Objective measurement of oral function in adults with spinal muscular atrophy.

BACKGROUND: Impairment of bulbar function in adult individuals with spinal muscular atrophy (SMA) usually is not assessed by established motor scores. Measurements of oral function including quantitative muscle and endurance tests are able to detect subtle changes. The aim of this study was to systematically evaluate the measurement of maximum bite force and endurance, maximum tongue pressure and endurance, as well as maximum mouth opening in adult individuals with SMA types 2 and 3. METHODS: Data from oral function tests in 43 individuals were analyzed. Differences in oral function between individuals with different SMA types and numbers of SMN2 copies were tested. Spearman´s rho correlations among oral function measures themselves as well as with established clinical outcome scales were analyzed. RESULTS: The absolute maximum measures of oral function (maximum bite force, maximum tongue pressure, maximum mouth opening) were able to discriminate between individuals with different SMA types, individuals with a different number of SMN2 copies and with different walking abilities. The pairwise correlations of the absolute maximum measures of oral function were fair to moderate in size; the same was true for their correlations with the established motor scores. All correlations assessing endurance measures of oral function were weaker and statistically insignificant. CONCLUSIONS: Among the oral function tests maximum tongue pressure and maximum mouth opening are particulary promising as clinical and sensitive outcome measures for clinical trials. Oral function tests may supplement existing motor scores, in particular concerning specific questions about bulbar function or in severely affected non-ambulatory individuals where mild (treatment-related) changes would otherwise remain undetected. Trial registration DRKS, DRKS00015842. Registered 30 July 2019, https://drks.de/search/de/trial/DRKS00015842.

Remote ultrasound diagnostics disrupting traditional military frontline healthcare delivery.

Accurate and reliable diagnostic capability is essential in deployed healthcare to aid decision-making and mitigate risk. This is important for both the patient and the deployed healthcare system, especially when considering the prioritisation of scarce aeromedical evacuation assets and frontline resources. Novel ultrasound tele-guidance technology presents a valuable diagnostic solution for remotely deployed military clinicians. This report discusses the first use of a consultant radiologist guiding a clinician, untrained in ultrasound, to perform an ultrasound scan via a live tele-guidance feed in the deployed environment using the Butterfly iQ+ tele-guidance system. Distance scanning provided a diagnostic quality report when compared with locally performed imaging to improve patient care and maintain operational output. This example demonstrates feasibility of remote point-of-care imaging systems in provision of location-agnostic high-quality diagnostic capability. Future opportunities to develop care pathways using bedside tele-diagnostics will democratise access, drive efficiency and improve patient care experience and outcomes.

Band-gap and strain engineering in GeSn alloys using post-growth pulsed laser melting.

The pseudomorphic growth of Ge1-xSnxon Ge causes in-plane compressive strain, which degrades the superior properties of the Ge1-xSnxalloys. Therefore, efficient strain engineering is required. In this article, we present strain and band-gap engineering in Ge1-xSnxalloys grown on Ge a virtual substrate using post-growth nanosecond pulsed laser melting (PLM). Micro-Raman and x-ray diffraction (XRD) show that the initial in-plane compressive strain is removed. Moreover, for PLM energy densities higher than 0.5 J cm-2, the Ge0.89Sn0.11layer becomes tensile strained. Simultaneously, as revealed by Rutherford Backscattering spectrometry, cross-sectional transmission electron microscopy investigations and XRD the crystalline quality and Sn-distribution in PLM-treated Ge0.89Sn0.11layers are only slightly affected. Additionally, the change of the band structure after PLM is confirmed by low-temperature photoreflectance measurements. The presented results prove that post-growth ns-range PLM is an effective way for band-gap and strain engineering in highly-mismatched alloys.

Growth environment influences B16.F10 mouse melanoma cell response to gene electrotransfer.

We developed and characterized a 3D collagen hydrogel model for B16.F10 melanoma tumors. Cells in this 3D environment exhibited lower proliferation than cells in the conventional 2D culture environment. Interestingly, the basal expression levels of several genes varied when compared to conventionally grown cells. In each growth environment, a significant number of melanoma cells were transfected by plasmid electroporation (electrotransfer), although expression could only be ascertained on the surface of the 3D constructs. Cellular responses to plasmid entry as demonstrated by pro-inflammatory cytokine and chemokine upregulation varied based on the growth environment, as did the mRNA levels of several putative DNA-specific pattern recognition receptors (DNA sensors). Unexpectedly, when plasmid DNA was delivered while cells where attached in the 2D or 3D environments, the mRNAs of the DNA sensor p204 and the inflammatory mediator TNFα were regulated in cells receiving pulses only. However, we were unable to confirm coordinate upregulation of TNFα and p204 proteins. This study confirms that cell responses differ significantly based on their environment, and demonstrates the difficulty of extending experimental observations between cell environments.

[Challenges of digitalization in trauma care]. / Herausforderungen der Digitalisierung in der Traumaversorgung.

The increasing digitalization of social life opens up new possibilities for modern health care. This article describes innovative application possibilities that could help to sustainably improve the treatment of severe injuries in the future with the help of methods such as big data, artificial intelligence, intelligence augmentation, and machine learning. For the successful application of these methods, suitable data sources must be available. The TraumaRegister DGU® (TR-DGU) currently represents the largest database in Germany in the field of care for severely injured patients that could potentially be used for digital innovations. In this context, it is a good example of the problem areas such as data transfer, interoperability, standardization of data sets, parameter definitions, and ensuring data protection, which still represent major challenges for the digitization of trauma care. In addition to the further development of new analysis methods, solutions must also continue to be sought to the question of how best to intelligently link the relevant data from the various data sources.

[Artificial intelligence in orthopedics and trauma surgery]. / Künstliche Intelligenz in der Orthopädie und Unfallchirurgie.

Artificial intelligence (AI) is a very relevant topic for the medicine of the future. This article focuses on the field of AI in the context of orthopedics and trauma surgery. The main focus is on the potentials of AI in the analysis of symptoms, radiological images, clinical data sets, use in hospitals and operating theaters as well as for training and education. For the orthopedics and trauma surgery of the future AI is much more than pure fiction; however, there is still a long way to go before the potential of an optimized and individualized patient care can be utilized. Interdisciplinary and international approaches, including personnel, economic, legal and ethical aspects will play a decisive role in this respect.

Use of Masquelet technique in treatment of septic and atrophic fracture nonunion.

BACKGROUND: Treatment of atrophic non-unions and large bone defects or infections remains a challenging task for the treating surgeon. In the herein study, we present our experience of the 'Masquelet technique' according to the 'diamond concept' for the treatment of complex long bone reconstruction procedures. METHODS: Between February 2010 and March 2015, 150 patients (mean age 51.4) with atrophic and- /or infected non-unions were included in this prospective study. All patients received autologous bone graft, a graft expander (TCP (tricalcium phosphate)) and BMP (bone morphogenic protein). Clinical and radiological parameters were assessed at 6 weeks, and at 3, 6 and 12 months. The SF-12 questionnaire was used to evaluate the subjective health of patients. RESULTS: A successful bony consolidation of the non-unions was observed in 120 (80%) cases with a median healing time of 12.1 months. The mean defect gap was 4.4cm. Initial infection was documented in 54 cases. The most frequently identified pathogen was staphylococcus epidermidis and staphylococcus aureus. A successful removal of microorganisms with subsequent healing was achieved in 39 cases (72%). The SF-12 scores of subjective physical and mental health increased from PCS 31.5 preoperatively to 36.7 one year postoperatively, while MCS increased from 45.5 to 48.7. CONCLUSIONS: Our study showed that the Masquelet technique according to the 'diamond concept' is a valid method to treat complex atrophic non-unions with large bone defects and associated infection. Following the principles of the 'diamond concept' (targeted optimization of tissue engineering and bone regeneration) a high rate of success can be expected in these difficult reconstruction cases.

Time-of-flight secondary ion mass spectrometry in the helium ion microscope.

A helium ion microscope, known for high resolution imaging and modification with helium or neon ions, has been equipped with a time-of-flight spectrometer for compositional analysis. Here we report on its design, implementation and show first results of this powerful add-on. Our design considerations were based on the results of detailed ion collision cascade simulations that focus on the physically achievable resolution for various detection limits. Different secondary ion extraction geometries and spectrometer types are considered and compared with respect to the demands and limitations of the microscope. As a result the development and evaluation of a secondary ion extraction optics and time-of-flight spectrometer that allows the parallel measurement of all secondary ion masses is reported. First experimental results demonstrate an excellent mass resolution as well as high-resolution secondary ion imaging capabilities with sub-8 nm lateral resolution. The combination of high resolution secondary electron images and mass-separated sputtered ion distributions have a high potential to answer open questions in microbiology, cell biology, earth sciences and materials research.

Evaluation of matrix metalloproteases as early biomarkers for bone regeneration during the applied Masquelet therapy for non-unions.

INTRODUCTION: In the current study, we sought to determine if serum concentrations of MMPs correlate with bone regeneration occurring during the course of the Masquelet-therapy and to identify if MMPs may serve as early biomarkers reflecting successful bone regeneration and tissue remodeling. MATERIAL AND METHODS: This study was designed as a prospective clinical observer study. We compared serum samples over the time of treatment, as a matched-pair analysis, from 10 patients who were treated successfully with the Masquelet-therapy (Responder) with 10 patients who did not respond to the Masquelet-therapy (Non-Responder). The quantitative measurement was performed with Luminex Performance Human High Sensitivity Assays according to manufacturer's instructions. The lab technician performing the Luminex assays was blinded to both patient data and clinical outcome. RESULTS: Analysis of the expression pattern of MMP-2, -8 and -9 showed significant differences between groups. Two days after the first step of the Masquelet therapy Responder showed peak values of MMP-8 and MMP-9 that where significantly higher (p = 0.003 and p = 0.042, respectively) than in Non-Responder. In contrast serum levels of MMP-2 were lower after the first step of the Masquelet therapy in the Non-Responder group. The ratio of MMP-9 and MMP-2 was significantly higher in the Responder group two days after step I (p = 0.031) as well as 4 weeks after step II (p = 0.030). CONCLUSION: The findings of the current study emphasize the potential role of MMPs as biomarkers in bone remodeling. In particular, a distinct expression of MMP-2 correlates with successful bone regeneration, whereas initial overexpression of MMP-2 serum levels might identify patients that have a higher risk for a poor outcome of the Masquelet-therapy. Furthermore, we were able to introduce the serum analysis of the ratio of MMP-9 and MMP-2 as promising novel modality for early prediction of the outcome of the Masquelet therapy. Further analysis of this ratio over time subsequent to the second step might serve as an early indicator of a favorable response to the induced membrane technique.

Combining advantages: Direct correlation of two-dimensional microcomputed tomography datasets onto histomorphometric slides to quantify three-dimensional bone volume in scaffolds.

Microcomputed tomography (mCT) belongs to the most powerful tools for the three-dimensional (3D) assessment of bone. While it is possible to refer to landmarks in mCT scans of actual bone structure, the assessment of calcified osteoid within scaffolds is problematic, due to the missing morphological correlates. Therefore, bone formation within scaffolds is mostly analyzed using indirect parameters such as changes in volume or surface alteration, preserving histomorphometry the gold standard in the direct analysis of bone formation. The presented method combines the advantages of mCT and histomorphometry: by creating an overlay image of the exact same histomorphometric and mCT slice, a grey-value-threshold representing calcified tissue was defined. Compared to the scaffolds global threshold, a direct evaluation of bone formation within scaffolds is possible by mCT-applied on the whole dataset, evaluation of bone volume is achievable. Two groups of human mesenchymal-stem-cell-seeded ß-Tricalciumphosphate-scaffolds were analyzed: whilst group B was stimulated with 0.1 µg/mL Bone Morphogenetic Protein-7, group A remained unstimulated during in vivo differentiation. Strong correlations (r > 0.8) were obtained between percentage bone area in mCT and histomorphometry, as well as for 3D bone volume. Using the presented method, 3D bone volume can be directly estimated within scaffolds by combination of histomorphometric and mCT-analysis. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1812-1821, 2018.

The feasibility of contraceptive injections at the community pharmacy.

PURPOSE: The progestogen-only intramuscular injectable Depo-Provera® (depot medroxyprogesterone acetate) is an effective contraceptive method, but users need to attend a clinic every 12-13 weeks for a repeat injection from a doctor/nurse. This limits convenience of the method and may affect continuation rates. We conducted a pilot study to examine the feasibility and acceptability of users receiving the subcutaneous form of the contraception injection from pharmacists in the community pharmacy setting. MATERIALS AND METHODS: Existing users of Depo-Provera®, who wished to switch to the subcutaneous preparation with the same active ingredient (Sayana Press®) were invited to attend 1 of 11 community pharmacies for up to three repeat injections, given by a pharmacist. Evaluation consisted of (i) self-administered questionnaires of women and (ii) interviews with participating pharmacists, at study exit on their respective experiences. RESULTS: Global unavailability of the product during the study adversely affected recruitment and retention. 50 women were recruited. Only 48 injections were delivered at the pharmacy out of a possible 150 (34%). About 26 participants received no injections at the pharmacy and only seven (14%) participants received all three injections at the pharmacy. Participants reported mixed experiences, with some welcoming the intervention but others experiencing difficulty with pharmacist availability. Pharmacists were enthusiastic about this expansion of their role, and did not view their availability as a barrier to service delivery. CONCLUSIONS: Delivery of the subcutaneous contraceptive injectable from a community pharmacy may be feasible but availability of sufficient numbers of pharmacists trained in this technique is necessary for a robust model of service delivery.

Genome sequence of a diabetes-prone rodent reveals a mutation hotspot around the ParaHox gene cluster.

The sand rat Psammomys obesus is a gerbil species native to deserts of North Africa and the Middle East, and is constrained in its ecology because high carbohydrate diets induce obesity and type II diabetes that, in extreme cases, can lead to pancreatic failure and death. We report the sequencing of the sand rat genome and discovery of an unusual, extensive, and mutationally biased GC-rich genomic domain. This highly divergent genomic region encompasses several functionally essential genes, and spans the ParaHox cluster which includes the insulin-regulating homeobox gene Pdx1. The sequence of sand rat Pdx1 has been grossly affected by GC-biased mutation, leading to the highest divergence observed for this gene across the Bilateria. In addition to genomic insights into restricted caloric intake in a desert species, the discovery of a localized chromosomal region subject to elevated mutation suggests that mutational heterogeneity within genomes could influence the course of evolution.

Serological evidence of Francisella tularensis in febrile patients seeking treatment at remote hospitals, northeastern Kenya, 2014-2015.

Tularaemia is a highly contagious infectious zoonosis caused by the bacterial agent Francisella tularensis. The aim of this study was to investigate the presence of antibodies to F. tularensis in febrile patients in northeastern Kenya. During 2014-2015, 730 patients were screened for anti-F. tularensis antibodies using a combination of ELISA and Western blot. Twenty-seven (3.7%) individuals were positive for F. tularensis. Tularaemia was not suspected by the treating clinicians in any of them. Our results suggest that tularaemia may be present in Kenya but remain unreported, and emphasizes the need for local clinicians to broaden their diagnostic repertoire when evaluating patients with undifferentiated febrile illness.

CCL-2 as a possible early marker for remission after traumatic spinal cord injury.

STUDY DESIGN: Prospective observational study. OBJECTIVES: To describe the correlation between CCL-2, CCL-3, CCL-4 and CXCL-5 serum levels and remission after traumatic spinal cord injury (SCI) in a human protocol compared with animal studies. SETTING: Germany, Rhineland-Palatinate (Rheinland-Pfalz). METHODS: We examined the serum levels of CCL-2, CCL-3, CCL-4 and CXCL-5 over a 12-week period; in particular, at admission and 4, 9 and 12 h, 1 and 3 days and 1, 2, 4, 8 and 12 weeks after trauma. According to our study design, we matched 10 patients with TSCI and neurological remission with 10 patients with an initial ASIA A grade and no neurological remission. In all, 10 patients with vertebral fracture without neurological deficits served as control. Our analysis was performed using a Luminex Cytokine Panel. Multivariate logistic regression models were used to examine the predictive value with respect to neurological remission vs no neurological remission. RESULTS: The results of our study showed differences in the serum expression patterns of CCL-2 in association with the neurological remission (CCL-2 at admission P=0.013). Serum levels of CCL-2 and CCL-4 were significantly different in patients with and without neurological remission. The favored predictive model resulted in an area under the curve (AUC) of 93.1% in the receiver operating characteristic (ROC) analysis. CONCLUSIONS: Our results indicate that peripheral serum analysis is a suitable concept for predicting the patient's potential for neurological remission after TSCI. Furthermore, the initial CCL-2 concentration provides an additional predictive value compared with the NLI (neurological level of injury). Therefore, the present study introduces a promising approach for future monitoring concepts and tracking techniques for current therapies. The results indicate that future investigations with an enlarged sample size are needed in order to develop monitoring, prognostic and scoring systems.

An open-source platform to study uniaxial stress effects on nanoscale devices.

We present an automatic measurement platform that enables the characterization of nanodevices by electrical transport and optical spectroscopy as a function of the uniaxial stress. We provide insights into and detailed descriptions of the mechanical device, the substrate design and fabrication, and the instrument control software, which is provided under open-source license. The capability of the platform is demonstrated by characterizing the piezo-resistance of an InAs nanowire device using a combination of electrical transport and Raman spectroscopy. The advantages of this measurement platform are highlighted by comparison with state-of-the-art piezo-resistance measurements in InAs nanowires. We envision that the systematic application of this methodology will provide new insights into the physics of nanoscale devices and novel materials for electronics, and thus contribute to the assessment of the potential of strain as a technology booster for nanoscale electronics.

Feasibility and acceptability of introducing routine antenatal contraceptive counselling and provision of contraception after delivery: the APPLES pilot evaluation.

OBJECTIVE: To determine the feasibility and acceptability of routine antenatal contraceptive counselling and contraception provision including long-acting reversible contraception (LARC) postpartum. DESIGN: Health service research evaluation. SETTING: Community antenatal clinics and hospital maternity settings in National Health Service, Scotland UK. POPULATION: Women booked for antenatal care. METHODS: Contraceptive counselling with a community midwife (22 weeks' gestation) and provision of contraception (with facilitated access to LARC methods) prior to discharge from maternity hospital. Evaluation consisted of (i) self administered questionnaire (32-34 weeks) of women's views of antenatal contraceptive counselling, (ii) database review of contraceptive methods provided at discharge, and (iii) focus groups with midwives and obstetricians. MAIN OUTCOME MEASURES: Women's views on antenatal contraceptive counselling. Secondary outcomes included (i) uptake of LARC methods and (ii) barriers and facilitators to providing antenatal counselling and contraception. RESULTS: There were 1369 women in the cohort. Questionnaires were distributed to 1064 women (78%) and completed by 794 (75%). In all, 78% of respondents (n = 621) discussed contraception antenatally with a community midwife and 74% (n = 461) found this helpful. Although 43% of respondents (n = 341) were planning to use LARC, only 9% of the cohort (118 of 1369) received LARC prior to discharge. Community midwives indicated that antenatal contraceptive counselling was now embedded in their role, but hospital staff indicated that workloads impacted upon ability to provide contraception for women. CONCLUSIONS: Antenatal contraceptive counselling, delivered by community midwives, is feasible and highly acceptable to women. However, providing contraception and LARC for women before they are discharged home remains a challenge. TWEETABLE ABSTRACT: Giving contraceptive advice antenatally is feasible and acceptable.

Exploratory study to suggest the possibility of MMP-8 and MMP-9 serum levels as early markers for remission after traumatic spinal cord injury.

STUDY DESIGN: A prospective observational study reporting the correlation between matrix metalloprotein serum levels and remission after traumatic spinal cord injury (SCI). OBJECTIVES: To investigate serum cytokine levels as predictive markers. SETTING: Germany, Rhineland-Palatinate (Rheinland-Pfalz). METHODS: Between 2010 and 2015, data sets from 115 patients (33 female, 82 male) after traumatic SCI were recorded at the BG Trauma Centre Ludwigshafen. We examined the serum levels of Matix metallopraoteinases (MMPs) MMP-2, MMP-8, MMP-9, MMP-10 and MMP-12 over a 12-week period, that is, at admission and 4, 9, 12 h, 1 and 3 days and 1, 2, 4, 8 and 12 weeks after trauma. Following the same match-pair procedure as in our previous studies, we selected 10 patients with SCI and neurological remission (Group 1) and 10 patients with an initial American Spinal Injury Association (ASIA) A grade and no neurological remission (Group 0). Ten patients with an isolated vertebral fracture without neurological deficits served as a control group (Group C). Our analysis was performed using a Luminex Performance Human High Sensitivity Cytokine Panel. Multivariate logistic regression models were used to examine the predictive value of MMPs with respect to neurological remission vs no neurological remission. RESULTS: MMP-8 and MMP-9 provided significantly different values. The favoured predictive model allows to differentiate between neurological remission and no neurological remission in 97% of cases. CONCLUSIONS: The results indicate that further studies with an enlarged collective are warranted in order to investigate current monitoring, prognostic and tracking techniques as well as scoring systems.

Extension of the clinical and molecular phenotype of DIAPH1-associated autosomal dominant hearing loss (DFNA1).

In about 20% of non-syndromic hearing loss (NSHL) cases, inheritance is autosomal dominant (ADNSHL). DIAPH1 mutations define the ADNSHL locus DFNA1. We identified two new families with heterozygous truncating DIAPH1 mutations (p.Ala1210Serfs*31 and p.Arg1213*). In contrast to the extensively studied original DFNA1 family, hearing loss was not confined to low frequencies, but congenital manifestation and rapid progression were confirmed. In line with a recent unrelated study, we identified an association with thrombocytopenia, reclassifying DFNA1 as a syndrome. Consequently, we suggest to include the blood count into the initial clinical workup of patients with autosomal dominant hearing loss to guide the genetic diagnosis. We provide the first data on DIAPH1 expression in the organ of Corti, where it localizes to the inner pillar cells, at the base of the outer hair cells. Homozygous truncating DIAPH1 mutations located N-terminally to the DFNA1 mutations have recently been identified in autosomal recessive microcephaly. It is therefore noteworthy that we found DIAPH1 expression also in spiral ganglion neurons and in the barrier between the myelinating glia of the peripheral nervous system and oligodendrocytes that form the myelinating glia of the central nervous system (CNS).