The lepidopteran mitochondrial control region: structure and evolution

For several species of lepidoptera, most of the approximately 350-bp mitochondrial control-region sequences were determined. Six of these species are in one genus, Jalmenus; are closely related; and are believed to have undergone recent rapid speciation. Recent speciation was supported by the observation of low interspecific sequence divergence. Thus, no useful phylogeny could be constructed for the genus. Despite a surprising conservation of control-region length, there was little conservation of primary sequences either among the three lepidopteran genera or between lepidoptera and Drosophila. Analysis of secondary structure indicated only one possible feature in common--inferred stem loops with higher-than-random folding energies-- although the positions of the structures in different species were unrelated to regions of primary sequence similarity. We suggest that the conserved, short length of control regions is related to the observed lack of heteroplasmy in lepidopteran mitochondrial genomes. In addition, determination of flanking sequences for one Jalmenus species indicated (i) only weak support for the available model of insect 12S rRNA structure and (ii) that tRNA translocation is a frequent event in the evolution of insect mitochondrial genomes.      

Subclinical Thyroid Dysfunction and Cognitive Decline in Old Age

Background

Subclinical thyroid dysfunction has been implicated as a risk factor for cognitive decline in old age, but results are inconsistent. We investigated the association between subclinical thyroid dysfunction and cognitive decline in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER).

Methods

Prospective longitudinal study of men and women aged 70–82 years with pre-existing vascular disease or more than one risk factor to develop this condition (N = 5,154). Participants taking antithyroid medications, thyroid hormone supplementation and/or amiodarone were excluded. Thyroid function was measured at baseline: subclinical hyper- and hypothyroidism were defined as thyroid stimulating hormones (TSH) <0.45 mU/L or >4.50 mU/L respectively, with normal levels of free thyroxine (FT4). Cognitive performance was tested at baseline and at four subsequent time points during a mean follow-up of 3 years, using five neuropsychological performance tests.

Results

Subclinical hyperthyroidism and hypothyroidism were found in 65 and 161 participants, respectively. We found no consistent association of subclinical hyper- or hypothyroidism with altered cognitive performance compared to euthyroid participants on the individual cognitive tests. Similarly, there was no association with rate of cognitive decline during follow-up.

Conclusion

We found no consistent evidence that subclinical hyper- or hypothyroidism contribute to cognitive impairment or decline in old age. Although our data are not in support of treatment of subclinical thyroid dysfunction to prevent cognitive dysfunction in later life, only large randomized controlled trials can provide definitive evidence.     

Onderwijs in het Nationaal Programma Ouderenzorg

The Netherlands Organisation of Health Research and Development started in 2008 the Dutch National Care for the Elderly Programme (in Dutch abbreviated as NPO) with the aim to improve the quality of life for the frail older people through better quality of care (health, social, community) which is tailored to the needs and wants of older people. The delivery of good care is related with competent professional behaviour which is inextricably linked to the education of professionals. This article presents an overview of 32 educational programmes developed within the NPO. Within the NPO different educational programmes were developed on relevant themes to improve elderly care. However, the programmes focused mainly on professionals in health care, especially those working in primary care. For nurses and nursing assistants and more or less for physicians also different educational programmes were developed. Educational programmes for paramedics or professionals working in social care, housing or in the municipalities were scarce. This is also the case for specific themes in elderly care like loneliness or (domestic) violence. Moreover, none of the experiments focused on older people or informal care givers. Although 22 of the 32 projects developed educational programmes for different groups, multi – or interdisciplinary education is rare in these programmes. Based on the overview we advise the development of more educational programmes on: target groups which were less or not addressed in the NPO, like professionals in social care and paramedics; multi- or interdisciplinary collaboration; and themes, like loneliness in older people and elder abuse.     

Omgaan met somberheid op oudere leeftijd: een kwalitatieve studie

Background

To gain new insights for support for older people with low mood, we explored the perceptions of ‘screenpositive’ older people on underlying causes and possible solutions.

Design and method

We conducted two in-depth interviews with 38 participants (≥77 years) who screened positive for depressive symptoms in general practice. To investigate the influence of the presence of complex health problems, we included 19 persons with and 19 without complex problems. Complex problems were defined as a combination of functional, somatic, psychological or social problems.

Results

All participants used several cognitive, social or practical coping strategies. Four patterns emerged: mastery, acceptance, ambivalence, and need for support. Some participants, especially those with complex problems, were ambivalent about possible interventions.

Conclusion

Most older participants perceived their coping strategies as sufficient. General practitioners can support self-management by exploring the (effectiveness of) personal coping strategies, providing information, elaborating on perceptions of risks and discussing alternative options with older persons.

     

Consequences of Interaction of Functional,Somatic, Mental and Social Problems in Community-Dwelling Older People

This study explores the combination of four common health problems in older people and whether problems on four domains result in an additional effect on indicators of poor health. For this purpose, a total of 2681 participants (32% male, mean age 82 years) of the Integrated Systematic Care for Older People (ISCOPE) study were screened on the presence of health problems on four domains (functional, somatic, mental, social) with the postal ISCOPE questionnaire. Extensive interview data on health indicators were obtained at baseline and at 12-months follow-up, including disability (Groningen Activities Restriction Scale, GARS), cognitive function (Mini-Mental State Examination, MMSE), depressive symptoms (Geriatric Depression Scale-15, GDS), loneliness (loneliness scale of De Jong Gierveld), and health-related quality of life (EQ-5D). General practitioner (GP) contact time (min/year) was estimated via GP electronic medical records. Of the study population, 9% had no health problems according to the screening, 8% had problems on one domain, 27% on two, 38% on three and 18% on four domains. At baseline, the number of health domains with problems was associated with poorer scores on the GARS, the MMSE, the GDS-15, the loneliness scale, the EQ-5D and with more GP contact time (p <0.001). Problems on all four domains had an additional negative effect on these health indicators (all p_interaction <0.001). At follow-up, an increased number of domains with problems was associated with an increased decline in health indicators (all p<0.001) and with an additional negative effect on GP contact time of the presence of problems on all four domains (p_interaction <0.001). We conclude that combinations of functional, somatic, mental and social problems are associated with poor health indicators in community-dwelling older people. Since problems on four domains have an additional effect on health, individuals with combined functional, somatic, mental and social problems could benefit from integrated care.

Trial registration

Netherlands Trial Register: NTR1946.     

Cryotherapy with liquid nitrogen versus topical salicylic acid application for cutaneous warts in primary care: randomized controlled trial

Background

Cryotherapy is widely used for the treatment of cutaneous warts in primary care. However, evidence favours salicylic acid application. We compared the effectiveness of these treatments as well as a wait-and-see approach.

Methods

Consecutive patients with new cutaneous warts were recruited in 30 primary care practices in the Netherlands between May 1, 2006, and Jan. 26, 2007. We randomly allocated eligible patients to one of three groups: cryotherapy with liquid nitrogen every two weeks, self-application of salicylic acid daily or a wait-and-see approach. The primary outcome was the proportion of participants whose warts were all cured at 13 weeks. Analysis was on an intention-to-treat basis. Secondary outcomes included treatment adherence, side effects and treatment satisfaction. Research nurses assessed outcomes during home visits at 4, 13 and 26 weeks.

Results

Of the 250 participants (age 4 to 79 years), 240 were included in the analysis at 13 weeks (loss to follow-up 4%). Cure rates were 39% (95% confidence interval [CI] 29%–51%) in the cryotherapy group, 24% (95% CI 16%–35%) in the salicylic acid group and 16% (95% CI 9.5%–25%) in the wait-and-see group. Differences in effectiveness were most pronounced among participants with common warts (n = 116): cure rates were 49% (95% CI 34%–64%) in the cryotherapy group, 15% (95% CI 7%–30%) in the salicylic acid group and 8% (95% CI 3%–21%) in the wait-and-see group. Cure rates among the participants with plantar warts (n = 124) did not differ significantly between treatment groups.

Interpretation

For common warts, cryotherapy was the most effective therapy in primary care. For plantar warts, we found no clinically relevant difference in effectiveness between cryotherapy, topical application of salicylic acid or a wait-and-see approach after 13 weeks. (ClinicalTrial.gov registration no. ISRCTN42730629)Cutaneous warts are common.^1–3 Up to one-third of primary school children have warts, of which two-thirds resolve within two years.^4,5 Because warts frequently result in discomfort,⁶ 2% of the general population and 6% of school-aged children each year present with warts to their family physician.^7,8 The usual treatment is cryotherapy with liquid nitrogen or, less frequently, topical application of salicylic acid.^9–12 Some physicians choose a wait-and-see approach because of the benign natural course of warts and the risk of side effects of treatment.^10,11A recent Cochrane review on treatments of cutaneous warts concluded that available studies were small, poorly designed or limited to dermatology outpatients.^10,11 Evidence on cryotherapy was contradictory,^13–18 whereas the evidence on salicylic acid was more convincing.^19–23 However, studies that compared cryotherapy and salicylic acid directly showed no differences in effectiveness.^24,25 The Cochrane review called for high-quality trials in primary care to compare the effects of cryotherapy, salicylic acid and placebo.We conducted a three-arm randomized controlled trial to compare the effectiveness of cryotherapy with liquid nitrogen, topical application of salicylic acid and a wait-and-see approach for the treatment of common and plantar warts in primary care.     

Combined monte carlo and molecular dynamics simulation of fully hydrated dioleyl and palmitoyl-oleyl phosphatidylcholine lipid bilayers

We have applied a new equilibration procedure for the atomic level simulation of a hydrated lipid bilayer to hydrated bilayers of dioleyl-phosphatidylcholine (DOPC) and palmitoyl-oleyl phosphatidylcholine (POPC). The procedure consists of alternating molecular dynamics trajectory calculations in a constant surface tension and temperature ensemble with configurational bias Monte Carlo moves to different regions of the configuration space of the bilayer in a constant volume and temperature ensemble. The procedure is applied to bilayers of 128 molecules of POPC with 4628 water molecules, and 128 molecules of DOPC with 4825 water molecules. Progress toward equilibration is almost three times as fast in central processing unit (CPU) time compared with a purely molecular dynamics (MD) simulation. Equilibration is complete, as judged by the lack of energy drift in 200-ps runs of continuous MD. After the equilibrium state was reached, as determined by agreement between the simulation volume per lipid molecule with experiment, continuous MD was run in an ensemble in which the lateral area was restrained to fluctuate about a mean value and a pressure of 1 atm applied normal to the bilayer surface. Three separate continuous MD runs, 200 ps in duration each, separated by 10,000 CBMC steps, were carried out for each system. Properties of the systems were calculated and averaged over the three separate runs. Results of the simulations are presented and compared with experimental data and with other recent simulations of POPC and DOPC. Analysis of the hydration environment in the headgroups supports a mechanism by which unsaturation contributes to reduced transition temperatures. In this view, the relatively horizontal orientation of the unsaturated bond increases the area per lipid, resulting in increased water penetration between the headgroups. As a result the headgroup-headgroup interactions are attenuated and shielded, and this contributes to the lowered transition temperature.     

Duplicate <Emphasis Type="Italic">dmbx1</Emphasis>genes regulate progenitor cell cycle and differentiation during zebrafish midbrain and retinal development

Background  

The Dmbx1 gene is important for the development of the midbrain and hindbrain, and mouse gene targeting experiments reveal that this gene is required for mediating postnatal and adult feeding behaviours. A single Dmbx1 gene exists in terrestrial vertebrate genomes, while teleost genomes have at least two paralogs. We compared the loss of function of the zebrafish dmbx1a and dmbx1b genes in order to gain insight into the molecular mechanism by which dmbx1 regulates neurogenesis, and to begin to understand why these duplicate genes have been retained in the zebrafish genome.