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ABSTRACTFunctional brain imaging of responses to thermal challenge in humans provides a viable method to implicate widespread neuroanatomical regions in the processes of thermoregulation. Thus far, functional neuroimaging techniques have been used infrequently in humans to investigate thermoregulation, although preliminary outcomes have been informative and certainly encourage further forays into this field of enquiry. At this juncture, sustained regional brain activations in response to prolonged changes in body temperature are yet to be definitively characterized, but it would appear that thermoregulatory regions are widely distributed throughout the hemispheres of the human brain. Of those autonomic responses to thermal challenge investigated so far, the loci of associated brainstem responses in human are homologous with other species. However, human imaging studies have also implicated a wide range of forebrain regions in thermal sensations and autonomic responses that extend beyond outcomes reported in other species. There is considerable impetus to continue human functional neuroimaging of thermoregulatory responses because of the unique opportunities presented by the method to survey regions across the whole brain in compliant, conscious participants.

The article looks at the water management in California particularly on the actions of the government in addressing the issues of flood and drought. Topics include the state's capacity of complex water system supply and irrigated agricultural lands, the state's record and experiences of droughts, and the aspects of the government's various actions to respond the issue including executive orders, improvement of water supply, and reduction of flood risk and impact mitigation.

Idiopathic toe walking (ITW) is a diagnosis given to children who walk with an absence or limitation of heel strike in the contact phase of the gait cycle, that are otherwise typically developing. There is emerging evidence that this gait pattern may occur in children who experience tactile sensory processing challenges. This feasibility study aimed to determine if children were able to respond to a sensory stimulus during a fMRI. Children aged between 8–16 years of age, with and without idiopathic toe walking were recruited from general public advertising. Participants were required to perform a two-point discrimination test (task block) and press a button without being tested (control block) during an fMRI using a standard block design. Activation differences were examined in the left frontal pole, left supramarginal gyrus, left parahippocampal gyrus, left paracingulate gyrus and the right superior temporal. Five children were in the typically developing (TD) group and three were in the ITW group. There were between-group activation differences in the decision-making block compared to the control block in the left frontal lobe, parahippocampal gyrus and the right superior temporal gyrus. There was greater variation in activation in the left supramarginal gyrus and the left paracingulate gyrus in the ITW group compared to the typically developing group. Based on this study a future sample size of 15 children per group will be required to detect an adequate effect across chosen regions of interest Conducting fMRI using two-point discrimination testing on this population is feasible. Further research is required with larger population sizes to determine if brain activation patterns during the sensory input decision-making process are different in this population.

Animal studies have identified the preoptic area as the key thermoregulatory region of the brain but no comparable information exists in humans. We used fMRI to study the preoptic area of human volunteers. Subjects lay in a 3T MRI scanner and were subjected to whole body heating by a water-perfused suit, to a level that resulted in a low rate of discrete sweating events (measured by finger skin resistance). Control scans were taken under thermoneutral conditions in another group. A discrete cluster of voxels in the preoptic area showed activity that was significantly correlated with thermal sweating events. We then used this cluster as a seed to investigate whether other brain areas had activity correlated with its signal, and whether that correlation depended on thermal state. Several brain regions including the dorsal cingulate cortex, anterior insula and midbrain showed ongoing activity that was correlated with that of the preoptic seed more strongly during heating than during thermoneutrality. These data provide the first imaging evidence for a thermoregulatory role of the human preoptic area. They further suggest that during thermal stress, the preoptic area communicates to several other brain regions with known relevance to the control of autonomic effectors.

The urge to cough is a clinical symptom of respiratory disease that precedes the motor act of coughing. Although previous studies have shown that cough is particularly susceptible to placebo suppression, it is unclear whether the perception of an urge to cough is also modifiable by placebo. Therefore, we tested the hypothesis that capsaicin-evoked urge to cough could be suppressed by placebo conditioning.

Introduction:Levetiracetam (LEV) is increasingly used in the treatment of neonatal seizures. The aim of this study was to determine pharmacokinetics in neonates with seizures and to obtain preliminary safety and efficacy data.Methods:Eighteen term neonates with seizures persisting after 20mg/kg of phenobarbital received intravenous LEV for 1?wk. LEV was administered as a 20 or 40?mg/kg bolus followed by 5–10?mg/kg/d. Pharmacokinetic data were analyzed using a nonlinear mixed-effects population approach. Continuous electroencephalogram monitoring allowed preliminary assessment of the efficacy of LEV in this population.Results:LEV clearance (CL) increased from a mean of 0.7?ml/min/kg (SD 0.27?ml/min/kg) on day 1 to 1.33?ml/min/kg (SD 0.35?ml/min/kg) by day 7. Mean half-life was 18.5?h (SD 7.1?h) on day 1 of the study and decreased to 9.1?h (SD 2.0?h) by day 7. The mean volume of distribution was 1.01 l/kg (SD 0.13 l/kg). No study-related serious adverse events were observed.Discussion:CL of LEV in neonates was higher than expected on the basis of immature renal function in term infants and increased significantly during the first week of life. More frequent dosing of LEV is needed in term infants to maintain serum concentrations in the range seen in children and adults.

People with Alzheimer's disease are administered fewer analgesics and report less clinical pain than cognitively intact peers with similar painful diseases or injuries, prompting speculation about the likely impact of neurodegeneration on central pain processing. The present study measured pain ratings and functional MRI (fMRI) brain responses following mechanical pressure simulation in 14 patients with Alzheimer's disease and 15 age-matched controls. Contrary to the prevailing hypothesis that this disease is likely to differentially reduce emotional responses to pain, we show that activity in both medial and lateral pain pathways is preserved. Moderate pain was evoked with similar stimuli in both groups, and was associated with a common network of pain-related activity incorporating cingulate, insula and somatosensory cortices. Between-group analyses showed no evidence of diminished pain-related activity in Alzheimer's disease patients compared with controls. In fact, compared with controls, patients showed greater amplitude and duration of pain-related activity in sensory, affective and cognitive processing regions consistent with sustained attention to the noxious stimulus. The results of this study show that pain perception and processing are not diminished in Alzheimer's disease, thereby raising concerns about the current inadequate treatment of pain in this highly dependent and vulnerable patient group.

ObjectiveTo determine predictors of disability depending on whether joint deformity and pain reporting exist independently or concurrently.MethodsSubjects were 154 volunteers for an osteoarthritis screening examination. Eligible subjects completed questionnaires for physical function, pain, and depressive symptoms; underwent evoked pain testing for tenderness assessment; and had anteroposterior and lateral radiographs taken of both knees. Two blinded rheumatologists scored the images using KellgrenLawrence criteria to determine presence of deformity.ResultsSubjects were divided into 3 subgroups based on radiographic evidence of deformity and selfreported pain. Disability was greatest when pain and deformity occurred together F2,151 18.8, P< 0.0001. Selfreported disability in the absence of deformity was predicted by body mass index, pain threshold, and anxiety symptoms; disability was predicted by the number of osteophytes and depressive symptoms when pain and deformity occurred together.ConclusionSelfreported disability in osteoarthritis of the knee is greatest with concurrent pain and joint deformity. When pain and deformity do not cooccur, disability appears to be related to separate factors, including anxiety and pain threshold e.g., tenderness.

To determine predictors of disability depending on whether joint deformity and pain reporting exist independently or concurrently.Subjects were 154 volunteers for an osteoarthritis screening examination. Eligible subjects completed questionnaires for physical function, pain, and depressive symptoms; underwent evoked pain testing for tenderness assessment; and had anteroposterior and lateral radiographs taken of both knees. Two blinded rheumatologists scored the images using Kellgren‐Lawrence criteria to determine presence of deformity.Subjects were divided into 3 subgroups based on radiographic evidence of deformity and self‐reported pain. Disability was greatest when pain and deformity occurred together (F[2,151] = 18.8, P < 0.0001). Self‐reported disability in the absence of deformity was predicted by body mass index, pain threshold, and anxiety symptoms; disability was predicted by the number of osteophytes and depressive symptoms when pain and deformity occurred together.Self‐reported disability in osteoarthritis of the knee is greatest with concurrent pain and joint deformity. When pain and deformity do not cooccur, disability appears to be related to separate factors, including anxiety and pain threshold (e.g., tenderness).

Zebrafish is a simple vertebrate that has many attributes that make it ideal for the study of developmental genetics. One feature that has been lacking in this model system is the ability to disable specifically targeted genes. Recently, double-stranded RNA has been used to silence gene expression in the nematode Caenorhabditis elegans.We have found that expression of the green fluorescent protein (GFP) from a microinjected plasmid vector can be suppressed in zebrafish embryos by the coinjection of a double-stranded RNA that is specifically targeted to GFP. To determine that double-stranded RNA can attenuate endogenous gene expression, single-cell zebrafish embryos were injected with double-stranded RNA specifically targeted to Zf-T and Pax6.1. We found that microinjection of double-stranded Zf-T RNA resulted in a high incidence of a phenotype similar to that of ntl.Furthermore, Zf-T gene expression could not be detected by in situhybridization and the message was decreased by 75% by semiquantitative RT-PCR in 12-h embryos that had been injected with the double-stranded RNA. Expression of the zebrafish genes sonic hedgehogand floating headwas altered in the embryos microinjected with the Zf-T double-stranded RNA in a manner that is remarkably similar to the zebrafish no-tailmutant. Microinjection of double-stranded RNA targeted to Pax6.1 was associated with depressed expression of Pax6.1 and resulted in absent or greatly reduced eye and forebrain development, similar to the phenotype seen in mouse mutants. Simultaneous injection of Pax6.1 and Zf-T resulted in embryos lacking notochords, eyes, and brain structures.

Abstract:  Mutations causing a visible phenotype in the adult serve as valuable visible genetic markers in multicellular genetic model organisms such as Drosophila melanogaster, Caenorhabditis elegans and Arabidopsis thaliana. In a large scale screen for mutations affecting early development of the zebrafish, we identified a number of mutations that are homozygous viable or semiviable. Here we describe viable mutations which produce visible phenotypes in the adult fish. These predominantly affect the fins and pigmentation, but also the eyes and body length of the adult. A number of dominant mutations caused visible phenotypes in the adult fish. Mutations in three genes, long fin, another long fin and wanda affected fin formation in the adult. Four mutations were found to cause a dominant reduction of the overall body length in the adult. The adult pigment pattern was found to be changed by dominant mutations in wanda, asterix, obelix, leopard, salz and pfeffer. Among the recessive mutations producing visible phenotypes in the homozygous adult, a group of mutations that failed to produce melanin was assayed for tyrosinase activity. Mutations in sandy produced embryos that failed to express tyrosinase activity. These are potentially useful for using tyrosinase as a marker for the generation of transgenic lines of zebrafish.

Total knee arthroplasties were performed as salvage procedures in 10 patients with irreversible knee destruction secondary to bacterial arthritis. All now have functioning knees that are pain-free and average 85 degrees of motion. None has evidence of clinical infection at present. These patients are not yet regarded as cured. They may remain at risk for the development of late reinfections. This procedure is not advocated as the operation of choice for patients with knee joint destruction secondary to bacterial arthritis. We emphasize the risk involved and the necessity for obtaining the informed consent of the patient before proceeding with total knee arthroplasty when there has been previous infection.

In this study, DNA constructs containing the putative zebrafish promoter sequences of GATA-1, an erythroid-specific transcription factor, and the green fluorescent protein reporter gene, were microinjected into single-cell zebrafish embryos. Erythroid-specific activity of the GATA-1 promoter was observed in living embryos during early development. Fluorescent circulating blood cells were detected in microinjected embryos 24 hours after fertilization and were still present in 2-month-old fish. Germline transgenic fish obtained from the injected founders continued to express green fluorescent protein in erythroid cells in the F1 and F2 generations. The green fluorescent protein expression patterns in transgenic fish were consistent with the pattern of GATA-1 mRNA expression detected by RNA in situ hybridization. These transgenic fish have allowed us to isolate, by fluorescence-activated cell sorting, the earliest erythroid progenitor cells from developing embryos for in vitro studies. By generating transgenic fish using constructs containing other zebrafish promoters and green fluorescent protein reporter gene, it should be possible to visualize the origin and migration of any lineage-specific progenitor cells in a living embryo.

Cough is a defense mechanism that protects the airways and lungs in response to airway irritation. The sensory neurons involved in detecting airway irritants and the neural pathways mediating cough share similarities with those that encode pain from the body. Painful conditioning stimuli applied to one body site are known to reduce the perception of pain at another. However, whether the neural regulation of cough is influenced by painful stimuli is not known.

Bats were netted at a desert spring in southern Nevada for a total of 70 nights covering each month of the year. Two species, Pipistrellus hesperus and Myotis californicus, were active throughout the year with peaks of seasonal activity during the warmer months. Antrozous pallidus was netted in all seasons of the year. Air temperature was a major factor affecting seasonal and nightly activity with more bats being netted at higher temperatures. However, both M. californicus and P. hesperus were active at air temperatures between −8° and 31 °C. During the warmer months, when air temperatures remained above 15°C for the entire night, both species sustained activity throughout much of the night, but in winter months, they were active only shortly after dusk and activity ceased when air temperatures dropped. Evidence for foraging and insect activity during the winter is presented. The hypothesis of continued year-round activity of bats in warmer areas of the southwest is presented as an alternative to hibernation or migration.