Spinal dementia: Don't miss it, it's treatable.

BACKGROUND & PURPOSE: Around 5% of dementia patients have a treatable cause. To estimate the prevalence of two rare diseases, in which the treatable cause is at the spinal level. METHODS: A radiology information system was searched using the terms CT myelography and the operation and classification system (OPS) code 3-241. The clinical charts of these patients were reviewed to identify patients with a significant cognitive decline. RESULTS: Among 205 patients with spontaneous intracranial hypotension (SIH) and proven CSF leaks we identified five patients with a so-called frontotemporal brain sagging syndrome: Four of those had CSF venous fistulas and significantly improved by occluding them either by surgery or transvenous embolization. Another 11 patients had infratentorial hemosiderosis and hearing problems and ataxia as guiding symptoms. Some cognitive decline was present in at least two of them. Ten patients had ventral dural tears in the thoracic spine and one patient a lateral dural tear at C2/3 respectively. Eight patients showed some improvement after surgery. DISCUSSION: It is mandatory to study the (thoracic) spine in cognitively impaired patients with brain sagging and/ or infratentorial hemosiderosis on MRI. We propose the term spinal dementia to draw attention to this region, which in turn is evaluated with dynamic digital subtraction and CT myelography.

Treatment of agitation in terminally ill patients with intranasal midazolam versus subcutaneous midazolam: study protocol for a randomised controlled open-label monocentric trial (MinTU Study).

BACKGROUND: Intranasal (i.n.) drug application is a widely known and low-invasive route of administration that may be able to achieve rapid symptom control in terminally ill patients. According to the German S3 guideline "Palliative care for patients with incurable cancer", benzodiazepines, such as midazolam, are recommended for the treatment of terminal agitation. To the best of our knowledge there is no evidence for i.n. midazolam in terminally ill patients. We aim to assess the use of i.n. midazolam as an alternative to subcutaneous administration of the drug. METHODS: In this monocentric, randomised, controlled, open-label investigator initiated trial, n = 60 patients treated at the palliative care unit of a University Hospital will be treated with 5 mg midazolam i.n. versus 5 mg subcutaneous (s.c.) midazolam in the control arm when terminal agitation occurs (randomly assigned 1:1). The estimated recruitment period is 18 months. Treatment efficacy is defined as an improvement on the Richmond Agitation Sedation Scale (Palliative Version) (RASS-PAL) and a study specific numeric rating scale (NRS) before and after drug administration. Furthermore, plasma concentration determinations of midazolam will be conducted at t1 = 0 min, t2 = 5 min, and t3 = 20 min using liquid chromatography/mass spectrometry (LC-MS). The primary objective is to demonstrate non-inferiority of midazolam i.n. in comparison to midazolam s.c. for the treatment of agitation in terminally ill patients. DISCUSSION: Midazolam i.n. is expected to achieve at least equivalent reduction of terminal agitation compared to s.c. administration. In addition, plasma concentrations of midazolam i.n. are not expected to be lower than those of midazolam s.c. and the dynamics of the plasma concentration with an earlier increase could be beneficial. TRIAL REGISTRATION: German Clinical Trials Registry DRKS00026775, registered 07.07.2022, Eudra CT No.: 2021-004789-36.

DNA identification of species of the Anopheles maculipennis complex and first record of An. daciae in Belgium.

The present study aimed at identifying the members of the Anopheles maculipennis complex (Diptera: Culicidae) occurring in Belgium. Therefore, the second internal transcribed spacer of nuclear ribosomal DNA (ITS2) and the mitochondrial cytochrome oxidase subunit I (COI) loci were sequenced in 175 and 111 specimens, respectively, collected between 2007 and 2019. In parallel, the suitability of two species-diagnostic PCR-RFLP assays was tested. The identified specimens included: An. maculipennis s.s. (N = 105), An. daciae (N = 62), An. atroparvus (N = 6) and An. messeae (N = 2). Each species was characterized by unique ITS2 haplotypes, whereas COI only supported the monophyly of An. atroparvus, a historical malaria vector in Belgium. Species identification results were further supported by unique PCR-RFLP banding patterns. We report for the first time An. daciae in Belgium, where it was found to co-occur with An. maculipennis s.s. The latter was the most prevalent in the collection studied (60%) and appears to have the widest distribution in Belgium. As in other studies, An. daciae and An. messeae appeared the most closely related species, up to the point that their species status remains debatable, while their ecological differences, including vector competences, need further study.

Multidrug-resistant organisms in allogeneic hematopoietic cell transplantation.

OBJECTIVE: Multidrug-resistant organisms (MDRO) are a challenge in allogeneic hematopoietic cell transplantation (HCT). However, in the literature there is no comprehensive analysis on MDRO in HCT. In this retrospective, single-center analysis, we appraised prevalence and clinical impact of MDRO in 98 consecutive allogeneic HCT patients. METHOD: Prior to the conditioning (baseline) and whenever clinically indicated patients underwent a full screening for MDRO (stool and urine cultures, swabs from several body regions). RESULTS: It turned out that 26 patients were colonized by 33 MDRO, either at baseline (n=16) or at any other time until day 100 post-transplantation. Of these 26 patients, eight developed an infection with MDRO, four of them by 4MRGN Pseudomonas aeruginosa, and three of them died MDRO-related. However, there was no significant difference between MDRO-colonized and non-colonized patients regarding overall survival (OS) and non-relapse-mortality (NRM). There was only a trend toward a higher NRM in patients already colonized by MDRO at baseline. This was due to the high NRM in multidrug-resistant P. aeruginosa-colonized patients. CONCLUSION: In summary, colonization with MDRO other than P. aeruginosa had no negative impact on NRM and OS. Patients colonized by multidrug-resistant P. aeruginosa had a dismal outcome. HCT of these patients should be considered with care. Screening for MDRO in the pretransplant work-up is suggested.

Monochorial diamniotic dizygotic twins in a German Shepherd Dog: A case report.

CASE REPORT: A 6.5-year-old clinically healthy German Shepherd Dog with regular oestrous cycles of 6 months was presented for pregnancy diagnosis on day 38 after ovulation (p.ov.). Ultrasonography revealed three individual placental sites in progressed resorption and two vital adequately developed foetuses sharing a joint placenta. On days 41 and 48 p.ov., sonographic signs indicated normal development of both foetuses, but on day 52 p.ov., both foetuses were found to be dead. A caesarean section was performed the same day. Examination of the removed uterus confirmed the diagnosis of a "twin" pregnancy with two foetuses sharing the same placental site but separate amniotic membranes. One foetus showed generalized oedema (anasarca). Bacterial culture of swabs taken from inside the placental cavity was negative. At histological examination of the uterus, no signs of inflammation were found. Serum relaxin concentrations (day 38, 41, 48 and 52. p.ov.) were consistent with those of bitches with normal pregnancies. Cytogenetic analysis of the two foetuses revealed dizygotic twins, one male and one female according to SRY-PCR. By genotyping 17 high-polymorphic canine microsatellites, it could be demonstrated that the two foetuses developed from two different oocytes.

[Intrahepatic cholestasis of pregnancy : Rare but important]. / Intrahepatische Schwangerschaftscholestase : Selten, aber relevant.

Intrahepatic cholestasis of pregnancy (ICP) is a liver-specific disorder occurring in approximately 0.5-2.0% of all pregnancies with a considerable variation in certain ethnic groups. ICP usually runs a benign course for the mother and is characterized by maternal pruritus mainly in the third trimester, elevated transaminases and fasting total serum bile salts and increased fetal adverse events. The etiology of ICP is only partially understood but seems to be multifactorial. Cholestasis-inducing effects of certain female sex hormones and their metabolites play an important role in genetically susceptible women. The mechanisms resulting in fetal complications such as spontaneous preterm labour, antepartum passage of meconium, asphyxia events, still birth and fetal death are not well understood. Certain sulfated progesterone metabolites are likely to play a role in the pathogenesis of pruritus in ICP. In contrast to pregnancy-related dermatoses, pruritus does not present with primary skin alterations. However, intense scratching may cause secondary skin changes such as abrasions, excoriations and sometimes prurigo nodularis. Treatment is based on ursodeoxycholate treatment to reduce pruritus and hepatic impairment as well as elective delivery between gestation week 37-38 to pre-empt potential stillbirths. This article reviews clinical symptoms, diagnosis, treatment and in particular pathogenesis of pruritus in ICP.

Mammalian-target of rapamycin inhibition with temsirolimus in myelodysplastic syndromes (MDS) patients is associated with considerable toxicity: results of the temsirolimus pilot trial by the German MDS Study Group (D-MDS).

The mammalian-target of rapamycin (also termed mechanistic target of rapamycin, mTOR) pathway integrates various pro-proliferative and anti-apoptotic stimuli and is involved in regulatory T-cell (TREG) development. As these processes contribute to the pathogenesis of myelodysplastic syndromes (MDS), we hypothesized that mTOR modulation with temsirolimus (TEM) might show activity in MDS. This prospective multicentre trial enrolled lower and higher risk MDS patients, provided that they were transfusion-dependent/neutropenic or relapsed/refractory to 5-azacitidine, respectively. All patients received TEM at a weekly dose of 25 mg. Of the 9 lower- and 11 higher-risk patients included, only 4 (20%) reached the response assessment after 4 months of treatment and showed stable disease without haematological improvement. The remaining patients discontinued TEM prematurely due to adverse events. Median overall survival (OS) was not reached in the lower-risk group and 296 days in the higher-risk group. We observed a significant decline of bone marrow (BM) vascularisation (P = 0·006) but were unable to demonstrate a significant impact of TEM on the balance between TREG and pro-inflammatory T-helper-cell subsets within the peripheral blood or BM. We conclude that mTOR-modulation with TEM at a dose of 25 mg per week is accompanied by considerable toxicity and has no beneficial effects in elderly MDS patients.

Implant placement under existing removable dental prostheses and its effect on masticatory performance.

OBJECTIVE: The aim of this within-subject study was to evaluate the outcome with implant-tooth-supported removable partial dental prostheses (RPDP group) and implant-supported removable complete dental prostheses (edentulous group) in terms of masticatory performance and self-assessment. MATERIALS AND METHODS: Thirty patients participated in this prospective clinical study (RPDP group: n = 12; edentulous group: n = 18). The prostheses were supported in strategically advantageous regions by placing implants with ball attachments and corresponding matrices in the existing dentures. The masticatory performance was evaluated with the Swallowing Threshold Test Index (STTI), the number of chewing strokes, and the time needed until swallowing at pre-treatment and 6 weeks after integration of ball attachments. Additionally, patients scored chewing satisfaction before and after implantation on a visual analogue scale. RESULTS: The STTI increased significantly (p ≤ 0.05) after implant therapy in the edentulous group but not in the RPDP group. Furthermore, the STTI was significantly higher (p ≤ 0.05) in the RPDP group than in the edentulous group at pre-treatment, however, not after therapy (P > 0.05). All patients were very satisfied after therapy concerning ability of speaking, chewing, and stability of their prosthesis. CONCLUSIONS: Patients of the edentulous group benefit more from strategically placed implants under the existing dentures than patients from the RPDP group. However, according to the subjective assessment, the chewing satisfaction generally increased for both groups after implant therapy. CLINICAL RELEVANCE: Patients with a strongly reduced dentition and edentulous patients benefit from strategically placed implants under the existing removable dentures.

First isolation of Coxiella burnetii from clinical material by cell-free medium (ACCM2).

A disadvantage in Q fever diagnostics and research is the insensitive and difficult culture of Coxiella burnetii. This intracellular organism can only be isolated using embryonated eggs, animal hosts, or mammalian cell culture. In consequence, it has only been possible to isolate a few strains from human patients. Here, we describe the first isolation of C. burnetii from a clinical specimen using the recently developed cell-free medium acidified citrate cysteine medium 2 (ACCM2). We screened the sera of 217 patients who had undergone valvular transplantation but detected one serum with an antibody constellation indicating chronic Q fever. Polymerase chain reaction (PCR) of the corresponding heart valve revealed 3.1 × 10(5) copies/rxn. The strain was successfully isolated using ACCM2. Genomic investigation by multilocus variable-number of tandem repeat (VNTR) analysis (MLVA) revealed the strain to be a new genotype, A10, closely related to one from sheep. As the sensitivity of ACCM2 for different human strains is unknown, we also investigated combining a robust test, egg propagation, with ACCM2. This combination produced four to six logs of growth of the bacteria. The use of ACCM2 in this combination simplified the otherwise elaborate purification steps. Cultivation in ACCM2 has the potential to simplify the isolation of C. burnetii in a clinical setting. As the success rates of cell culture for virulent C. burnetii strains are variable, the sensitivity of ACCM2 for different strains is unknown, and many specimens may contain much fewer bacteria than in our case, the combination of the robust method of egg propagation with ACCM2 is a good alternative to existing single methods for investigating critical specimens.

[Capacity Building for Prevention and Health Promotion for Children and Parents in a Deprived Urban Quarter: Lenzgesund]. / Strukturbildung für Prävention und Gesundheitsförderung bei Kindern und Eltern in einem benachteiligten Quartier: Lenzgesund.

In 2005 the local health authority Hamburg-Eimsbüttel developed a prevention programme for the disadvantaged quarter "Lenzsiedlung" which has been implemented by the stakeholders committee "Round Table Lenzgesund" and other partners led by the health authority. The Department of Medical Sociology and Health Economics of the University Medical Centre had taken on the accompanying analysis and long-term evaluation with a mixture of qualitative and quantitative methods for health reporting and evaluation and a new instrument for measuring capacity building in the quarter (KEQ).

Murine solid tumours as a novel model to study bacterial biofilm formation in vivo.

Bacteria of many species are able to invade and colonize solid tumours in mice. We have focused on Salmonella enterica serovar Typhimurium. Detailed analysis revealed that such tumour-invading Salmonella form biofilms, thus providing a versatile in vivo test system for studying bacterial phenotypes and host-pathogen interactions. It appears that biofilm formation by S. typhimurium is induced as a defence against the immune system of the host, and in particular against neutrophils. Further, we extended our work to the clinically more relevant biofilm infection by Pseudomonas aeruginosa. The induction of P. aeruginosa biofilms in neoplastic tissue appears to be elicited as a reaction against the immune system. Reconstitution experiments reveal that T cells are responsible for biofilm induction. Isogenic mutants that are no longer able to form biofilms can be used for comparison studies to determine antimicrobial resistance, especially therapeutic efficacy against P. aeruginosa located in biofilms.

Effect of short-term scrotal hyperthermia on spermatological parameters, testicular blood flow and gonadal tissue in dogs.

The objective was to assess the effect of a short-term scrotal hyperthermia in dogs on quantitative and qualitative ejaculate parameters, testicular blood flow and testicular and epididymal histology. After a control period, the scrotum of seven normospermic adult beagle dogs was insulated with a self-made suspensory for 48 h. Nine weeks later, two animals were castrated, while in five animals, scrotal hyperthermia was repeated. Dogs were castrated either 10 or 40 days thereafter. In each phase of scrotal insulation, average scrotal surface temperature increased by 3.0°C. Semen was collected twice weekly throughout the experiment. Total sperm count did not change after the first hyperthermia, but it slightly decreased after the second (p < 0.05). Profiles of sperm morphology and velocity parameters (CASA) rather indicated subtle physiological variations in sperm quality than effects of a local heat stress. Chromatin stability of ejaculated spermatozoa as indicated by SCSA remained constant throughout the experiment. Perfusion characteristics of the gonads, that is, systolic peak velocity, pulsatility and resistance index at the marginal location of the testicular artery, did not change due to hyperthermia (p > 0.05). Histological examination of excised testes and epididymides for apoptotic (TUNEL and activated caspase-3) and proliferating cells (Ki-67 antigen) indicated only marginal effects of scrotal insulation on tissue morphology. In conclusion, a mild short-term scrotal hyperthermia in dogs does not cause substantial changes in sperm quantity and quality. In contrast to other species, canine testes and epididymides may have a higher competence to compensate such thermal stress.

[Expression, identification and experience of emotions in mental diseases. An overview]. / Ausdruck, Erkennen und Erleben von Emotion bei psychischen Störungen. Eine Übersicht.

Several studies in clinical neuroscience have focused on the analysis of expression of emotions, identification of emotions and experience of emotions. These empirical studies produced certain insights into emotional competency in different mental diseases, most of them in schizophrenia. The current article gives a description of the scientific data about alterations in emotional competency in several mental diseases (e.g. schizophrenia, depression, bipolar and borderline diseases) and links the data, if possible, with clinical relevance with a special focus on emotional competency in prodromal schizophrenia.

Multimodal sensor-based fall detection within the domestic environment of elderly people.

BACKGROUND: Falls represent a major threat to the health of the elderly and are a growing burden on the healthcare systems. With the growth of the elderly population within most societies efficient fall detection becomes increasingly important; however, existing fall detection systems still fail to produce reliable results. OBJECTIVES: A study was carried out on sensor-based fall detection, analysis of falls with the help of fall protocols and the analysis of user acceptance of fall detection sensor technology through questionnaires. MATERIAL AND METHODS: A total of 28 senior citizens were recruited from a German community-dwelling population. The primary goal was a sensor-based detection of falls with accelerometers, video cameras and microphones. Details of the falls were analyzed with the help of medical geriatric assessments and standardized fall protocols. The study duration was 8 weeks and required a maximum of nine visits per subject. RESULTS: The study participants were 28 subjects with a mean age of 74.3 and a standard deviation (SD) of ± 6.3 years of which 12 were male and 16 female. A total of 1225.7 measurement days were recorded from all participants and the algorithms detected 2.66 falls per day. During the study period 15 falls occurred and 12 of these falls were correctly recognized by the fall detection system. CONCLUSION: Current fall detection technologies work well under laboratory conditions but it is still problematic to produce reliable results when these technologies are applied to real life conditions. Acceptance towards the sensors decreased after study participation although the system was generally perceived as useful or very useful.

A novel approach for discovering human behavior patterns using unsupervised methods.

BACKGROUND: As is well known, elderly people gradually lose the ability of self-care. The decline can be reflected in changes in their daily life behavior. A solution to assess their health status is to design sensor-enhanced living environments to observe their behavior, in which unobtrusive sensors are usually used. With respect to information extraction from the dataset collected by means of these kinds of sensors, unsupervised methods have to be relied on for practical application. Under the assumption that human lifestyle is associated with health status, this study intends to propose a novel approach to discover behavior patterns using unsupervised methods. METHODS: To evaluate the feasibility of this approach it was applied to datasets collected in the GAL-NATARS study. The study is part of the Lower Saxony research network Design of Environments for Aging (GAL) and conducted in subjects' home environments. The subjects recruited in GAL-NATARS study are older people (age ≥ 70 years), who are discharged from hospital to live alone again at their homes after treatment of a femoral fracture. RESULTS: The change of lifestyle regularity is measured. By analyzing the correlation between the extracted information and medical assessment results of four subjects, two of them exhibited impressive association and the other two showed less association. CONCLUSIONS: The approach may provide complementary information for health assessment; however, the dominant relationship between the change of behavior patterns and the health status has to be shown and datasets from more subjects must be collected in future studies. LIMITATIONS: Merely environmental data were used and no wearable sensor for activity detection or vital parameter measurement is taken into account. Therefore, this cannot comprehensively reflect reality.

Characterization of a human thyroid microtissue model for testing thyroid disrupting chemicals.

Perturbation of thyroid hormone (T4) synthesis is known to cause numerous developmental, metabolic, and cognitive disorders in humans. Due to species differences in sensitivity to chemical exposures, there is a need for human-based in vitro approaches that recapitulate thyroid cellular architecture and T4 production when screening. To address these limitations, primary human thyrocytes, isolated from healthy adult donor tissues and cryopreserved at passage one (p'1) were characterized for cellular composition, 3D follicular architecture, and thyroglobulin (TG)/T4 expression and inhibition by prototype thyroid disrupting chemicals (TDC). Flow analysis of the post-thaw cell suspension showed >80% EpCAM-positive cells with 10%-50% CD90-positive cells. When seeded onto 96-well Matrigel®-coated plates and treated with bovine thyroid stimulating hormone (TSH), thyrocytes formed 3D microtissues during the initial 4-5 days of culture. The microtissues exhibited a stable morphology and size over a 14-day culture period. TG and T4 production were highest in microtissues when the proportion of CD90-positive cells, seeding density and thyroid stimulating hormone concentrations were between 10%-30%, 6K-12K cells per well, and 0.03-1 mIU/mL, respectively. At maximal TG and T4 production levels, average microtissue diameters ranged between 50 and 200 µm. The T4 IC50 values for two prototype TPO inhibitors, 6-propyl-2-thiouracil and methimazole, were ∼0.7 µM and ∼0.5 µM, respectively, in microtissue cultures treated between days 9 and 14. Overall, p'1 cryopreserved primary human thyrocytes in 3D microtissue culture represent a promising new model system to prioritize potential TDC acting directly on the thyroid as part of a weight-of-evidence hazard characterization.

[Prospective description of the course of psychopathological symptoms in schizophrenia: evaluation of the short form of the Eppendorf Schizophrenia Inventory]. / Prospektive Verlaufsbeschreibung psychopathologischer Symptome bei Schizophrenie: Evaluation der Kurzform des Eppendorfer Schizophrenie-Inventars.

BACKGROUND: The Eppendorf Schizophrenia Inventory (ESI-K) is a self-assessment procedure which can now be considered as the standard procedure in the diagnostics of schizophrenia. It has been evaluated in many studies and is widely used in research and clinical treatment. In contrast little is known about the psychometric characteristics of the short form of the ESI (ESI-K) which was designed in particular for prospective descriptive courses. MATERIALS AND METHODS: The ESI-K was completed for 40 patients with schizophrenia undergoing complete inpatient psychiatric treatment together with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions (CGI) form and the Nurses' Observation Scale for Inpatient Evaluation (NOSIE). Of the patients 31 participated in a total of 4 measurements at 1-week intervals. RESULTS: The reliability (Cronbachs α) of the ESI-K was high at all measurement time points and was comparable to the reliability of the standard version. The reliability of the PANSS was roughly the same level but that of the NOSIE was poor. The ESI-K correlated in particular with cognitive syndrome and the positive syndrome of the PANSS. All four instruments showed a decrease in scores over the observational time period which indicated a decline in the psychopathological symptoms. CONCLUSIONS: The ESI-K is a valid time-saving procedure for documentation of the course of symptoms in patients with schizophrenia. It reflects clinically relevant aspects from the spectrum of psychotic symptoms.

Development and pilot study of a bed-exit alarm based on a body-worn accelerometer.

BACKGROUND: Falls are a major problem in hospitals and nursing homes. The consequences of falls can be severe, both for the individual and for the caring institution. OBJECTIVE: The aim of the work presented here is to reduce the number of falls on a geriatric ward by monitoring patients more closely. To achieve this goal, a bed-exit alarm that reliably detects an attempt to get up has been constructed. MATERIALS AND METHODS: A requirements analysis revealed the nurses' and physicians' needs and preferences. Based on the gathered information, an incremental design process generated different prototypes. These were tested for the reliability of their ability to detect attempts to get up in both laboratory settings and with geriatric patients. Based on the result of these tests, a scalable technical solution has been developed and proven its reliability in a 1-year, randomized controlled pilot clinical trial on a geriatric ward. RESULTS: The developed system is unobtrusive and easy to deploy. It has been tested in laboratory settings, usability tests and a 1-year randomized clinical trial with 98 patients. This paper focuses on the technical development of the system. We present different prototypes, the experiments and the pilot study used to evaluate their performance. Last but not least, we discuss the lessons learned so far. CONCLUSION: The developed bed-exit alarm is able to reliably detect patients' attempts to get up. The results of the clinical trial show that the system is able to reduce the number of falls on a geriatric ward. Next steps are the design of a specialized sensor node that is easier to use and can be applied on an even larger scale due to its reduced cost. A multicenter trial with a larger number of patients is required to confirm the results of this pilot study.

Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation.

Infection with the human immunodeficiency virus type 1 (HIV-1) requires the presence of a CD4 receptor and a chemokine receptor, principally chemokine receptor 5 (CCR5). Homozygosity for a 32-bp deletion in the CCR5 allele provides resistance against HIV-1 acquisition. We transplanted stem cells from a donor who was homozygous for CCR5 delta32 in a patient with acute myeloid leukemia and HIV-1 infection. The patient remained without viral rebound 20 months after transplantation and discontinuation of antiretroviral therapy. This outcome demonstrates the critical role CCR5 plays in maintaining HIV-1 infection.

Cathepsin L is required for endothelial progenitor cell-induced neovascularization.

Infusion of endothelial progenitor cells (EPC), but not of mature endothelial cells, promotes neovascularization after ischemia. We performed gene expression profiling of EPC and endothelial cells to identify genes that might be important for the neovascularization capacity of EPC. Notably, the protease cathepsin L (CathL) was highly expressed in EPC as opposed to endothelial cells and was essential for matrix degradation and invasion by EPC in vitro. CathL-deficient mice showed impaired functional recovery following hind limb ischemia, supporting the concept of a crucial role for CathL in postnatal neovascularization. Infused CathL-deficient progenitor cells neither homed to sites of ischemia nor augmented neovascularization. Forced expression of CathL in mature endothelial cells considerably enhanced their invasive activity and sufficed to confer their capacity for neovascularization in vivo. We concluded that CathL has a critical role in the integration of circulating EPC into ischemic tissue and is required for EPC-mediated neovascularization.