Functional MRI for language lateralization in individuals with intellectual and cognitive dysfunction: Two clinical case examples.

OBJECTIVE: Task-based functional MRI (fMRI) is a common non-invasive method of confirming hemispheric language dominance prior to neurosurgery in epilepsy. However, the use of this method is not recommended for individuals with cognitive dysfunction and in those with IQ below 70 due to concerns about accuracy of task performance in the scanner. This manuscript describes successful use of task-based functional MRI to lateralize language dominance in two individuals with cognitive dysfunction and intellectual disability. METHODS: Two patients completed a pre-surgical epilepsy work-up at the QEII Health Sciences Centre in Halifax, Nova Scotia, which included comprehensive neuropsychological assessment. They also completed an fMRI paradigm that involved semantic category fluency, sentence completion, naming to description and passage listening tasks with stimuli delivered both visually and auditorily. RESULTS: In both cases, fMRI maps were successful in lateralizing language dominance in relation to other clinical data, including intraoperative cortical mapping in one of the cases. CONCLUSIONS: This manuscript is the first to demonstrate that task-based fMRI can be used successfully to lateralize language in adult patients with cognitive and intellectual disabilities, and is the first to propose a specific paradigm for this purpose.

An Update on Health-Related Quality of Life and Patient-Reported Outcomes in Hidradenitis Suppurativa.

Hidradenitis suppurativa is a common inflammatory skin condition which causes recurrent abscesses, sinuses and scarring in the axillae, groin and inframammary areas. As well as causing significant physical distress due to pain and discharge, the condition impacts psychological well-being with markedly impaired quality of life. Patients suffer pain, embarrassment and psychological distress with impairment of their work and intimate relationships marking it as one of the most distressing dermatological conditions. Numerous studies have documented markers of psychological distress encompassing the physical effects such as pain and itch, affects on mood and impaired function.

Accurate prediction of X-ray pulse properties from a free-electron laser using machine learning.

Free-electron lasers providing ultra-short high-brightness pulses of X-ray radiation have great potential for a wide impact on science, and are a critical element for unravelling the structural dynamics of matter. To fully harness this potential, we must accurately know the X-ray properties: intensity, spectrum and temporal profile. Owing to the inherent fluctuations in free-electron lasers, this mandates a full characterization of the properties for each and every pulse. While diagnostics of these properties exist, they are often invasive and many cannot operate at a high-repetition rate. Here, we present a technique for circumventing this limitation. Employing a machine learning strategy, we can accurately predict X-ray properties for every shot using only parameters that are easily recorded at high-repetition rate, by training a model on a small set of fully diagnosed pulses. This opens the door to fully realizing the promise of next-generation high-repetition rate X-ray lasers.

Data systems for the Linac coherent light source.

The data systems for X-ray free-electron laser (FEL) experiments at the Linac coherent light source (LCLS) are described. These systems are designed to acquire and to reliably transport shot-by-shot data at a peak throughput of 5 GB/s to the offline data storage where experimental data and the relevant metadata are archived and made available for user analysis. The analysis and monitoring implementation (AMI) and Photon Science ANAlysis (psana) software packages are described. Psana is open source and freely available.

Prolonged constant load cycling exercise is associated with reduced gross efficiency and increased muscle oxygen uptake.

This study investigated the effects of prolonged constant load cycling exercise on cycling efficiency and local muscle oxygen uptake responses. Fourteen well-trained cyclists each completed a 2-h steady-state cycling bout at 60% of their maximal minute power output to assess changes in gross cycling efficiency (GE) and muscle oxygen uptake (mVO2 ) at time points 5, 30, 60, 90, and 120 min. Near-infrared spatially resolved spectroscopy (NIRS) was used to continually monitor tissue oxygenation of the Vastus Lateralis muscle, with arterial occlusions (OCC) applied to assess mVO2 . The half-recovery time of oxygenated hemoglobin (HbO2 ) was also assessed pre and post the 2-h cycling exercise by measuring the hyperemic response following a 5-min OCC. GE significantly declined during the 2-h cycling bout (18.4 ± 1.6 to 17.4 ± 1.4%; P < 0.01). Conversely, mVO2 increased, being significantly higher after 90 and 120 min than at min 5 (+0.04 mlO2 /min/100 g; P = 0.03). The half-recovery time for HbO2 was increased comparing pre and post the 2-h cycling exercise (+7.1 ± 19s), albeit not significantly (d: 0.48; P = 0.27). This study demonstrates that GE decreases during prolonged constant load cycling exercise and provides evidence of an increased mVO2 , suggestive of progressive mitochondrial or contractile inefficiency.

Measurement of high-dynamic range x-ray Thomson scattering spectra for the characterization of nano-plasmas at LCLS.

Atomic clusters can serve as ideal model systems for exploring ultrafast (∼100 fs) laser-driven ionization dynamics of dense matter on the nanometer scale. Resonant absorption of optical laser pulses enables heating to temperatures on the order of 1 keV at near solid density conditions. To date, direct probing of transient states of such nano-plasmas was limited to coherent x-ray imaging. Here we present the first measurement of spectrally resolved incoherent x-ray scattering from clusters, enabling measurements of transient temperature, densities, and ionization. Single shot x-ray Thomson scattering signals were recorded at 120 Hz using a crystal spectrometer in combination with a single-photon counting and energy-dispersive pnCCD. A precise pump laser collimation scheme enabled recording near background-free scattering spectra from Ar clusters with an unprecedented dynamic range of more than 3 orders of magnitude. Such measurements are important for understanding collective effects in laser-matter interactions on femtosecond time scales, opening new routes for the development of schemes for their ultrafast control.

Phase IIa randomized, placebo-controlled study of antimicrobial photodynamic therapy in bacterially colonized, chronic leg ulcers and diabetic foot ulcers: a new approach to antimicrobial therapy.

BACKGROUND: With increasing problems of antibiotic resistance, photodynamic therapy (PDT) is being developed as a novel antimicrobial treatment. Following light activation, cationic photosensitizer PPA904 [3,7-bis(N,N-dibutylamino) phenothiazin-5-ium bromide] kills a broad spectrum of bacteria in vitro and this has a variety of potential clinical applications. OBJECTIVES: To determine if PDT in bacterially colonized chronic leg ulcers and chronic diabetic foot ulcers can reduce bacterial load, and potentially lead to accelerated wound healing. METHODS: Sixteen patients with chronic leg ulcers and 16 patients with diabetic foot ulcers (each eight active treatment/eight placebo) were recruited into a blinded, randomized, placebo-controlled, single-treatment, Phase IIa trial. All patients had ulcer duration > 3 months, bacterially colonized with > 10 colony-forming units cm . After quantitatively assessing pretreatment bacterial load via swabbing, PPA904 or placebo was applied topically to wounds for 15 min, followed immediately by 50 J cm of red light and the wound again sampled for quantitative microbiology. The wound area was measured for up to 3 months following treatment. RESULTS: Treatment was well tolerated with no reports of pain or other safety issues. In contrast to placebo, patients on active treatment showed a reduction in bacterial load immediately post-treatment (P < 0·001). After 3 months, 50% (four of eight) of patients with actively treated chronic leg ulcer showed complete healing, compared with 12% (one of eight) of patients on placebo. CONCLUSIONS: This first controlled study of PDT in chronic wounds demonstrated significant reduction in bacterial load. An apparent trend towards wound healing was observed; further study of this aspect with larger patient numbers is indicated.

Anti-D immunoglobulin treatment for thrombocytopenia associated with primary antibody deficiency.

AIMS: To review our experience of anti-D immunoglobulin for immune thrombocytopenia (ITP) in patients with primary antibody deficiency. METHODS/PATIENTS: A retrospective case notes review of four Rhesus positive patients with ITP and primary antibody deficiency, treated with anti-D. Patients were refractory to steroids and high dose intravenous immunoglobulin (IVIG). Two patients were previously splenectomised. RESULTS: All patients responded to anti-D immunoglobulin. Improved platelet counts were sustained for at least three months. Side effects included a fall in haemoglobin in all cases; one patient required red blood cell transfusion. Two patients had transient neutropenia (< 1 x 10(9)/litre). CONCLUSION: Anti-D immunoglobulin may be an effective treatment for antibody deficiency associated thrombocytopenia, even after splenectomy. Anti-D immunoglobulin may have considerable clinical advantages in this group of patients, where treatments resulting in further immunosuppression are relatively contraindicated.

Histopathological features of ocular toxoplasmosis in the fetus and infant.

BACKGROUND: Ocular disease is a frequent manifestation of congenital Toxoplasma gondii infection. There are only limited data available in the literature concerning early stages of this disease in fetuses and infants. The purpose of our study was to characterize histopathological features in the eyes of 10 fetuses and 2 infants with congenital toxoplasmosis. METHODS: Fifteen eyes from 10 fetuses, 3 eyes from 2 premature infants, and both eyes from a 2-year-old child with congenital toxoplasmosis were examined by light microscopy. Immunohistochemical analysis to identify inflammatory cells and T gondii antigens was performed. The findings in infected eyes were compared with those of age-matched control eyes. RESULTS: Retinitis (10/18 eyes), retinal necrosis (4/18 eyes), disruption of the retinal pigment epithelium (12/18 eyes), and choroidal inflammation and congestion (15/18 eyes) were characteristic findings. Optic neuritis was present in 5 of 8 fetal eyes with associated optic nerve available for evaluation. An eye obtained from a 32-week-old fetus showed retinal rosettes at the edge of a scar. T cells predominated in retinal lesions and choroid. Parasites were identified by immunohistochemical analysis in 10 of 18 eyes. CONCLUSIONS: Ocular toxoplasmosis causes irreversible damage to the retina in utero. The fetus and infant mount inflammatory responses that may contribute to ocular damage. These findings have important implications for serological screening programs and in utero therapy.

Presence of pro-opiomelanocortin peptides and corticotropin-releasing factor in human placenta.

Immunoreactive adrenocorticotropin (ACTH), beta-endorphin (BEP) and corticotropin-releasing factor (CRF) were detected in human term placenta obtained from elective Caesarian surgery. The concentrations of ACTH, BEP and CRF in placenta detected by radioimmunoassay (RIA) were 2.83 +/- 0.36, 0.52 +/- 0.05 and 0.56 +/- 0.15 ng/g wet weight of tissue respectively. Pro-opiomelanocortin (POMC) peptides were also detected in the amnion and chorion membranes and in the decidua. The concentrations of ACTH were 1.72 +/- 0.20, 4.43 +/- 0.39 and 5.80 +/- 0.17 ng/g and the levels of BEP were 0.42 +/- 0.18, 0.65 +/- 0.20 and 3.66 +/- 1.10 ng/g in the amnion, chorion and decidua respectively. In contrast to placenta, immunoreactive CRF was not detected in the amnion, chorion and decidua. Immunoreactive N-acetylated BEP was also not detected in all the placental subfractions. Comparison of the amounts of both ACTH and BEP in the various placental components indicated the following distribution: decidua > chorion > placenta > amnion. In decidua, POMC peptides were present in an equi-molar ratio but in the other three placental fractions, ACTH levels were three to five-fold higher than BEP. In immunohistochemical studies, only a positive staining for ACTH was obtained for decidua. Our results confirm the presence of POMC peptides and CRF in placenta and their physiological roles in pregnancy and parturition.

Insulin-like growth factor II overexpression in myoblasts induces phenotypic changes typical of the malignant phenotype.

The objective of this study was to examine the role of insulin-like growth factor II (IGF-II) in the pathogenesis of human rhabdomyosarcomas (RMS). We have demonstrated previously that RMS express high levels of IGF-II mRNA, secrete IGF-II peptide, and express both IGF-I and IGF-II receptors. Moreover, we showed that IGF-II functions as an autocrine growth and motility factor in RMS. Since IGF-II is expressed at high levels in fetal muscle cells and RMS are tumors thought to derive from skeletal myoblasts arrested along the normal myogenic pathway, autocrine production of IGF-II by RMS may be an etiological event in the development of this tumor. We have developed a model system which enabled us to study the effects of endogenous IGF-II overprotection in muscle myoblasts. Human cDNA for pre-prohormone IGF-II was transfected into mouse myoblasts in order to achieve high, constant expression of this growth factor, which is normally down-regulated at the end of the differentiation process. Expression of high IGF-II levels resulted in: (a) an increased proliferative rate; (b) impairment of the ability to differentiate into myoblasts; and (c) acquisition of the capability of anchorage-independent growth. No changes in the expression of IGF-I receptors were noted. We conclude that IGF-II overexpression in muscle myoblasts induces morphological and biological changes typical of the malignant phenotype and represents a fundamental event in the pathogenesis of RMS and possibly of other embryonal tumors.