at grain boundaries. In the diode analysis, the facilitated phase formation suppressed the shunt path, decreasing the values of the diode factor (A), shunt conductance (G), and saturated current (Jo), thereby improving the cell performance. In this study, ACIGS solar cells with an efficiency of 7.21% prepared via the nonvacuum process were first demonstrated.
Gaining consensus on family carer needs when caring for someone dying at home to develop the Carers' Alert Thermometer (CAT): a modified Delphi study
Authors: Knighting Katherine , O'Brien Mary R. , Roe Brenda , Gandy Rob , Lloyd‐Williams Mari , Nolan Mike , Jack Barbara A.
Published: September 2015

Aim

To report a multi‐phase modified Delphi study conducted with carers and professionals to identify the priority areas for inclusion in an alert screening tool for carers providing support to someone dying at home.

Background

Internationally, there is a growing emphasis on increasing choice for patients who wish to die at home which relies heavily on care provided by the unpaid family carers. Family carers can have high levels of unmet needs comprising their psychological and physical health and their ability to provide effective care and support. Development of an alert tool to identify carers' needs in everyday practice required identification and consensus of the priority areas of need for inclusion.

Design

Multi‐phase modified Delphi study and instrument development.

Method

Qualitative and quantitative data collection took place between 2011–2013 with 111 carers and 93 professionals to identify carers' needs and gain consensus on the priority areas for inclusion in the alert tool. An expert panel stage and final evidence review post‐Delphi were used.

Results

The Delphi panels had high levels of agreement and consensus. Ten areas of carer need across two themes of ‘the current caring situation’ and ‘the carer's own health and well‐being’ were prioritized for inclusion in the alert tool. An optional end‐of‐life planning question was included following the final stages.

Conclusions

The results provide evidence of carers' needs to be assessed, areas for consideration in the education of those who support carers and someone dying at home and targeting of services, while demonstrating the usefulness and adaptability of the Delphi method.
The Conundrum of Training and Capacity Building for People with Learning Disabilities Doing Research
Authors: Nind Melanie , Chapman Rohhss , Seale Jane , Tilley Liz
Published: September 2015

Background

This study explores the training involved when people with learning disabilities take their place in the community as researchers. This was a theme in a recent UK seminar series where a network of researchers explored pushing the boundaries of participatory research.

Method

Academics, researchers with learning disabilities, supporters and other inclusive researchers considered important themes arising from presentations about developments in participatory research. The paper emerges from critical reflection on these rich discussions.

Results

A seminar series is a form of research training and capacity building, albeit a dynamic, interactive and collegial one. More formal training in research skills for people with learning disabilities is being developed but raises questions regarding the best contribution people with learning disabilities can make to the research process.

Conclusion

There are various models of training for inclusive research, but these need to be reciprocal if they are not to undermine the inclusive goal.
Savanna ant species richness is maintained along a bioclimatic gradient of increasing latitude and decreasing rainfall in northern Australia
Authors: Andersen Alan N. , Del Toro Israel , Parr Catherine L.
Published: September 2015

Aim

Using a standardized sampling protocol along a 600‐km transect in northern Australia, we tested whether ant diversity within a single biome, tropical savanna, decreases with increasing latitude (as a surrogate of temperature) and decreasing rainfall, as is expected for biodiversity in general.

Location

Northern Australia.

Methods

Ants were sampled using pitfall traps on three occasions at 1‐ha sand, loam and clay sites at each of five locations along the Northern Australian Tropical Transect (NATT), from 12°50′ S (1400 mm mean annual rainfall) to 17°21′ S (650 mm).

Results

We recorded a total of 246 species from 37 genera. Mean observed species richness pooled across sampling periods was similar at sand (85.4) and loam (82.2) sites, but was less than half this at clay sites (40.0). Ant communities were also compositionally distinct on clay soils compared with sands and loams. Individual genera showed variable diversity patterns, ranging from a linear increase to a linear decrease in species richness along the NATT. However, total species richness was relatively uniform along the gradient. Patterns of ant species turnover were consistent with previously recognized biogeographical boundaries, with a primary disjunction between the arid and monsoonal zones in the south, and a secondary disjunction between the semi‐arid and mesic zones in the north.

Main conclusions

Patterns of ant diversity in Australian savannas do not conform to global patterns of biodiversity declines with increasing latitude and decreasing rainfall. We believe this is due to a lack of significant temperature change across the latitudinal gradient, and, in particular, to the fauna's evolutionary history in association with aridification, which makes it unusually resilient to increasing aridity. The diversity of other important faunal groups such as termites and lizards is also exceptionally high in arid Australia and is likewise not closely linked to rainfall in Australian savannas. We predict that these taxa are far more sensitive to increasing aridity in savannas elsewhere in the world, and especially in the Neotropics, where savannas have an evolutionary association with humid rain forest rather than desert.