Treatment of hemispatial neglect by means of rTMS--a review

Hemispatial neglect - defined as the failure to attend, explore, and act upon the contralesional side of space - is a frequent and disabling neurological syndrome. Interhemispheric rivalry is considered as a major pathophysiological mechanism underlying hemispatial neglect. According to this account, the contralesional, intact hemisphere undergoes a pathological hyperactivity due to a deficient transcallosal inhibition from the damaged hemisphere. This model offers a framework for possible therapeutic interventions with repetitive transcranial magnetic stimulation (rTMS), i.e. a reduction of the pathological hyperactivity with a rTMS protocol that has lasting inhibitory effects. In the present work, we will first review evidence for the interhemispheric rivalry account coming from animals and humans. We will then describe studies showing the possibility to perturb and to restore interhemispheric balance in healthy subjects as a proof of concept for therapeutic rTMS application. Finally, we will consider studies applying rTMS as a therapeutic approach in hemispatial neglect. We conclude that rTMS is a promising approach to reduce the interhemispheric imbalance in neglect patients and to ameliorate symptoms. Newly developed protocols such as Theta Burst Stimulation (TBS) - with short stimulation times and long offline effects - seem to be particularly convenient. However, future studies should assess stimulation effects not only in clinical testing, but also on disability, considering combination with traditional therapies as well.

On the terminal homologation of physiologically active peptides as a means of increasing stability in human serum--neurotensin, opiorphin, B27-KK10 epitope, NPY

The terminal homologation by CH(2) insertion into the peptides mentioned in the title is described. This involves replacement of the N-terminal amino acid residue by a β(2) - and of the C-terminal amino acid residue by a β(3) -homo-amino acid moiety (β(2) hXaa and β(3) hXaa, resp.; Fig. 1). In this way, the structure of the peptide chain from the N-terminal to the C-terminal stereogenic center is identical, and the modified peptide is protected against cleavage by exopeptidases (Figs. 2 and 3). Neurotensin (NT; 1) and its C-terminal fragment NT(8-13) are ligands of the G-protein-coupled receptors (GPCR) NT1, NT2, NT3, and NT analogs are promising tools to be used in cancer diagnostics and therapy. The affinities of homologated NT analogs, 2b-2e, for NT1 and NT2 receptors were determined by using cell homogenates and tumor tissues (Table 1); in the latter experiments, the affinities for the NT1 receptor are more or less the same as those of NT (0.5-1.3 vs. 0.6 nM). At the same time, one of the homologated NT analogs, 2c, survives in human plasma for 7 days at 37° (Fig. 6). An NMR analysis of NT(8-13) (Tables 2 and 4, and Fig. 8) reveals that this N-terminal NT fragment folds to a turn in CD(3) OH. - In the case of the human analgesic opiorphin (3a), a pentapeptide, and of the HIV-derived B27-KK10 (4a), a decapeptide, terminal homologation (→3b and 4b, resp.) led to a 7- and 70-fold half-life increase in plasma (Fig. 9). With N-terminally homologated NPY, 5c, we were not able to determine serum stability; the peptide consisting of 36 amino acid residues is subject to cleavage by endopetidases. Three of the homologated compounds, 2b, 2c, and 5c, were shown to be agonists (Fig. 7 and 11). A comparison of terminal homologation with other stability-increasing terminal modifications of peptides is performed (Fig. 5), and possible applications of the neurotensin analogs, described herein, are discussed.

Estimation of the postmortem interval by means of ¹H MRS of decomposing brain tissue: influence of ambient temperature

Standard methods for the estimation of the postmortem interval (PMI, time since death), based on the cooling of the corpse, are limited to about 48 h after death. As an alternative, noninvasive postmortem observation of alterations of brain metabolites by means of (1)H MRS has been suggested for an estimation of the PMI at room temperature, so far without including the effect of other ambient temperatures. In order to study the temperature effect, localized (1)H MRS was used to follow brain decomposition in a sheep brain model at four different temperatures between 4 and 26°C with repeated measurements up to 2100 h postmortem. The simultaneous determination of 25 different biochemical compounds at each measurement allowed the time courses of concentration changes to be followed. A sudden and almost simultaneous change of the concentrations of seven compounds was observed after a time span that decreased exponentially from 700 h at 4°C to 30 h at 26°C ambient temperature. As this represents, most probably, the onset of highly variable bacterial decomposition, and thus defines the upper limit for a reliable PMI estimation, data were analyzed only up to this start of bacterial decomposition. As 13 compounds showed unequivocal, reproducible concentration changes during this period while eight showed a linear increase with a slope that was unambiguously related to ambient temperature. Therefore, a single analytical function with PMI and temperature as variables can describe the time courses of metabolite concentrations. Using the inverse of this function, metabolite concentrations determined from a single MR spectrum can be used, together with known ambient temperatures, to calculate the PMI of a corpse. It is concluded that the effect of ambient temperature can be reliably included in the PMI determination by (1)H MRS.

Phosphatidylethanol (PEth) as a Biomarker of Alcohol Consumption in HIV-Positive Patients in Sub-Saharan Africa

Background:  Alcohol is heavily consumed in sub-Saharan Africa and affects HIV transmission and treatment and is difficult to measure. Our goal was to examine the test characteristics of a direct metabolite of alcohol consumption, phosphatidylethanol (PEth). Methods:  Persons infected with HIV were recruited from a large HIV clinic in southwestern Uganda. We conducted surveys and breath alcohol concentration (BRAC) testing at 21 daily home or drinking establishment visits, and blood was collected on day 21 (n = 77). PEth in whole blood was compared with prior 7-, 14-, and 21-day alcohol consumption. Results:  (i) The receiver operator characteristic area under the curve (ROC-AUC) was highest for PEth versus any consumption over the prior 21 days (0.92; 95% confidence interval [CI]: 0.86 to 0.97). The sensitivity for any detectable PEth was 88.0% (95% CI: 76.0 to 95.6) and the specificity was 88.5% (95% CI: 69.8 to 97.6). (ii) The ROC-AUC of PEth versus any 21-day alcohol consumption did not vary with age, body mass index, CD4 cell count, hepatitis B virus infection, and antiretroviral therapy status, but was higher for men compared with women (p = 0.03). (iii) PEth measurements were correlated with several measures of alcohol consumption, including number of drinking days in the prior 21 days (Spearman r = 0.74, p < 0.001) and BRAC (r = 0.75, p < 0.001). Conclusions:  The data add support to the body of evidence for PEth as a useful marker of alcohol consumption with high ROC-AUC, sensitivity, and specificity. Future studies should further address the period and level of alcohol consumption for which PEth is detectable.

Hip abductor defect repair by means of a vastus lateralis muscle shift

Scarring or detachment of the hip abductors, particularly of the gluteus medius, from their insertion may lead to severe abductor weakness, recurrent dislocations, pain, and diminished quality of life. We performed a retrospective study to evaluate whether vastus lateralis shift is associated with satisfactory results and low rate of complications. Eleven adults underwent vastus lateralis shift to bridge a well-documented abductor muscles' insertion defect. Preoperative and postoperative hip functions were assessed applying the Merle d'Aubigne score, British Medical Council scale, and Visual Analog Scale. Significant postoperative improvement was noted in mean Merle d'Aubigne score, gluteus medius muscle force, and quality of life. Vastus lateralis shift represents a viable treatment option for hip abductor deficiency, significantly improving abductor strength and overall quality of life.

Comparison of implant stability by means of resonance frequency analysis for flapless and conventionally inserted implants

Background: Resonance frequency analysis (RFA) is a noninvasive technique for the quantitative assessment of implant stability. Information on the implant stability quotient (ISQ) of transmucosally inserted implants is limited. Purpose: The aim of this investigation was to compare the ISQ of conventionally inserted implants by raising a muco-periostal flap with implants inserted using a flapless procedure. Materials and Methods: Forty elderly patients with complete edentulous maxilla were consecutively admitted for treatment with implant-supported prostheses. A computer tomography was obtained for the computer-assisted implant planning. One hundred ten implants were placed conventionally in 23 patients (flap-group) and 85 implants in 17 patients by means of the flapless method (flapless-group) using a stereolithographic template. RFA measurements were performed after implant placement (baseline) and after a healing time of 12 weeks (reentry). Results: All implants exhibited clinically and radiographically successful osseointegration. Bone level did not change significantly neither for genders nor type of surgical protocol. Mean ISQ values of the flapless-group were significantly higher at baseline (p < .001) and at reentry (p < .001) compared with the flap-group. The ISQ values were significantly lower at reentry compared with baseline for the flap-group (p = .028) but not for the flapless-group. This group showed a moderate, but insignificant increase. RFA measurements of males resulted in ISQ values that were thoroughly higher as compared with females at both time-points in both groups. Correlation between RFA and bone level was not found. Conclusions: The flapless procedure showed favorable conditions with regard to implant stability and crestal bone level. Some changes of the ISQ values that represent primary (mechanical) and secondary (bone remodeling) implant stability were observed in slight favor of the flapless method and male patients. In properly planned and well-selected cases, the minimal invasive transmucosal technique using a drill-guide is a safe procedure.

Pulse-front tilt for short-wavelength lasing by means of traveling-wave plasma-excitation

Generation of coherent short-wavelength radiation across a plasma column is dramatically improved under traveling-wave excitation (TWE). The latter is optimized when its propagation is close to the speed of light, which implies small-angle target-irradiation. Yet, short-wavelength lasing needs large irradiation angles in order to increase the optical penetration of the pump into the plasma core. Pulse-front back-tilt is considered to overcome such trade-off. In fact, the TWE speed depends on the pulse-front slope (envelope of amplitude), whereas the optical penetration depth depends on the wave-front slope (envelope of phase). Pulse-front tilt by means of compressor misalignment was found effective only if coupled with a high-magnification front-end imaging/focusing component. It is concluded that speed matching should be accomplished with minimal compressor misalignment and maximal imaging magnification.