A case report of posttraumatic stress disorder at the end of life

Wiener Medizinische Wochenschrift - A case of posttraumatic stress disorder (PTSD) in the last days of life is presented. It shows insufficient pharmacological therapy and PTSD that was...     

Local and transient inhibition of p21 expression ameliorates age‐related delayed wound healing

Nonhealing chronic wounds in the constantly growing elderly population represent a major public health problem with high socioeconomic burden. Yet, the underlying mechanism of age‐related impairment of wound healing remains elusive. Here, we show that the number of dermal cells expressing cyclin‐dependent kinase inhibitor p21 was elevated upon skin injury, particularly in aged population, in both man and mouse. The nuclear expression of p21 in activated wound fibroblasts delayed the onset of the proliferation phase of wound healing in a p53‐independent manner. Further, the local and transient inhibition of p21 expression by in vivo delivered p21‐targeting siRNA ameliorated the delayed wound healing in aged mice. Our results suggest that the increased number of p21⁺ wound fibroblasts enforces the age‐related compromised healing, and targeting p21 creates potential clinical avenues to promote wound healing in aged population.     

Multiscale photonic imaging of the native and implanted cochlea

The cochlea of our auditory system is an intricate structure deeply embedded in the temporal bone. Compared with other sensory organs such as the eye, the cochlea has remained poorly accessible for investigation, for example, by imaging. This limitation also concerns the further development of technology for restoring hearing in the case of cochlear dysfunction, which requires quantitative information on spatial dimensions and the sensorineural status of the cochlea. Here, we employed X-ray phase-contrast tomography and light-sheet fluorescence microscopy and their combination for multiscale and multimodal imaging of cochlear morphology in species that serve as established animal models for auditory research. We provide a systematic reference for morphological parameters relevant for cochlear implant development for rodent and nonhuman primate models. We simulate the spread of light from the emitters of the optical implants within the reconstructed nonhuman primate cochlea, which indicates a spatially narrow optogenetic excitation of spiral ganglion neurons.

In the case of profound sensorineural hearing impairment, cochlear implants (CIs) partially restore hearing by providing auditory information to the brain via electrical stimulation of the spiral ganglion neurons (SGNs). CIs enable speech understanding in the majority of the ∼700,000 users worldwide. However, current clinical CIs are limited by their wide current spread (1) resulting in poor coding of spectral information (2). Recently, cochlear optogenetics was proposed for stimulating the auditory nerve by light (3–10). As light can be better confined in space, the spread of excitation in the cochlea is lower (3, 9–11) and, hence, future optical CIs (oCIs) promise improved speech comprehension—especially in noisy background—as well as greater music appreciation.For the technical development of oCIs toward a future medical device, major efforts are currently being undertaken to devise multichannel optical stimulators for the cochlea (10, 12–17). As is the case for the electrodes of current CIs, future oCIs will place multiple stimulation channels, here microscale emitters, along the tonotopic axis of the cochlea. Further development of the oCIs requires precise estimates of parameters such as scala tympani size, optimal probe stiffness, and bending radius. Moreover, cochlear optogenetics employs gene transfer to the SGNs for which adeno-associated viruses (AAVs) seem promising candidate vectors (3–5, 8). AAV delivery has used injection of virus suspension via the round window (4, 8) or directly into Rosenthal’s canal (5, 9, 10). Therefore, the volumes of Rosenthal’s canal and the scalae tympani, vestibuli and media needed to be evaluated in order to estimate the required virus load for injection. Finally, the sensorineural status of the cochlea is highly relevant for future gene therapy and CI stimulation, and hence, quantitative imaging of sensory cells and neurons is an important objective.Here, we employed multiscale X-ray phase-contrast tomography (XPCT) and light-sheet fluorescence microscopy (LSFM) and provide an analysis of cochlear morphology for mice, rats, gerbils, guinea pigs, and marmosets. Each of these animal models offers unique advantages for auditory research. The mouse is readily available for genetic manipulation (e.g., ref. 18). Channelrhodopsin-expressing transgenic lines are available also for rats (19, 20) that offer a larger cochlea and can carry heavier implants than mice (21–24). Similarly, gerbils and guinea pigs are established rodent models for auditory research with larger-sized cochleae. Moreover, gerbils, which have low-frequency hearing more similar to humans, have already been employed for cochlear optogenetics (5, 9, 10, 24). Finally, we analyzed the cochlea of the common marmoset, as an established nonhuman primate model for auditory research (e.g., refs. 25, 26). Marmosets possess a rich vocalization repertoire and share a pitch perception mechanism with humans (27). Therefore, we compared cochlear insertion of newly designed oCIs with electrical cochlear implants (eCI) and modeled the optical spread of excitation in the marmoset cochlea.     

Investigations of Platelet Function in Whole Blood with BAPA as Anticoagulant

BACKGROUND: Citrate anticoagulation of blood results in non-physiologically low calcium concentration and rapid deterioration of platelet viability. Benzylsulfonyl-D-Arg-Pro-4-amidinobenzylamide (BAPA) as anticoagulant maintains the physiological calcium level and seems to retain platelet function (PF) over a time period of at least 24 h. We evaluated PF in BAPA-anticoagulated peripheral whole blood (WB) between 0.5 and 30 h after blood collection. METHODS: In WB from 21 healthy volunteers (15 women, 6 men, age range 19-57 years) platelet aggregation (PA) was determined by impedance method and ATP release by luminometry. Platelet response was tested by ADP (10 and 20 μmol/l) and collagen (1 and 2 μg/ml) between 0.5 and 30 h after blood collection. RESULTS: Parameters of ADP-induced PA showed stable values until 6.5 h after blood collection followed by a significant decline. PA in response to collagen was stable up to 25 h of storage. ATP release induced by collagen displayed a continuous, significant decrease over time. CONCLUSION: Preservation of platelet response in BAPA-anticoagulated blood depends on the applied agonist showing that collagen-induced PA is more stable compared to ADP known as a weak agonist in WB.     

The Torg-Pavlov ratio for the prediction of acute spinal cord injury after a minor trauma to the cervical spine

Background contextAcute cervical spinal cord injury (SCI) has been observed in some patients after a minor trauma to the cervical spine. The discrepancy between the severity of the trauma and the clinical symptoms has been attributed to spinal canal stenosis. However, to date, there is no universally established radiological parameter for identifying critical spinal stenosis in these patients. The spinal canal–to–vertebral body ratio (Torg-Pavlov ratio) has been proposed for assessing developmental spinal canal stenosis. The relevance of the Torg-Pavlov ratio for predicting the occurrence and severity of acute cervical SCI after a minor trauma to the cervical spine has not yet been established.PurposeTo investigate the Torg-Pavlov ratio values of the cervical spine in patients suffering from acute cervical SCI after a minor trauma to the cervical spine and the use of the Torg-Pavlov ratio for identifying patients at risk of cervical SCI and predicting the severity and course of symptoms.Study design/settingRetrospective radiological study of consecutive patients.Patient sampleForty-five patients suffering from acute cervical SCI and 68 patients showing no neurologic symptoms after a minor trauma to the cervical spine.Outcome measuresMidvertebral sagittal cervical spinal canal diameter and the sagittal vertebral body diameter. Calculation of the Torg-Pavlov ratio values.MethodsConventional lateral radiographs of the cervical spine (C3–C7) were analyzed to determine the Torg-Pavlov ratio values. Receiver operating characteristic curves were calculated for evaluating the classification accuracy of the Torg-Pavlov ratio for predicting SCI.ResultsThe Torg-Pavlov ratio values in the SCI group were significantly (p<.04) smaller compared with that in the control group. A Torg-Pavlov ratio cutoff value of 0.7 yielded the greatest positive likelihood ratio for predicting the occurrence of SCI. However, there were no significant differences in the Torg-Pavlov ratio values between the different American Spinal Injury Association Impairment Score groups and between patients with complete, partial, and no recovery of symptoms.ConclusionsDevelopmental cervical spinal canal stenosis assessed by the Torg-Pavlov ratio was characteristic for patients suffering from acute cervical SCI after a minor trauma to the cervical spine. Patients at risk of SCI after a minor trauma to the cervical spine can be identified by applying a Torg-Pavlov ratio cutoff value of 0.7. Other factors in addition to the spinal canal–to–vertebral body ratio affect the severity and course of symptoms as a result of cervical SCI.     

Influence of virtual reality soccer game on walking performance in robotic assisted gait training for children

Background

Virtual reality (VR) offers powerful therapy options within a functional, purposeful and motivating context. Several studies have shown that patients' motivation plays a crucial role in determining therapy outcome. However, few studies have demonstrated the potential of VR in pediatric rehabilitation. Therefore, we developed a VR-based soccer scenario, which provided interactive elements to engage patients during robotic assisted treadmill training (RAGT). The aim of this study was to compare the immediate effect of different supportive conditions (VR versus non-VR conditions) on motor output in patients and healthy control children during training with the driven gait orthosis Lokomat^®.

Methods

A total of 18 children (ten patients with different neurological gait disorders, eight healthy controls) took part in this study. They were instructed to walk on the Lokomat in four different, randomly-presented conditions: (1) walk normally without supporting assistance, (2) with therapists' instructions to promote active participation, (3) with VR as a motivating tool to walk actively and (4) with the VR tool combined with therapists' instructions. The Lokomat gait orthosis is equipped with sensors at hip and knee joint to measure man-machine interaction forces. Additionally, subjects' acceptance of the RAGT with VR was assessed using a questionnaire.

Results

The mixed ANOVA revealed significant main effects for the factor CONDITIONS (p < 0.001) and a significant interaction CONDITIONS × GROUP (p = 0.01). Tests of between-subjects effects showed no significant main effect for the GROUP (p = 0.592). Active participation in patients and control children increased significantly when supported and motivated either by therapists' instructions or by a VR scenario compared with the baseline measurement "normal walking" (p < 0.001).

Conclusions

The VR scenario used here induces an immediate effect on motor output to a similar degree as the effect resulting from verbal instructions by the therapists. Further research needs to focus on the implementation of interactive design elements, which keep motivation high across and beyond RAGT sessions, especially in pediatric rehabilitation.