The age-dependent relationship between resting heart rate variability and functional brain connectivity.

Resting heart rate variability (HRV), an index of parasympathetic cardioregulation and an individual trait marker related to mental and physical health, decreases with age. Previous studies have associated resting HRV with structural and functional properties of the brain - mainly in cortical midline and limbic structures. We hypothesized that aging affects the relationship between resting HRV and brain structure and function. In 388 healthy subjects of three age groups (140 younger: 26.0 ±â€¯4.2 years, 119 middle-aged: 46.3 ±â€¯6.2 years, 129 older: 66.9 ±â€¯4.7 years), gray matter volume (GMV, voxel-based morphometry) and resting state functional connectivity (eigenvector centrality mapping and exploratory seed-based functional connectivity) were related to resting HRV, measured as the root mean square of successive differences (RMSSD). Confirming previous findings, resting HRV decreased with age. For HRV-related GMV, there were no statistically significant differences between the age groups, nor similarities across all age groups. In whole-brain functional connectivity analyses, we found an age-dependent association between resting HRV and eigenvector centrality in the bilateral ventromedial prefrontal cortex (vmPFC), driven by the younger adults. Across all age groups, HRV was positively correlated with network centrality in the bilateral posterior cingulate cortex. Seed-based functional connectivity analysis using the vmPFC cluster revealed an HRV-related cortico-cerebellar network in younger but not in middle-aged or older adults. Our results indicate that the decrease of HRV with age is accompanied by changes in functional connectivity along the cortical midline. This extends our knowledge of brain-body interactions and their changes over the lifespan.

Investigation of the confounding effects of vasculature and metabolism on computational anatomy studies.

Computational anatomy studies typically use T1-weighted magnetic resonance imaging contrast to look at local differences in cortical thickness or grey matter volume across time or subjects. This type of analysis is a powerful and non-invasive tool to probe anatomical changes associated with neurodevelopment, aging, disease or experience-induced plasticity. However, these comparisons could suffer from biases arising from vascular and metabolic subject- or time-dependent differences. Differences in blood flow and volume could be caused by vasodilation or differences in vascular density, and result in a larger signal contribution of the blood compartment within grey matter voxels. Metabolic changes could lead to differences in dissolved oxygen in brain tissue, leading to T1 shortening. Here, we analyze T1 maps and T1-weighted images acquired during different breathing conditions (ambient air, hypercapnia (increased CO2) and hyperoxia (increased O2)) to evaluate the effect size that can be expected from changes in blood flow, volume and dissolved O2 concentration in computational anatomy studies. Results show that increased blood volume from vasodilation during hypercapnia is associated with an overestimation of cortical thickness (1.85%) and grey matter volume (3.32%), and that both changes in O2 concentration and blood volume lead to changes in the T1 value of tissue. These results should be taken into consideration when interpreting existing morphometry studies and in future study design. Furthermore, this study highlights the overlap in structural and physiological MRI, which are conventionally interpreted as two independent modalities.

The role of microRNAs in Anopheles biology-an emerging research field.

In the last years, microRNAs (miRNAs) have been established as important post-transcriptional regulators of critical physiological processes in animals and plants. Here, we summarize what is known about miRNA biosynthesis, expression and function in the malaria vector mosquito Anopheles gambiae with a particular emphasis on the mosquito-parasite interactions. We discuss the important gaps in the current knowledge, including the potential of miRNA manipulation for future vector control strategies.

Psychological management of unipolar depression.

OBJECTIVE: To be used in conjunction with 'Pharmacological management of unipolar depression' [Malhi et al. Acta Psychiatr Scand 2013;127(Suppl. 443):6-23] and 'Lifestyle management of unipolar depression' [Berk et al. Acta Psychiatr Scand 2013;127(Suppl. 443):38-54]. To provide clinically relevant recommendations for the use of psychological treatments in depression derived from a literature review. METHOD: Medical databases including MEDLINE and PubMed were searched for pertinent literature, with an emphasis on recent publications. RESULTS: Structured psychological treatments such as cognitive behaviour therapy and interpersonal therapy (IPT) have a robust evidence base for efficacy in treating depression, even in severe cases of depression. However, they may not offer benefit as quickly as antidepressants, and maximal efficacy requires well-trained and experienced therapists. These therapies are effective across the lifespan and may be preferred where it is desired to avoid pharmacotherapy. In some instances, combination with pharmacotherapy may enhance outcome. Psychological therapy may have more enduring protective effects than medication and be effective in relapse prevention. Newer structured psychological therapies such as mindfulness-based cognitive therapy and acceptance and commitment therapy lack an extensive outcome literature, but the few published studies yielding positive outcomes suggest they should be considered options for treatment. CONCLUSION: Cognitive behaviour therapy and IPT can be effective in alleviating acute depression for all levels of severity and in maintaining improvement. Psychological treatments for depression have demonstrated efficacy across the lifespan and may present a preferred treatment option in some groups, for example, children and adolescents and women who are pregnant or postnatal.

Getting depression clinical practice guidelines right: time for change?

OBJECTIVE: As part of a series of papers ['Chronobiology of mood disorders' Malhi & Kuiper. Acta Psychiatr Scand 2013;128(Suppl. 444):2-15; and 'It's time we managed depression: The emerging role of chronobiology' Malhi et al. Acta Psychiatr Scand 2013;128(Suppl. 444):1] examining chronobiology in the context of depression, this article examines recent western clinical practice guidelines (CPGs) for the treatment of depression with respect to the recommendations they make, in particular as regards chronobiological treatments, and briefly considers the implications of their methodology and approach. METHOD: Five international treatment guidelines, which had been published in the past 5 years, were identified, representing North American and European views. Chosen guidelines were reviewed by the authors, and the relevant recommendations were distributed for discussion and subsequent synthesis. RESULTS: Most current guidelines do not address chronobiology in detail. Chronotherapeutic recommendations are tentative, although agomelatine is considered as an option for major depression and bright light therapy for seasonal affective disorder. Sleep deprivation is not routinely recommended. CONCLUSION: Recommendations are limited by the lack of reliable therapeutic markers for chronotherapeutics. Current evidence supports use of light therapy in seasonal depression, but in non-seasonal depression there is insufficient evidence to support reliance on chronotherapeutics over existing treatment modalities.

Serum BDNF levels correlate with regional cortical thickness in minor depression: a pilot study.

Serum brain-derived neurotrophic factor (BDNF) reflects state changes in mood disorders. But its relation to brain changes in depression has rarely been investigated in humans. We assessed the association between serum BDNF, cortical thickness, or gray matter volume in 20 subjects with a minor depressive episode and 40 matched healthy subjects. Serum BDNF positively correlated with cortical thickness and volume in multiple brain regions in the minor depression group: the bilateral medial orbitofrontal cortex and rostral anterior cingulate cortex, left insula, and cingulum, right superior frontal gyrus, and other regions-regions typically affected by major depression. Interestingly, these correlations were driven by subjects with first episode depression. There was no significant association between these imaging parameters and serum BDNF in the healthy control group. Interaction analyses supported this finding. Our findings point to a specific association between serum BDNF and magnetic resonance imaging parameters in first-episode minor depression in a region- and condition-dependent manner. A positive correlation between serum BDNF and structural gray matter estimates was most consistently observed for cortical thickness. We discuss why cortical thickness should be preferred to volumetric estimates for such analyses in future studies. Results of our pilot study have to be proven in future larger-scale studies yielding higher statistical power.

Clinical practice recommendations for depression.

OBJECTIVE: To provide clinically relevant evidence-based recommendations for the management of depression in adults that are informative, easy to assimilate and facilitate clinical decision making. METHOD: A comprehensive literature review of over 500 articles was undertaken using electronic database search engines (e.g. MEDLINE, PsychINFO and Cochrane reviews). In addition articles, book chapters and other literature known to the authors were reviewed. The findings were then formulated into a set of recommendations that were developed by a multidisciplinary team of clinicians who routinely deal with mood disorders. The recommendations then underwent consultative review by a broader advisory panel that included experts in the field, clinical staff and patient representatives. RESULTS: The clinical practice recommendations for depression (Depression CPR) summarize evidence-based treatments and provide a synopsis of recommendations relating to each phase of the illness. They are designed for clinical use and have therefore been presented succinctly in an innovative and engaging manner that is clear and informative. CONCLUSION: These up-to-date recommendations provide an evidence-based framework that incorporates clinical wisdom and consideration of individual factors in the management of depression. Further, the novel style and practical approach should promote uptake and implementation.

Clinical practice recommendations for bipolar disorder.

OBJECTIVE: To provide clinically relevant evidence-based recommendations for the management of bipolar disorder in adults that are informative, easy to assimilate and facilitate clinical decision-making. METHOD: A comprehensive literature review of over 500 articles was undertaken using electronic database search engines (e.g. MEDLINE, PsychINFO and Cochrane reviews). In addition articles, book chapters and other literature known to the authors were reviewed. The findings were then formulated into a set of recommendations that were developed by a multidisciplinary team of clinicians who routinely deal with mood disorders. These preliminary recommendations underwent extensive consultative review by a broader advisory panel that included experts in the field, clinical staff and patient representatives. RESULTS: The clinical practice recommendations for bipolar disorder (bipolar CPR) summarise evidence-based treatments and provide a synopsis of recommendations relating to each phase of the illness. They are designed for clinical use and have therefore been presented succinctly in an innovative and engaging manner that is clear and informative. CONCLUSION: These up-to-date recommendations provide an evidence-based framework that incorporates clinical wisdom and consideration of individual factors in the management of bipolar disorder. Further, the novel style and practical approach should promote their uptake and implementation.

Placental macrophage contact potentiates the complete replicative cycle of human cytomegalovirus in syncytiotrophoblast cells: role of interleukin-8 and transforming growth factor-beta1.

Although syncytiotrophoblast (ST) cells can be infected by human cytomegalovirus (HCMV), in vitro studies have indicated that ST cells do not support the complete viral reproductive cycle, or HCMV replication may occur in less than 3% of ST cells. The present study tested the possibility that placental macrophages might enhance activation of HCMV carried in ST cells and, further, that infected ST cells would be capable of transmitting virus to neighboring macrophages. For this purpose, we studied HCMV replication in ST cells grown alone or cocultured with uninfected placental macrophages. Our results demonstrated that HCMV gene expression in ST cells was markedly upregulated by coculture with macrophages, resulting in release of substantial amounts of infectious virus from HCMV-infected ST cells. After having become permissive for viral replication, ST cells delivered HCMV to the cocultured macrophages, as evidenced by detection of virus-specific antigens in these cells. The stimulatory effect of coculture on HCMV gene expression in ST cells was mediated by marked interleukin-8 (IL-8) and transforming growth factor-beta1 (TGF-beta1) release from macrophages, an effect caused by contact between the different placental cells. Our findings indicate an interactive role for the ST layer and placental macrophages in the dissemination of HCMV among placental tissue. Eventually, these interactions may contribute to the transmission of HCMV from mother to the fetus.

Effects of simulated microgravity (HDT) on blood fluidity.

Exposures to microgravity and head-down tilt (HDT) produce similar changes in body fluid. This causes an increase in hematocrit that significantly affects hemorheological values. Lack of physical stimulation under bed rest conditions and the relative immobility of the crew during spaceflight also affects the blood fluidity. A group of six healthy male subjects participated as volunteers, and blood samples were collected 10 days before, on day 2 and day 9, and 2 days after the HDT phase. Blood rheology was quantified by plasma viscometry, red cell aggregability, and red cell deformability. A reduced red cell deformability, an indication of the diminished quality of the red blood cells, was measured under HDT conditions that finally led to the so-called "space flight anemia." Enhanced red cell membrane fragility induced by diminished physical activity and an increase in hemoglobin concentration are responsible for this effect. Plasma viscosity is reduced as a result of diminished plasma proteins. However, despite the reduction in plasma proteins, including fibrinogen, alpha 2-macroglobulin, and immunoglobulin M, red cell aggregation was enhanced, principally because of the increase in hematocrit. Our results of hemorheological alterations under HDT conditions may help to elucidate the formerly documented hematologic changes during spaceflight.

Two modifications of the intrauterine membrane contraceptive device.

The intrauterine membrane (IUM) is an intrauterine contraceptive device designed to be compliant with a range of uterine shapes and sizes and with transient dimensional changes resulting from uterine motility. This compliance was expected to contribute to low rates for removal due to bleeding and pain, but the use of the IUM resulted in heavy bleeding among its early users. Consequently, two modifications of the device were made to decrease bleeding. One group of IUMs was modified by using ethylene vinyl acetate to provide a high level of lateral compliance and another was modified by using a tissue-compatible Hydron coating in order to decrease the inflammatory response of the endometrium. One hundred of each of these modified IUMs were tested along with 100 of the standard IUMs in a double-blind study conducted at the Noi Klinika in Debrecen, Hungary. The findings of this study suggested that these two modifications did not improve the over-all performance of the IUM.

Effective contraception with the levonorgestrel-releasing intrauterine device: 12-month report of a European multicenter study.

The use-effectiveness of an intrauterine contraceptive device releasing 20 mcg of levonorgestrel daily (Lng-IUD), and of a Nova T copper-releasing IUD, were studied in a randomized, comparative multicenter trial. The Lng-IUD was inserted in 1821, and the Nova T in 937 women. The 12-month net pregnancy rate with the Lng-IUD (0.1 per hundred women) was significantly lower than that with the Nova T (0.9 per hundred). Removal rates for menstrual problems and/or pain were similar for the two methods (net rates 7.5 and 8.7, respectively). The 12-month continuation rates were 82.2 for the Nova T and 79.7 for the Lng-IUD. The reduction of the bleeding led to oligomenorrhea and amenorrhea in users of the Lng-IUD; the removal rate for these reasons was 1.4. The removal rate for hormonal side effects with the Lng-IUD was 2.4. Blood hemoglobin concentrations increased among users of the Lng-IUD and decreased among users of the Nova T. The results show that the Lng-IUD was a highly effective contraceptive method which reduced menstrual bleeding. It is a promising alternative for women desiring a highly effective method for long-term use.

PIP: The use-effectiveness of an intrauterine contraceptive device releasing 20 mcg of levon ISZ orgestrel daily (Lng-IUD), and of a Nova T copper-releasing IUD, were studied in a randomized comparative mulicenter trial. The Lng-IUD was inserted in 1821, and the Nova T in 937 women. The 12-month net pregnancy rate with the Lng-IUD (0.1/100 women) was significantly lower than that with the Nova T (0.9/100). Removal rates for menstrual problems and/or pain were similar for the 2 methods (net rates 7.5 and 8.7 respectively). The 12-moth continuation rates were 82.2 for the Nova T and 79.7 for the Lng-IUD. The reduction of the bleeding led to oligomenorrhea and amenorrhea in users of the Lng-IUD; the removal rate for these reasons was 1.4. The removal rate for hormonal side effects with the Lng-IUD was 2.4. Blood hemoglobin concentrations increased among users of the Lng-IUD and decreased among users of the Nova T. The results show that the Lng-IUD was highly effective contraceptive method which reduced menstrual bleeding. It it a promising alternative for women desiring a highly-effective method for long-term use.

Avoidant personality disorder: empirical support for DSM-IV revisions.

This article attempts to answer three questions about avoidant personality disorder (AVPD): (a) Is it a coherent unidimensional entity, (b) Is the requirement that four or more of the criteria be met in order to make the diagnosis justified, and (c) Are the changes made in DSM-IV supported? Four hundred thirty-four people presenting for treatment for anxiety were assessed with the Personality Disorder Examination. The criteria met were factor analyzed to indicate the unidimensionality of the diagnosis. Measures of internal consistency were calculated to validate the instruction to diagnose AVPD if four or more criteria were observed. Confirmatory factor analysis showed that a single factor was the best fit to the observed pattern of relationships between the seven AVPD criteria. The internal consistency of the seven criteria was moderate (Cronbach's alpha = .76) with a median intercriterion correlation of .29. The data provided good support for the hypothesis that the seven DSM-III-R AVPD criteria assess a single dimension. Three of the criteria did not reflect this factor as highly as the remaining four and these three have either been dropped in DSM-IV or substantially revised.

Indications for induction of labour.

Induction of labour is an important prophylactic procedure in the obstetric practice. Two major types of indications developed: induction because of advanced relevant obstetric complication, and the so called elective induction.

Treatment of vulvar craurosis and leucoplakia by split skin grafting.

In the treatment of a 72-year-old patient with vulvar craurosis and leucoplakia which had been proven resistant to earlier surgical and medical treatment attempts--the authors employed a split-skin graft from the forearm. The methods of the successful treatment with regard to the skin and its grafting, as well as the post-operative case, are described.

Ovarian malignancies in childhood and adolescence.

We retrospectively reviewed all cases of ovarian malignancies during a 10-year period at the Department of Obstetrics and Gynecology, University Medical School of Debrecen, Hungary. The experience with 16 cases: three epithelial tumors, one granulosa cell tumor, 11 germ cell tumors (six dysgerminoma, four teratoma, one endodermal sinus tumor), and one metastatic ovarian cancer is discussed. Malignant ovarian tumors can best be treated with conservative surgery, followed by adjuvant chemotherapy. Survival mainly depends on tumor type and stage at the time of diagnosis.

The role of preoperative brachytherapy as an adjunct to surgery and postoperative radiotherapy in the treatment of stage I endometrial carcinoma.

PURPOSE: Between 1978 and 1993, 817 cases of endometrial carcinoma were treated with simple hysterectomy with bilateral salpingo-oophorectomy. Five hundred and twenty-six cases had preoperative brachytherapy (Preo), and 291 cases underwent surgery without preoperative radiotherapy (Nopre). The aim of the study was to compare disease-free survival of the two groups. METHODS AND MATERIALS: Survival comparison of the two groups was controlled for postoperative treatment type, according to stage, histological type, degree of differentiation, depth of myometrial invasion and age. The life-table method was used for survival analysis. Cumulative disease-free survival probabilities were calculated as a function of the proportion of normal remaining life elapsed from the time of diagnosis. RESULTS: Five-year disease-free survival of patients with and without preoperative brachytherapy in stage IA, IB and IC was 93 and 93.6%, 93 and 94%, and 80 and 65%, respectively. In well differentiated tumors and poorly differentiated tumors, there was no difference in disease-free survival between patients with and without preoperative brachytherapy. Patients with moderately differentiated tumor treated with preoperative brachytherapy had significantly better disease-free survival than those without preoperative radiotherapy, however, this was confounded by uneven distribution of invasion depth. CONCLUSION: Preoperative brachytherapy plays a limited role in the treatment of early stage endometrial carcinoma.

The value of bed rest in twin pregnancies.

The effect of bed rest on the duration of pregnancy, the birth weight of newborns, the frequency of premature birth, and perinatal mortality was examined in 491 twin pregnancies. Cases were divided into two groups - women hospitalized from the 24th-26th week of pregnancy until delivery (rested group, 242 patients) and outpatients (unrested group, 249 patients). The premature birth rate was considerably less for patients in the rested group: in this group 41.0% of the newborns were delivered earlier than the 38th week and 42.9% of them weighed less than 2 500 g, whereas in the unrested group 75.0% were delivered earlier than the 38th week and 77.2% weighed less than 2 500 g. In addition, the perinatal mortality rates observed in the two groups were significantly different. Based on these findings, we conclude that the high premature birth rates and subsequent high perinatal mortality may be considerably reduced if twin pregnancies are diagnosed early and patients are hospitalized from the 26th week until delivery.

Cervical cancer in young women: a poorer prognosis?

OBJECTIVE: The existence of an aggressive form of cervical carcinoma affecting young women is studied by survival analysis of a large patient population. METHOD: Between 1969 and 1986, 1577 cases of cervical cancer were treated according to well-defined policies at the University Department of Obstetrics and Gynaecology in Debrecen, Hungary. Patients' records were reviewed to obtain data for survival analysis. Kaplan-Meier survival curves were generated for each stage and stratified for age. The log-rank test was used to compare the survival of younger and older patients at each stage. Multivariate analysis was performed to control for stage and treatment type when 5-year survival trends across four different age groups were examined. RESULTS: Comparison of survival of patients under 35 and over 35 years of age, and also those under 40 and over 40 years of age revealed no significant differences. Five-year survival across the < 30, 30-39, 40-49 and > or = 50 years age groups showed no significant trend. No differences in survival were revealed when the comparison was controlled for stage of disease and treatment type. CONCLUSION: Results suggest that cervical carcinoma in young women is not more aggressive than in other age groups.

Clinical experiences with intrauterine devices inserted with and without tail.

Nova T and TCu 200 Ag IUDs were inserted with or without a tail in order to study the possible role of the thread on the occurrence of PID. The five-year gross cumulative termination rate for infection was 3.7 in the group with a tail and 1.3 in the group without a tail. The results indicate a lower risk of genital infection if the device is inserted without the tailstrings.