Control of Tumor Bioenergetics and Survival Stress Signaling by Mitochondrial HSP90s

Tumors successfully adapt to constantly changing intra- and extracellular environments, but the wirings of this process are still largely elusive. Here, we show that heat-shock-protein-90-directed protein folding in mitochondria, but not cytosol, maintains energy production in tumor cells. Interference with this process activates a signaling network that involves phosphorylation of nutrient-sensing AMP-activated kinase, inhibition of rapamycin-sensitive mTOR complex 1, induction of autophagy, and expression of an endoplasmic reticulum unfolded protein response. This signaling network confers a survival and proliferative advantage to genetically disparate tumors, and correlates with worse outcome in lung cancer patients. Therefore, mitochondrial heat shock protein 90s are adaptive regulators of tumor bioenergetics and tractable targets for cancer therapy.     

Choroidal neovascularization and angioid streaks in pseudoxanthoma elasticum

AIM: To report a case of pseudoxanthoma elasticum (PXE) in a 48 year old woman that presented with bilateral blurry vision. METHODS: A case report RESULTS: A 48-year-old woman presented with bilateral blurry vision and right eye metamorphopsia. The patient had a history of angioid streaks in the left eye ten years ago for which she had received laser surgery and had poor residual vision. Visual acuity was 20/60 in the right eye and count fingers at 6 feet in the left. Fundus examination showed subretinal hemorrhage and macular thickening on the right and a disciform macular scar with focal atrophic pigment epithelial lesions on the left. Both eyes had angioid streaks and peau d’orange pigmentary pattern of the retina. External examination showed several, yellow skin papules and plaques on the lateral and posterior neck, as well as prominent mental creases. Pathologic examination of skin biopsy confirmed the diagnosis of PXE, showing calcium deposition and fragmented, clumped elastic fibers in the deep reticular dermis. She responded well to intravitreal bevacizumab injections and visual acuity improved to 20/25 OD. Preventative care was emphasized and the patient was referred to cardiology, gastroenterology and human genetics for counseling. CONCLUSION: PXE is a multisystem disorder affecting the dermatologic, ocular, and cardiovascular systems. Ophthalmic findings of angioid streaks and choroidal neovascularization in the presence of stereotypical skin changes and prominent mental creases should prompt evaluation for PXE.     

Disease severity and quality of life in a follow-up study of patients with occupational contact dermatitis

Background Few studies have investigated how occupational contact dermatitis and its severity affect patients' quality of life (QoL). Objectives To investigate the impact of occupational contact dermatitis and its severity on patients' QoL, and to examine the association between different QoL measures. Method Patients previously diagnosed with occupational contact dermatitis completed the Short Form Health Survey (SF‐36) and Dermatology Life Quality Index (DLQI). Disease severity was rated both by the patient and by the physician. Results Of a possible 725, a total of 119 patients (16.4%) were included in the study, and, at follow‐up, just over 21% had normal skin and 18.3% had progressed to persistent dermatitis. The SF‐36 median physical component summary score was 52 [interquartile range (IQR): 43–56] and the mental component summary median score was 51 (IQR: 44–57). The correlation between patient‐rated and physician‐rated disease severity was moderate (r = 0.708, p < 0.00001). The correlation between the disease severity measures and DLQI was moderate, whereas the SF‐36 correlated poorly with both the DLQI and disease severity measures. Conclusions QoL was generally reduced in this group of patients with occupational contact dermatitis, with some correlation between severity and DLQI. The DLQI was a more sensitive measurement of QoL than the SF‐36 in this patient population. Incorporating disease severity rating with a QoL questionnaire is valuable in occupational contact dermatitis and is recommended.     

Pacinioma of the cauda equina

Lesions composed of Pacinian corpuscles or showing Pacinian corpuscle differentiation have usually been described in relation to benign tumours of the peripheral nervous system or reactive hyperplastic processes. On the other hand, mature Pacinian corpuscles have occasionally been detected as part of intraspinal lumbosacral lipomas, a rare developmental anomaly usually associated with spina bifida. A lesion of the cauda equina composed of numerous mature Pacinian corpuscles and nerve fascicles embedded in adipose tissue in association with spina bifida occulta is described in a 5-month-old male with a sacral red papula. Magnetic resonance imaging (MRI) revealed a cord-like mass in the region of the cauda equina, presumably connected to the subcutis. With the exception of a low lying, tethered spinal cord, there was no neurological deficit and the range of motor development was normal. In March 2005, at 17 months, surgery was carried out. A cord of yellow tissue was found running from the subcutis through the bone defect into the lumbosacral spinal canal. Intradurally, it ran parallel to the cauda equina, terminating at the conus medullaris. Fifteen months after the surgery the development of the child was normal. Only two similar cases have been reported so far. Due to their occurrence in the sacrococcygeal region and association with developmental anomalies, they have been regarded as malformations and the term Pacinioma has been suggested. Our case with clusters of Pacinian corpuscles may represent a rare variant of complex intraspinal lumbosacral lipomas, closely related to Paciniomas reported by Bale.     

The persistence of flood-borne pathogens on building surfaces under drying conditions

Previous research into microbial persistence on material surfaces following flooding has produced a wide range of results due to differing experimental conditions, including the temperature and humidity conditions of the experimental material and/or surrounding air. However, investigations to identify and quantify these factors and their links to the hygrothermal properties of building materials and the transient environmental conditions are rarely reported. This paper examines the viability of bacterial species on drying material surfaces that have been saturated with water or synthetic sewage. Escherichia coli and Enterococcus faecalis were inoculated on brick, wood, or plaster and allowed to dry at the conditions intended to mimic the remediation environments commonly found in domestic dwellings following a flood event. The inactivation rates were compared between environmental conditions, water type and the material properties of the surfaces. Significant differences were found in the declines in E. coli according to water type, the surface relative humidity and air relative humidity and between drying rates for sewage floods. Simulations using hygrothermal software were performed to illustrate the wide variation in material drying rates under different scenarios, taking into account material size, wall composition, and ventilation. The significantly differing rates of microbial death on flooded building materials under different drying regimes suggest that building simulation models can be useful tools for predicting the level and duration of microbial contamination in buildings following a flood event. A better understanding of microbial survival on drying surfaces can be used to assess the health risks to occupants in flood affected properties.