Design of an Auxiliary Artificial Lymphatic Vessel in Treatment of Secondary Lymphedema Due to Breast Cancer

Breast cancer is the most common malignant tumor that affects women in the United States, Europe, and Mexico. As an adverse effect when performing treatments for this condition, secondary lymphedema associated with breast cancer occurs in some cases. This complication occurs due to the interruption of lymphatic flow in the upper extremities in conjunction with other factors such as radiation, sedentary lifestyle, removal of lymph nodes, damage to lymphatic vessels, and others. This article reviews breast cancer incidence, mortality, and survival patterns, confirming that, specifically, lymphedema has high health, social, and economic impacts. Research demonstrates that it fundamentally affects women at an early age. In approximately a third of the cases, it becomes a chronic disease. Therefore, physical therapy is essential for a better quality of life in patients who survive this disease. Surgeries and manual and pharmacological treatments are the current procedures done to reduce to reduce the alterations suffered by patients with lymphedema; however, the success of the treatments depends on each patient’s characteristics. To face this problem, the design of a lymphatic vessel has been proposed to assist the mechanical failure of the damaged lymphatic system. In this work, the design methodology used for the blueprint of the lymphatic vessel is presented, as well as the computer analysis of fluid simulation and the selection of the proposed material, resulting in the production of a micrometric design. In the future, it is expected that a surgeon will be able to implant the design of the vessel to restore lymph flow through the lymphatic system, thus helping to combat lymphedema.

Evolution, Chance, and Aging

Aging has provided fruitful challenges for evolutionary theory, and evolutionary theory has deepened our understanding of aging. A great deal of genetic and molecular data now exists concerning mortality regulation and there is a growing body of knowledge concerning the life histories of diverse species. Assimilating all relevant data into a framework for the evolution of aging promises to significantly advance the field. We propose extensions of some key concepts to provide greater precision when applying these concepts to age-structured contexts. Secondary or byproduct effects of mutations are proposed as an important factor affecting survival patterns, including effects that may operate in small populations subject to genetic drift, widening the possibilities for mutation accumulation and pleiotropy. Molecular and genetic studies have indicated a diverse array of mechanisms that can modify aging and mortality rates, while transcriptome data indicate a high level of tissue and species specificity for genes affected by aging. The diversity of mechanisms and gene effects that can contribute to the pattern of aging in different organisms may mirror the complex evolutionary processes behind aging.

Effects of Thermal Acclimation on the Tolerance of Bactrocera zonata (Diptera: Tephritidae) to Hydric Stress

Insects, similarly to other small terrestrial invertebrates, are particularly susceptible to climatic stress. Physiological adjustments to cope with the environment (i.e., acclimation) together with genetic makeup eventually determine the tolerance of a species to climatic extremes, and constrain its distribution. Temperature and desiccation resistance in insects are both conditioned by acclimation and may be interconnected, particularly for species inhabiting xeric environments. We determined the effect of temperature acclimation on desiccation resistance of the peach fruit fly (Bactrocera zonata, Tephritidae) – an invasive, polyphagous pest, currently spreading through both xeric and mesic environments in Africa and the Eurasian continent. Following acclimation at three constant temperatures (20, 25, and 30°C), the survival of adult flies deprived of food and water was monitored in extreme dry and humid conditions (<10 and >90% relative humidity, respectively). We found that flies acclimated at higher temperatures were significantly heavier, and contained more lipids and protein. Acclimation temperature significantly and similarly affected the survival of males and females at both high and low humidity conditions. In both cases, flies maintained at 30°C survived longer compared to 20 and 25°C – habituated counterparts. Regardless of the effect of acclimation temperature on survival, overall life expectancy was significantly shortened when flies were assayed under desiccating conditions. Additionally, our experiments indicate no significant difference in survival patterns between males and females, and that acclimation temperature had similar effects after both short (5–10 days) and long (11–20 days) acclimation periods. We conclude that acclimation at 30°C prolongs the survival of B. zonata, regardless of ambient humidity levels. Temperature probably affected survival through modulating feeding and metabolism, allowing for accumulation of larger energetic reserves, which in turn, promoted a greater ability to resist starvation, and possibly desiccation as well. Our study set the grounds for understanding the phenotypic plasticity of B. zonata from the hydric perspective, and for further evaluating the invasion potential of this pest.

Variation in colon cancer survival for patients living and receiving care in London, 2006–2013: does where you live matter?

BackgroundMarked geographical disparities in survival from colon cancer have been consistently described in England. Similar patterns have been observed within London, almost mimicking a microcosm of the country’s survival patterns. This evidence has suggested that the area of residence plays an important role in the survival from cancer.MethodsWe analysed the survival from colon cancer of patients diagnosed in 2006–2013, in a pre-pandemic period, living in London at their diagnosis and received care in a London hospital. We examined the patterns of patient pathways between the area of residence and the hospital of care using flow maps, and we investigated whether geographical variations in survival from colon cancer are associated with the hospital of care. To estimate survival, we applied a Bayesian excess hazard model which accounts for the hierarchical structure of the data.ResultsGeographical disparities in colon cancer survival disappeared once controlled for hospitals, and the disparities seemed to be augmented between hospitals. However, close examination of patient pathways revealed that the poorer survival observed in some hospitals was mostly associated with higher proportions of emergency diagnosis, while their performance was generally as expected for patients diagnosed through non-emergency routes.DiscussionThis study highlights the need to better coordinate primary and secondary care sectors in some areas of London to improve timely access to specialised clinicians and diagnostic tests. This challenge remains crucially relevant after the recent successive regroupings of Clinical Commissioning Groups (which grouped struggling areas together) and the observed exacerbation of disparities during the COVID-19 pandemic.

Comparative survival analyses among captive chimpanzees (Pan troglodytes) in America and Japan

Detailed, long-term datasets on the life histories of long-lived species such as great apes are necessary to understand their survival patterns but are relatively rare. Such information requires prolonged and consistent record-keeping over many generations, so for chimpanzees (Pan troglodytes), this equates to many decades of input. As life history variables can be altered by differences in environmental influences (whether natural or artificial), there is substantial value to being able to compare across populations. Here, we present the first comparative analysis of life history data for two ex situ chimpanzee populations residing in North America (1975–2020; n = 730) and Japan (1980–2020; n = 660). Overall, survival patterns were similar between regions, and the median life expectancy from birth is estimated at 35.7 (95% CI = [32.4–40.0]) years for females and 30.1 (27.3–34.3) years for males across both populations. Females who survive to their first birthday are estimated to survive 42.4 (40.0–46.3) years and males 35.5 (32.6–38.0) years. We found that birth type (wild-born or captive-born) did not influence survival patterns in either population, but there were differential effects of sex on longevity. In the America population, males had higher mortality rates than females, whereas in the Japan population we found no differences between the sexes. First year mortality did not differ between populations for males (18–20%), but for females it was lower in America (15%) compared to Japan (25%). Survival patterns of chimpanzees in the present study will be useful for future investigation into potential causes of regional differences and cross-species comparisons.

Treatment and Survival Patterns of Primary Adenosquamous Carcinoma of the Liver: A Retrospective Analysis

Background and AimsPrimary adenosquamous carcinoma (ASC) is a rare liver malignancy with very little data published so far. We describe the clinical characteristics of this tumor and analyze its survival pattern to improve the diagnosis and treatment.Materials and MethodsThis study collected data of 15 patients with primary hepatic ASC in our hospital within 10 years (from 2009 to 2018). We analyzed the clinical characteristics, imaging data, treatment, and survival of ASC in the study. Two of these cases have been reported.ResultsThe common clinical symptoms of hepatic ASC are liver pain and jaundice. Laboratory examination showed that carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) increased, but Alpha-FetoProtein (AFP) did not. Primary hepatic ASC is a rare subtype of intrahepatic cholangiocarcinoma (ICC) and meets the requirements of pathological diagnosis: CK20 (-), CK7 (+), CK19 (+), and p63 (+). Of the 15 patients, 11 were treated surgically, of which 3 patients received adjuvant chemotherapy. The prognosis of ASC patients is poor with a median survival time (MST) of 6 months (range: 2 to 15). The duration of MST in surgically treated patients was longer than that of nonsurgical patients (7.0 months vs. 3.0 months). Patients that received adjuvant chemotherapy survived longer (MST: 15 months). Patients with lymph node metastasis had a worse prognosis.ConclusionPrimary hepatic ASC is a rare malignant tumor with a poor prognosis. Radical surgery may be an effective treatment for prolonging survival. Surgical treatment combined with adjuvant therapy may further improve survival.

Clinical and molecular features of acquired resistance to immunotherapy in non-small cell lung cancer

Although cancer immunotherapy with PD-(L)1 blockade is now routine treatment for patients with lung cancer, remarkably little is known about acquired resistance. We examined 1,201 patients with NSCLC treated with PD-(L)1 blockade to clinically characterize acquired resistance, finding it to be common (occurring in more than 60% of initial responders), with persistent but diminishing risk over time, and with distinct metastatic and survival patterns compared to primary resistance. To examine the molecular phenotype and potential mechanisms of acquired resistance, we performed whole transcriptome and exome tumor profiling in a subset of NSCLC patients (n=29) with acquired resistance. Systematic immunogenomic analysis revealed that tumors with acquired resistance generally had enriched signals of inflammation (including IFNγ signaling and inferred CD8+ T cells) and could be separated into IFNγ upregulated and stable subsets. IFNγ upregulated tumors had putative routes of resistance with signatures of dysfunctional interferon signaling and mutations in antigen presentation genes. Transcriptomic profiling of cancer cells from a murine model of acquired resistance to PD-(L)1 blockade also showed evidence of dysfunctional interferon signaling and acquired insensitivity to in vitro interferon gamma treatment. In summary, we characterized clinical and molecular features of acquired resistance to PD-(L)1 blockade in NSCLC and found evidence of ongoing but dysfunctional IFN response. The persistently inflamed, rather than excluded or deserted, tumor microenvironment of acquired resistance informs therapeutic strategies to effectively reprogram and reverse acquired resistance.