Synaptopodin-2 induces assembly of peripheral actin bundles and immature focal adhesions to promote lamellipodia formation and prostate cancer cell migration

Synaptopodin-2 (Synpo2), an actin-binding protein and invasive cancer biomarker, induces formation of complex stress fiber networks in the cell body and promotes PC3 prostate cancer cell migration in response to serum stimulation. The role of these actin networks in enhanced cancer cell migration is unknown. Using time-course analysis and live cell imaging of mock- and Synpo2-transduced PC3 cells, we now show that Synpo2 induces assembly of actin fibers near the cell periphery and Arp2/3-dependent lamellipodia formation. Lamellipodia formed in a non-directional manner or repeatedly changed direction, explaining the enhanced chemokinetic activity of PC3 cells in response to serum stimulation. Myosin contraction promotes retrograde flow of the Synpo2-associated actin filaments at the leading edge and their merger with actin networks in the cell body. Enhanced PC3 cell migration correlates with Synpo2-induced formation of lamellipodia and immature focal adhesions (FAs), but is not dependent on myosin contraction or FA maturation. The previously reported correlation between Synpo2-induced stress fiber assembly and enhanced PC3 cell migration therefore reflects the role of Synpo2 as a newly identified regulator of actin bundle formation and nascent FA assembly near the leading cell edge.     

Intracranial granulocytic sarcoma in postpolycythemia myeloid metaplasia

A 57-year-old man with a ten-year history of polycythemia vera had myeloid metaplasia, extramedullary hematopoiesis, and terminally, possible leukemic transformation with intracranial granulocytic sarcoma. Radiation therapy produced a partial and temporary beneficial response. Intracranial granulocytic sarcoma is typically associated with acute or chronic myelogenous leukemia and has not been previously associated with postpolycythemia myeloid metaplasia.     

Influenza A pneumonia with rhabdomyolysis

Influenza A pneumonia accounts for a significant number of the community-acquired pneumonias in the United States. While myalgia is a common complaint in influenza A infection, few cases of rhabdomyolysis associated with this virus have been described. Although it has been recently recognized that rhabdomyolysis complicating certain bacterial pneumonias has important prognostic implications, rhabdomyolysis in the setting of influenza A pneumonia does not appear to carry the same prognostic significance.     

Nonverbal imitation skills in children with specific language delay

Research in children with language problems has focussed on verbal deficits, and we have less understanding of children's deficits with nonverbal sociocognitive skills which have been proposed to be important for language acquisition. This study was designed to investigate elicited nonverbal imitation in children with specific language delay (SLD). It is argued that difficulties in nonverbal imitation, which do not involve the processing of structural aspects of language, may be indicative of sociocognitive deficits. Participants were German-speaking typically developing children (n = 60) and children with SLD (n = 45) aged 2–3½ years. A novel battery of tasks measured their ability to imitate a range of nonverbal target acts that to a greater or lesser extent involve sociocognitive skills (body movements, instrumental acts on objects, pretend acts). Significant group differences were found for all body movement and pretend act tasks, but not for the instrumental act tasks. The poorer imitative performance of the SLD sample was not explained by motor or nonverbal cognitive skills. Thus, it appeared that the nature of the task affected children's imitation performance. It is argued that the ability to establish a sense of connectedness with the demonstrator was at the core of children's imitation difficulty in the SLD sample.     

Making errorless learning more active: Self-generation in an error free learning context is superior to standard errorless learning of face–name associations in people with Alzheimer's disease

Errorless learning (EL) principles have been shown to enable people with memory impairments to acquire various types of information (Grandmaison & Simard, 2003; Wilson, 2005). However, the effects of EL, based on simple repetition only, tend to be limited with regards to their size and longevity. The present study investigated whether EL could be improved by actively engaging people with Alzheimer's disease in the learning process. Patients learned the names of famous faces over 10 training sessions, treated either with a non-learning control, a simple repetition EL procedure, or an EL condition in which responses had to be self-generated. Cued recall rates after the final training session were significantly greater for the names treated with the self-generated EL technique compared to the control and the repetition EL conditions. In addition, there was evidence that patients with less severe general cognitive impairment benefit more from active generation than more severely impaired patients. The implications of this research for individualised memory rehabilitation programmes are discussed.     

Exercise in a Cold Climate

Dr. Shephard reviews practical advice required by the winter sportsman in relation to more fundamental aspects of the bodily response to cold. Heat loss occurs by radiation, convection, conduction, and evaporation of sweat; this loss must be made good by metabolism if the body is not to be chilled. Convection is the main source of heat loss in the sportsman, and must be minimized by appropriate clothing. Chilling below a body temperature of 95°F is undesirable; temperatures below 90°F are rapidly fatal. Heat is restored to the body by warming, by the “waste” energy of physical activity, and by shivering.     

Amiodarone-induced alveolar hemorrhage

Amiodarone is increasingly prescribed for patients with ventricular and supraventricular tachyarrhythmias. Many adverse effects have been reported due to this drug and include injury to the liver, thyroid, cornea, skin, and neuromuscular system. Pulmonary toxicity is one of the more serious side effects of this anti-arrhythmic drug and is potentially fatal. Since the first case of amiodarone-induced pneumonitis was described in the early 1980s, amiodarone pneumonitis has been recognized as a distinctive and not uncommon form of drug-induced lung injury. On the other hand, amiodarone-induced pulmonary toxicity resulting in alveolar hemorrhage is rare. The authors report a patient with amiodarone-induced alveolar hemorrhage and review the literature.     

Prevalence of undiagnosed hypoxemia in adults and children in an under-resourced district hospital in Zambia

Background

In adequately resourced clinical environments, diagnosis of hypoxemia via pulse oximetry is routine. Unfortunately, pulse oximetry is rarely utilized in under-resourced hospitals in developing countries.

Aim

The prevalence of undiagnosed hypoxemia among adults and children with illnesses other than pneumonia in these environments remains poorly described.

Methods

This cross-sectional analysis of the prevalence of hypoxemia was conducted in Kapiri Mposhi, Zambia, at the 60-bed District Hospital, which serves a population of 320,000. The resting room air oxygen saturations of two consecutive samples of all adult and pediatric inpatients were measured in December 2008 and March 2009 using handheld pulse oximetry. Hypoxemia was defined as resting room air SpO₂ less than 90%.

Results

A total of 192 patients were enrolled: 68 young children (<5 years old), 15 older children (5–17 years old), and 109 adults (≥18 years old). Five young children (7%), 0 older children (0%), and 10 adults (9%) were hypoxemic. No hypoxemic patients were receiving oxygen therapy at the time of diagnosis. Pneumonia, tuberculosis, and malnutrition were the most common conditions among those with hypoxemia. Oximetry data changed clinical management in all observed cases of hypoxemia and several cases of normoxemia, leading to application of supplemental oxygen, initiation of further diagnostic testing, prolongation of inpatient stay, or expedited discharge home.

Conclusions

Undiagnosed hypoxemia is present among inpatients at this district hospital in rural Zambia with high prevalence in both adults and young children. These results support routine screening for hypoxemia in similar facilities in both age groups. Further investigation is warranted into the clinical impact and cost-effectiveness of pulse oximetry, provision of oxygen concentrators, and training on their use in developing countries.     

Mitochondrial dysfunction in rabies virus infection of neurons

Infection with the challenge virus standard-11 (CVS) strain of fixed rabies virus induces neuronal process degeneration in adult mice after hindlimb footpad inoculation. CVS-induced axonal swellings of primary rodent dorsal root ganglion neurons are associated with 4-hydroxy-2-nonenal protein adduct staining, indicating a critical role of oxidative stress. Mitochondrial dysfunction is the major cause of oxidative stress. We hypothesized that CVS infection induces mitochondrial dysfunction leading to oxidative stress. We investigated the effects of CVS infection on several mitochondrial parameters in different cell types. CVS infection significantly increased maximal uncoupled respiration and complex IV respiration and complex I and complex IV activities, but did not affect complex II–III or citrate synthase activities. Increases in complex I activity, but not complex IV activity, correlated with susceptibility of the cells to CVS infection. CVS infection maintained coupled respiration and rate of proton leak, indicating a tight mitochondrial coupling. Possibly as a result of enhanced complex activity and efficient coupling, a high mitochondrial membrane potential was generated. CVS infection reduced the intracellular ATP level and altered the cellular redox state as indicated by a high NADH/NAD+ ratio. The basal production of reactive oxygen species (ROS) was not affected in CVS-infected neurons. However, a higher rate of ROS generation occurred in CVS-infected neurons in the presence of mitochondrial substrates and inhibitors. We conclude that CVS infection induces mitochondrial dysfunction leading to ROS overgeneration and oxidative stress.