Impaired phase synchronization of motor‐evoked potentials reflects the degree of motor dysfunction in the lesioned human brain

The functional corticospinal integrity (CSI) can be indexed by motor‐evoked potentials (MEP) following transcranial magnetic stimulation of the motor cortex. Glial brain tumors in motor‐eloquent areas are frequently disturbing CSI resulting in different degrees of motor dysfunction. However, this is unreliably mirrored by MEP characteristics. In 59 consecutive patients with diffuse glial tumors and 21 healthy controls (CTRL), we investigated the conventional MEP features, that is, resting motor threshold (RMT), amplitudes and latencies. In addition, frequency‐domain MEP features were analyzed to estimate the event‐related spectral perturbation (ERSP), and the induced phase synchronization by intertrial coherence (ITC). The clinical motor status was captured including the Medical Research Council Scale (MRCS), the Grooved Pegboard Test (GPT), and the intake of antiepileptic drugs (AED). Motor function was classified according to MRCS and GPT as no motor deficit (NMD), fine motor deficits (FMD) and gross motor deficits (GMD). CSI was assessed by diffusion‐tensor imaging (DTI). Motor competent subjects (CTRL and NMD) had similar ERSP and ITC values. The presence of a motor deficit (FMD and GMD) was associated with an impairment of high‐frequency ITC (150–300 Hz). GMD and damage to the CSI demonstrated an additional reduction of high‐frequency ERSP (150–300 Hz). GABAergic AED increased ERSP but not ITC. Notably, groups were indistinguishable based on conventional MEP features. Estimating MEP phase synchronization provides information about the corticospinal transmission after transcranial magnetic stimulation and reflects the degree of motor impairment that is not captured by conventional measures.     

Effects of hemodynamic instability on brain death-induced prepreservation liver damage

BACKGROUND: Brain death (BD) is an important multifactorial variable contributing to donor-specific liver damage. Our study aimed at assessing the specific effects of hemodynamic instability on systemic and hepatic parameters of perfusion, bowel ischemia, and oxidative stress in a porcine model of BD. METHODS: BD was induced in 16 pigs (German Landrace, 18-28 kg) in two groups (hypotension-BD [HYPO-BD], n=8; normotension-BD [NORM-BD], n=8), which were compared with control animals/living donors (n=6) for a period of 2 hr. We analyzed systemic hemodynamic parameters, bowel ischemia (intramucosal pH in the stomach and colon, plasma endotoxin levels, and endotoxin-neutralizing capacity [ENC]), and oxidative stress (total glutathione levels in erythrocytes) and compared the findings with hepatic parameters of perfusion (hepatic arterial flow, portal venous flow, and microperfusion) and liver oxidative stress (reduced glutathione and oxidized glutathione levels in the liver). RESULTS: Independent of the hemodynamic stability, liver macrocirculation and microcirculation decreased (HYPO-BD, 79+/-6 to 69+/-10 mL/100 g/min; NORM-BD, 81+/-10 to 73+/-7 mL/100 g/min; P<0.05). Hepatocellular damage (aspartate aminotransferase: NORM-BD, 49+/-20 units/L; HYPO-BD, 170+/-140 units/L; P<0.01) and hepatic oxidative stress (reduced glutathione in the liver/oxidized glutathione in the liver: NORM-BD, 29.4+/-2.3 to 13.0+/-1.3; HYPO-BD, 29.4+/-2.3 to 9.05+/-0.81; P<0.001) increased in both BD groups. With dependence on systemic hemodynamic parameters, bowel ischemia increased (intramucosal pH in the colon, 7.22+/-0.01, P<0.01; ENC, 75+/-14 endotoxin-neutralizing units/mL, P<0.01; endotoxin levels, 7+/-2 to 43+/-10 pg/mL, P<0.01) in the HYPO-BD group but not in the NORM-BD group or the living donor group. Furthermore, systemic oxidative stress was increased in the HYPO-BD group only (total glutathione levels in erythrocytes, 2.65+/-0.25 to 0.15+/-0.25 mM; P<0.01). CONCLUSIONS: During BD, liver-specific parameters (portal venous flow, microperfusion, aspartate aminotransferase activity, ENC, and hepatic oxidative stress) were compromised, independent of the hemodynamic status. Therefore, the systemic hemodynamic status does not reflect the functional status of the liver during BD.     

Decreased intercellular coupling improves the function of cardiac pacemakers derived from mouse embryonic stem cells

The aim of this study was to determine if embryonic stem cell derived cardiomyocyte aggregates (ESdCs) can act as pacemakers in spontaneously active cardiomyocyte preparations when their connexin isoform expression is tuned toward a more sinus nodal phenotype. Using microelectrode array recordings (MEAs), we demonstrate that mouse ESdCs establish electrical coupling with spontaneously active cardiomyocyte preparations (HL-1 monolayer) and obtain pacemaker dominance. WT- and Cx43(−/−)-ESdCs comparably established intercellular coupling with cardiac host tissue (Cx43(−/−): 86% vs. WT: 91%). Although both aggregates had a 100% success rate in pacing quiescent cardiac preparations, Cx43(−/−)-ESdCs had an increased likelihood of gaining pacemaker dominance (Cx43(−/−): 40% vs. WT: 13%) in spontaneously active preparations. No differences in size, beating frequency, V_m, or differentiation were detected between WT- and Cx43(−/−)-ESdCs but the intercellular coupling resistance in Cx43(−/−)-ESdCs was significantly increased (Cx43(−/−): 1.2nS vs. WT: 14.8nS). Lack of Cx43 prolonged the time until Cx43(−/−)-ESdCs established frequency synchronization with the host tissue. It further hampered the excitation spread from the cardiomyocyte preparation into the ESdC. However rectifying excitation spread in these co-cultures could not be unequivocally identified. In summary, ESdCs can function as dominant biological pacemakers and Cx43 expression is not a prerequisite for their electrical integration. Maintenance of pacemaker dominance depends critically on the pacemaker's gap junction expression benefiting those with increased intercellular coupling resistances. Our results provide important insight into the design of biological pacemakers that will benefit the use of cardiomyocytes for cell replacement therapy.     

Rolle der Diabetesberatung im digitalen Zeitalter

Digitization has long since taken hold in the diabetes sector. Digital support including pumps, rtCGM (CGM: continuous glucose monitoring, rtCGM: real time CGM), iscCGM (intermittent scanning CGM), apps as well as measuring devices with pattern recognition and a reminder function has become commonplace in many areas. Training to become a diabetes advisor provides diabetes professionals with appropriate basic knowledge to advise the patient in self-management with technical support. Continuous medical training to empower and support patients in health literacy, data protection and the use of telemedicine is imperative.     

Undergraduate students’ perspectives of healthcare professionals’ use of shared decision-making skills

Essential for future healthcare professionals (HCPs) to delivering ethical and empathetic patient-centred care (PCC) as a team is the understanding of appropriate shared decision-making (SDM) responses when facilitating discussions with patients and family members. The purpose of this study was to evaluate undergraduate students’ perspectives about HCPs’ use of SDM as described in a case-study reflection assignment. An exploratory qualitative approach was used to analyse student-reflection assignments. The sample included 42 undergraduate students enrolled in an interprofessional education (IPE) course at a Midwest university based in the United States. Data consisted of student responses in a course reflection assignment that captured their perspectives about recommended SDM responses by HCPs. Student assignments were randomly selected using stratified sampling to provide representation of eight HCP roles. Analysis revealed two themes related to students’ use of SDM responses. Results provide evidence supporting the tenet that through IPE, healthcare students can develop an understanding of SDM and ethical principles related to PCC.     

Characterization of pigmented dermo‐epidermal skin substitutes in a long‐term in vivo assay

In our laboratory, we have been using human pigmented dermo‐epidermal skin substitutes for short‐term experiments since several years. Little is known, however, about the long‐term biology of such constructs after transplantation. We constructed human, melanocyte‐containing dermo‐epidermal skin substitutes of different (light and dark) pigmentation types and studied them in a long‐term animal experiment. Developmental and maturational stages of the epidermal and dermal compartment as well as signs of homoeostasis were analysed 15 weeks after transplantation. Keratinocytes, melanocytes and fibroblasts from human skin biopsies were isolated and assembled into dermo‐epidermal skin substitutes. These were transplanted onto immuno‐incompetent rats and investigated 15 weeks after transplantation. Chromameter evaluation showed a consistent skin colour between 3 and 4 months after transplantation. Melanocytes resided in the epidermal basal layer in physiological numbers and melanin accumulated in keratinocytes in a supranuclear position. Skin substitutes showed a mature epidermis in a homoeostatic state and the presence of dermal components such as Fibrillin and Tropoelastin suggested advanced maturation. Overall, pigmented dermo‐epidermal skin substitutes show a promising development towards achieving near‐normal skin characteristics and epidermal and dermal tissue homoeostasis. In particular, melanocytes function correctly over several months whilst remaining in a physiological, epidermal position and yield a pigmentation resembling original donor skin colour.     

Comparative developmental biology of the uterus: insights into mechanisms and developmental disruption

The uterus is an essential organ for reproduction in mammals that derives from the Müllerian duct. Despite the importance of the uterus for the fertility and health of women and their offspring, relatively little is known about the hormonal, cellular and molecular mechanisms that regulate development of the Müllerian duct and uterus. This review aims to summarize the hormonal, cellular and molecular mechanisms and pathways governing development of the Müllerian duct and uterus as well as highlight developmental programming effects of endocrine disruptor compounds. Organogenesis, morphogenesis, and functional differentiation of the uterus are complex, multifactorial processes. Disruption of uterine development in the fetus and neonate by genetic defects and exposure to endocrine disruptor compounds can cause infertility and cancer in the adult and their offspring via developmental programming. Clear conservation of some factors and pathways are observed between species; therefore, comparative biology is useful to identify candidate genes and pathways underlying congenital abnormalities in humans.