Synthesis and biological assessment of 3,7-dihydroxytropolones.

3,7-Dihydroxytropolones (3,7-dHTs) are highly oxygenated troponoids that have been identified as lead compounds for several human diseases. To date, structure-function studies on these molecules have been limited due to a scarcity of synthetic methods for their preparation. New synthetic strategies towards structurally novel 3,7-dHTs would be valuable in further studying their therapeutic potential. Here we describe the successful adaptation of a [5 + 2] oxidopyrilium cycloaddition/ring-opening for 3,7-dHT synthesis, which we apply in the synthesis of a plausible biosynthetic intermediate to the natural products puberulic and puberulonic acid. We have also tested these new compounds in several biological assays related to human immunodeficiency virus (HIV), hepatitis B virus (HBV) and herpes simplex virus (HSV) in order to gain insight into structure-functional analysis related to antiviral troponoid development.

Spark erosion: a high production rate method for producing Bi(0.5)Sb(1.5)Te3 nanoparticles with enhanced thermoelectric performance.

We report a new 'spark erosion' technique for producing high-quality thermoelectric nanoparticles at a remarkably high rate and with enhanced thermoelectric properties. The technique was utilized to synthesize p-type Bi(0.5)Sb(1.5)Te(3) nanoparticles with a production rate as high as 135 g h(-1), using a relatively small laboratory apparatus and low energy consumption. The compacted nanocomposite samples made from these nanoparticles exhibit a well-defined, 20-50 nm size nanograin microstructure, and show an enhanced figure of merit, ZT, of 1.36 at 360 K. Such a technique is essential for providing inexpensive, oxidation-free nanoparticles which are required for the fabrication of high performance thermoelectric devices for power generation from waste heat, and for refrigeration.

Renal amyloidosis in dogs: a retrospective study of 91 cases with comparison of the disease between Shar-Pei and non-Shar-Pei dogs.

BACKGROUND: Renal amyloidosis (RA) is a progressive and fatal renal disease. HYPOTHESIS: Clinical and pathologic manifestations of RA differ between Chinese Shar-Pei (CSPs) and non-Shar-Pei (NSPs) dogs. ANIMALS: 91 client-owned dogs. METHODS: Retrospective review of medical records of dogs with a histological diagnosis of RA. Clinical and clinicopathologic data, hospitalization, complications, and outcome were compared between CSPs and NSPs. RESULTS: Comorbid diseases were present in 64% of all dogs. CSPs were significantly younger compared to NSPs (median, 4.8 years; range: 3.6-17 versus median: 9.0 years; range: 2.4-11.1; P < .0001). The frequency of hypoalbuminemia, the most common biochemical abnormality, was higher in NSPs compared to CSPs (100% versus 64.7%, respectively; P < .001). Median serum creatinine concentration at presentation was 5.5 mg/dL, and was 3-fold higher in CSPs compared to NSPs (P = .005). Increased urine protein : creatinine ratio was present in 96% of all dogs. Nephrotic syndrome was present in 10% of NSPs but not in CSPs. Glomerular amyloid deposition, present in both CSPs (78.6%) and NSPs (95.6%) was most commonly diffuse, global, and severe. Renal medullar amyloidosis was more common in CSPs (100%) compared to NSPs (49.0%, P = .002), as was extrarenal amyloid deposition. The median survival time of all dogs was 5 days (range: 0-443 days). Serum creatinine concentration was significantly and negatively associated with survival (P = .025). CONCLUSIONS AND CLINICAL RELEVANCE: The clinical and pathologic manifestations of amyloidosis differ between CSPs and NSPs. The survival time observed herein was unexpectedly low, and argues for early surveillance and management of the underlying predisposing conditions.

Description of the pathology of a gazelle that died during a major outbreak of foot-and-mouth disease in Israel.

Naturally occurring foot-and-mouth disease (FMD) in wildlife is a relatively mild condition but occasionally it can be devastating as has been documented in impala in South Africa and in mountain gazelles in Israel. This report describes pathological changes in an adult male gazelle with FMD from an outbreak in the Nature Reserve of Ramot-Issachar region and the lower Galilee in Israel. The outbreak was characterised by the malignant form of the disease, which is uncommon among domestic animals. Lesions observed included, ulceration in the oral cavity, oesophagus and ruminal pillars, coronitis, multifocal cardiac necrosis and pancreatic necrosis and inflammation. Pneumonia, caused by Muellerius capillaries was an incidental finding.

Prognostic value of FDG-PET scan imaging in lymphoma patients undergoing autologous stem cell transplantation.

We conducted a retrospective analysis of 50 lymphoma patients (Hodgkin's disease and non-Hodgkin's lymphoma) who had an 18F-fluoro-deoxyglucose positron emission tomography (FDG-PET) scan after at least two cycles of salvage chemotherapy and before autologous stem cell transplantation (ASCT) at our institution. The patients were categorized into FDG-PET negative (N = 32) and positive (N = 18) groups. The median follow-up after ASCT was 19 months (range: 3-59). In the FDG-PET-negative group, the median progression-free survival (PFS) was 19 months (range: 2-59) with 15 (54%) patients without progression at 12 months after ASCT. The median overall survival (OS) for this group was not reached. In the FDG-PET-positive group, the median PFS was 5 months (range: 1-19) with only one (7%) patient without progression at 12 months after ASCT. The median OS was 19 months (range: 1-34). In the FDG-PET-negative group, chemotherapy-resistant patients by CT-based criteria had a comparable outcome to those with chemotherapy-sensitive disease. A positive FDG-PET scan after salvage chemotherapy and prior ASCT indicates an extremely poor chance of durable response after ASCT.

New magnetic order in buried native iron oxide layers.

The properties of a magnetically ordered buried Fe oxide layer are presented. This oxide has a room-temperature magnetization exceeding that of Fe3O4 by 42% and of gamma-Fe2O3 by 89%. The oxide consists of a component (70%) with a net moment of 2.0 micro(B)/Fe ion, while the remaining spins yield no net moment. The oxide magnetization is stabilized in part by the proximate Fe metal.

Broadly tuned spinal neurons for each form of fictive scratching in spinal turtles.

Behavioral choice can be mediated either by a small number of sharply tuned neurons or by large populations of broadly tuned neurons. This issue can be conveniently examined in the turtle spinal cord, which generates each of three forms of scratching-rostral, pocket, and caudal-in response to mechanical stimulation in each of three adjacent regions of the body surface. Previous research showed that many propriospinal neurons are broadly tuned to either the rostral scratch region or the pocket scratch region, but responses to caudal scratch stimulation could not be examined in that reduced preparation. In the current study, individual spinal neurons were recorded extracellularly from the gray matter of the turtle spinal cord hindlimb enlargement, while sites in the rostral, pocket, and caudal scratch regions were mechanically stimulated. Many neurons were broadly tuned to the caudal scratch region; other neurons were broadly tuned to either the pocket scratch or rostral scratch region. All three types were typically found within a single animal. These data are consistent with the hypothesis that the turtle spinal cord relies on large populations of broadly tuned neurons to select each of the three forms of scratching. In addition, neurons that were broadly tuned to each of the scratch regions were typically found in each spinal cord segment and within the same range of mediolateral and dorsoventral locations. Providing that these neurons are related to the selection and generation of the three forms of scratching, this would indicate that cells of this type are not segregated into distinct regions of the spinal cord gray matter.

Rhythmicity of spinal neurons activated during each form of fictive scratching in spinal turtles.

Are behaviors that rely on common muscles and motoneurons generated by separate or overlapping groups of pattern-generating neurons? This question was investigated for the three forms of scratching in immobilized, spinal turtles. Individual neurons were recorded extracellularly from the gray matter through most of the spinal cord hindlimb enlargement gray matter, but were avoided in the region of motoneuron cell bodies. Each form of fictive scratching was elicited by mechanical stimulation of the body surface. The rhythmic modulation of spinal neurons was assessed using phase histograms and circular statistics. The degree of rhythmic modulation and the phase preference of each rhythmically active neuron were measured with respect to the activity cycle of the ipsilateral hip flexor nerve. The action potentials of rhythmic neurons tended to be concentrated in a particular phase of the ipsilateral hip flexor activity cycle no matter which form of fictive scratching was elicited. This consistent phase preference suggests that some of these neurons may contribute to generation of the hip rhythm for all three forms of scratching, strengthening the case that vertebrate pattern-generating circuitry for distinct behaviors can be overlapping. The degree of rhythmic modulation of each unit during fictive scratching was consistently correlated with the dorsoventral location of the recording, but not with the mediolateral or rostrocaudal location; neurons located more ventrally tended to be more rhythmic. The phase preferences of units were related to the region of the body surface to which each neuron responded maximally (i.e., the region to which each unit was broadly tuned). Units tuned to the rostral scratch or pocket scratch region tended to have a phase preference during ipsilateral hip flexor activity, whereas units tuned to the caudal scratch region did not. This suggests the hypothesis that the hip flexes further during rostral and pocket scratching, and extends further during caudal scratching, due to the net effects of a population of spinal interneurons that are both broadly tuned and rhythmically active.

Sensitivity of prefrontal cortex to changes in target probability: a functional MRI study.

Electrophysiological studies suggest sensitivity of the prefrontal cortex to changes in the probability of an event. The purpose of this study was to determine if subregions of the prefrontal cortex respond differentially to changes in target probabilities using functional magnetic resonance imaging (fMRI). Ten right-handed adults were scanned using a gradient-echo, echo planar imaging sequence during performance of an oddball paradigm. Subjects were instructed to respond to any letter but "X". The frequency of targets (i.e., any letter but X) varied across trials. The results showed that dorsal prefrontal regions were active during infrequent events and ventral prefrontal regions were active during frequent events. Further, we observed an inverse relation between the dorsal and ventral prefrontal regions such that when activity in dorsal prefrontal regions increased, activity in ventral prefrontal regions decreased, and vice versa. This finding may index competing cognitive processes or capacity limitations. Most importantly, these findings taken as a whole suggest that any simple theory of prefrontal cortex function must take into account the sensitivity of this region to changes in target probability.

Aggressive digital papillary adenocarcinoma: a case report and review of the literature.

We report a case of an aggressive digital papillary adenocarcinoma (ADPA) on the right thumb of a 48-year-old white man. Histologic evaluation of the initial biopsy demonstrated features consistent with those proposed for aggressive digital papillary adenoma; however, re-excision of the remaining lesion revealed histologic features consistent with aggressive digital papillary adenocarcinoma. These tumors have a high rate of local recurrence and can metastasize, occasionally resulting in mortality. Our case demonstrates that even if the histologic criteria of aggressive digital papillary adenocarcinoma are met, the lesion may still represent an aggressive digital papillary adenocarcinoma (ADPAca). In agreement with a recent study by Duke et al., this case supports the idea that aggressive digital papillary lesions should be classified as aggressive digital papillary adenocarcinoma.

The wreathing protocol: the imbrication of hypnosis and EMDR in the treatment of dissociative identity disorder and other dissociative responses. Eye Movement Desensitization Reprocessing.

Dissociative Identity Disorder (DID), a chronic childhood onset posttraumatic stress disorder, is currently recognized as a treatable condition. It is considered the paradigmatic dissociative condition and carries with it extreme posttraumatic symptomatology. Therapists skilled in the treatment of DID are typically fluent in the uses of hypnosis for stabilization, affect management, building a safe place and grounding to name of few. EMDR, which has come to the forefront of clinical awareness in the last ten years, seems aptly suited for the treatment of trauma, but can be destabilizing. This paper proposes a protocol, called Wreathing Protocol, for the imbricated use of EMDR and hypnosis in the treatment of not only DID (though this will be the primary focus of the paper), but also Dissociative Disorder Not Otherwise Specified (DDNOS) and chronic Posttraumatic Stress Disorder (PTSD). This protocol is useful to advanced clinicians skilled in both modalities independently. The sequential steps of the Wreathing Protocol will be described and illustrated by a clinical vignette on DID. The clinical implications of the use of the Wreathing Protocol will be discussed in DID as well as the chronic post traumatic spectrum.

A developmental functional MRI study of spatial working memory.

Functional magnetic resonance imaging (fMRI) was used to examine patterns of cortical activity in children during performance of a spatial working memory task. Six children (8-10 years) and six adults (19-26 years) searched a linear array of four boxes for the appearance of a dot. In the visual blocks, participants made no response. In the motor blocks, participants were instructed to indicate the location of the dot on each trial using a button-press response. In the working memory blocks, participants were instructed to indicate at which location the dot had appeared 1 or 2 trials previously. Both children and adults showed activity in the left precentral and postcentral gyri, as well as the right cerebellum for the motor condition as compared to the visual condition. Comparison of the memory and motor conditions revealed reliable activity in the right superior frontal gyrus (BA 8), right dorsolateral prefrontal cortex (BA 10/46), right superior parietal cortex, and bilateral inferior parietal cortex for both adults and children. These results suggest that spatial working memory tasks activate very similar cortical regions for school-age children and adults. The findings differ from previous imaging studies of nonspatial working memory tasks in that the prefrontal activations observed in the current work tend to be more dorsal. Results are discussed in light of the significant behavioral performance differences observed between child and adult participants.

Correlation between two-point discrimination and median nerve sensory response.

Static two-point discrimination (2PD) has been relied upon clinically to gauge the extent of median neuropathy in patients with carpal tunnel syndrome (CTS). Correlation with median nerve sensory conduction findings has not been well-established. We determined the median sensory nerve action potential parameters from the first and third digits of 83 hands referred primarily for suspected CTS. These results were compared to 2PD carried out in a standardized fashion by a group of hand surgeons. A lack of correlation was found in most electrodiagnostic parameters, with the exception of peak and onset latencies to the thumb; on further analysis, 2PD to the thumb was found to be useful if abnormal, but contributed nothing if negative. We conclude that static 2PD results may correlate with latency, but do not overall adequately predict the findings on sensory nerve conduction examination of the median nerve.

Postexcitatory inhibition of the crayfish lateral giant neuron: a mechanism for sensory temporal filtering.

Crayfish escape from threats by either giant neuron-mediated "reflex" tail flexions that occur with very little delay but do not allow for much sensory guidance of trajectory or by "nongiant" tail flexion responses that allow for sensory guidance but occur much less promptly. Thus, when a stimulus occurs, the nervous system must make a rapid assessment of whether to use the faster reflex system or the slower nongiant one. It does this on the basis of the abruptness of stimulus onset; only stimuli of very abrupt onset trigger giant-mediated responses. We report here that stimuli which excite the lateral giant (LG) command neurons for one form of reflex escape also produce a slightly delayed postexcitatory inhibition (PEI) of the command neurons. As a result, only stimuli that become strong enough to excite the command neurons to firing threshold before the onset of PEI, within a few milliseconds of stimulus onset, can cause giant-mediated responses. This inhibition is directed to distal dendrites of the LG neurons, which allows for some location specificity of PEI within the sensory field of a single hemisegment.

Local control of leg movements and motor patterns during grooming in locusts.

This study demonstrates that the thoracic and abdominal nervous system of locusts is sufficient to mediate several site-specific and distinct grooming leg movements. Locusts can use a hindleg or middle leg to groom at least four ipsilateral thoracic and abdominal sites, without input from the brain, subesophageal ganglion, or prothoracic ganglion. The hindleg is used to groom the posterior abdomen, the ventral or posterior hindleg coxa, and the ear; the middle leg is used to groom the anterior hindleg coxa. Grooming movements are often rhythmic and display site-specific intralimb coordination patterns. During grooming of the posterior abdomen or ventral hindleg coxa, for example, hindleg tibial extension occurs nearly simultaneously with femur elevation, in contrast with locust hindleg movements during walking. Electromyographic (EMG) recordings during these movements show that rhythmic bursts of tibial extensor activity occur nearly in-phase with those of trochanteral levators, in contrast to hindleg EMGs during walking. During grooming of the ear, hindleg tibial extension/flexion and tibial extensor/flexor muscle bursts can occur independently of the femur elevation/depression and trochanteral levator/depressor muscle bursts, suggesting that the neural modules controlling tibial and femoral movements can be uncoupled during this behavior. Tibial extension can occur before, or even in the absence of, tibial extensor muscle activity, suggesting that spring-like properties of the leg and energy transfer from femur motion may play important roles in such leg movements. Adjacent legs sometime show coordinated femur movement during grooming with one hindleg, suggesting that grooming may also involve interlimb coordination.

Central generation of grooming motor patterns and interlimb coordination in locusts.

Coordinated bursts of leg motoneuron activity were evoked in locusts with deefferented legs by tactile stimulation of sites that evoke grooming behavior. This suggests that insect thoracic ganglia contain central pattern generators for directed leg movements. Motoneuron recordings were made from metathoracic and mesothoracic nerves, after eliminating all leg motor innervation, as well as all input from the brain, subesophageal ganglion, and prothoracic ganglion. Strong, brief trochanteral levator motoneuron bursts occurred, together with silence of the slow and fast trochanteral depressor motoneurons and activation of the common inhibitor motoneuron. The metathoracic slow tibial extensor motoneuron was active in a pattern distinct from its activity during walking or during rhythms evoked by the muscarinic agonist pilocarpine. Preparations in which the metathoracic ganglion was isolated from all other ganglia could still produce fictive motor patterns in response to tactile stimulation of metathoracic locations. Bursts of trochanteral levator and depressor motoneurons were clearly coordinated between the left and right metathoracic hemiganglia and also between the mesothoracic and the ipsilateral metathoracic ganglia. These data provide clear evidence for centrally generated interlimb coordination in an insect.