Warming temperatures exacerbate effects of microplastics in a widespread zooplankton species.

The emergence of microplastics as a global contaminant of concern has coincided with climate change induced temperature warming in aquatic ecosystems. Warmer temperatures have been previously demonstrated to increase the toxicity of certain contaminants, but it is currently unclear if microplastics are similarly affected by temperature. As aquatic organisms simultaneously face microplastic pollution and both increasing and variable temperatures, understanding how temperature affects microplastic toxicity is pertinent in this era of human-induced global change. In this study, we investigate the effects of environmentally relevant microplastic exposure to Daphnia pulex survival, reproduction, and growth at three different temperatures. To simulate an environmentally relevant exposure scenario, we created microplastics with physicochemical characteristics often detected in nature, and exposed organisms to concentrations close to values reported in inland waters and 1-2 orders of magnitude higher. The three temperatures tested in this experiment included 12 °C, 20 °C, and 24 °C, to simulate cool/springtime, current, and warming scenarios. We found the highest concentration of microplastics significantly impacted survival and total offspring compared to the control at 20 °C and 24 °C, but not at 12 °C. The adverse effect of high microplastic concentrations on total offspring at warmer temperatures was driven by the high mortality of the juveniles. We observed no effect of microplastics on time to first reproduction or average growth rate at any temperature. Warmer temperatures exacerbated microplastic toxicity, although only for concentrations of microplastics not currently observed in nature, but these concentrations are possible in pollution hotspots, through pulses pollution events or future worsening environmental contamination. The results of our study illustrate the continued need to further investigate climate change related co-stressors such as warming temperatures in microplastic and pollution ecology, through environmentally realistic exposure scenarios.

No Effect of Realistic Concentrations of Polyester Microplastic Fibers on Freshwater Zooplankton Communities.

Zooplankton are a conduit of energy from autotrophic phytoplankton to higher trophic levels, and they can be a primary point of entry of microplastics into the aquatic food chain. Investigating how zooplankton communities are affected by microplastic pollution is thus a key step toward understanding ecosystem-level effects of these global and ubiquitous contaminants. Although the number of studies investigating the biological effects of microplastics has grown exponentially in the last decade, the majority have used controlled laboratory experiments to quantify the impacts of microplastics on individual species. Given that all organisms live in multispecies communities in nature, we used an outdoor 1130-L mesocosm experiment to investigate the effects of microplastic exposure on natural assemblages of zooplankton. We endeavored to simulate an environmentally relevant exposure scenario by manually creating approximately 270 000 0.015 × 1- to 1.5-mm polyester fibers and inoculating mesocosms with zero, low (10 particles/L), and high (50 particles/L) concentrations. We recorded zooplankton abundance and community composition three times throughout the 12-week study. We found no effect of microplastics on zooplankton abundance, Shannon diversity, or Pielou's evenness. Nonmetric multidimensional scaling plots also revealed no effects of microplastics on zooplankton community composition. Our study provides a necessary and realistic baseline on which future studies can build. Because numerous other stressors faced by zooplankton (e.g., food limitation, eutrophication, warming temperatures, pesticides) are likely to exacerbate the effects of microplastics, we caution against concluding that polyester microfibers will always have no effect on zooplankton communities. Instead, we encourage future studies to investigate the triple threats of habitat degradation, climate warming, and microplastic pollution on zooplankton community health. Environ Toxicol Chem 2024;43:418-428. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

No Effect of Realistic Microplastic Exposure on Growth and Development of Wild-caught Culex (Diptera: Culicidae) Mosquitoes.

Microplastic (MP) pollution is a threat to environments around the world and mosquitoes are particularly affected because of their high chance of encountering MP as larvae. Mosquitoes have been shown to readily consume microplastics and they have a significant impact on health in society, yet we have limited knowledge on the effects of MP exposure on fitness-related traits. Additionally, the data we do have come primarily from studies that have used unrealistically high microplastic concentrations, or unrealistic methods of exposure. Here we exposed wild-type first instar Culex pipiens and Culex tarsalis larvae to two 4.8-5.8 µm polystyrene microplastic concentrations (0 particles/ml, 200 particles/ml, 20,000 particles/ml) to evaluate the effect of MP exposure on body size, development, and growth rate. We found no effect of microplastics on any of the traits in either species. These results indicate microplastic exposures comparable to levels found in nature have minimal effects on these fitness-related traits. Future directions for this work include examining whether the effects of MP exposure are exacerbated when evaluated in combination with other common stressors, such as warming temperatures, pesticides, and food limitation.

Combined modality management of advanced cervical cancer including novel sensitizers.

The management of advanced cervical cancer has evolved with time. Combined modality treatments for cervical cancer have been shown to improve clinical outcomes for these patients. The role of surgery is reviewed in this article for specific situations such as the treatment of bulky lymph nodes and even in the metastatic setting. External beam radiotherapy and brachytherapy techniques have improved which has decreased patient toxicity. Systemic therapy such as chemotherapy, immunotherapy, and novel sensitizing agents have been extensively studied and have shown promising results. The combination of these three different modalities of treatment can be tailored to each specific patient to achieve the best outcomes. We review the recent advances and various international guidelines for the management of cervical cancer in this article.

Outcomes of oesophageal cancer treated with neoadjuvant compared with definitive chemoradiotherapy.

INTRODUCTION: We report outcomes of patients with oesophageal cancer treated with neoadjuvant chemoradiotherapy (NACRT) plus surgery or definitive chemoradiotherapy (chemoRT) at our institution. METHODS: We retrospectively reviewed patients who underwent chemoRT from 2005 to 2017. The primary outcome was overall survival (OS). Secondary outcomes were disease-free survival (DFS) and toxicities. RESULTS: We identified 96 patients with median age of 64 years and squamous cell carcinoma in 82.3%. Twenty-nine patients (30.2%) received NACRT plus surgery, 67 patients (69.8%) received definitive chemoRT. Median follow-up was 13.5 months. The 3/5-year OS were 26.4%/13.4%, and 59.6%/51.6% in the definitive chemoRT and NACRT plus surgery groups, respectively. The 3/5-year DFS were 19.3%/12.3%, and 55.7%/37.2% in the definitive chemoRT and NACRT plus surgery groups, respectively. NACRT plus surgery significantly improved OS (hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.22-0.72, P<0.01) and DFS (subhazard ratio [SHR] 5.21, 95 CI 1.20-22.7, P=0.03). Multivariable analysis for OS in the definitive chemoRT group indicated stage (1-2 vs 3-4a; HR 2.17, 95% CI 1.15-4.11, P=0.02) and feeding tube (no tube versus tube; HR 1.85, 95% CI 1.00-3.43, P=0.05) as significantly associated with OS. The cumulative incidence of local recurrence was significantly higher in the definitive chemoRT group (SHR 5.21, 95 CI 1.2022.7, P=0.03). Nineteen patients (65.5%) had postoperative complications. CONCLUSION: NACRT plus surgery improved OS and DFS. However, in view of treatment-related complications, careful selection of patients is warranted. With the predominant histology of our cohort being squamous cell carcinoma (SCC), our results may be more relevant for those with SCC.

Radiation oncology training in Singapore - A non-Australasian RANZCR training site.

The Radiation Oncology Department at The National Cancer Institute, Singapore (NCIS) and the Royal Australian and New Zealand College of Radiology (RANZCR) has had a well-established relationship that began as a partnership to grow a pool of local radiation oncologists to meet a nation's demand for radiotherapy services. This journey has surpassed its initial aims and now has produced a generation of radiation oncologists leading a national cancer institute. We recount the history and progress of this partnership here, as well as the unique success of its product; the only RANZCR-accredited radiation oncology training site outside of Australia and New Zealand since 2002. We outline the mutual benefits through many years of collaboration and deliberate efforts to grow the partnership. We also outline the distinctive specialist training path that our trainees take to meet both the local accreditation body as well as the RANZCR requirements.

Phase 1 Study of Low-Dose Fractionated Whole Abdominal Radiation Therapy in Combination With Weekly Paclitaxel for Platinum-Resistant Ovarian Cancer (GCGS-01).

PURPOSE: Low-dose fractionated whole abdominal radiation therapy (LDFWART) has synergistic activity with paclitaxel in preclinical models. The aim of this phase 1 trial was to determine the recommended phase 2 dose and preliminary activity of weekly paclitaxel (wP) concurrent with LDFWART in patients with platinum-resistant ovarian cancer (PROC). METHODS AND MATERIALS: Patients were enrolled at de-escalating dose levels of wP (part A), starting at 80 mg/m2, concurrent with fixed-dose LDFWART delivered in 60 cGy fractions twice-daily, 2 days per week, for 6 continuous weeks. After completing the 6-week course of wP + LDFWART, patients received wP until disease progression. Dose-limiting toxicity was evaluated during the first 3 weeks of wP + LDFWART. At wP (80 mg/m2) + LDFWART, no dose-limiting toxicities were observed; this was the established maximum tolerated dose. The trial was expanded (part B) with 7 additional patients with platinum-resistant, high-grade serous ovarian cancer to confirm toxicity and activity. RESULTS: A total of 10 heavily pretreated patients were recruited (3 patients to part A, 7 patients to part B). They had received a median of 5 prior lines of therapy, and 70% of patients had received prior wP; 60% of patients completed 6 weeks of wP + LDFWART. Common related grade ≥3 adverse events were neutropenia (60%) and anemia (30%). Median progression-free survival was 3.2 months, and overall survival was 13.5 months. Of patients evaluable for response, 33% (3 of 9) achieved confirmed biochemical response (CA125 decrease >50% from baseline), 11% (1) achieved a partial response, and 5 patients had stable disease, giving a disease control rate of 66.7% (6 of 9). Four patients had durable disease control of ≥12 weeks, completing 12 to 21 weeks of wP. CONCLUSIONS: The recommended phase 2 dose of wP + LDFWART for 6 weeks is 80 mg/m2. Encouraging efficacy in heavily pretreated PROC patients was observed, suggesting that further development of this therapeutic strategy in PROC should be considered.

Emerging radiotherapy technologies and trends in nasopharyngeal cancer.

Technology has always driven advances in radiotherapy treatment. In this review, we describe the main technological advances in radiotherapy over the past decades for the treatment of nasopharyngeal cancer (NPC) and highlight some of the pressing issues and challenges that remain. We aim to identify emerging trends in radiation medicine. These include advances in personalized medicine and advanced imaging modalities, standardization of planning and delineation, assessment of treatment response and adaptive re-planning, impact of particle therapy, and role of artificial intelligence or automation in clinical care. In conclusion, we expect significant improvement in the therapeutic ratio of radiotherapy treatment for NPC over the next decade.

Post mastectomy radiotherapy for elderly patients with intermediate risk (T1-2N1 OR T3N0) breast cancer: a systematic review and meta-analysis.

BACKGROUND: To determine if PMRT for elderly patients (>65 years old) with intermediate risk breast cancer (T1-2N1, T3N0) improves outcomes. METHODS: We performed a systematic review and meta-analysis to compare the effects of PMRT to no PMRT for elderly patients with intermediate-risk breast cancer. We searched PubMed for eligible studies from Jan 2008 to Dec 2018. We assessed the methodological quality of the included studies using the ROBINS-I tool and performed the meta-analysis with random effects model. The primary outcome of interest was overall survival (OS); secondary outcomes were breast cancer specific survival (BCSS), loco-regional (LRR) and distant disease recurrence (DDR). RESULTS: We found 2 retrospective cohort studies with 743 patients directly comparing PMRT to no PMRT. Both studies were judged to have serious risk of bias in their methodological quality. The pooled results suggest that PMRT was associated with a 20% relative reduction in the hazard in death, ranging from 41% relative reduction, a substantial negative association to 10% relative increase, a small positive association (HR 0.80, 95% CI: 0.59-1.1, P=0.62, I2=0%). PMRT was also associated with a 17% relative reduction in the hazard for breast cancer related death, ranging from 52% relative reduction, a substantial negative association to 41% relative increase, a substantial positive association (HR 0.83, 95% CI: 0.48-1.41, P=0.48, I2=0%). One study did not observe any significant differences in LRR and DDR between the two groups. CONCLUSIONS: The survival benefits from PMRT in unselected elderly patients with intermediate risk breast cancer is unclear. Further research to better select elderly patients who may benefit from PMRT is warranted. Patients with a multiple pathological risk factors suggestive of high risk of loco-regional recurrence post-mastectomy should consider PMRT.

Radiation therapy for rectal cancer.

Radiotherapy (RT) has remained an important pillar in the multi-modality management of rectal cancer. Adjuvant RT with concurrent chemotherapy (chemo-RT) was once the standard of care for locally advanced rectal cancer, but with time, that has now changed and neoadjuvant chemo-RT followed by total mesorectal excision (TME) surgery is the new standard. Alternatively, neoadjuvant RT alone remains an option and clinicians are tasked to choose between the two. In an era of personalised oncological management, it is unsurprising that the treatment for rectal cancer is following suit and upcoming trials are studying ways to improve outcomes and minimise toxicity for patients while tailoring treatments specific to each patient's tumour. We review the evolution of the role of RT in rectal cancer and look forward to what the future holds.

Quality of head and neck radiotherapy reporting in randomized controlled trials.

BACKGROUND: The purpose of this clinical review was to determine the quality reporting of radiotherapy (RT) in randomized controlled trials (RCTs) of head and neck cancer and its impact on reporting of the trial primary efficacy and toxicity outcomes. METHODS: We searched MEDLINE for eligible RCTs published between 1994 and 2015. We assessed the quality of RT reporting and bias in the reporting of trial outcomes using published criteria. RESULTS: We found 67 eligible trial reports. There was significant variability in the quality of RT treatment reporting among the included trials. Thirty-two trials had adequate quality RT reporting. Cooperative group trials were more likely to have adequate quality reporting (odds ratio [OR] 3.02; 95% confidence interval [CI] 1.04-9.85). The quality of RT reporting did not influence the bias in the reporting of trial outcomes. CONCLUSION: The quality of head and neck RT reporting in RCTs is variable and did not impact on bias in reporting of trial outcomes.

Decreases in beetle body size linked to climate change and warming temperatures.

Body size is a fundamental ecological trait and is correlated with population dynamics, community structure and function, and ecosystem fluxes. Laboratory data from broad taxonomic groups suggest that a widespread response to a warming world may be an overall decrease in organism body size. However, given the myriad of biotic and abiotic factors that can also influence organism body size in the wild, it is unclear whether results from these laboratory assays hold in nature. Here we use datasets spanning 30 to 100 years to examine whether the body size of wild-caught beetles has changed over time, whether body size changes are correlated with increased temperatures, and we frame these results using predictions derived from a quantitative review of laboratory responses of 22 beetle species to temperature. We found that 95% of laboratory-reared beetles decreased in size with increased rearing temperature, with larger-bodied species shrinking disproportionately more than smaller-bodied beetles. In addition, the museum datasets revealed that larger-bodied beetle species have decreased in size over time, that mean beetle body size explains much of the interspecific variation in beetle responses to temperature, and that long-term beetle size changes are explained by increases in autumn temperature and decreases in spring temperature in this region. Our data demonstrate that the relationship between body size and temperature of wild-caught beetles matches relatively well with results from laboratory studies, and that variation in this relationship is largely explained by interspecific variation in mean beetle body size. This long-term beetle dataset is one of the most comprehensive arthropod body size datasets compiled to date, it improves predictions regarding the shrinking of organisms with global climate change, and together with the meta-analysis data, call for new hypotheses to explain why larger-bodied organisms may be more sensitive to temperature.

Outcomes of neoadjuvant chemoradiotherapy followed by total mesorectal excision surgery for locally advanced rectal cancer: a single-institution experience.

INTRODUCTION: Neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision (TME) surgery for locally advanced rectal cancer has been shown to improve local control and reduce toxicity, as compared to adjuvant CRT. We reported the outcomes of our patients with locally advanced rectal cancer treated at National University Hospital, Singapore. METHODS: From April 2002 to December 2014, 117 patients with T3/4, N0/+, M0 rectal cancer received neoadjuvant CRT followed by TME surgery. The treatment regimen comprised a total radiotherapy dose of 50.4 Gy in 28 daily fractions delivered concurrently with 5-fluorouracil or capecitabine chemotherapy over 5.5 weeks. All patients were planned for TME surgery. Local control, disease-free survival, overall survival and treatment toxicities were analysed. RESULTS: Median follow-up was 34 (range 2-122) months. 11.5% (13/113) of patients achieved a pathological complete response (pCR) and 72.6% (85/117) had either tumour or nodal downstaging following neoadjuvant CRT. 5.2% (5/96) of patients had Grade 3 acute toxicities (dermatitis and diarrhoea) and 3.1% (3/96) had Grade 3 late toxicities (fistula and stricture). There was no Grade 4 toxicity noted. The five-year local recurrence, disease-free survival and overall survival rates were 4.5%, 65.7% and 80.6%, respectively. Multivariate analysis showed that nodal positivity was a predictor of poor disease-free survival and poor overall survival. Tumour downstaging and pCR did not improve outcomes. CONCLUSION: Our outcomes were comparable to internationally published data, and this treatment regimen remains the standard of care for locally advanced rectal cancer in our local population.

Outcomes of Asian patients with localized prostate cancer treated with combined intensity modulated radiation therapy (IMRT) and high dose rate (HDR) brachytherapy: A single institution experience.

AIM: External beam radiotherapy (EBRT) followed by high dose rate (HDR) brachytherapy boost has demonstrated minimal toxicities and improved disease control rate compared with EBRT alone in observational and randomized studies with predominantly Caucasian patients. This study aims to report the outcomes of patients treated with this approach in our predominantly Asian population. METHODS: Medical records for patients with localized prostate cancer who received combined EBRT delivered via intensity modulated radiotherapy (IMRT) technique followed by HDR brachytherapy boost were retrospectively reviewed. Outcomes evaluated included 5-year biochemical recurrence-free survival (per Phoenix definition), overall survival and treatment toxicities. RESULTS: From June 2009 to March 2015, 75 patients were treated with IMRT followed by HDR brachytherapy boost. Twenty patients (27%) had intermediate risk, 55 (74%) had high-risk disease. Median follow up was 64 months. All patients received IMRT to a median dose of 45 Gy to the pelvis followed by HDR brachytherapy boost. Sixty, 10 and 5 patients received boost of 21 Gy in two fractions, 19 Gy in two fractions and 15 Gy in a single fraction, respectively. All patients met the planning criteria adapted from RTOG 0815. The 5-year prostate-specific antigen (PSA) control was 85.2% (80.3% and 100% for high-risk and intermediate-risk group, respectively). Cancer-specific survival and overall survival are 97.3% and 92.0%, respectively. Eleven (15%) patients developed biochemical failure, six of which had distant metastasis. Three (4%) developed grade 3 genitourinary toxicity (urethral stricture and/or cystitis) and none developed grade 3 radiation proctitis. CONCLUSION: Our outcomes are comparable to internationally published data and demonstrate reproducibility of this approach in our population.

Life-threatening Bleed Secondary to Tumor Shrinkage Effectively Palliated with Radiotherapy.

Inverted papilloma is a typically benign, but locally aggressive tumor arising from the nasal cavity and paranasal sinuses. Malignant transformation can occur in up to 10% of cases. Although spontaneous tumor bleeding can occur with malignancies, hemorrhage secondary to tumor shrinkage has not been reported. We present a patient with metastatic squamous cell carcinoma (from inverted papilloma) who developed a life-threatening bleed shortly after chemotherapy initiation. She was managed successfully with life-saving palliative radiotherapy (RT), delivered based on clinical markup. She was subsequently re-treated with highly conformal RT and chemotherapy to achieve a marked clinical response without surgery.

The Effect of Parasitism and Interpopulation Hybridization on Aedes albopictus (Diptera: Culicidae) Fitness.

Recent research in mosquito population genetics suggests that interpopulation hybridization has likely contributed to the rapid spread of the container-breeding mosquitoes. Here, I used laboratory experiments to investigate whether interpopulation Aedes (Stegomyia) albopictus (Skuse) F1 and F2 hybrids exhibit higher fitness than parental populations, and whether hybrid mosquito performance is related to infection by the coevolved protozoan parasite Ascogregarina taiwanensis (Lien and Levine). Overall, there were significant differences in development time, wing length, and survival between the two parental mosquito populations, but no difference in per capita growth rate r. Hybrid mosquitoes were generally intermediate in phenotype to the parentals, except that F2 females were significantly larger than the midparent average. In addition, As. taiwanensis parasites produced fewest oocysts when they were reared in hosts of hybrid origin. These data suggest that hybridization between previously isolated mosquito populations can result in slight increases in potential mosquito reproductive success, via increased hybrid body size, and via the temporary escape from coevolved parasites. These findings are significant because studies have shown that even slight hybrid vigor can have positive fitness consequences for population persistence. Although this was a laboratory experiment extending only to the F2 generation, many other invasive insects also carry coevolved parasites, and thus the patterns seen in this mosquito system may be broadly relevant.

Phylogeography of the coastal mosquito Aedes togoi across climatic zones: testing an anthropogenic dispersal hypothesis.

The coastal mosquito Aedes togoi occurs more or less continuously from subarctic to subtropic zones along the coasts of the Japanese islands and the East Asian mainland. It occurs also in tropical Southeast Asia and the North American Pacific coast, and the populations there are thought to have been introduced from Japan by ship. To test this hypothesis, the genetic divergence among geographic populations of A. togoi was studied using one mitochondrial and three nuclear gene sequences. We detected 71 mitochondrial haplotypes forming four lineages, with high nucleotide diversity around temperate Japan and declining towards peripheral ranges. The major lineage (L1) comprised 57 haplotypes from temperate and subarctic zones in Japan and Southeast Asia including southern China and Taiwan. Two other lineages were found from subtropical islands (L3) and a subarctic area (L4) of Japan. The Canadian population showed one unique haplotype (L2) diverged from the other lineages. In the combined nuclear gene tree, individuals with mitochondrial L4 haplotypes diverged from those with the other mitochondrial haplotypes L1-L3; although individuals with L1-L3 haplotypes showed shallow divergences in the nuclear gene sequences, individuals from Southeast Asia and Canada each formed a monophyletic group. Overall, the genetic composition of the Southeast Asian populations was closely related to that of temperate Japanese populations, suggesting recent gene flow between these regions. The Canadian population might have originated from anthropogenic introduction from somewhere in Asia, but the possibility that it could have spread across the Beringian land bridge cannot be ruled out.

The relationship between parasite fitness and host condition in an insect--virus system.

Research in host-parasite evolutionary ecology has demonstrated that environmental variation plays a large role in mediating the outcome of parasite infection. For example, crowding or low food availability can reduce host condition and make them more vulnerable to parasite infection. This observation that poor-condition hosts often suffer more from parasite infection compared to healthy hosts has led to the assumption that parasite productivity is higher in poor-condition hosts. However, the ubiquity of this negative relationship between host condition and parasite fitness is unknown. Moreover, examining the effect of environmental variation on parasite fitness has been largely overlooked in the host-parasite literature. Here we investigate the relationship between parasite fitness and host condition by using a laboratory experiment with the cabbage looper Trichoplusia ni and its viral pathogen, AcMNPV, and by surveying published host-parasite literature. Our experiments demonstrated that virus productivity was positively correlated with host food availability and the literature survey revealed both positive and negative relationships between host condition and parasite fitness. Together these data demonstrate that contrary to previous assumptions, parasite fitness can be positively or negatively correlated with host fitness. We discuss the significance of these findings for host-parasite population biology.

Strategies for whole lung tissue engineering.

Recent work has demonstrated the feasibility of using decellularized lung extracellular matrix scaffolds to support the engineering of functional lung tissue in vitro. Rendered acellular through the use of detergents and other reagents, the scaffolds are mounted in organ-specific bioreactors where cells in the scaffold are provided with nutrients and appropriate mechanical stimuli such as ventilation and perfusion. Though initial studies are encouraging, a great deal remains to be done to advance the field and transition from rodent lungs to whole human tissue engineered lungs. To do so, a variety of hurdles must be overcome. In particular, a reliable source of human-sized scaffolds, as well as a method of terminal sterilization of scaffolds, must be identified. Continued research in lung cell and developmental biology will hopefully help identify the number and types of cells that will be required to regenerate functional lung tissue. Finally, bioreactor designs must be improved in order to provide more precise ventilation stimuli and vascular perfusion in order to avoid injury to or death of the cells cultivated within the scaffold. Ultimately, the success of efforts to engineer a functional lung in vitro will critically depend on the ability to create a fully endothelialized vascular network that provides sufficient barrier function and alveolar-capillary surface area to exchange gas at rates compatible with healthy lung function.