Impairment of movement initiation and execution but not preparation in idiopathic dystonia

Imaging studies have reported impaired activation of the striatum and their frontal projection sites in dsytonia, areas which are considered to play a role in motor preparation, movement initiation and execution. The aim of this study was to investigate the processes of motor preparation, response initiation and execution in patients with idiopathic torsion dystonia (ITD). We assessed 12 patients with ITD and 12 age-matched controls on a number of reaction time (RT) tasks that differed in degree of motor preparation possible. Subjects performed a visual simple RT (SRT) task, an uncued four-choice reaction time (CRT) task and a fully precued four-choice RT task. A stimulus 1-stimulus 2 (S1-S2) paradigm was used. The warning signal/precue (S1) preceded the imperative stimulus (S2) by either 0 ms (no warning signal or precue) 200 ms, 800 ms, 1,600 ms or 3,200 ms. The patients with ITD had significantly slower RTs and movement times than normals across all RT tasks. The unwarned SRT trials were significantly faster than the uncued CRT trials for both groups. For both groups, precued CRTs were significantly faster than the uncued CRTs. The results show that while response initiation and execution are significantly slower in patients with ITD than normals, movement preparation is not quantitatively or qualitatively different. The results are discussed in relation to previous imaging, behavioural and electrophysiological studies and models of fronto-striatal dysfunction in ITD.     

Functional analysis of novel KCNQ2 mutations found in patients with Benign Familial Neonatal Convulsions

Benign Familial Neonatal Convulsions (BFNC) are a rare epilepsy disorder with an autosomal-dominant inheritance. It is linked to mutations in the potassium channel genes KCNQ2 and KCNQ3. These encode for Kv7.2 and Kv7.3 potassium ion channels, which produce an M-current that regulates the potential firing action in neurons through modulation of the membrane potential. We report on the biophysical and biochemical properties of V589X, T359K and P410fs12X mutant-KCNQ2 ion channels that were detected in three BFNC families. Mutant KCNQ2 cDNAs were co-expressed with WT-KCNQ2 and KCNQ3 cDNAs in HEK293 cells to mimic heterozygous expression of the KCNQ2 mutations in BFNC patients. The resulting potassium currents were measured using patch-clamp techniques and showed an approximately 75% reduction in current and a depolarized shift in the voltage dependence of activation. Furthermore, the time-constant of activation of M-currents in cells expressing T359K and P410fs12X was slower compared to cells expressing only wild-type proteins. Immunofluorescent labeling of HEK293 cells stably expressing GFP-tagged KCNQ2-WT or mutant α-subunits indicated cell surface expression of WT, V589X and T359K mutants, suggesting a loss-of-function, while P410fs12X was predominantly retained in the ER and sub-cellular compartments outside the ER suggesting an effectively haplo-insufficient effect.     

Diagnostic methods for differentiation of Entamoeba histolytica and Entamoeba dispar in carriers: performance and clinical implications in a non-endemic setting

Unpreserved faecal samples, suspected to contain Entamoeba histolytica/Entamoeba dispar cysts or trophozoites on the basis of microscopic examination, and serum samples from 416 patients were collected in a prospective study to determine whether stool antigen assays and detection of antibodies in serum are reliable methods to distinguish between carriers of E. histolytica and E. dispar in comparison to the reference test: real-time PCR. In 283 patients (68%) DNA of E. histolytica or E. dispar was amplified by real-time PCR: 6 patients with amoebic colitis (2%), 19 carriers of E. histolytica (6.7%), and 258 carriers of E. dispar (91.2%). In 133 patients (31%) no DNA of E. histolytica or E. dispar could be amplified in the stool samples. This patient group was used as control for the evaluation of diagnostic tests. Using real-time PCR as a reference test, the sensitivity and specificity of (1) the Entamoeba test for the diagnosis of E. histolytica/E. dispar carrier were 59% and 98%, (2) E. histolytica II for the diagnosis of E. histolytica carrier was 71% and 100%, and (3) serology for the diagnosis of E. histolytica infection was 83.3% and 95.2%, respectively. Applied to carriers that did not originate from an endemic country the sensitivity of serology for E. histolytica infection was 90% and specificity was 98.8%. In comparison to real-time PCR the performances of Entamoeba test and E. histolytica II lacked sensitivity for a reliable diagnosis of E. histolytica/E. dispar infection in a non-endemic setting. In carriers of E. histolytica/E. dispar from non-endemic countries the high specificity of serology can be used to establish the diagnosis of E. histolytica infection if antibodies are present.     

Immunoregulatory gene polymorphisms are associated with ANCA-related vasculitis

T cell activation is regulated by inhibitory molecules such as PD-1 and CTLA-4, whose expression may be affected by gene polymorphisms. Increased T cell activation is present in patients with ANCA-associated vasculitis (AAV). We investigated two single-nucleotide polymorphisms (SNPs) in PDCD1 and five polymorphisms in CTLA4 in 102 patients with AAV and 188 healthy controls (HC). The distributions of the PD-1.3 and PD-1.5 SNPs, and the distributions of the CTLA4 promoter polymorphisms -1722T/C, -1661A/G, -318 C/T, and the (AT)(n) microsatellite in the 3'-untranslated region of CTLA4, did not differ between patients and HC. However, the +49 G allele was significantly more often present in patients with AAV. Furthermore, the co-occurrence of the PD-1.5 T allele with CTLA4 +49 AA homozygosity (i.e., the absence of a G allele) was less often present in patients compared to HC. These genetic polymorphisms may lead to hyperreactivity of T cells and thus may contribute to the pathogenesis of AAV.     

Impaired oxidative status as a potential predictor in clinical manifestations of herpes zoster

Oxidative stress, caused by an imbalance between reactive oxygen species and antioxidants, is related to many dermatologic diseases. Increased reactive oxygen species is also associated with various decreased T‐cell immune responses. The incidence and severity of herpes zoster (HZ), which is caused by the reactivation of varicella ‐ zoster virus, increase with age because of declining cell‐mediated immunity. The main purpose of this study was to assess the levels of oxidative stress biomarkers in patients with HZ compared with control subjects. In this case‐control study, the serum levels of total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index, glutathione, superoxide dismutase, and total polyphenol content (TPC) in 43 patients with HZ and 47 age‐matched controls were determined, and their biomarker patterns were compared. TAC and TPC levels were significantly lower in patients with HZ; however, TOS and oxidative stress index levels were significantly higher in comparison with the control (P < .001). In addition, a signi?cantly strong negative correlation was found between TAC and TPC with TOS levels in patients with HZ (r = ?.79, P < .001; r = ?.81, P < .001, respectively). Our findings showed an oxidative stress imbalance in HZ. Whether this change correlates with HZ pathogenesis or is a consequence of the inflammatory response to HZ needs more investigation.     

The Ariadne principles: how to handle multimorbidity in primary care consultations

Multimorbidity is a health issue mostly dealt with in primary care practice. As a result of their generalist and patient-centered approach, long-lasting relationships with patients, and responsibility for continuity and coordination of care, family physicians are particularly well placed to manage patients with multimorbidity. However, conflicts arising from the application of multiple disease oriented guidelines and the burden of diseases and treatments often make consultations challenging. To provide orientation in decision making in multimorbidity during primary care consultations, we developed guiding principles and named them after the Greek mythological figure Ariadne. For this purpose, we convened a two-day expert workshop accompanied by an international symposium in October 2012 in Frankfurt, Germany. Against the background of the current state of knowledge presented and discussed at the symposium, 19 experts from North America, Europe, and Australia identified the key issues of concern in the management of multimorbidity in primary care in panel and small group sessions and agreed upon making use of formal and informal consensus methods. The proposed preliminary principles were refined during a multistage feedback process and discussed using a case example. The sharing of realistic treatment goals by physicians and patients is at the core of the Ariadne principles. These result from i) a thorough interaction assessment of the patient’s conditions, treatments, constitution, and context; ii) the prioritization of health problems that take into account the patient’s preferences – his or her most and least desired outcomes; and iii) individualized management realizes the best options of care in diagnostics, treatment, and prevention to achieve the goals. Goal attainment is followed-up in accordance with a re-assessment in planned visits. The occurrence of new or changed conditions, such as an increase in severity, or a changed context may trigger the (re-)start of the process. Further work is needed on the implementation of the formulated principles, but they were recognized and appreciated as important by family physicians and primary care researchers.Please see related article: http://www.biomedcentral.com/1741-7015/12/222.     

Relatives’ perspectives on the quality of care in an Intensive Care Unit: The theoretical concept of a new tool

Objective

To examine the potential of a questionnaire (CQI ‘R-ICU’) to measure the quality of care from the perspective of relatives in the Intensive Care Unit (ICU).

Methods

A quantitative survey study has been undertaken to explore the psychometric properties of the instrument, which was sent to 282 relatives of ICU patients from the Erasmus MC, an academic hospital in Rotterdam, the Netherlands. Factor-analyses were performed to explore the underlying theoretical structure.

Results

Survey data from 211 relatives (response rate 78%) were used for the analysis. The overall reliability of the questionnaire was sufficiently high; two of the four underlying factors, namely ‘Communication’ and ‘Involvement’, were significant predictors. Two specific aspects of care that needed the most improvement were missing information about meals and offering an ICU diary. There is a significant difference in mean communication with nurses among the four wards in Erasmus MC.

Conclusions

The CQI ‘R-ICU’ seems to be a valid, reliable and usable instrument. The theoretical fundament appears to be related to communication.

Practice implications

The newly developed instrument can be used to provide feedback to health care professionals and policy makers in order to evaluate quality improvement projects with regard to relatives in the ICU.     

Bone Mineral Density in Transgender Individuals After Gonadectomy and Long-Term Gender-Affirming Hormonal Treatment

IntroductionEstablishing the influence of long-term, gender-affirming hormonal treatment (HT) on bone mineral density (BMD) in transgender individuals is important to improve the therapeutic guidelines for these individuals.AimTo examine the effect of long-term HT and gonadectomy on BMD in transgender individuals.Methods68 transwomen and 43 transmen treated with HT who had undergone gonadectomy participated in this study. Dual-energy x-ray absorptiometry (DXA) scans were performed to measure BMD at the lumbar spine and total hip. Laboratory values related to sex hormones were collected within 3 months of performing the DXA scan and analyzed.Main Outcome MeasureBMD and levels of sex hormones in transwomen and transmen.ResultsIn transwomen, the mean BMD values at the lumbar spine and total hip at the first DXA scan were, respectively, 0.99 ± 0.15 g/cm² (n = 68) and 0.94 ± 0.28 g/cm² (n = 65). In transmen, the mean BMD values at the lumbar spine and total hip at the first DXA scan were, respectively, 1.08 ± 0.16 g/cm² (n = 43) and 1.01 ± 0.18 g/cm² (n = 43). A significant decrease in total hip BMD was found in both transwomen and transmen after 15 years of HT compared with 10 years of HT (P = .02).ConclusionIn both transwomen and transmen, a decrease was observed in total hip bone mineral density after 15 years of HT compared to the first 10 years of HT.Dobrolińska M, van der Tuuk K, Vink P, et al. Bone Mineral Density in Transgender Individuals After Gonadectomy and Long-Term Gender-Affirming Hormonal Treatment. J Sex Med 2019; 16:1469–1477.     

Clinical aspects of infertile 47,XYY patients: a retrospective study

47,XYY syndrome is a sex chromosomal anomaly in men, which may be associated with infertility and has an incidence of 0.1% of male births. The clinical and paraclinical characteristics of men suffering from this anomaly have not been fully described. In this retrospective study, we present 37 cases of 47,XYY infertile men with sperm counts varying from normal to azoospermia, referred to the Genetics Laboratory at the Royan Institute, Iran. Thirteen individuals were mosaic and 24 non-mosaics. Non-mosaic patients were classified as azoospermic (nine cases) and normospermic/oligozoospermic men (15 cases). Two of the non-mosaic and three mosaic patients had secondary infertility. In addition, 13 of them underwent IUI, IVF or ICSI, and in seven cases, there was a biochemical pregnancy. The remaining 14 patients did not have ART. The 47,XYY syndrome is relatively unusual and can be missed clinically because of the lack of symptoms and of diverse phenotypes. Diagnosis of this aneuploidy can provide valuable data for counselling and early management of the patients who undergo fertility evaluation.