Stretchable Tissue-Like Gold Nanowire Composites with Long-Term Stability for Neural Interfaces.

Soft and stretchable nanocomposites can match the mechanical properties of neural tissue, thereby minimizing foreign body reactions to provide optimal stimulation and recording specificity. Soft materials for neural interfaces should simultaneously fulfill a wide range of requirements, including low Young's modulus (<<1 MPa), stretchability (≥30%), high conductivity (>> 1000 S cm-1), biocompatibility, and chronic stability (>> 1 year). Current nanocomposites do not fulfill the above requirements, in particular not the combination of softness and high conductivity. Here, this challenge is addressed by developing a scalable and robust synthesis route based on polymeric reducing agents for smooth, high-aspect ratio gold nanowires (AuNWs) of controllable dimensions with excellent biocompatibility. AuNW-silicone composites show outstanding performance with nerve-like softness (250 kPa), high conductivity (16 000 S cm-1), and reversible stretchability. Soft multielectrode cuffs based on the composite achieve selective functional stimulation, recordings of sensory stimuli in rat sciatic nerves, and show an accelerated lifetime stability of >3 years. The scalable synthesis method provides a chemically stable alternative to the widely used AgNWs, thereby enabling new applications within electronics, biomedical devices, and electrochemistry.

Microcirculatory response to cold stress test in the healthy hand.

OBJECTIVE: Cold sensitivity of the fingers is common in several conditions. It has been linked to digital vasospasm, microvascular dysfunction, and neural mechanisms. This study aimed to investigate the normal digital microvascular response to a cold stress test in healthy individuals using Laser Speckle Contrast Imaging (LSCI). METHODS: Twenty-six healthy individuals, mean age 31 (SD 9) years were included. Skin perfusion of digits II-V was measured using Laser Speckle Contrast Imaging before and after a standardized cold stress test. Changes in skin perfusion from baseline were analyzed between hands, digits, and sexes. RESULTS: Skin perfusion was significantly (p < 0.0001) affected by cold provocation in both the cold exposed and the contralateral hands in all participants of the study. This effect was significantly different between the radial (digit II and III) and the ulnar (digit V) side of the hands (p < 0.001). There was a trend towards a larger decrease in perfusion in men (ns), and a faster recovery to baseline values in women (ns). A larger inter subject variability was seen in perfusion values in women. CONCLUSIONS: The normal microvascular response to cold provocation may involve both centrally and regionally mediated processes. When exposing one hand to a cold stress test, the contralateral hand responds with simultaneous but smaller decreases in perfusion.

Distal ulna fractures in adults-subcapitular, transverse fractures did not benefit from surgical treatment.

INTRODUCTION: Fractures of the distal ulna, excluding the styloid, are rare. The cause of injury is often a fall on an outstretched hand with an extended wrist, and in most cases there is a concomitant distal radius fracture. The aims of this retrospective study were to investigate the results of the current treatment of distal ulna fractures in adults, with or without a concomitant distal radius fracture, and if a recently presented fracture classification could predict outcome. MATERIALS AND METHODS: Patients, 18 years or older, treated for a fracture of the distal third of ulna in our county, were included. Fractures of the styloid tip were excluded. The radiographs of the fractures were independently classified by two specialists in radiology according to the 2018 AO/OTA classification. Follow-up was performed 5-7 years after the injury, through the questionnaire Patient-Rated Wrist Evaluation (PRWE) and new radiographs of both wrists. RESULTS: Ninety-six patients with 97 fractures were included and filled out the PRWE. 65 patients also had new radiographs taken. 79 patients were women and the mean age at the time of injury was 63 years (SD 14.5). The most common fracture class was the extra-articular transverse fracture, 2U3A2.3 (42%). We found that 40% of the fractures had been treated by internal fixation and only 2 fractures had not healed, one conservatively treated and one operated. The median PRWE was 15 (IQR 33.5). The PRWE score was significantly worse in the operated ulna fractures (p = 0.01) and this was also true for extra-articular transverse fractures 2U3A2.3 (p = 0.001). Initial displacement was more common in operated transverse fractures, but it could not be proven that this was the reason for the inferior result. CONCLUSIONS: Distal ulna fractures almost always unite and the result is comparable to that of isolated distal radius fractures when measured by PRWE. Based on the opinions of the radiologists and how often a consensus discussion was needed for classification, we found the updated AO classification system difficult to use, if dependent only on standard radiographic views. In the present study, transverse extra-articular ulna fractures did not benefit from internal fixation regardless if associated with a distal radius fracture or isolated.

Poor reliability and reproducibility of 3 different radiographical classification systems for distal ulna fractures.

BACKGROUND AND PURPOSE: Classification of fractures can be valuable for research purposes but also in clinical work. Especially with  are fractures, such as distal ulna fractures, a treatment algorithm based on a classification can be helpful. We compared 3 different  classification systems of distal ulna fractures and investigated their reliability and reproducibility. PATIENTS AND METHODS: patients with 97 fractures of the distal ulna, excluding the ulnar styloid, were included. All fractures were  independently classified by 3 observers according to the classification by Biyani, AO/OTA 2007, and AO/OTA 2018. The classification process was repeated after a minimum of 3 weeks. We used Kappa value analysis to determine inter- and intra-rater agreement. RESULTS: The inter-rater agreement of the AO/OTA 2007 classification was judged as fair, ĸ 0.40, whereas the agreement of AO/OTA 2018 and Biyani was moderate at ĸ 0.42 and 0.43 respectively. The intra-rater agreement was judged as moderate for all classifications. INTERPRETATION: The differences between the classifications were small and the overall impression was that neither of them was good enough to be of substantial clinical value. The Biyani classification, being developed specifically for distal ulna fractures, was the easiest and most fitting for the fracture patterns seen in our material, but lacking options for fractures of the distal diaphysis. Standard radiographs were considered insufficient for an accurate classification. A better radiographic method combined with a revised classification might improve accuracy, reliability, and reproducibility.

Objective assessment of skin microcirculation using a smartphone camera.

BACKGROUND: Existing techniques for assessment of microcirculation are limited by their large size and high costs and are often not so easy to use. Advances in mobile technology have enabled great improvements in smartphone sensor technology. In this study, we used SkinSight, an app for iPhone and iPad, to measure changes in skin microcirculation during physiological provocations. The system estimates changes in the concentration of hemoglobin in the skin by analyzing the reflected light emitted from the built-in light-emitting diode and detected by the camera of the smartphone. METHODS: A relative hemoglobin (Hb) index was measured during a 5-min arterial occlusion, post-occlusive reactive hyperemia, and a 5-min venous occlusion in 10 healthy subjects, on two separate days. The index was calculated in an area of the skin from the color information in the images acquired by the phone camera. Polarized light spectroscopy imaging was used to measure changes in red blood cell concentration for comparison. RESULTS: During arterial occlusion, relative Hb index was unchanged compared to baseline (P = .40). After release of the cuff, a sudden 60%-75% increase in Hb index was observed (P < .001) followed by a gradual return to baseline. During venous occlusion, Hb index increased by 80% (P < .001) followed by a gradual decrease to baseline after reperfusion. Day-to-day reproducibility of the relative Hb index was excellent (ICC: 0.92, r = 0.94), although relative Hb index was consistently higher during the second day, possibly as a result of changed lighting conditions or calibration issues. CONCLUSION: Microvascular responses to physiological provocations in the skin can be accurately and reproducibly measured using a smartphone application. Although the system offers a handheld, easy to use and flexible technique for skin microvascular assessment, the effects of lighting on the measured values and need for calibration need to be further investigated.

Effect of NG -monomethyl l-arginine on microvascular blood flow and glucose metabolism after an oral glucose load.

OBJECTIVE: The aim of this study was to investigate whether the effects on local blood flow and metabolic changes observed in the skin after an endogenous systemic increase in insulin are mediated by the endothelial nitric oxide pathway, by administering the nitric oxide synthase inhibitor NG -monomethyl l-arginine using microdialysis. METHODS: Microdialysis catheters, perfused with NG -monomethyl l-arginine and with a control solution, were inserted intracutaneously in 12 human subjects, who received an oral glucose load to induce a systemic hyperinsulinemia. During microdialysis, the local blood flow was measured by urea clearance and by laser speckle contrast imaging, and glucose metabolites were measured. RESULTS: After oral glucose intake, microvascular blood flow and glucose metabolism were both significantly suppressed in the NG -monomethyl l-arginine catheter compared to the control catheter (urea clearance: P < .006, glucose dialysate concentration: P < .035). No significant effect of NG -monomethyl l-arginine on microvascular blood flow was observed with laser speckle contrast imaging (P = .81). CONCLUSION: Local delivery of NG -monomethyl l-arginine to the skin by microdialysis reduces microvascular blood flow and glucose delivery in the skin after oral glucose intake, presumably by decreasing local insulin-mediated vasodilation.

Assessment of oxygenation with polarized light spectroscopy enables new means for detecting vascular events in the skin.

INTRODUCTION: Impaired oxygenation in the skin may occur in disease states and after reconstructive surgery. We used tissue viability imaging (TiVi) to measure changes in oxygenation and deoxygenation of haemoglobin in an in vitro model and in the dermal microcirculation of healthy individuals. MATERIALS AND METHODS: Oxygenation was measured in human whole blood with different levels of oxygenation. In healthy subjects, changes in red blood cell concentration (CRBC,TiVi), oxygenation (ΔCOH,TiVi) and deoxygenation (ΔCDOH,TiVi) of haemoglobin were measured during and after arterial and venous occlusion using TiVi and were compared with measurements from the enhanced perfusion and oxygen saturation system (EPOS). RESULTS: During arterial occlusion, CRBC,TiVi remained unchanged while ΔCOH,TiVi decreased to -44.2 (10.4) AU (p = 0.04), as compared to baseline. After release, CRBC,TiVi increased to 39.2 (18.8) AU (p < 0.001), ΔCOH,TiVi increased to 38.5. During venous occlusion, CRBC,TiVi increased to 28.9 (11.2) AU (p < 0.001), ΔCOH,TiVi decreased to -52.2 (46.1) AU (p < 0.001) compared to baseline after 5 min of venous occlusion. There was a significant correlation between the TiVi Oxygen Mapper and EPOS, for arterial (r = 0.92, p < 0.001) and venous occlusion (r = 0.87, p < 0.001), respectively. CONCLUSION: This study shows that TiVi can measure trends in oxygenation and deoxygenation of haemoglobin during arterial and venous stasis in healthy individuals.

Skin blood flow response to topically applied methyl nicotinate: Possible mechanisms.

BACKGROUND: Methyl nicotinate (MN) induces a local cutaneous erythema in the skin and may be valuable as a local provocation in the assessment of microcirculation and skin viability. The mechanisms through which MN mediates its vascular effect are not fully known. The aim of this study was to characterize the vasodilatory effects of topically applied MN and to study the involvement of nitric oxide (NO), local sensory nerves, and prostaglandin-mediated pathways. METHODS: MN was applied on the skin of healthy subjects in which NO-mediated (L-NMMA), nerve-mediated (lidocaine/prilocaine), and cyclooxygenase-mediated (NSAID) pathways were selectively inhibited. Microvascular responses in the skin were measured using laser speckle contrast imaging (LSCI). RESULTS: NSAID reduced the MN-induced perfusion increase with 82% (P < .01), whereas lidocaine/prilocaine reduced it with 32% (P < .01). L-NMMA did not affect the microvascular response to MN. CONCLUSION: The prostaglandin pathway and local sensory nerves are involved in the vasodilatory actions of MN in the skin.

Incidence of distal ulna fractures in a Swedish county: 74/100,000 person-years, most of them treated non-operatively.

Background and purpose - Fractures of the distal ulna can occur in isolation or in conjunction with a distal radius fracture. They may result in incongruence and instability of the distal radioulnar joint. We investigated the incidence of distal ulna fractures, whether any fracture types were more common, and the methods of treatment used.Patients and methods - Data were collected from patients 18 years or older, treated for a fracture of the distal ulna in Östergötland, Sweden, during 2010-2012. Patients were identified in the patient registry. The fractures were classified according to the AO comprehensive classification of fractures.Results - The incidence of distal ulna fractures was 74/100,000 person-years. The most common fracture type was that of the ulnar styloid Q1 (79%), followed by the ulnar neck Q2 (11%). Rarest was ulna head fracture, type Q4 (1%). Incidental findings were a mean age of 63 years (SD 18), a concomitant distal radius fracture in 92% of the patients and that 79% were caused by falling from standing height. Internal fixation was performed in 30% of the Q2-Q6 fractures. This indicates that most were considered stable without internal fixation or stable after fixation of a concomitant radius fracture.Interpretation - Our results show that fractures of the distal ulna are not very common, and some fracture types are even rare. There seem to be no consensus on treatment.

The microvascular response in the skin to topical application of methyl nicotinate: Effect of concentration and variation between skin sites.

BACKGROUND: Methyl nicotinate (MN) induces a local cutaneous erythema in the skin and may be used as a local provocation in the assessment of microcirculation and skin viability. The aims were to measure the effects of increasing doses of MN, to find the concentration that yields the most reproducible effect from day to day and between sites, and to study the variation between skin sites. METHODS: Microvascular responses to topically applied MN at different concentrations were measured in 12 subjects on separate days and on contralateral sides, using laser speckle contrast imaging (LSCI). MN effects were measured in four different body sites. RESULTS: At 20 mmol/L, the response to MN was most reproducible day-to-day and site-to-site, and resulted in a plateau response between 5 and 20 min after application. The skin region of the lower back had a lower perfusion value compared to the epigastric region (p = 0.007). When responses were compared to nearby, unprovoked areas, a significantly larger increase in perfusion was seen in the forearm, compared to all other anatomical sites (p < 0.03). CONCLUSION: A concentration of 20 mmol/L MN generated the most reproducible microvascular response in the skin. The response varies between different body sites.

The presence of synchronized perfusion dips in the microcirculation of the resting nail bed.

OBJECTIVES: Laser speckle contrast imaging (LSCI) has seen limited use in the study of perfusion dynamics such as vasomotion. The aim of this study was to investigate the effects of a prolonged seated position on perfusion dynamics in the nail bed using LSCI. METHODS: Perfusion was recorded in digits II to IV bilaterally for 20 min during two separate sessions in ten healthy volunteers. The acclimatization period was 5 min for the 1st session and 20 min for the 2nd. Perfusion variability and the presence of recurring perfusion dips were analyzed. A digital nerve block was done to verify suspected nervous origin of phenomenon. RESULTS: Synchronized phases of vasoconstriction were observed in all subjects with perfusion dips in all digits bilaterally and simultaneously. Application of a digital nerve block abolished perfusion dips. The frequency of this phenomenon increased by 25.0% (95% CI: 1.6 to 49.2%) in the left-hand digits after a prolonged seated position. Perfusion variability increased by 11.6% (95% CI: 2.6 to 20.3%) in the digits of the left hand. Perfusion changes in right-hand digits did not significantly increase. During the 1st session, temperature increased by 2.7 °C (1.1 to 4.2) while it decreased by 1.3 °C (0.2 to 2.4) during the 2nd session. CONCLUSION: The observed perfusion dips are of a centrally mediated nervous origin but are also affected by local factors. They are affected by seating duration and differ between left and right hands, likely because of local micro perfusion dips. This phenomenon seems related to digital thermoregulation.

Acute effects of coffee on skin blood flow and microvascular function.

OBJECTIVE: Studies on the acute effects of coffee on the microcirculation have shown contradicting results. This study aimed to investigate if intake of caffeine-containing coffee changes blood flow and microvascular reactivity in the skin. METHODS: We measured acute changes in cutaneous vascular conductance (CVC) in the forearm and the tip of the finger, the microvascular response to transdermal iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) and post-occlusive reactive hyperemia (PORH) in the skin, after intake of caffeinated or decaffeinated coffee. RESULTS: Vasodilatation during iontophoresis of ACh was significantly stronger after intake of caffeinated coffee compared to after intake of decaffeinated coffee (1.26±0.20PU/mmHg vs. 1.13±0.38PU/mmHg, P<0.001). Forearm CVC before and after PORH were not affected by caffeinated and decaffeinated coffee. After intake of caffeinated coffee, a more pronounced decrease in CVC in the fingertip was observed compared to after intake of decaffeinated coffee (-1.36PU/mmHg vs. -0.52PU/mmHg, P=0.002). CONCLUSIONS: Caffeine, as ingested by drinking caffeinated coffee acutely improves endothelium-dependent microvascular responses in the forearm skin, while endothelium-independent responses to PORH and SNP iontophoresis are not affected. Blood flow in the fingertip decreases markedly during the first hour after drinking caffeinated coffee compared to decaffeinated coffee.

Changes in skin microcirculation during radiation therapy for breast cancer.

BACKGROUND: The majority of breast cancer patients who receive radiation treatment are affected by acute radiation-induced skin changes. The assessment of these changes is usually done by subjective methods, which complicates the comparison between different treatments or patient groups. This study investigates the feasibility of new robust methods for monitoring skin microcirculation to objectively assess and quantify acute skin reactions during radiation treatment. MATERIAL AND METHODS: Laser Doppler flowmetry, laser speckle contrast imaging, and polarized light spectroscopy imaging were used to measure radiation-induced changes in microvascular perfusion and red blood cell concentration (RBC) in the skin of 15 patients undergoing adjuvant radiation therapy for breast cancer. Measurements were made before treatment, once a week during treatment, and directly after the last fraction. RESULTS: In the treated breast, perfusion and RBC concentration were increased after 1-5 fractions (2.66-13.3 Gy) compared to baseline. The largest effects were seen in the areola and the medial area. No changes in perfusion and RBC concentration were seen in the untreated breast. In contrast, Radiation Therapy Oncology Group (RTOG) scores were increased only after 2 weeks of treatment, which demonstrates the potential of the proposed methods for early assessment of skin changes. Also, there was a moderate to good correlation between the perfusion (r = 0.52) and RBC concentration (r = 0.59) and the RTOG score given a week later. CONCLUSION: We conclude that radiation-induced microvascular changes in the skin can be objectively measured using novel camera-based techniques before visual changes in the skin are apparent. Objective measurement of microvascular changes in the skin may be valuable in the comparison of skin reactions between different radiation treatments and possibly in predicting acute skin effects at an earlier stage.

Skin glucose metabolism and microvascular blood flow during local insulin delivery and after an oral glucose load.

OBJECTIVE: Insulin causes capillary recruitment in muscle and adipose tissue, but the metabolic and microvascular effects of insulin in the skin have not been studied in detail. The aim of this study was to measure glucose metabolism and microvascular blood flow in the skin during local insulin delivery and after an oral glucose load. METHODS: Microdialysis catheters were inserted intracutanously in human subjects. In eight subjects two microdialysis catheters were inserted, one perfused with insulin and one with control solution. First the local effects of insulin was studied, followed by a systemic provocation by an oral glucose load. Additionally, as control experiment, six subjects did not recieve local delivery of insulin or the oral glucose load. During microdialysis the local blood flow was measured by urea clearance and by laser speckle contrast imaging (LSCI). RESULTS: Within 15 minutes of local insulin delivery, microvascular blood flow in the skin increased (urea clearance: P=.047, LSCI: P=.002) paralleled by increases in pyruvate (P=.01) and lactate (P=.04), indicating an increase in glucose uptake. An oral glucose load increased urea clearance from the catheters, indicating an increase in skin perfusion, although no perfusion changes were detected with LSCI. The concentration of glucose, pyruvate and lactate increased in the skin after the oral glucose load. CONCLUSION: Insulin has metabolic and vasodilatory effects in the skin both when given locally and after systemic delivery through an oral glucose load.

Modeling Perfusion Dynamics in the Skin During Iontophoresis of Vasoactive Drugs Using Single-Pulse and Multiple-Pulse Protocols.

OBJECTIVE: After iontophoresis of vasoactive drugs into the skin, a decrease in perfusion is commonly observed. We delivered vaso-active drugs by iontophoresis using different delivery protocols to study how these affect this decrease in perfusion as measured using LDF. METHODS: We measured skin perfusion during iontophoresis of (ACh), MCh, and NA using a single pulse or separate pulses at different skin sites, and during repeated delivery of ACh at the same site. RESULTS: Perfusion half-life was 6.1 (5.6-6.6) minutes for ACh and 41 (29-69) minutes for MCh (p < 0.001). The maximum response with multiple pulses of ACh iontophoresis was lower than with a single pulse, 30 (22-37) PU vs. 43 (36-50) PU, p < 0.001. Vasoconstriction to NA was more rapid with a single pulse than with multiple pulses. The perfusion half-life of ACh decreased with repeated delivery of ACh at the same site-first 16 (14-18), second 5.9 (5.1-6-9) and third 3.2 (2.9-3.5) minutes, p < 0.001. CONCLUSIONS: The drug delivery protocol affects microvascular responses to iontophoresis, possibly as a result of differences in the dynamics of local drug concentrations. Perfusion half-life may be used as a measure to quantify the rate of perfusion recovery after iontophoresis of vasoactive drugs.

Assessment of microcirculation of the skin using Tissue Viability Imaging: A promising technique for detecting venous stasis in the skin.

BACKGROUND: Venous occlusion in the skin is difficult to detect by existing measurement techniques. Our aim was to find out whether Tissue Viability Imaging (TiVi) was better at detecting venous occlusion by comparing it with results of laser Doppler flowmetry (LDF) during graded arterial and venous stasis in human forearm skin. METHODS: Arterial and venous occlusions were simulated in 10 healthy volunteers by inflating a blood pressure cuff around the upper right arm. Changes in the concentration of red blood cells (RBC) were measured using TiVi, while skin perfusion and concentration of moving red blood cells (CMBC) were measured using static indices of LDF during exsanguination and subsequent arterial occlusion, postocclusive reactive hyperaemia, and graded increasing and decreasing venous stasis. RESULTS: During arterial occlusion there was a significant reduction in the mean concentration of RBC from baseline, as well as in perfusion and CMBC (p<0.008). Venous occlusion resulted in a significant 28% increase in the concentration of RBC (p=0.002), but no significant change in perfusion (mean change -14%) while CMBC decreased significantly by 24% (p=0.02). With stepwise increasing occlusion pressures there was a significant rise in the TiVi index and reduction in perfusion (p=0.008), while the reverse was seen when venous flow was gradually restored. CONCLUSION: The concentration of RBC measured with TiVi changes rapidly and consistently during both total and partial arterial and venous occlusions, while the changes in perfusion, measured by LDF, were less consistent. This suggests that TiVi could be a more useful, non-invasive clinical monitoring tool for detecting venous stasis in the skin than LDF.

Reconstruction of the tendon-bone insertion with decellularized tendon-bone composite grafts: comparison with conventional repair.

PURPOSE: Injuries involving the tendon-bone interface (TBI) are difficult to address. Standard techniques typically lead to diminished strength of the healed insertion site. We hypothesized that these injuries would benefit from being reconstructed with decellularized composite grafts replacing both tendon and bone. To test this hypothesis, decellularized grafts were compared with conventional pullout repairs in an in vivo animal model. METHODS: We harvested 48 Achilles TBI grafts from rats and decellularized them. Tendon-bone interface graft reconstruction and pullout repairs were compared using a pair-matched design. Biomechanical properties were evaluated at 2, 4, 8, and 12 weeks. We evaluated histological analysis of insertion morphology and collagen type I/III content. RESULTS: There was a significant increase in ultimate failure load (35 ± 11 vs 24 ± 7 N) and ultimate tensile stress (1.5 ± 0.3 vs 1.0 ± 0.4 N/mm(2)) of the TBI grafts compared with pullout repairs at 2 weeks. These differences remained at 4 weeks. At 12 weeks, both TBI grafts and pullout repairs were as strong as native tissue and not significantly different from each other. Histology showed a more organized extracellular matrix in the TBI graft group at the early time points. Repopulation of the decellularized grafts increased over time. At 12 weeks, the insertion points of both groups were richly populated with cells that possessed morphologies similar to those found in native TBI. CONCLUSIONS: This study showed that decellularized TBI grafts were stronger compared with conventional pullout repairs at 2 and 4 weeks but were comparable at 12 weeks. A more organized extracellular matrix and different collagen composition in the early time points may explain the observed differences in strength. CLINICAL RELEVANCE: In the future, decellularized TBI grafts may be used to reconstruct tendon-bone insertion tears in multiple areas including the flexor tendon system.

The research question: the What, Why and How in hand surgery.

Identifying a good research question is one of the most important steps when laying the foundation of a research project. A good research question can aim to answer a hotly debated clinical issue, challenge a pre-existing dogma or make a contribution to specific aspects of a broader field of study. The difficulty in defining the question lies with pinpointing an important research topic or an area that is characterized by a lack of knowledge (the What), grasping the significance of how a precisely defined study can potentially impact on clinical practices (the Why) and determining the optimal study design tailored to answer the specific question (the How). These three domains constitute pivotal concepts in the process of shaping the research question.

Muscle preservation in proximal nerve injuries: a current update.

Optimal recovery of muscle function after proximal nerve injuries remains a complex and challenging problem. After a nerve injury, alterations in the affected muscles lead to atrophy, and later degeneration and replacement by fat-fibrous tissues. At present, several different strategies for the preservation of skeletal muscle have been reported, including various sets of physical exercises, muscle massage, physical methods (e.g. electrical stimulation, magnetic field and laser stimulation, low-intensity pulsed ultrasound), medicines (e.g. nutrients, natural and chemical agents, anti-inflammatory and antioxidants, hormones, enzymes and enzyme inhibitors), regenerative medicine (e.g. growth factors, stem cells and microbiota) and surgical procedures (e.g. supercharge end-to-side neurotization). The present review will focus on methods that aimed to minimize the damage to muscles after denervation based on our present knowledge.

Skin perfusion and oxygen saturation after mastectomy and radiation therapy in breast cancer patients.

The pathophysiological mechanism behind complications associated with postmastectomy radiotherapy (PMRT) and subsequent implant-based breast reconstruction are not completely understood. The aim of this study was to examine if there is a relationship between PMRT and microvascular perfusion and saturation in the skin after mastectomy and assess if there is impaired responsiveness to a topically applied vasodilator (Methyl nicotinate - MN). Skin microvascular perfusion and oxygenation >2 years after PMRT were measured using white light diffuse reflectance spectroscopy (DRS) and laser Doppler flowmetry (LDF) in the irradiated chest wall of 31 women with the contralateral breast as a control. In the non-irradiated breast, the perfusion after application of MN (median 0.84, 25th-75th centile 0.59-1.02 % RBC × mm/s) was higher compared to the irradiated chest wall (median 0.51, 25th-75th centile 0.21-0.68 % RBC × mm/s, p < 0.001). The same phenomenon was noted for saturation (median 91 %, 25th-75th centile 89-94 % compared to 89 % 25th-75th centile 77-93 %, p = 0.001). Eight of the women (26%) had a ≥10 % difference in skin oxygenation between the non-irradiated breast and the irradiated chest wall. These results indicate that late microvascular changes caused by radiotherapy of the chest wall significantly affect skin perfusion and oxygenation.