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Environmental variability is an inherent feature of natural systems which complicates predictions of species interactions. Primarily, the complexity in predicting the response of organisms to environmental fluctuations is in part because species' responses to abiotic factors are non-linear, even in stable conditions. Temperature exerts a major control over phytoplankton growth and physiology, yet the influence of thermal fluctuations on growth and competition dynamics is largely unknown. To investigate the limits of coexistence in variable environments, stable mixed cultures with constant species abundance ratios of the marine diatoms, Phaeodactylum tricornutum and Thalassiosira pseudonana, were exposed to different temperature fluctuation regimes ( n  = 17) under high and low nitrogen (N) conditions. Here we demonstrate that phytoplankton exhibit substantial resilience to temperature variability. The time required to observe a shift in the species abundance ratio decreased with increasing fluctuations, but coexistence of the two model species under high N conditions was disrupted only when amplitudes of temperature fluctuation were high (±8.2°C). N limitation caused the thermal amplitude for disruption of species coexistence to become lower (±5.9°C). Furthermore, once stable conditions were reinstated, the two species differed in their ability to recover from temperature fluctuations. Our findings suggest that despite the expectation of unequal effect of fluctuations on different competitors, cycles in environmental conditions may reduce the rate of species replacement when amplitudes remain below a certain threshold. Beyond these thresholds, competitive exclusion could, however, be accelerated, suggesting that aquatic heatwaves and N availability status are likely to lead to abrupt and unpredictable restructuring of phytoplankton community composition., Competing Interests: The authors declare no competing interests., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Despite their relatively high thermal optima (T opt ), tropical taxa may be particularly vulnerable to a rising baseline and increased temperature variation because they live in relatively stable temperatures closer to their T opt . We examined how microbial eukaryotes with differing thermal histories responded to temperature fluctuations of different amplitudes (0 control, ±2, ±4°C) around mean temperatures below or above their T opt . Cosmopolitan dinoflagellates were selected based on their distinct thermal traits and included two species of the same genus (tropical and temperate Coolia spp.), and two strains of the same species maintained at different temperatures for >500 generations (tropical Amphidinium massartii control temperature and high temperature, CT and HT, respectively). There was a universal decline in population growth rate under temperature fluctuations, but strains with narrower thermal niche breadth (temperate Coolia and HT) showed ~10% greater reduction in growth. At suboptimal mean temperatures, cells in the cool phase of the fluctuation stopped dividing, fixed less carbon (C) and had enlarged cell volumes that scaled positively with elemental C, N, and P and C:Chlorophyll-a. However, at a supra-optimal mean temperature, fixed C was directed away from cell division and novel trait combinations developed, leading to greater phenotypic diversity. At the molecular level, heat-shock proteins, and chaperones, in addition to transcripts involving genome rearrangements, were upregulated in CT and HT during the warm phase of the supra-optimal fluctuation (30 ± 4°C), a stress response indicating protection. In contrast, the tropical Coolia species upregulated major energy pathways in the warm phase of its supra-optimal fluctuation (25 ± 4°C), indicating a broadscale shift in metabolism. Our results demonstrate divergent effects between taxa and that temporal variability in environmental conditions interacts with changes in the thermal mean to mediate microbial responses to global change, with implications for biogeochemical cycling., (© 2022 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Abstract: This article guides nurses through the journal publication process, specifically how to choose a topic, send a query email, establish authorship, avoid predatory journals, and successfully advance on the publication path., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Concern that many graduate medical students do not know sufficient anatomy to safely and effectively assess and treat patients is a frequent complaint by clinicians. Although downgrading of anatomy relative to newer basic sciences is often blamed, there is evidence students rapidly forget anatomy. However, there are a number of ways instructors can foster long-term retention of anatomy, the most powerful involving intertwining clinical and anatomical information and assessing in-depth processing. Assisting this process is 'triaging' the curriculum so it contains only clinically engaged anatomy. Students are far more likely to remember information which they consider to be relevant to their future vocation. Therefore, teaching only anatomy which is likely to be useful in a clinical context tends to improve long-term retention of anatomy by medical students. Other helpful techniques include incorporating surface and radiological anatomy in a vertically integrated curriculum, reciprocal peer teaching and employing clinically qualified instructors.

Predicting spatiotemporal distributions of phytoplankton biomass and community composition heavily relies on experimental studies that document how environmental conditions influence population growth rates. In unicellular phytoplankton, the net population growth rate is the difference between the cell division rate and the death rate. Along with predation and disease, phytoplankton mortality arises from abiotic stress. Although the effect of temperature on the net population growth rate is well understood, studies examining thermally induced death rates in phytoplankton are scarce. We investigated how cell division and death rates of the diatom Phaeodactylum tricornutum varied within its thermal tolerance limits (thermal niche), and at temperatures just above its upper thermal tolerance limit. We show that death rates were largely independent of temperature when P. tricornutum was grown within its thermal niche, but increased significantly at temperatures that approached or exceeded its upper thermal tolerance limit. Furthermore, the sensitivity of mortality increased with the duration of exposure to heat stress and was affected by the pre-acclimation temperature. Heat waves can be expected to significantly affect phytoplankton mortality episodically. The increasing frequency of heat waves accompanying global warming can be expected to drive changes in phytoplankton community structure due to interspecific variability of thermal niches with potential implications for food web dynamics and biogeochemical cycles., (© 2021 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

The distribution of marine phytoplankton will shift alongside changes in marine environments, leading to altered species frequencies and community composition. An understanding of the response of mixed populations to abiotic changes is required to adequately predict how environmental change may affect the future composition of phytoplankton communities. This study investigated the growth and competitive ability of two marine diatoms, Phaeodactylum tricornutum and Thalassiosira pseudonana , along a temperature gradient (9-35°C) spanning the thermal niches of both species under both high-nitrogen nutrient-replete and low-nitrogen nutrient-limited conditions. Across this temperature gradient, the competitive outcome under both nutrient conditions at any assay temperature, and the critical temperature at which competitive advantage shifted from one species to the other, was well predicted by the temperature dependencies of the growth rates of the two species measured in monocultures. The temperature at which the competitive advantage switched from P. tricornutum to T. pseudonana increased from 18.8°C under replete conditions to 25.3°C under nutrient-limited conditions. Thus, P. tricornutum was a better competitor over a wider temperature range in a low N environment. Being able to determine the competitive outcomes from physiological responses of single species to environmental changes has the potential to significantly improve the predictive power of phytoplankton spatial distribution and community composition models., Competing Interests: None declared., (© 2020 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Experimentation at sea provides insight into which traits of ocean microbes are linked to performance in situ. Here we show distinct patterns in thermal tolerance of microbial phototrophs from adjacent water masses sampled in the south-west Pacific Ocean, determined using a fluorescent marker for reactive oxygen species (ROS). ROS content of pico-eukaryotes was assessed after 1, 5 and 25 h of incubation along a temperature gradient (15.6-32.1 °C). Pico-eukaryotes from the East Australian Current (EAC) had relatively constant ROS and showed greatest mortality after 25 h at 7 °C below ambient, whereas those from the Tasman Sea had elevated ROS in both warm and cool temperature extremes and greatest mortality at temperatures 6-10 °C above ambient, interpreted as the outcome of thermal stress. Tracking of water masses within an oceanographic circulation model showed populations had distinct thermal histories, with EAC pico-eukaryotes experiencing higher average temperatures for at least 1 week prior to sampling. While acclimatization and community assembly could both influence biological responses, this study clearly demonstrates that phenotypic divergence occurs along planktonic drift trajectories.

Land-based plants and ocean-dwelling microbial phototrophs known as phytoplankton, are together responsible for almost all global primary production. Habitat warming associated with anthropogenic climate change has detrimentally impacted marine primary production, with the effects observed on regional and global scales. In contrast to slower-growing higher plants, there is considerable potential for phytoplankton to evolve rapidly with changing environmental conditions. The energetic constraints associated with adaptation in phytoplankton are not yet understood, but are central to forecasting how global biogeochemical cycles respond to contemporary ocean change. Here, we demonstrate a number of potential trade-offs associated with high-temperature adaptation in a tropical microbial eukaryote, Amphidinium massartii (dinoflagellate). Most notably, the population became high-temperature specialized (higher fitness within a narrower thermal envelope and higher thermal optimum), and had a greater nutrient requirement for carbon, nitrogen and phosphorus. Evidently, the energetic constraints associated with living at elevated temperature alter competiveness along other environmental gradients. While high-temperature adaptation led to an irreversible change in biochemical composition (i.e., an increase in fatty acid saturation), the mechanisms underpinning thermal evolution in phytoplankton remain unclear, and will be crucial to understanding whether the trade-offs observed here are species-specific or are representative of the evolutionary constraints in all phytoplankton., (© 2018 Phycological Society of America.)

Australia's tropical waters represent predicted 'hotspots' for nitrogen (N2) fixation based on empirical and modelled data. However, the identity, activity and ecology of diazotrophs within this region are virtually unknown. By coupling DNA and cDNA sequencing of nitrogenase genes (nifH) with size-fractionated N2 fixation rate measurements, we elucidated diazotroph dynamics across the shelf region of the Arafura and Timor Seas (ATS) and oceanic Coral Sea during Austral spring and winter. During spring, Trichodesmium dominated ATS assemblages, comprising 60% of nifH DNA sequences, while Candidatus Atelocyanobacterium thalassa (UCYN-A) comprised 42% in the Coral Sea. In contrast, during winter the relative abundance of heterotrophic unicellular diazotrophs (δ-proteobacteria and γ-24774A11) increased in both regions, concomitant with a marked decline in UCYN-A sequences, whereby this clade effectively disappeared in the Coral Sea. Conservative estimates of N2 fixation rates ranged from <1 to 91 nmol l(-1) day(-1), and size fractionation indicated that unicellular organisms dominated N2 fixation during both spring and winter, but average unicellular rates were up to 10-fold higher in winter than in spring. Relative abundances of UCYN-A1 and γ-24774A11 nifH transcripts negatively correlated to silicate and phosphate, suggesting an affinity for oligotrophy. Our results indicate that Australia's tropical waters are indeed hotspots for N2 fixation and that regional physicochemical characteristics drive differential contributions of cyanobacterial and heterotrophic phylotypes to N2 fixation.

Despite differing target audiences and scope it is possible to compare the Fifth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) [American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Arlington: American Psychiatric Association, 2013] and the Second International Working Group for New Research Criteria for the Diagnosis of Alzheimer's Disease (IWG-2) [Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, et al. Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria. Lancet Neurol 2014;13:614-29] diagnostic criteria for both Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). With regard to the diagnosis of AD the principal difference is the inclusion of biomarkers in the IWG-2 diagnostic criteria for this condition. This creates a number of difficulties including a lack of regulatory approval, cultural and other objections to the collection of cerebrospinal fluid (CSF), and a lack of facilities for collection and analysis restricting analysis of CSF proteins to larger tertiary centres [Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, et al. Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria. Lancet Neurol 2014;13:614-29]. With regard to diagnostic criteria for DLB, IWG-2 research criteria designate the co-occurrence of AD and DLB as 'mixed AD'. However, Alzheimer's type pathology (ADTP) and Lewy body pathology frequently occur together rendering a separate 'mixed AD' category superfluous. The reality is that routine clinical diagnosis of AD and DLB will continue to be based on a thorough general and neurological examination indicating a preponderance of signs and symptoms for one or other of these conditions [Seeley WW, Miller BL. Alzheimer's disease and other dementias. In: Hauser SL, Josephson SA, editors. Harrison's neurology in clinical medicine, 3rd ed. New York: McGraw Hill, 2013]. Similarly, AD and DLB research will continue to primarily depend on clinically focussed DSM-5 criteria, making DSM-5 superior to IWG-2 in both clinical and research settings.

Identification of simple and complex finger flexion movements using surface electromyography (sEMG) and a muscle activation strategy is necessary to control human-computer interfaces such as prosthesis and orthoses. In order to identify these movements, sEMG sensors are placed on both anterior and posterior muscle compartments of the forearm. In general, the accuracy of myoelectric classification depends on several factors, which include number of sensors, features extraction methods, and classification algorithms. Myoelectric classification using a minimum number of sensors and optimal electrode configuration is always a challenging task. Sometimes, using several sensors including high density electrodes will not guarantee high classification accuracy. In this research, we investigated the dependence and independence nature of anterior and posterior muscles during simple and complex finger flexion movements. The outcome of this research shows that posterior parts of the hand muscles are dependent and hence responsible for most of simple finger flexion. On the other hand, this study shows that anterior muscles are responsible for most complex finger flexion. This also indicates that simple finger flexion can be identified using sEMG sensors connected only on anterior muscles (making posterior placement either independent or redundant), and vice versa is true for complex actions which can be easily identified using sEMG sensors on posterior muscles. The result of this study is beneficial for optimal electrode configuration and design of prosthetics and other related devices using a minimum number of sensors.

Background/aim: Stroke is the greatest contributor to disability in Australian adults and much of this disability results from a stroke-affected upper limb. This study aimed to determine the validity of hierarchal scoring for the upper limb subscale of the Motor Assessment Scale (UL-MAS) in acute stroke using Rasch analysis., Method: This study applied Rasch analysis to 40 UL-MAS assessment results across 25 subjects to determine the validity of the hierarchy of the three upper limb subsets: upper arm function (six), hand movements (seven) and advanced hand activities (eight). Rasch analysis examines the relationship between 'item difficulty' and 'person ability' and produces an output which represents the difficulty of each item in relation to each other., Results: As hypothesised, the hierarchy was upheld within subset 6. In subset 7, the hierarchy was not upheld. Results indicated that item 3 was the least difficult, followed by items 1, 4, 2, 5 and 6 in order of increasing difficulty. In subset 8 the hierarchy was not upheld. Results indicated that item 1 was the least difficult, followed by item 6, then 2 and 5 of equal value and then 3 and 4 of equal value., Conclusions: The hierarchal scoring is not supported for subsets 7 and 8 and future research is required to explore the validity of alternate scoring methods. At present, the authors recommend that the UL-MAS should be scored non-hierarchally, meaning that every item within the subsets should be scored regardless of its place within the hierarchy (UL-MAS-NH).

Rationale and Objectives: The purpose of this study was to evaluate the accuracy of contrast material-enhanced sonography in the detection of liver lesions by using an animal model., Materials and Methods: A total of 36 rabbits, 12 normal and 24 with one, two, or more VX2 tumors implanted percutaneously, were imaged on an Acuson 128XP/10 with a 7-MHz sector transducer by a sonographer blinded to the study assignments. The sonographer assigned rabbits to four groups (no, one, two, more than two tumors) based on the number of lesions detected before and then after the intravenous bolus injection of 0.5 mL of AF0150. S-VHS video segments or pre- and postcontrast images were separated, randomized, and evaluated by a blinded reader. Necropsy served as the gold standard., Results: Classification of rabbits as normal or tumor bearing on the precontrast images produced three false-positive results and three false-negative results for the blinded sonographer and six false-positive results and two false-negative results for the blinded reader. On postcontrast images, all rabbits were correctly classified by both observers. The correlation of the classification of whether rabbits had no, one, two, or more tumors relative to the pathologic classification on precontrast images was poor to fair (K = 0.349 +/- 0.099 for the sonographer and 0.274 +/- 0.111 for the reader), whereas the postcontrast correlation was good to excellent (K = 0.924 +/- 0.099 for the sonographer and 0.809 +/- 0.076 for the reader)., Conclusion: AF0150 markedly increased the ability of the sonographer and the blinded reader to distinguish normal from tumor-bearing animals and improved the classification of rabbits with more than one liver tumor.

Background and Purpose: Therapeutic ultrasound is one of the most widely and frequently used electrophysical agents. Despite over 60 years of clinical use, the effectiveness of ultrasound for treating people with pain, musculoskeletal injuries, and soft tissue lesions remains questionable. This article presents a systematic review of randomized controlled trials (RCTs) in which ultrasound was used to treat people with those conditions. Each trial was designed to investigate the contributions of active and placebo ultrasound to the patient outcomes measured. Depending on the condition, ultrasound (active and placebo) was used alone or in conjunction with other interventions in a manner designed to identify its contribution and distinguish it from those of other interventions., Methods: Thirty-five English-language RCTs were published between 1975 and 1999. Each RCT identified was scrutinized for patient outcomes and methodological adequacy., Results: Ten of the 35 RCTs were judged to have acceptable methods using criteria based on those developed by Sackett et al. Of these RCTs, the results of 2 trials suggest that therapeutic ultrasound is more effective in treating some clinical problems (carpal tunnel syndrome and calcific tendinitis of the shoulder) than placebo ultrasound, and the results of 8 trials suggest that it is not., Discussion and Conclusion: There was little evidence that active therapeutic ultrasound is more effective than placebo ultrasound for treating people with pain or a range of musculoskeletal injuries or for promoting soft tissue healing. The few studies deemed to have adequate methods examined a wide range of patient problems. The dosages used in these studies varied considerably, often for no discernable reason.

Almost 2 decades ago, it was pointed out that physical therapists tended to overlook the tenuous nature of the scientific basis for the use of therapeutic ultrasound. The purpose of this review is to examine the literature regarding the biophysical effects of therapeutic ultrasound to determine whether these effects may be considered sufficient to provide a reason (biological rationale) for the use of insonation for the treatment of people with pain and soft tissue injury. This review does not discuss articles that examined the clinical usefulness of ultrasound (see article by Robertson and Baker titled "A Review of Therapeutic Ultrasound: Effectiveness Studies" in this issue). The frequently described biophysical effects of ultrasound either do not occur in vivo under therapeutic conditions or have not been proven to have a clinical effect under these conditions. This review reveals that there is currently insufficient biophysical evidence to provide a scientific foundation for the clinical use of therapeutic ultrasound for the treatment of people with pain and soft tissue injury.

Rationale and Objectives: This study was performed to (a) test the hypothesis that filling the arterial lumen with echoes at B-mode ultrasound (US) enables the assessment of wall and luminal abnormalities and (b) compare contrast material-enhanced B-mode US with color and power Doppler US angiography., Materials and Methods: Atherosclerotic lesions were created in 14 rabbit aortas and imaged with color Doppler and B-mode US before and after the intravenous administration of 0.3 mL of AF0150, a US contrast agent. In addition, four replicas of diseased human carotid arteries were immersed in a tissue-mimicking phantom and imaged with B-mode and color and power Doppler US before and after the administration of 1 mL of AF0150 per liter of porcine blood. Radiopaque plastic casts of the rabbit aortas and contact radiographs of the plastic replicas served as standards., Results: Although color and power Doppler US allowed immediate localization of the lumen, precise estimation of stenoses and reliable visualization of surface irregularities were not possible. After AF0150 administration, angiogram-like images of the lumen were created with B-mode US, allowing rapid assessment of the entire vessel lumen and wall. Consequently, luminal stenoses were more accurately measured than with unenhanced B-mode US (r2 = 0.94, P < .0001 vs r2 = 0.21, P = .25) or Doppler (r2 = 0.42, P < .03). In addition, plaques and ulcerations were visible only with contrast-enhanced B-mode US., Conclusion: Microbubbles fill the arterial lumen with echoes at B-mode US, creating an angiogram-like image. The ability to visualize the inner and outer surfaces of the vascular wall improved the evaluation of luminal and wall abnormalities.

This study compares contrast-enhanced fundamental and second harmonic B-mode sonography using a rabbit renal infarct model. Segmental renal infarctions were produced in 13 rabbits by embolizing a 0.7 mm bead into the renal artery 1 day prior to imaging. An ultrasonographic unit equipped with an L10-5 transducer and second harmonic imaging capability was used. Real-time recordings were made during the injection of 0.5 ml of an experimental formulation of a perfluorohexane vapor-stabilized microbubble (AF0145) given into the ear vein, and the imaging technique alternated between standard and harmonic imaging every 20 s. Each rabbit received two injections 1 h apart. To control for the effect of peak bolus enhancement, the initial imaging technique used for the first injection was randomized, and the other technique was used initially for the second injection. The videointensity difference between the infarcted and the normal cortex was then calculated and evaluated as a function of time. The infarcted segment could not be seen before administration of contrast agent with either technique. Although the infarction could be seen after injection of contrast agent with either technique, image contrast and contrast duration were nearly 75% greater for the harmonic technique than for the standard technique. AF0145 allows the visualization of segmental renal infarction on standard B-mode imaging. The second harmonic B-mode technique significantly increases image contrast and contrast duration.

Rationale and Objectives: The authors evaluated the time-echogenicity response of liver, kidney, and implanted VX2 tumor after injection of a microbubble contrast medium and assessed use of an avascular lesion as an internal standard., Materials and Methods: Twenty-one New Zealand White rabbits were studied. To evaluate use of an internal standard and the dose-response relationship, nine rabbits with 7-day-old avascular liver lesions created by alcohol ablation received 0.1, 0.25, 0.5, and 1.0 mL of AF0145, a microbubble contrast agent. To evaluate tumor echogenicity, 12 rabbits implanted with VX2 tumor in the liver (six also underwent alcohol ablation) received 0.5 mL of AF0145. Videodensitometry was used to analyze echogenicity changes over 10 minutes., Results: Echogenicity of the alcohol-ablated liver was not affected by contrast material administration. Liver and kidney echogenicity relative to ablation increased linearly with dose, peaking 1 minute after injection and decaying to baseline over 9 minutes. Contrast material administration defined the size and margins of VX2 lesions more clearly. In the arterial phase, the tumor rim was hyperechoic relative to surrounding liver, becoming isoechoic during the portal venous phase then hypoechoic during the late phase parenchymal phase., Conclusions: Lesions created by alcohol ablation can be used as an internal standard for quantitative analysis of adjacent tissues. AF0145 enhances perfused tissues, including vascular tumors, at gray-scale, real-time ultrasonography and enhances the liver.

We showed that tissue enhancement with microbubbles is dependent upon transmit power. Because intermittent imaging decreases bubble exposure to ultrasound, and also decreases the ability of the sonographer to maintain anatomic orientation, we aimed to determine the optimum frame rate that maximizes enhancement and allows for continued anatomic orientation. Seven rabbits with an avascular liver lesion created by percutaneous injection of 1 mL ethyl alcohol 7 days earlier were imaged with an Acuson 128XP/10 using a 7-MHz sector transducer at fixed transmit power. Each rabbit was imaged 5 times in random order, at 1 frame/30 s, 1frame/5 s, 1frame/s, 4 frames/s, and 28 frames/s. The same plane was imaged at all frame rates from before to 15 min after the bolus injection of 0.3-mL (0.1-0.12 mL/kg) of AF0150 (Imagent, Alliance Pharmaceutical Corp., San Diego, CA). Liver and portal vein videointensity relative to the lesion were evaluated over time. In this study, liver enhancement progressively increased as the frame rate was reduced (p<0.001). Peak, duration, and area under the time-intensity curve were all greater at the lower frame rates (1 fr/30 s, 1 fr/5 s, and 1 fr/s) than at 28 fr/s (p<0.05). Anatomic orientation was maintained at 1 frame/s rate at which peak enhancement was 44% greater and duration was 100% longer than at 28 frames/s (p<.05). Portal vein enhancement was not affected by frame rate. In conclusion, with intermittent imaging, enhancement was dependent upon frame rate and the ability of the region being imaged to replenish its bubbles between consecutive acquisitions. The 1 frame/s allowed for anatomic orientation and adequate tissue contrast.

This study examines the effect of chronic alcohol consumption on the human cerebellum using operational criteria for case selection [Caine D. et al. (1997) J. Neurol. Neurosurg. Psychiat. 62, 51-60] and unbiased stereological techniques. We describe, for the first time, structural changes in different functional zones of the cerebellum of chronic alcoholics and correlate these changes with specific clinical symptoms. No consistent changes in the number of neurons or the structural volume for any cerebellar region were observed in the chronic alcoholics without the clinical signs of Wernicke's encephalopathy. In all cerebellar measures, these chronic alcoholics did not differ significantly from the non-alcoholic controls, suggesting that chronic alcohol consumption per se does not necessarily damage human cerebellar tissue. However, several cerebellar changes were noted in the thiamine-deficient alcoholics studied. There was a significant decrease in Purkinje cell density (reduced on average by 43%) and molecular layer volume (reduced by 32%) in the cerebellar vermis in all thiamine-deficient chronic alcoholics. A decrease in cell density and atrophy of the molecular layer, where the dendritic trees of the Purkinje cells are found, without significant cell loss suggests loss of cellular dendritic structure and volume. These thiamine-deficient alcoholics also had a significant decrease (36% loss) in the estimated Purkinje cell number of the flocculi, disrupting vestibulocerebellar pathways. These results indicate that cerebellar Purkinje cells are selectively vulnerable to thiamine deficiency. There is evidence that this damage contributes significantly to the clinical signs of Wernicke's encephalopathy. There was a 36% loss of Purkinje cells in the lateral lobe in alcoholics with mental state signs and 42% atrophy of vermal white matter in ataxic alcoholics. The finding of a 57% loss of Purkinje cells and a 43% atrophy of the molecular layer of the vermis in alcoholics with cerebellar dysfunction supports previous findings highlighting the importance of spinocerebellar pathways to these symptoms.

Previous studies have identified alcohol, thiamine deficiency and liver disease as contributing to the neuropathology of alcohol-related brain damage. In order to examine the effects of alcohol toxicity and thiamine deficiency on serotonergic neurons in the median raphe nucleus (MnR), alcoholic and previously published Wernicke-Korsakoff syndrome (WKS) cases without liver disease, were compared with age-matched non-alcoholic controls. While there was no difference between the estimated number of serotonergic neurons in either controls or alcoholics without WKS (means of 63,010 +/- 8,900 and 59,560 +/- 8,010 respectively), a substantial loss of serotonergic neurons was previously found in WKS cases (mean of 19,050 +/- 13,140). Further analysis revealed a significant difference in the maximum daily alcohol consumption between these groups. However, analysis of covariance showed that the number or serotonergic neurons in the MnR did not correlate with the amount of alcohol consumed. Therefore, our results suggest that cell loss in the MnR can be attributed to thiamine deficiency rather than alcohol per se.

Despite the considerable evidence that alcoholics have perturbation of serotonergic function, there is little pathological evidence for alcohol directly affecting the nervous system. The present study aims to assess neuronal loss that occurs as a consequence of alcohol neurotoxicity in the serotonergic dorsal raphe nucleus (DRN). To that end, the brains of eight alcoholics and eight age-matched control cases were carefully screened to eliminate serious liver disease, the sequela of thiamine deficiency, Wernicke-Korsakoff syndrome (WKS), and other pathological abnormalities. Brains were formalin-fixed for 2 weeks, cut, and then immunohistochemically stained using a monoclonal PH8 antibody specific for the rate-limiting enzyme of serotonin synthesis, tryptophan hydroxylase. The morphology of the serotonin-synthesizing neurons and their average size was similar in all cases. However, there was a reduction in the staining intensity of the reaction product in the DRN serotonergic neurons of most alcoholics. Neuronal counts on spaced serial sections revealed that there were an estimated average total of 106,100 +/- 19,500 serotonergic neurons in the DRN of alcoholics and 108,300 +/- 11,800 in the DRN of controls, indicating that in most alcoholics there is no reduction in the number of these neurons. Therefore, the effect of chronic alcohol consumption on the serotonergic system, in the absence of WKS or liver disease, seems to be functional rather than neuropathological.

A case report is presented of a 10-month-old child with a 1-month history of respiratory symptoms, followed by 3 to 4 days of fever, progressing to poor feeding, vomiting, and weight loss. The child is cared for by his mentally disabled young parents. A chest radiograph revealed a metallic foreign body obstructing the proximal esophagus. Esophagoscopy and removal of a penny resulted in immediate resolution of the acute gastrointestinal symptoms; the respiratory symptoms resolved shortly thereafter. Diagnostic and therapeutic considerations in the management of pediatric aerodigestive foreign bodies are discussed. High-risk parenting, such as in this case, is a risk factor for pediatric foreign-body ingestion.

Rationale and Objectives: Recent clinical work suggests that the Doppler resistive index (RI) may be useful in distinguishing obstructive from nonobstructive hydronephrosis. We evaluated the usefulness of the RI in a rabbit model of hydronephrosis., Methods: Unilateral partial ureteral obstruction was produced in nine rabbits and complete obstruction in another nine. Three sham operations were performed, and these animals served as control subjects. The RI was measured in all kidneys before and 6 hr after surgery and on days 1, 4, and 7 postoperatively. The RI and the difference in RI (delta RI) between the obstructed and normal kidney were evaluated over time using a two-way analysis of variance. The intravenous urography and Whitaker tests served as gold standards., Results: Hydronephrosis was observed on sonograms in all obstructed kidneys. Comparing groups, there was no significant difference in mean RI or delta RI between the three groups at any time point. Looking at individual groups over time, there was no significant change in mean delta RI, whereas the change in mean RI was significantly elevated above baseline only in the complete obstruction group at 6 hr (p = .002) and on days 4 (p = .008) and 7 (p = .006). In evaluating varying thresholds of RI and delta RI, we could not consistently discriminate between normal and obstructed kidneys., Conclusion: Although complete obstruction caused a significant increase in RI, partial obstruction failed to do so. RI and delta RI values proved to be insensitive predictors of obstruction in this rabbit model.

Manganese (II) N,N'-dipyridoxylethylenediamine-N,N'-diacetate 5,5'-bis(phosphate) (DPDP) is a paramagnetic magnetic resonance (MR) contrast agent that enhances the liver and is predominantly excreted through the biliary tree. The authors evaluated its utility in diffuse liver disease by assessing liver and gallbladder enhancement in 24 rabbits. Total (n = 6) or segmental (n = 6) biliary occlusion or galactosamine-induced hepatitis (n = 6) was induced 3 days before imaging. Six rabbits served as normal controls. T1- and T2-weighted axial MR images were acquired at baseline, followed by T1-weighted images every 10 minutes for 1 hour after the intravenous administration of 20 mumol/kg Mn-DPDP. Except for the segmental occlusion group, the baseline study did not allow distinction between normal and abnormal livers. The temporal hepatic enhancement pattern was statistically different for each group. The normal, segmental occlusion, and hepatitis groups showed patterns similar to one another but markedly higher signal intensity than the total-occlusion group throughout the observation period. In contrast, the gallbladder showed a greater difference in both degree of enhancement and time to peak enhancement among the four groups. Mn-DPDP produces a temporal hepatic enhancement pattern that allows recognition of markedly impaired livers, and gallbladder enhancement patterns that allow distinction of more subtly impaired livers.

Despite reduced levels of noradrenaline and increased cortical beta-adrenergic receptor binding, there is controversy regarding the effect of chronic alcohol consumption on the noradrenergic neurons of the locus coeruleus (LC). The aim of this study is to investigate the effects of chronic alcohol consumption on the LC; in particular, to determine whether or not there is any alteration in the size or number of neurons, or other significant changes in this nucleus. Eight chronic alcoholics without additional medical complications and eight age-matched controls were selected for this study. Immunohistochemistry with antibodies against tyrosine hydroxylase (TH) was used to visualize TH-positive neurons in spaced serial 50-microns sections throughout the length of the LC. These neurons were counted and no correction factors applied. There was no significant loss of TH-positive neurons in the LC of alcoholics compared with controls who had up to 20% variation in the number of neurons between individuals. This confirms published results from one alcoholic without complications, but contradicts recent findings of a significant neuronal loss in five alcoholics, all with liver pathology. Our analysis suggests that central noradrenergic neurons in alcoholics without significant medical complications are not susceptible to alcohol neurotoxicity.

We have shown using a Vx2 rabbit model that 3 and 5ml/kg of perflubron emulsion were highly effective in imaging liver tumors. The results from preliminary clinical trials suggested that should the infusion rate be increased, a 1.5ml/kg may be efficacious. This study determined whether 1.5ml/kg given as a bolus IV would be efficacious to image liver tumors using a Vx2 rabbit model. Vx2 tumors were implanted in 5 NZW rabbits, CT of the liver was performed during held expiration at 80kV and 800mAS, before and shortly after 1.5ml/kg Imagent BP (ImBP), again at 30 minutes and 3 days. Regions of interest (ROIs) were drawn over the CT image of the spleen, liver, inferior vena cava, and tumor, CT# obtained and average enhancement of each tissue calculated at each time point. 4 animals had tumors .5cm or greater. Precontrast, tumors were faintly seen on CT. Blood was brighter than liver shortly after infusion and isointense with liver at 30 minutes. Tumors did not enhance following contrast. Except for the liver and spleen, all tissues returned to baseline on the 3rd day. Therefore a clinical trial to determine the efficacy of 1.5ml/kg ImBP to image the liver is warranted.

The accurate quantitation of liver tumor burden and visualization of lesions in three dimensions (3D) can assist in treatment planning and can allow monitoring of therapy. Previous attempts have used CT and standard contrast media. Because the iodinated agents rapidly diffuse into tumors, usually effacing, and at time enhancing tumor edges, they decrease accuracy and make image segmentation difficult. CT portography suffers from flow related artifacts and does not allow the distinction of tumors from hemangiomas. Blood pool contrast is ideal in this setting since it enhances liver, liver vessels and hemangiomas, but not tumors, 'physiologically' splitting the image into normal and abnormal tissues. This ongoing study assesses the feasibility of this technique to visualize tumor and presents a scheme to automatically quantitate tumor volume. It utilized a rabbit VX2 liver tumor model and CT scanning shortly after the infusion of 3 ml/kg perflubron emulsion. Cut sections of the frozen carcass served as gross pathologic correlation. Images were imported onto a Sparc workstation, 3D reformatted and tumor and liver volume calculated. Histograms of pixel intensity clearly separated tumors from liver and liver from surrounding structures allowing the easy demarcation of tumor and liver margins.

We have employed immunohistochemical and morphometric procedures to study serotonin-synthesizing (PH8-immunoreactive) neurons in the pontine reticular formation of the adult human. PH8-immunoreactive neurons were found in three cytoarchitectural regions: the median raphe nucleus (MnR), oral pontine reticular nucleus (PnO), and supralemniscal region (group B9). On the basis of cell size, morphology, and position, it was possible to distinguish distinct subgroups within the MnR (dorsal, midline, and paramedian cell clusters) and within the PnO (dorsal and central cell clusters), whereas within the B9 there were no distinct cell clusters. We have estimated that there are approximately 125,000 PH8-immunoreactive neurons in the human pontine tegmentum; 64,400 in the MnR, 30,700 in PnO and 29,000 in B9. The large numbers of serotonin-synthesizing neurons in the human pontine tegmentum contrasts with their relative paucity in nonprimate species such as rats and cats. Nonhuman primates also have large numbers of pontine serotonergic neurons but the morphology of these neurons and their spatial arrangement is significantly different in humans. These results are discussed with respect to the possible projections and functions of these neurons in humans.

The distribution, morphology and number of serotonin-, catecholamine- and substance P-containing neurons in the human dorsal raphe nucleus were studied. Parallel series of sections were prepared from 10 human brainstems obtained at autopsy from patients without neurological disease aged between 42 and 88 years. The neurons were identified using immunohistochemistry with antibodies raised against phenylalanine hydroxylase (tryptophan hydroxylase-containing, serotonin neurons), tyrosine hydroxylase (catecholamine neurons) and substance P. A reference series of Nissl-stained sections was also prepared and data published separately were used to delineate the subnuclear divisions of the dorsal raphe nucleus and to establish the total number of neurons in each subnucleus. The following principal findings emerged. (1) Serotonin-synthesizing neurons are present in all regions of the dorsal raphe nucleus and their total number is 165,000 +/- 34,000. The same types of neurons as those seen in Nissl material characterize each of the five subnuclei (caudal, dorsal, ventral, ventrolateral and interfascicular). (2) Substance P-containing neurons mostly occupy the rostral part of the nucleus and their number is 74,600 +/- 17,600. (3) Catecholamine cells are only found in the rostral part of the dorsal raphe nucleus and their number is 5600 +/- 3400. (4) In the ventral and interfascicular subnuclei the combined number of serotonin-synthesizing and substance P-containing neurons exceeds the total number of Nissl-stained neurons suggesting that serotonin and substance P co-exist in a substantial part of the cell population of the dorsal raphe nucleus. This is further supported by the highly similar morphology and size of these neurons. It is concluded that there are demonstrable chemical differences between the various subregions of the human dorsal raphe nucleus. These differences are in harmony with the results of hodological studies in animals, which have demonstrated differential projection pathways emerging from this nucleus.

Serial 50 microns Nissl-stained sections through the midbrain and pontine central gray of four adult humans (mean age 56 years, mean postmortem delay 3 hours) were analysed and the subnuclei of the dorsal raphe nucleus (DR) delineated on the basis of neuronal morphology and density. Five subnuclei were apparent: the interfascicular, ventral, ventrolateral, dorsal, and caudal. The area of each subnucleus was measured in sections selected at regular intervals throughout the length of the DR. The number of neurons was counted and their density within each subnucleus calculated. The dorsal subnucleus was the largest and contained the majority of neurons but had the lowest neuronal density. The ventrolateral subnucleus had the highest density of neurons. A total of 235,000 +/- 15,000 neurons (average of 1,200 +/- 200 neurons per section) were found within a volume of 71.3 +/- 4.5 mm3 of DR with a mean neuronal density of 3,300 +/- 200 neurons/mm3. Morphometric and morphological analysis of DR neurons revealed four distinct neuron types: round, ovoid, fusiform, and triangular. These types of neurons characterized particular subnuclei. The location and boundaries of the subnuclei of the human dorsal raphe are presented in the form of an atlas. The subdivisions described are similar to that described in other mammals. On the basis of this information the location of particular projection neurons within the human dorsal raphe can be predicted and the effects of disease on this nucleus may be forecast.

The CA (catecholamine/catecholaminergic) cell populations of the locus coeruleus (LC) and subcoeruleus (SubC) were studied using serial sections of the human brainstem immunostained with an antibody against tyrosine hydroxylase. The tyrosine hydroxylase-immunoreactive (TH-IR) neurons were plotted in a computer reconstruction system and their number and soma size determined. Serial section computer analysis was then used to create a three dimensional reconstruction of the LC complex. The number of cells containing neuromelanin pigment was also determined and compared with the number of TH-IR cells. In our sample there were 53,900 TH-IR cells in the LC and a further 6260 cells in the SubC. These numbers were very similar to our estimates of the number of cells containing neuromelanin pigment and we concluded that virtually all of these cells were also tyrosine hydroxylase positive. The average soma size of the TH-IR cells of the LC was 37 microns and in the SubC 34 microns. In addition to these quantitative observations the morphology of the TH-IR and the Nissl stained cells is described in some detail. We also compared the groups of immunoreactive cells in the human pons with the noradrenergic groups A5-A7 described in the rat. Although in the human these groups are contiguous, A5 is not part of the LC complex. However we did find that the A7 group is equivalent to the rostroventral part of SubC while the remainder of SubC is formed by ventral A6.

The purpose of the group sessions in our hospital was to relieve patient anxiety by offering the patients an opportunity to discuss lifestyle changes necessary for adjustment in living with CAD in order to better adapt to the illness. A series of informal group sessions accomplished these purposes admirably. It is the opinion of these authors that nurses educated in group skills should institute group sessions for patients with CAD. The benefits to both the nurse and patient are unlimited.

Scheuermann's disease (or more correctly, spinal osteochondrosis) is not confined to the thoracic spine: all parts of the spine may be affected. Major signs are endplate irregularity, more than 5° vertebral wedging, and sagittal overgrowth. Minor signs are Schmorl's nodes, anterior flattening of the vertebral endplate, and anterior detachment of a ring apophysis. Symptoms are of little diagnostic value. Scheuermann's affects 20 per cent to 30 percent of the population; males and females equally. A hereditary predisposition is a major factor in the aetiology of Scheuermann's disease. There is evidence that this condition follows an autosomal dominant pattern of inheritance. Treatment consists of either exercises; bracing and exercises; or in very severe cases, surgery., (Copyright © 1988 Australian Physiotherapy Association. Published by . All rights reserved.)

Consultation-liaison (C-L) psychiatry has long been implemented in hospitals and clinics. The HMO is a natural setting for the further development of this service because of its commitment to comprehensive patient care. The Psychiatry Department of a large urban HMO initiated a C-L service as a pilot project. Results of this project included coordinated multidisciplinary patient care and enhancement of interprofessional relationships within the organization.