New Technologies and Concepts for Rehabilitation in the Acute Phase of Stroke: A Collaborative Matrix

The process of developing a successful stroke rehabilitation methodology requires four key components: a good understanding of the pathophysiological mechanisms underlying this brain disease, clear neuroscientific hypotheses to guide therapy, adequate clinical assessments of its efficacy on multiple timescales, and a systematic approach to the application of modern technologies to assist in the everyday work of therapists. Achieving this goal requires collaboration between neuroscientists, technologists and clinicians to develop well-founded systems and clinical protocols that are able to provide quantitatively validated improvements in patient rehabilitation outcomes. In this article we present three new applications of complementary technologies developed in an interdisciplinary matrix for acute-phase upper limb stroke rehabilitation – functional electrical stimulation, arm robot-assisted therapy and virtual reality-based cognitive therapy. We also outline the neuroscientific basis of our approach, present our detailed clinical assessment protocol and provide preliminary results from patient testing of each of the three systems showing their viability for patient use.

Common noncoding UMOD gene variants induce salt-sensitive hypertension and kidney damage by increasing uromodulin expression

Hypertension and chronic kidney disease (CKD) are complex traits representing major global health problems1,2. Multiple genome-wide association studies have identified common variants in the promoter of the UMOD gene3–9, which encodes uromodulin, the major protein secreted in normal urine, that cause independent susceptibility to CKD and hypertension. Despite compelling genetic evidence for the association between UMOD risk variants and disease susceptibility in the general population, the underlying biological mechanism is not understood. Here, we demonstrate that UMOD risk variants increased UMOD expression in vitro and in vivo. Uromodulin overexpression in transgenic mice led to salt-sensitive hypertension and to the presence of age-dependent renal lesions similar to those observed in elderly individuals homozygous for UMOD promoter risk variants. The link between uromodulin and hypertension is due to activation of the renal sodium cotransporter NKCC2. We demonstrated the relevance of this mechanism in humans by showing that pharmacological inhibition of NKCC2 was more effective in lowering blood pressure in hypertensive patients who are homozygous for UMOD promoter risk variants than in other hypertensive patients. Our findings link genetic susceptibility to hypertension and CKD to the level of uromodulin expression and uromodulin’s effect on salt reabsorption in the kidney. These findings point to uromodulin as a therapeutic target for lowering blood pressure and preserving renal function.

Implantation of Prophylactic Nonabsorbable Intraperitoneal Mesh in Patients With Peritonitis Is Safe and Feasible

BACKGROUND: Patients with peritonitis undergoing emergency laparotomy are at increased risk for postoperative open abdomen and incisional hernia. This study aimed to evaluate the outcome of prophylactic intraperitoneal mesh implantation compared with conventional abdominal wall closure in patients with peritonitis undergoing emergency laparotomy. METHOD: A matched case-control study was performed. To analyze a high-risk population for incisional hernia formation, only patients with at least two of the following risk factors were included: male sex, body mass index (BMI) >25 kg/m(2), malignant tumor, or previous abdominal incision. In 63 patients with peritonitis, a prophylactic nonabsorbable mesh was implanted intraperitoneally between 2005 and 2010. These patients were compared with 70 patients with the same risk factors and peritonitis undergoing emergency laparotomy over a 1-year period (2008) who underwent conventional abdominal closure without mesh implantation. RESULTS: Demographic parameters, including sex, age, BMI, grade of intraabdominal infection, and operating time were comparable in the two groups. Incidence of surgical site infections (SSIs) was not different between groups (61.9 vs. 60.3 %; p = 0.603). Enterocutaneous fistula occurred in three patients in the mesh group (4.8 %) and in two patients in the control group (2.9 %; p = 0.667). The incidence of incisional hernia was significantly lower in the mesh group (2/63 patients) than in the control group (20/70 patients) (3.2 vs. 28.6 %; p < 0.001). CONCLUSIONS: Prophylactic intraperitoneal mesh can be safely implanted in patients with peritonitis. It significantly reduces the incidence of incisional hernia. The incidences of SSI and enterocutaneous fistula formation were similar to those seen with conventional abdominal closure.

Spielen mit Gott. Computerspiele im Religionsunterricht

Populäre Computerspiele gehören in den Religionsunterricht. Nicht nur, weil sie Teil der Lebenswirklichkeit vieler Kinder und Jugendlicher sind, sondern auch, weil in ihnen eine Auseinandersetzung mit religiösen Werten, Aussagen und Fragen stattfindet, zum Beispiel nach Gott gefragt wird.

High resolution immunoelectron microscopic localization of functional domains of laminin, nidogen, and heparan sulfate proteoglycan in epithelial basement membrane of mouse cornea reveals different topological orientations

Thin and ultrathin cryosections of mouse cornea were labeled with affinity-purified antibodies directed against either laminin, its central segments (domain 1), the end of its long arm (domain 3), the end of one of its short arms (domain 4), nidogen, or low density heparan sulfate proteoglycan. All basement membrane proteins are detected by indirect immunofluorescence exclusively in the epithelial basement membrane, in Descemet's membrane, and in small amorphous plaques located in the stroma. Immunoelectron microscopy using the protein A-gold technique demonstrated laminin domain 1 and nidogen in a narrow segment of the lamina densa at the junction to the lamina lucida within the epithelial basement membrane. Domain 3 shows three preferred locations at both the cellular and stromal boundaries of the epithelial basement membrane and in its center. Domain 4 is located predominantly in the lamina lucida and the adjacent half of the lamina densa. The low density heparan sulfate proteoglycan is found all across the basement membrane showing a similar uniform distribution as with antibodies against the whole laminin molecule. In Descemet's membrane an even distribution was found with all these antibodies. It is concluded that within the epithelial basement membrane the center of the laminin molecule is located near the lamina densa/lamina lucida junction and that its long arm favors three major orientations. One is close to the cell surface indicating binding to a cell receptor, while the other two are directed to internal matrix structures. The apparent codistribution of laminin domain 1 and nidogen agrees with biochemical evidence that nidogen binds to this domain.