Macrophage-targeted photosensitizer conjugate delivered by intratumoral injection

A conjugate between maleylated albumin and a photosensitizer (PS) shows cell type specific targeting to macrophages via the scavenger receptor. Administration of this conjugate to a tumor-bearing mouse followed by illumination may allow selective destruction of macrophages within tumors. There is accumulating evidence that tumor-associated macrophages contribute to tumor growth, invasiveness, metastasis, and immune suppression. We tested the intravenous (IV) injection of a conjugate between maleylated albumin and chlorin(e6) to BALB/c mice bearing three tumor types with differing proportions of tumor-associated macrophages. The accumulation of PS within the tumors after IV injection and 24 h incubation time was disappointing, and we therefore investigated intratumoral (IT) injection. This gave 20-50 times greater concentrations of PS within the tumor compared to IV injection as determined by tissue extraction. Furthermore the amounts of PS in each tumor type correlated well with the numbers of macrophages both as determined by extraction from bulk tumor and fluorescence quantification and as determined by tissue dissociation to a single cell suspension and two-color flow cytometry with macrophage-specific antibodies. IT injection of nonconjugated PS gave lower tumor accumulation that did not correlate with macrophage content. IT injection of targeted macromolecular delivery systems is an underexplored area and worthy of further study.     

Maintenance of subcutaneous cavities with CO2

Since mechanical retractors in endoscopic plastic surgery cause certain drawbacks, we developed a model in dogs, which, by insufflating CO2 into a subcutaneous cavity, we were able to maintain. We evaluated the magnitude of subcutaneous emphysema and absorption of CO2 by insufflating different pressures and the efficacy of external pressure on the skin with the purpose of limiting the subcutaneous emphysema. Sixteen dogs were divided in 3 groups, A, B, and C. We controlled the pulmonary function by using a volume-cycle ventilator. In all groups, we maintained a subcutaneous cavity by insufflating CO2. Groups A and C were insufflated at 15 mm Hg; group B, at 8 mm Hg. We placed circumferential Esmarch bandages on the thorax of groups B and C to delimit superiorly and inferiorly the surgical area. Arterial blood gas analyses (ABGA) were taken from the femoral artery 60 minutes after intubation, 60 minutes after Esmarch bandage was placed and at the end of the CO2 insufflation. Statistically, results were analyzed by Wilcoxon test. P < 0.05 was considered statistically significant. Group A showed extensive subcutaneous emphysema. Two dogs died. The systemic increase of the CO2 showed a median of 9.6 mm Hg (P < 0.05). In Group B, Esmarch bandages caused increase in CO2, with a median of 1.65 mm Hg (P < 0.028). None of these dogs showed subcutaneous emphysema during the insufflation after CO2 insufflation pressure augmented with a median of 3.7 mm Hg (P < 0.028). In Group C, chest restriction increased CO2 median of 6.1 mm Hg (P < 0.043), and subcutaneous emphysema shown was less extensive than group A. The CO2 increased after insufflation a median of 16 mm Hg (P < 0.043). CONCLUSIONS: Subcutaneous cavities can be maintained open with CO2 insufflation at 8 mm Hg, limiting perfectly the surgical area; as done with Esmarch bandages, it reduces CO2 absorption and makes this procedure safe.     

Description of Maritrema formicae sp. nov. (Digenea, Microphallidae) parasitic in the kelp gull, Larus dominicanus, from the Patagonian coast, Argentina

Maritrema formicae sp. nov. is described from the Patagonian coast, Argentina, based on adults obtained from the kelp gull, Larus dominicanus. The new species fits with the "eroliae complex" and can be distinguished from other related species mainly in shape and size of body, shape, size, and pattern of distribution of cirrus spines, uterus extension, number and size of eggs, vitellarium in a complete ring in all specimens, and its Neotropical distribution. The new species is sympatric with another species of the genus, Maritrema madrynense, which was recorded in the same host and locality.     

Comparing baseline symptom severity and demographics over two time periods in an outpatient palliative radiotherapy clinic

Purpose

The primary objective of this study was to compare the symptom severity in two different patient populations assessed in an outpatient palliative radiotherapy clinic over two time periods spanning 10?years. The secondary objective was to assess any changes in the baseline demographics of these patients.

Methods

Data were collected from 1999 to 2009. Upon initial presentation to the clinic, the Edmonton Symptom Assessment Scale (ESAS) was administered to patients to capture symptom severity. This validated assessment tool asks patients to score their level of pain, tiredness, nausea, depression, anxiety, drowsiness, loss of appetite, well-being, and dyspnea on an 11-point Likert scale. Differences between the two patient groups were assessed using chi-squared analysis and Wilcoxon rank–sum tests. A p value of <0.05 was considered significant.

Results

A total of 1,439 patients completed the ESAS from 1999 to 2009. Patients were divided into two time periods 1999–2002 (n?=?689) and 2006–2009 (n?=?750). Pain, depression, nausea, fatigue, anxiety, drowsiness, and dyspnea were significantly better in 2006–2009 (p?<?0.0001). Loss of appetite was not statistically different between the two time periods (p?=?0.236). Significantly more patients with genitourinary cancers (p?=?0.03) or a referral for a mass (p?<?0.0001) were seen in 2006–2009. More patients with breast cancer (p?=?0.04) and bone pain (p?=?0.0002) were seen in 1999–2002. The median age was significantly higher (70?years vs. 68?years, p?=?0.03) for patients seen in 2006–2009. No significant differences were seen in performance status or gender between the two groups.

Conclusion

There have been statistically significant lower scores in the severity of the majority of symptoms as scored by the latter patient cohort; however, whether this difference in magnitude is clinically significant is debatable. The reason for referral and demographics in patients sent for palliative radiotherapy has changed over a 10-year period. This may be a reflection of the changes in systemic therapies and improvements in supportive care for patients with advanced cancer.     

Do elderly patients with metastatic cancer have worse quality of life scores?

Purpose

The purpose of this study is to compare self-reported quality of life (QOL) scores in old and young patients with metastatic cancer using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C15-PAL questionnaire.

Materials and methods

Patients receiving palliative radiotherapy (RT) for bone metastases and brain metastases completed the QLQ-C15-PAL questionnaire prior to treatment. Using multiple linear regression analysis, a parametric test, the QLQ-C15-PAL scores were compared using 65 and 70?years as cutoff ages.

Results

A total of 340 patients were referred for palliative RT for bone metastases (n?=?190) or brain metastases (n?=?150). Physical functioning and appetite were worse in the older group using either 65 or 70?years as the cutoff age. Age-related differences in the QLQ-C15-PAL scores varied as a function of age cutoff used and location of metastatic site irradiated.

Conclusion

Based on the (EORTC) QLQ-C15-PAL, elderly advanced cancer patients have a different QOL profile. Similar observations have been reported with the (EORTC) QLQ-C30 questionnaire.     

Energy and material flows of megacities

Understanding the drivers of energy and material flows of cities is important for addressing global environmental challenges. Accessing, sharing, and managing energy and material resources is particularly critical for megacities, which face enormous social stresses because of their sheer size and complexity. Here we quantify the energy and material flows through the world’s 27 megacities with populations greater than 10 million people as of 2010. Collectively the resource flows through megacities are largely consistent with scaling laws established in the emerging science of cities. Correlations are established for electricity consumption, heating and industrial fuel use, ground transportation energy use, water consumption, waste generation, and steel production in terms of heating-degree-days, urban form, economic activity, and population growth. The results help identify megacities exhibiting high and low levels of consumption and those making efficient use of resources. The correlation between per capita electricity use and urbanized area per capita is shown to be a consequence of gross building floor area per capita, which is found to increase for lower-density cities. Many of the megacities are growing rapidly in population but are growing even faster in terms of gross domestic product (GDP) and energy use. In the decade from 2001–2011, electricity use and ground transportation fuel use in megacities grew at approximately half the rate of GDP growth.The remarkable growth of cities on our planet during the past century has provoked a range of scientific inquires. From 1900–2011, the world’s urban population grew from 220 million (13% of the world’s population) to 3,530 million (52% of the world’s population) (1, 2). This phenomenon of urbanization has prompted the development of a science of cities (3, 4), including interdisciplinary contributions on scaling laws (5, 6), networks (7), and the thermodynamics of cities (8, 9). The growth of cities also has been strongly linked to global challenges of environmental sustainability, making the study of urban energy and material flows, e.g., for determining greenhouse gas emissions from cities and urban resource efficiency (10–19), important.At the pinnacle of the growth of cities is the formation of megacities, i.e., metropolitan regions with populations in excess of 10 million people. In 1970, there were only eight megacities on the planet (SI Appendix, Fig. S1). By 2010, the number had grown to 27, and a further 10 megacities likely will exist by 2020 (20). In 2010, 460 million people (6.7% of the global population) lived in the 27 megacities. The sheer size and complexity of megacities gives rise to enormous social and environmental challenges. Megacities often are perceived to be areas of high global risk (i.e., threatened by economic, environmental, geopolitical, societal, and technological risks with potential impacts across entire countries) with extreme levels of poverty, vulnerability, and social–spatial fragmentation (21–24). To provide adequate water and wastewater services, many megacities require massive technical investment and appropriate institutional development (25, 26). Many inhabitants of megacities also suffer severe health impacts from air pollution (27). However, these factors present only one side; the megacities include some of the wealthiest cities in the world (albeit with large disparities between citizens). Even the poorer megacities are seen by some as potential centers of innovation, where high levels of resource efficiency might reduce global environmental burdens (21, 28, 29). Whether megacities can develop as sustainable cities depends to a large extent on how they obtain, share, and manage their energy and material resources.The aims of our study are first to quantify the energy and material flows for the world’s 27 megacities, based on 2010 population, and second to identify physical and economic characteristics that underlie these resource flows at multiple scales. This goal entailed developing a common data-collection process applied to all the megacities. The cities were identified based on Brinkhoff’s database of metropolitan regions (www.citypopulation.de/world/Agglomerations.html; SI Appendix, Fig. S2). The megacities are essentially common commuter-sheds of more than 10 million people; most are contiguous urban regions, but a contiguous area is not a requirement; for example, the London megacity includes a ring of commuter towns outside the Greater London area. Megacities can spread across political borders. They include large tracts of suburban regions, which can have higher per capita resource flows than central areas (30, 31). We quantify energy flows for the dominant direct forms of consumption in megacities. A wide and complex range of materials flow through cities; here the focus is on water, concrete, steel, and waste. We show how values of aggregate resource use of all megacities generally are consistent with the scaling laws that have been developed for cities (5, 6). We then analyze factors correlated with energy and material flow at macro- and microscales; discuss megacities with low, high, and efficient use of resources; and examine changes over time.