Deep Brain Stimulation of Caudal Zona Incerta for Parkinson's Disease: One-Year Follow-Up and Electric Field Simulations

ObjectiveTo evaluate the effects of bilateral caudal zona incerta (cZi) deep brain stimulation (DBS) for Parkinson's disease (PD) one year after surgery and to create anatomical improvement maps based on patient-specific simulation of the electric field.Materials and MethodsWe report the one-year results of bilateral cZi-DBS in 15 patients with PD. Patients were evaluated on/off medication and stimulation using the Unified Parkinson's Disease Rating Scale (UPDRS). Main outcomes were changes in motor symptoms (UPDRS-III) and quality of life according to Parkinson's Disease Questionnaire-39 (PDQ-39). Secondary outcomes included efficacy profile according to sub-items of UPDRS-III and simulation of the electric field distribution around the DBS lead using the finite element method. Simulations from all patients were transformed to one common magnetic resonance imaging template space for the creation of improvement maps and anatomical evaluation.ResultsMedian UPDRS-III score off medication improved from 40 at baseline to 21 on stimulation at one-year follow-up (48%, p < 0.0005). PDQ-39 summary index did not change, but the subdomain activities of daily living (ADL) and stigma improved (25%, p < 0.03 and 75%, p < 0.01), whereas communication worsened (p < 0.03). For UPDRS-III sub-items, stimulation alone reduced median tremor score by 9 points, akinesia by 3, and rigidity by 2 points at one-year follow-up in comparison to baseline (90%, 25%, and 29%, respectively, p < 0.01). Visual analysis of the anatomical improvement maps based on simulated electrical fields showed no evident relation with the degree of symptom improvement and neither did statistical analysis show any significant correlation.ConclusionsBilateral cZi-DBS alleviates motor symptoms, especially tremor, and improves ADL and stigma in PD patients one year after surgery. Improvement maps may be a useful tool for visualizing the spread of the electric field. However, there was no clear-cut relation between anatomical location of the electric field and the degree of symptom relief.     

Microarray-based molecular detection of foot-and-mouth disease, vesicular stomatitis and swine vesicular disease viruses, using padlock probes

The World Organization for Animal Health (Office International des Epizooties, OIE) includes the diseases caused by foot-and-mouth disease virus (FMDV), swine vesicular disease virus (SVDV), and vesicular stomatitis virus (VSV), as "Diseases Notifiable to the OIE". Foot-and-mouth disease (FMD) outbreaks have severe economical as well as social effects and cannot be differentiated from the diseases caused by the other two viruses on the basis of clinical symptoms. Efficient laboratory techniques are therefore required for detection and identification of the viruses causing similar vesicular symptoms in swine. A rapid method is described using padlock probes and microarrays to detect simultaneously and differentiate the three viruses in a single reaction, as well as providing serotype information in cases of VSV infection. The padlock probe/microarray assay detected successfully and identified 39 cDNA samples of different origin representing the three viruses. The results were in complete agreement with identities and serotypes determined previously. This novel virus detection method is discussed in terms of usefulness and further development.     

Focusing on body sites: the role of spatial attention in action perception

Humans use the same representations to code self-produced and observed actions. Neurophysiological evidence for this view comes from the discovery of the so-called mirror neurons in premotor cortex of the macaque monkey. These neurons respond when the monkey performs a particular action but also when it observes the same behavior in another individual. In humans, such direct links between perception and action seem to mediate action priming, where a response is facilitated when a similar action is observed. An issue that has not been fully resolved concerns the role of selective attention in these processes. Action priming appears to be an automatic process in the sense that the observed action can be irrelevant to the observer's task and nevertheless prime similar responses. However, it is not known whether attention has to be oriented to the action for these processes to be engaged. It is demonstrated here that spatial attention indeed has to be oriented to the action related body site for action priming to take place. Furthermore, if attention is oriented to the appropriate body site, there need be no visual cues to action for action priming to emerge.     

Correlation between salivary and serum melatonin: dependence on serum melatonin levels

Saliva and serum samples were collected from eight healthy volunteers every two hours during a 26-hour period. Melatonin concentrations were measured by radioimmunoassay after chloroform extraction using radioiodinated melatonin as a tracer. Five of the subjects had high serum melatonin levels at night (peak levels higher than 75 pg/ml); in three subjects the highest serum melatonin concentration was 20-40 pg/ml. All subjects had low levels (less than 10 pg/ml) during the day. The correlations between salivary and serum levels were calculated. The regression line y = 0.33x + 3.7 pg/ml, r = 0.95, P less than 0.001, was obtained for all detectable value pairs (n = 73). The regression and correlation coefficients were almost equal for the peak values of melatonin and during the rising and descending phases of the secretion patterns. However, no significant correlation was found between low daytime salivary and serum concentrations when calculated separately. In the five high-secretors the melatonin levels in saliva reflected reliably the changes in serum, but in the three low-secretors the correlation between salivary and serum melatonin was not significant. The proportion of melatonin found in saliva decreased with increasing serum melatonin levels. Circadian rhythm parameters were estimated by single cosinor analysis. The acrophases did not differ significantly within a subject in the concomitant measurements of serum and salivary melatonin. The measurements of salivary melatonin levels seem valid for studies on melatonin rhythms, but the melatonin concentrations measured in saliva do not always consistently reflect the absolute concentrations in blood.     

On the modulating effects of ovaries on neonatal androgen programming of rat liver enzymes.

The metabolism of 4-[4-14C]androstene-3,17-dione in rat liver microsomal and cytosol fractions was investigated in adult female rats treated with 1.45 mumole of testosterone propionate at birth. The effects of ovariectomy at 14 and 43 days of age on neonatal testosterone imprinting of enzyme levels were studied. Animals spayed 14 days after birth showed a typical masculinized hepatic enzyme activity pattern with a decreased level of the 5alpha-reductase activity and increased level of 5beta-reductase, 16alpha-hydroxylase and 17alpha- and 3beta-hydroxysteroid reductase levels. The pattern was essentially the same in testosterone propionate-treated rats spayed 43 days after birth - with the exception of a feminized 5alpha-reductase activity - whereas a completely feminized ("de-imprinted") pattern of enzyme activities was found in the rats with intact ovaries at the time of death. It is concluded that de-imprinting action of ovaries is mainly of a reversible nature.     

Roles of pilin and PilC in adhesion of Neisseria meningitidis to human epithelial and endothelial cells.

Pili and pilin antigenic variation play important roles in adhesion of Neisseria meningitidis (MC) to human epithelial and endothelial cells. We recently identified one pilin variant that confers high adhesiveness of MC to human epithelial cells in culture. However, other factor(s) also play a role in MC adhesiveness, since some nonadhesive variants of MC strain 8013 are piliated and produce the same pilin variant as adhesive derivatives. PilC1 and PilC2, high molecular weight outer membrane proteins in Neisseria gonorrhoeae, are proposed to play roles in pilus assembly. Strain 8013 also contains pilC1 and pilC2; their products function in a similar if not identical manner in pilus biogenesis. PilC1 has an additional function in that it also modulates adhesiveness of strain 8013.     

Rationale and Design of LAPLACE‐2: A Phase 3, Randomized,Double‐Blind,Placebo‐ and Ezetimibe‐Controlled Trial Evaluating the Efficacy and Safety of Evolocumab in Subjects With Hypercholesterolemia on Background Statin Therapy

Low‐density lipoprotein cholesterol (LDL‐C) levels are significantly associated with atherosclerotic cardiovascular disease (ASCVD) risk, and studies using interventions that lower LDL‐C levels have been shown to reduce the risk of ASCVD events and mortality. Statin treatment is the current first‐line therapy for lowering LDL‐C and reducing ASCVD risk. However, many patients are still unable to reach recommended LDL‐C goals on maximally tolerated statin therapy. Monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9, including evolocumab (previously AMG 145), dramatically lowered LDL‐C in phase 2 clinical trials when administered alone or in combination with a statin. The aim of this phase 3 study is to evaluate the efficacy of 12 weeks of subcutaneous evolocumab (vs placebo) administered every 2 weeks or every month in combination with a statin in patients with hypercholesterolemia and mixed dyslipidemia. This study will also provide comparative efficacy, safety, and tolerability data between evolocumab and ezetimibe when added to background atorvastatin therapy.     

Restoration of humeral head geometry in posttraumatic fracture sequelae with stemless or resurfacing arthroplasty: a matched-paired analysis

Background

The objective of this study was to analyze proximal humeral geometry in two groups of patients with posttraumatic fracture sequelae who were treated with either resurfacing (R) or stemless (S) arthroplasty. The hypothesis was that there is no difference in the radiographic restoration of postoperative proximal humeral geometry after resurfacing or stemless arthroplasties.

Material and methods

A match-paired analysis of 48 cases was completed (R?=?24, S?=?24). Proximal geometry was assessed reviewing true anterior–posterior x-rays, measuring the inclination angle of osteotomy (IAO), distance above tuberosity (DAT), superior humeral translation (SHT) according to Torchia, medial offset (MO), and lateral offset (LO).

Results

The average follow-up was 32.4?±?9.2 months for group R and 37.9?±?22.9 months for group S (p?=?0.317). Except for MO and SHT, no significant differences were found. Restoration of the anatomical MO was more accurate for group S. SHT of the humerus was detected more frequently for group R.

Conclusions

In this match-paired analysis, stemless arthroplasty reconstructed an anatomic MO more consistently than resurfacing arthroplasty as evaluated on x-rays; we did not document differences in the remaining evaluated parameters. However, no significant differences were found between both groups regarding clinical outcomes.     

Evaluation of the impact of organ-specific dose reduction on image quality in pediatric chest computed tomography

Background

Organ-specific dose reduction significantly reduces the radiation exposure of radiosensitive organs.

Objective

The purpose of this study was to assess the impact of a novel organ-specific dose reduction algorithm on image quality of pediatric chest CT.

Materials and methods

We included 28 children (mean age 10.9?±?4.8 years, range 3–18 years) who had contrast-enhanced chest CT on a 128-row scanner. CT was performed at 100 kV using automated tube current modulation and a novel organ-specific dose-reduction algorithm (XCare?; Siemens, Forchheim, Germany). Seven children had a previous chest CT performed on a 64-row scanner at 100 kV without organ-specific dose reduction. Subjective image quality was assessed using a five-point scale (1-not diagnostic; 5-excellent). Contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) were assessed in the descending aorta.

Results

Overall mean subjective image quality was 4.1?±?0.6. In the subgroup of the seven children examined both with and without organ-specific dose reduction, subjective image quality was comparable (score 4.4?±?0.5 with organ-specific dose reduction vs. 4.4?±?0.7 without it; P?>?0.05). There was no significant difference in mean signal-to-noise ratio and contrast-to-noise ratio with organ-specific dose reduction (38.3?±?10.1 and 28.5?±?8.7, respectively) and without the reduction (35.5?±?8.5 and 26.5?±?7.8, respectively) (P?>?0.05). Volume computed tomography dose index (CTDI_vol) and size-specific dose estimates did not differ significantly between acquisitions with the organ-specific dose reduction (1.7?±?0.8 mGy) and without the reduction (1.7?±?0.8 mGy) (P?>?0.05).

Conclusion

Organ-specific dose reduction does not have an impact on image quality of pediatric chest CT and can therefore be used in clinical practice to reduce radiation dose of radiosensitive organs such as breast and thyroid gland.