The combined self- and parent-rated SDQ score profile predicts care use and psychiatric diagnoses

European Child & Adolescent Psychiatry - The Strengths and Difficulties Questionnaire (SDQ) is widely used, based on evidence of its value for screening. This evidence primarily regards the...     

Control strategies for active lower extremity prosthetics and orthotics: a review

Technological advancements have led to the development of numerous wearable robotic devices for the physical assistance and restoration of human locomotion. While many challenges remain with respect to the mechanical design of such devices, it is at least equally challenging and important to develop strategies to control them in concert with the intentions of the user.This work reviews the state-of-the-art techniques for controlling portable active lower limb prosthetic and orthotic (P/O) devices in the context of locomotive activities of daily living (ADL), and considers how these can be interfaced with the user’s sensory-motor control system. This review underscores the practical challenges and opportunities associated with P/O control, which can be used to accelerate future developments in this field. Furthermore, this work provides a classification scheme for the comparison of the various control strategies.As a novel contribution, a general framework for the control of portable gait-assistance devices is proposed. This framework accounts for the physical and informatic interactions between the controller, the user, the environment, and the mechanical device itself. Such a treatment of P/Os – not as independent devices, but as actors within an ecosystem – is suggested to be necessary to structure the next generation of intelligent and multifunctional controllers.Each element of the proposed framework is discussed with respect to the role that it plays in the assistance of locomotion, along with how its states can be sensed as inputs to the controller. The reviewed controllers are shown to fit within different levels of a hierarchical scheme, which loosely resembles the structure and functionality of the nominal human central nervous system (CNS). Active and passive safety mechanisms are considered to be central aspects underlying all of P/O design and control, and are shown to be critical for regulatory approval of such devices for real-world use.The works discussed herein provide evidence that, while we are getting ever closer, significant challenges still exist for the development of controllers for portable powered P/O devices that can seamlessly integrate with the user’s neuromusculoskeletal system and are practical for use in locomotive ADL.     

N-Chlorotaurine Exhibits Fungicidal Activity against Therapy-Refractory Scedosporium Species and Lomentospora prolificans

N-Chlorotaurine (NCT), a well-tolerated endogenous long-lived oxidant that can be applied topically as an antiseptic, was tested on its fungicidal activity against Scedosporium and Lomentospora, opportunistic fungi that cause severe infections with limited treatment options, mainly in immunocompromised patients. In quantitative killing assays, both hyphae and conidia of Scedosporium apiospermum, Scedosporium boydii, and Lomentospora prolificans (formerly Scedosporium prolificans) were killed by 55 mM (1.0%) NCT at pH 7.1 and 37°C, with a 1- to 4-log₁₀ reduction in CFU after 4 h and a 4- to >6-log₁₀ reduction after 24 h. The addition of ammonium chloride to NCT markedly increased this activity. LIVE/DEAD staining of conidia treated with 1.0% NCT for 0.5 to 3 h increased the permeability of the cell wall and membrane. Preincubation of the test fungi in 1.0% NCT for 10 to 60 min delayed the time to germination of conidia by 2 h to >12 h and reduced their germination rate by 10.0 to 100.0%. Larvae of Galleria mellonella infected with 1.0 × 10⁷ conidia of S. apiospermum and S. boydii died at a rate of 90.0 to 100% after 8 to 12 days. The mortality rate was reduced to 20 to 50.0% if conidia were preincubated in 1.0% NCT for 0.5 h or if heat-inactivated conidia were used. Our study demonstrates the fungicidal activity of NCT against different Scedosporium and Lomentospora species. A postantifungal effect connected with a loss of virulence occurs after sublethal incubation times. The augmenting effect of ammonium chloride can be explained by the formation of monochloramine.     

Evidence that Meningeal Mast Cells Can Worsen Stroke Pathology in Mice

Stroke is the leading cause of adult disability and the fourth most common cause of death in the United States. Inflammation is thought to play an important role in stroke pathology, but the factors that promote inflammation in this setting remain to be fully defined. An understudied but important factor is the role of meningeal-located immune cells in modulating brain pathology. Although different immune cells traffic through meningeal vessels en route to the brain, mature mast cells do not circulate but are resident in the meninges. With the use of genetic and cell transfer approaches in mice, we identified evidence that meningeal mast cells can importantly contribute to the key features of stroke pathology, including infiltration of granulocytes and activated macrophages, brain swelling, and infarct size. We also obtained evidence that two mast cell-derived products, interleukin-6 and, to a lesser extent, chemokine (C-C motif) ligand 7, can contribute to stroke pathology. These findings indicate a novel role for mast cells in the meninges, the membranes that envelop the brain, as potential gatekeepers for modulating brain inflammation and pathology after stroke.Stroke, the leading cause of adult disability and the fourth most common cause of death in the Unites States,^1,2 occurs when there is insufficient blood flow to the brain, and the resultant injury initiates a cascade of inflammatory events, including immune cell infiltration into the brain.^3–5 This post-stroke inflammation is a critical determinant of damage and recovery after stroke; understanding the interplay between the immune system and the brain after stroke holds much promise for therapeutic intervention.^4–7 However, successfully exploiting this therapeutic potential requires a detailed understanding of the interplay between the immune system and the brain after stroke.⁴An understudied but important aspect of this interplay is the role of meningeal-located immune cells in modulating brain pathology. The meninges have long been recognized as an anatomical barrier that protects the central nervous system (CNS). However, accumulating evidence suggests that the meninges are important for communication between the CNS and immune system during health and disease.^8–10 All blood vessels pass through the meningeal subarachnoid space before entering the brain, and this vascular connection and the close proximity of the meninges to the underlying parenchymal nervous tissue make them ideally located to act as a gatekeeper to modulate immune cell trafficking to the CNS. To support this gatekeeper function is evidence that the meninges modulate brain infiltration of T cells, neutrophils, and monocytes during meningitis and autoimmune conditions,^11–14 with immune cells observed in some instances accumulating in the meninges before they infiltrate into the parenchyma.^11,13Emerging evidence suggests that the actions of immune cells resident in the meninges are important for this gatekeeper function.^11,12,15 Mast cells (MCs), best known as proinflammatory effector cells, can play critical roles in the development of inflammation in many disease settings.^16–18 MCs reside in high numbers within the meninges, but their function in this site has not been fully investigated in stroke pathology. Unlike most immune cells, mature MCs do not circulate in the blood but are long-term residents of tissues, often in perivascular locations, and can rapidly perform their functions in situ. CNS MCs are found in the brain parenchyma and the meninges of rodents and humans.¹⁸ It has been proposed that brain parenchymal MCs can enhance brain neutrophil numbers after stroke and can exacerbate stroke pathology.^19–24 However, much of the evidence to support such conclusions is indirect. For example, some of the studies that implicate MCs in stroke pathology used pharmacologic approaches to interfere with MC activation,^19,20,22 but such drugs can have effects on other cell types.²⁵ Moreover, the role of the meningeal MCs in modulating post-stroke inflammation and pathology is unknown. Finally, little is understood about which among the many MC-derived mediators may be important in stroke pathology.^17,26To address these questions, we used genetic and cell transfer approaches to study the role of MCs in the pathology of ischemic stroke in mice. Specifically, we tested a c-kit–mutant mouse model (ie, WBB6F₁-Kit^W/W-v mice) which is profoundly MC deficient and can be repaired of this deficiency by engraftment of in vitro-derived MCs from wild-type (WT) mice. This MC knock-in approach enables the MC-dependent effects in the mutant mice to be separated from effects due to other abnormalities associated with their mutation,^11,17,26,27 because only the MC deficiency is repaired by MC engraftment. Furthermore, one can investigate the mechanisms by which MCs influence stroke pathology by engrafting MCs from transgenic mice that lack specific MC-associated products. We also tested our newly described Cpa3-Cre; Mcl-1^fl/fl mice, in which MC (and basophil) numbers are reduced constitutively via Cre-mediated depletion of the anti-apoptotic factor, myeloid cell leukemia sequence 1 (Mcl-1), in the affected lineages.²⁸ Cpa3-Cre; Mcl-1^fl/fl mice lack the other abnormalities associated with the c-kit mutations in WBB6F₁-Kit^W/W-v mice.²⁸With the use of these in vivo models, we identified meningeal MCs as important contributors to key features of stroke pathology, including increased numbers of brain granulocytes and activated macrophages, brain swelling, and infarct size. We also obtained evidence that two potentially proinflammatory MC-derived products, IL-6 and, to a lesser extent, chemokine (C-C motif) ligand 7 (CCL7), can contribute to pathology in this setting.     

Neuroendocrine Changes in Patients with Spontaneous Supratentorial Intracerebral Hemorrhage

Background

Neuroendocrine changes have been reported after ischemic stroke, subarachnoid hemorrhage, and brain trauma. As there are no corresponding data in patients with intracerebral hemorrhage (ICH) we analyzed various neuroendocrine parameters to investigate possible alterations in hormone profiles of patients with ICH.

Methods

Twenty patients with ICH were prospectively enrolled in the study. Patients were a priori parted into two groups: Ten non-ventilated patients treated on the stroke-unit (hemorrhage volumes <20 ml, “small ICH”), and 10 ventilated patients treated on the neurocritical care unit (hematoma volumes >20 ml with possible additional ventricular involvement (“large ICH”). Neuroendocrine parameters were compared between both groups referring to reference values. The following parameters were obtained over a period of 9 days in 20 patients with spontaneous supratentorial ICH: thyrotropin, free thiiodothyronine and thyroxine, human growth hormone, insulin-like growth factor 1, luteinizing hormone, follicle-stimulating hormone, testosterone, prolactin, adrenocorticotropic hormone, and cortisol.

Results

Small ICH patients were in a median 71 (54–88) years old and had a mean ICH volume of 9.5 ± 6.5 ml, whereas large ICH patients were 65 (47–80) years old and showed a mean volume of 56 ± 30.2 ml. None of the patients revealed pathological alterations for thyrotropin, free thiiodothyronine, thyroxine, human growth hormone, insulin-like growth factor 1, and testosterone. There was only a mild decrease of adrenocorticotropic hormone and cortisol on day 3 in large ICH patients. Small ICH patients showed pathologically elevated levels of luteinizing and follicle-stimulating hormone throughout the observation period. Large ICH patients showed a marked increase of prolactin that developed during the course.

Conclusions

Overall, neuroendocrine changes in ICH patients are not as profound as reported for ischemic stroke or subarachnoid hemorrhage. The clinical significance of increased LH and FSH levels in small ICH is unclear, whereas elevation of prolactin in large ICH was anticipated. Future randomized controlled trials should also focus on neuroendocrine parameters to clarify the impact of possible hormonal alterations on functional outcome.     

Interest and attitudes of patients,cancer physicians,medical students and cancer researchers towards a spectrum of genetic tests relevant to breast cancer patients

The perspectives of patients and healthcare professionals towards breast cancer genetic tests that are becoming increasingly available is unexplored in Asians. We surveyed the interest and attitudes of 200 breast cancer patients, 67 cancer physicians, 485 medical students and cancer researchers towards three genetic tests, BRCA1/2 mutation, CYP2D6 genotype and Oncotype DX testing, using hypothetical scenarios. Approximately 60% of patients expressed initial interest in each genetic test, although the majority reversed their decisions once test limitations were conveyed, with <15% maintaining interest in each test. Cancer physicians were most likely to recommend BRCA1/2 mutation testing (73%) and least likely to recommend CYP2D6 genotyping (12%), while patients were more likely to choose Oncotype DX testing (28%) over CYP2D6 (21%) and BRCA1/2 testing (15%). Cost concerns, low educational level and lack of prior awareness of genetic testing were the main barriers against breast cancer genetic testing among Asian patients.     

Distribution of injected technetium99m‐labeled mesenchymal stem cells in horses with naturally occurring tendinopathy

This study aimed to investigate immediate cell survival and distribution following different administration routes of mesenchymal stem cells (MSCs) into naturally occurring tendon injuries. Ten million MSCs, labeled with technetium‐99m hexamethylpropyleneamine oxime, were implanted into 13 horses with naturally occurring tendon or ligament injuries intra‐lesionally, intravenously and by regional perfusion, and traced for up to 48 h using planar gamma scintigraphy. Labeling efficiencies varied between 1.8% and 18.5% (mean 9.3%). Cells were retained in the damaged area after intra‐lesional administration but only 24% of cells were still present within the tendon after 24 h. After intravenous injection, cells largely distributed to the lung fields, with no detectable cells in the tendon lesions. Significant labeling of the tendon lesions was observed in 11/12 horses following regional perfusion but at a lower level to intra‐lesional injection. The highest cell numbers were retained after intra‐lesional injection, although with considerable cell loss, while regional perfusion may be a viable alternative for MSC delivery. Cells did not “home” to damaged tendon in large numbers after intravenous administration. Cells were detected in the lungs most frequently after intravascular administration, although with no adverse effects. Low cell retention has important implications for designing effective clinical therapies for human clinical use. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1096–1102, 2013     

Laparoendoscopic single-site (LESS) varicocelectomy with reusable components: comparison with the conventional laparoscopic technique

Background

This study aimed to compare laparoendoscopic single-site varicocelectomy (LESSV) with multiport laparoscopic varicocelectomy (MLV) in terms of intraoperative parameters and postoperative outcomes.

Methods

A retrospective case–control study investigated 10 male adolescents and 89 adults who underwent either LESSV or MLV at the authors’ center. The reusable X-Cone single port was inserted transumbilically. A 5-mm 30° telescope was used together with a straight and a prebent laparoscopic instrument. The MLV procedure was performed using two 5-mm ports and one 10-mm port.

Results

Between January 2009 and November 2012, 20 patients underwent LESSV and 79 patients underwent MLV. The demographic data were comparable between the two groups. The mean operating time was 59.1 ± 15.5 min for LESSV and 51.2 ± 14.4 min for MLV (P = 0.04). In the LESSV group, no conversion to MLV was necessary. The hospital stay was 1.6 ± 0.7 days in the LESSV group versus 1.8 ± 0.5 days in the MLV group (P = 0.17). The postoperative pain scores did differ between the two groups. By day 2, significantly more patients in the LESSV group than in the MLV group fully recovered their normal physical activity (P = 0.02). Comparison of pre- and postoperative values showed relief of testicular pain and improvement of semen parameters for the majority of the patients. The overall incidence of complications was distributed equally between the two groups as follows: paresthesia of the upper thigh (8 %), wound infection (5 %), epididymitis (3 %) and hydrocele (4 %). All the patients in the LESSV group were fully satisfied with their cosmetic results compared with only 76 % of the patients in the MLV group (P = 0.01).

Conclusions

The LESSV procedure performed with the reusable X-Cone is as safe and efficient as MLV. After LESSV, the parameters measuring postoperative patient satisfaction are significantly improved. Given its reusable components, including prebent laparoscopic instruments, the X-Cone platform is a cost-effective alternative to disposable or homemade single ports.