Iron-based biomarkers for personalizing pharmacological ascorbate therapy in glioblastoma: insights from a phase 2 clinical trial.

BACKGROUND: Pharmacological ascorbate (intravenous delivery reaching plasma concentrations ≈ 20 mM; P-AscH-) has emerged as a promising therapeutic strategy for glioblastoma. Recently, a single-arm phase 2 clinical trial demonstrated a significant increase in overall survival when P-AscH- was combined with temozolomide and radiotherapy. As P-AscH- relies on iron-dependent mechanisms, this study aimed to assess the predictive potential of both molecular and imaging-based iron-related markers to enhance the personalization of P-AscH- therapy in glioblastoma participants. METHODS: Participants (n = 55) with newly diagnosed glioblastoma were enrolled in a phase 2 clinical trial conducted at the University of Iowa (NCT02344355). Tumor samples obtained during surgical resection were processed and stained for transferrin receptor and ferritin heavy chain expression. A blinded pathologist performed pathological assessment. Quantitative susceptibility mapping (QSM) measures were obtained from pre-radiotherapy MRI scans following maximal safe surgical resection. Circulating blood iron panels were evaluated prior to therapy through the University of Iowa Diagnostic Laboratory. RESULTS: Through univariate analysis, a significant inverse association was observed between tumor transferrin receptor expression and overall and progression-free survival. QSM measures exhibited a significant, positive association with progression-free survival. Subjects were actively followed until disease progression and then were followed through chart review or clinical visits for overall survival. CONCLUSIONS: This study analyzes iron-related biomarkers in the context of P-AscH- therapy for glioblastoma. Integrating molecular, systemic, and imaging-based markers offers a multifaceted approach to tailoring treatment strategies, thereby contributing to improved patient outcomes and advancing the field of glioblastoma therapy.

HIGHLIGHTS: Pharmacological ascorbate shows significant promise to enhance glioblastoma clinical outcomes. Transferrin receptor and ferritin heavy chain expression represent potential molecular markers to predict pharmacological ascorbate treatment response. Quantitative Susceptibility Mapping is an MRI technique that can serve as a non-invasive marker of iron metabolism to evaluate progression-free survival. Systemic iron metabolic markers are readily available diagnostic tests that can potentially be used to prognosticate overall survival.

A Randomised Clinical Feasibility Trial of a Breast Immobilisation Device: The SuPPORT 4 All Bra.

AIMS: Despite the breast being a mobile organ, there is currently no standard suitable immobilisation device to optimise radiotherapy for women with larger breasts treated after a wide local excision. The SuPPORT 4 All (S4A) bra was co-designed with patients and radiotherapy professionals. The purpose of this study was to test the feasibility of using the S4A bra in the existing breast cancer radiotherapy pathway. MATERIALS AND METHODS: A randomised feasibility trial was conducted in a single institution; the primary feasibility endpoint was the recruitment of 50 participants. Efficacy endpoints were also tested, including assessment of skin reactions, dose to organs at risk and patient comfort. Fifty women were randomised to receive either standard radiotherapy with no immobilisation (control) or radiotherapy with the S4A bra (intervention). A separate planning study was undertaken on the cases randomised to receive the S4A bra. Participants in the intervention arm (S4A bra) underwent two planning computed tomography scans, one with the bra on and one without the bra; allowing direct comparison of organs at risk data for S4A bra versus no bra. RESULTS: All women who started radiotherapy wearing the S4A bra completed treatment with the bra; patient comfort did not change across the 3 weeks of treatment. Positional accuracy using the bra was comparable with existing published accuracy for methods without immobilisation. The mean ipsilateral lung doses showed some improvement when positioning with the S4A bra was compared with the no bra set-up (3.72 Gy versus 4.85 Gy for right-sided cases, 3.23 Gy versus 3.62 Gy for left-sided cases). CONCLUSIONS: The S4A bra is feasible to use in the radiotherapy pathway with good patient adherence. The S4A bra has potential to reduce dose to organs at risk (specifically ipsilateral lung dose) while maintaining good breast tissue coverage, and improved patient dignity, warranting further investigation on a larger scale.

Type 2 diabetes candidate genes, including PAX5, cause impaired insulin secretion in human pancreatic islets.

Type 2 diabetes (T2D) is caused by insufficient insulin secretion from pancreatic ß cells. To identify candidate genes contributing to T2D pathophysiology, we studied human pancreatic islets from approximately 300 individuals. We found 395 differentially expressed genes (DEGs) in islets from individuals with T2D, including, to our knowledge, novel (OPRD1, PAX5, TET1) and previously identified (CHL1, GLRA1, IAPP) candidates. A third of the identified expression changes in islets may predispose to diabetes, as expression of these genes associated with HbA1c in individuals not previously diagnosed with T2D. Most DEGs were expressed in human ß cells, based on single-cell RNA-Seq data. Additionally, DEGs displayed alterations in open chromatin and associated with T2D SNPs. Mouse KO strains demonstrated that the identified T2D-associated candidate genes regulate glucose homeostasis and body composition in vivo. Functional validation showed that mimicking T2D-associated changes for OPRD1, PAX5, and SLC2A2 impaired insulin secretion. Impairments in Pax5-overexpressing ß cells were due to severe mitochondrial dysfunction. Finally, we discovered PAX5 as a potential transcriptional regulator of many T2D-associated DEGs in human islets. Overall, we have identified molecular alterations in human pancreatic islets that contribute to ß cell dysfunction in T2D pathophysiology.

Teaching of Veterinary Parasitology to University students in Trinidad, West Indies; are our local wildlife species neglected? / Ensino de parasitologia veterinária para estudantes universitários em Trinidad, Índias Ocidentais; nossas espécies selvagens locais são negligenciadas?

Abstract Parasites of veterinary importance have been heavily focused on domesticated livestock that was introduced into the neo-tropics. The text used in the teaching parasitology to veterinary students in Trinidad has only investigated the parasites of domesticated species. In the reviewed veterinary parasitology text no mention was made on the parasites that affect wild neo-tropical animals. Information on wild neo-tropical animals had to be sourced from texts on the management of wild life animals in the Neotropics. The texts that were reviewed in this document spanned from the mid-1950s to 2020. The information presented in this review reveals the exhaustive work done on the parasites of domesticated species but also revealed little information on neo-tropical animals with the potential for domestication. In conclusion, this review reveals the gap of information that is missing from parasitology texts used in the teaching of veterinary students. In the future these parasitology texts can be revised to include chapters on the parasites of neo-tropical animals with the potential for domestication. At present students that graduate from the veterinary parasitology course has little information on the parasites of animals which are present in their 'backyards'.

Resumo Parasitas de importância veterinária têm se concentrado fortemente em animais domésticos que foram introduzidos na região neotrópica. O texto usado no ensino de parasitologia para estudantes de veterinária em Trinidad investigou apenas os parasitas de espécies domesticadas. No texto de parasitologia veterinária revisado, nenhuma menção foi feita sobre os parasitas que afetam os animais selvagens neotropicais. As informações sobre animais selvagens neotropicais tiveram que ser obtidas a partir de textos sobre o manejo de animais selvagens nos Neotrópicos. Os textos revisados neste documento vão de meados da década de 1950 até 2020. As informações apresentadas nesta revisão revelam o trabalho exaustivo realizado sobre os parasitas de espécies domesticadas, mas também revelaram poucas informações sobre animais neotropicais com potencial para domesticação. Em conclusão, esta revisão revela a lacuna de informação que existe nos textos de parasitologia utilizados no ensino de estudantes de veterinária. No futuro, esses textos de parasitologia podem ser revisados ​​para incluir capítulos sobre os parasitas de animais neotropicais com potencial para domesticação. Atualmente, os alunos que se formam no curso de parasitologia veterinária têm poucas informações sobre os parasitas de animais que estão presentes em seus "quintais".

Anthelmintic usage on the performance of the Agouti (Dasyprocta leporina) reared intensively in Trinidad and Tobago, West Indies / Uso de anti-helmíntico no desempenho da cutia (Dasyprocta leporina) criada intensivamente em Trinidad e Tobago, Índias Ocidentais

Abstract Anthelmintic drugs have been used strategically in livestock reared in the tropics. These drugs have been used in the treatment of endoparasitism which have resulted in an increase in the animals' performance. The agouti (Dasyprocta leporina) is a neo-tropical rodent with the potential for domestication and has been farmed intensively in Trinidad. However, the objective of this research was to investigate the effect of anthelmintic use of the growth performance of the agouti. In searching the literature, it was found that this type of study on the agouti has not been done. In this experiment fourteen weaned agoutis weighing 1kg were divided into two groups randomly. The first group (T1) was not given any anthelmintic treatment but the second group (T2) was treated with Endovet Ces® subcutaneously every three months. There were no significant differences (p > 0.05) between the two groups in the carcass weight, weight gain, dressing percentage (hot and cold), heart, lungs, skin, head and feet. However, a significant difference (p < 0.05) was seen between groups in the weight of liver and pluck. To the authors knowledge this is the first time that carcass parameters has been presented in literature. The live weight of the animals at the end of the experiment ranged from 2.4 kg to 2.6 kg and animals had a dressing percentage of 57% to 55%. The results are suggestive that the use of anthelmintic drugs in agoutis reared intensively had no significant effect on weight gain and dressing percentage.

Resumo Drogas anti-helmínticas têm sido usadas estrategicamente em rebanhos criados nos trópicos. Essas drogas têm sido utilizadas no tratamento do endoparasitismo, o que resultou em um aumento no desempenho dos animais. A cutia (Dasyprocta leporina) é um roedor neotropical com potencial para domesticação e tem sido criada intensivamente em Trinidad. Porém, o objetivo desta pesquisa foi investigar o efeito do uso de anti-helmínticos no desempenho de crescimento da cutia. Através de uma busca na literatura, constatou-se que esse tipo de estudo na cutia não foi realizado. Neste experimento, quatorze cutias desmamadas pesando 1kg foram divididas em dois grupos aleatoriamente. O primeiro grupo (T1) não recebeu nenhum tratamento anti-helmíntico, mas o segundo grupo (T2) foi tratado com Endovet Ces® por via subcutânea a cada três meses. Não houve diferenças significativas (p> 0,05) entre os dois grupos no peso da carcaça, ganho de peso, porcentagem de cobertura (quente e frio), coração, pulmão, pele, cabeça e pés. No entanto, uma diferença significativa (p <0,05) foi observada entre os grupos no peso do fígado e depenagem. Para os autores, esta é a primeira vez que parâmetros de carcaça são apresentados na literatura. O peso vivo dos animais ao final do experimento variou de 2,4 kg a 2,6 kg e os animais tinham uma porcentagem de curativo de 57% a 55%. Os resultados sugerem que o uso de anti-helmínticos em cutias criadas intensivamente não teve efeito significativo no ganho de peso e na porcentagem de curativo.

Anthelmintic usage on the performance of the Agouti (Dasyprocta leporina) reared intensively in Trinidad and Tobago, West Indies / Uso de anti-helmíntico no desempenho da cutia (Dasyprocta leporina) criada intensivamente em Trinidad e Tobago, Índias Ocidentais

Anthelmintic drugs have been used strategically in livestock reared in the tropics. These drugs have been used in the treatment of endoparasitism which have resulted in an increase in the animals’ performance. The agouti (Dasyprocta leporina) is a neo-tropical rodent with the potential for domestication and has been farmed intensively in Trinidad. However, the objective of this research was to investigate the effect of anthelmintic use of the growth performance of the agouti. In searching the literature, it was found that this type of study on the agouti has not been done. In this experiment fourteen weaned agoutis weighing 1kg were divided into two groups randomly. The first group (T1) was not given any anthelmintic treatment but the second group (T2) was treated with Endovet Ces® subcutaneously every three months. There were no significant differences (p > 0.05) between the two groups in the carcass weight, weight gain, dressing percentage (hot and cold), heart, lungs, skin, head and feet. However, a significant difference (p < 0.05) was seen between groups in the weight of liver and pluck. To the authors knowledge this is the first time that carcass parameters has been presented in literature. The live weight of the animals at the end of the experiment ranged from 2.4 kg to 2.6 kg and animals had a dressing percentage of 57% to 55%. The results are suggestive that the use of anthelmintic drugs in agoutis reared intensively had no significant effect on weight gain and dressing percentage.

Drogas anti-helmínticas têm sido usadas estrategicamente em rebanhos criados nos trópicos. Essas drogas têm sido utilizadas no tratamento do endoparasitismo, o que resultou em um aumento no desempenho dos animais. A cutia (Dasyprocta leporina) é um roedor neotropical com potencial para domesticação e tem sido criada intensivamente em Trinidad. Porém, o objetivo desta pesquisa foi investigar o efeito do uso de anti-helmínticos no desempenho de crescimento da cutia. Através de uma busca na literatura, constatou-se que esse tipo de estudo na cutia não foi realizado. Neste experimento, quatorze cutias desmamadas pesando 1kg foram divididas em dois gruposale atoriamente. O primeiro grupo (T1) não recebeu nenhum tratamento anti-helmíntico, mas o segundo grupo (T2) foi tratado com Endovet Ces® por via subcutânea a cada três meses. Não houve diferenças significativas (p> 0,05) entre os dois grupos no peso da carcaça, ganho de peso, porcentagem de cobertura (quente e frio), coração, pulmão, pele, cabeça e pés. No entanto, uma diferença significativa (p <0,05) foi observada entre os grupos no peso do fígado e depenagem. Para os autores, esta é a primeira vez que parâmetros de carcaça são apresentados na literatura. O peso vivo dos animais ao final do experimento variou de 2,4 kg a 2,6 kg e os animais tinham uma porcentagem de curativo de 57% a 55%. Os resultados sugerem que o uso de anti-helmínticos em cutias criadas intensivamente não teve efeito significativo no ganho de peso e na porcentagem de curativo.

Teaching of Veterinary Parasitology to University students in Trinidad, West Indies: are our local wildlife species neglected? / Ensino de parasitologia veterinária para estudantes universitários em Trinidad, Índias Ocidentais: nossas espécies selvagens locais são negligenciadas?

Parasites of veterinary importance have been heavily focused on domesticated livestock that was introduced into the neo-tropics. The text used in the teaching parasitology to veterinary students in Trinidad has only investigated the parasites of domesticated species. In the reviewed veterinary parasitology text no mention was made on the parasites that affect wild neo-tropical animals. Information on wild neo-tropical animals had to be sourced from texts on the management of wild life animals in the Neotropics. The texts that were reviewed in this document spanned from the mid-1950s to 2020. The information presented in this review reveals the exhaustive work done on the parasites of domesticated species but also revealed little information on neo-tropical animals with the potential for domestication. In conclusion, this review reveals the gap of information that is missing from parasitology texts used in the teaching of veterinary students. In the future these parasitology texts can be revised to include chapters on the parasites of neo-tropical animals with the potential for domestication. At present students that graduate from the veterinary parasitology course has little information on the parasites of animals which are present in their 'backyards'.

Parasitas de importância veterinária têm se concentrado fortemente em animais domésticos que foram introduzidos na região neotrópica. O texto usado no ensino de parasitologia para estudantes de veterinária em Trinidad investigou apenas os parasitas de espécies domesticadas. No texto de parasitologia veterinária revisado, nenhuma menção foi feita sobre os parasitas que afetam os animais selvagens neotropicais. As informações sobre animais selvagens neotropicais tiveram que ser obtidas a partir de textos sobre o manejo de animais selvagens nos Neotrópicos. Os textos revisados neste documento vão de meados da década de 1950 até 2020. As informações apresentadas nesta revisão revelam o trabalho exaustivo realizado sobre os parasitas de espécies domesticadas, mas também revelaram poucas informações sobre animais neotropicais com potencial para domesticação. Em conclusão, esta revisão revela a lacuna de informação que existe nos textos de parasitologia utilizados no ensino de estudantes de veterinária. No futuro, esses textos de parasitologia podem ser revisados para incluir capítulos sobre os parasitas de animais neotropicais com potencial para domesticação. Atualmente, os alunos que se formam no curso de parasitologia veterinária têm poucas informações sobre os parasitas de animais que estão presentes em seus "quintais".

Anthelmintic usage on the performance of the Agouti (Dasyprocta leporina) reared intensively in Trinidad and Tobago, West Indies

Abstract Anthelmintic drugs have been used strategically in livestock reared in the tropics. These drugs have been used in the treatment of endoparasitism which have resulted in an increase in the animals performance. The agouti (Dasyprocta leporina) is a neo-tropical rodent with the potential for domestication and has been farmed intensively in Trinidad. However, the objective of this research was to investigate the effect of anthelmintic use of the growth performance of the agouti. In searching the literature, it was found that this type of study on the agouti has not been done. In this experiment fourteen weaned agoutis weighing 1kg were divided into two groups randomly. The first group (T1) was not given any anthelmintic treatment but the second group (T2) was treated with Endovet Ces® subcutaneously every three months. There were no significant differences (p > 0.05) between the two groups in the carcass weight, weight gain, dressing percentage (hot and cold), heart, lungs, skin, head and feet. However, a significant difference (p 0.05) was seen between groups in the weight of liver and pluck. To the authors knowledge this is the first time that carcass parameters has been presented in literature. The live weight of the animals at the end of the experiment ranged from 2.4 kg to 2.6 kg and animals had a dressing percentage of 57% to 55%. The results are suggestive that the use of anthelmintic drugs in agoutis reared intensively had no significant effect on weight gain and dressing percentage.

Resumo Drogas anti-helmínticas têm sido usadas estrategicamente em rebanhos criados nos trópicos. Essas drogas têm sido utilizadas no tratamento do endoparasitismo, o que resultou em um aumento no desempenho dos animais. A cutia (Dasyprocta leporina) é um roedor neotropical com potencial para domesticação e tem sido criada intensivamente em Trinidad. Porém, o objetivo desta pesquisa foi investigar o efeito do uso de anti-helmínticos no desempenho de crescimento da cutia. Através de uma busca na literatura, constatou-se que esse tipo de estudo na cutia não foi realizado. Neste experimento, quatorze cutias desmamadas pesando 1kg foram divididas em dois grupos aleatoriamente. O primeiro grupo (T1) não recebeu nenhum tratamento anti-helmíntico, mas o segundo grupo (T2) foi tratado com Endovet Ces® por via subcutânea a cada três meses. Não houve diferenças significativas (p> 0,05) entre os dois grupos no peso da carcaça, ganho de peso, porcentagem de cobertura (quente e frio), coração, pulmão, pele, cabeça e pés. No entanto, uma diferença significativa (p 0,05) foi observada entre os grupos no peso do fígado e depenagem. Para os autores, esta é a primeira vez que parâmetros de carcaça são apresentados na literatura. O peso vivo dos animais ao final do experimento variou de 2,4 kg a 2,6 kg e os animais tinham uma porcentagem de curativo de 57% a 55%. Os resultados sugerem que o uso de anti-helmínticos em cutias criadas intensivamente não teve efeito significativo no ganho de peso e na porcentagem de curativo.

Teaching of Veterinary Parasitology to University students in Trinidad, West Indies; are our local wildlife species neglected?

Abstract Parasites of veterinary importance have been heavily focused on domesticated livestock that was introduced into the neo-tropics. The text used in the teaching parasitology to veterinary students in Trinidad has only investigated the parasites of domesticated species. In the reviewed veterinary parasitology text no mention was made on the parasites that affect wild neo-tropical animals. Information on wild neo-tropical animals had to be sourced from texts on the management of wild life animals in the Neotropics. The texts that were reviewed in this document spanned from the mid-1950s to 2020. The information presented in this review reveals the exhaustive work done on the parasites of domesticated species but also revealed little information on neo-tropical animals with the potential for domestication. In conclusion, this review reveals the gap of information that is missing from parasitology texts used in the teaching of veterinary students. In the future these parasitology texts can be revised to include chapters on the parasites of neo-tropical animals with the potential for domestication. At present students that graduate from the veterinary parasitology course has little information on the parasites of animals which are present in their backyards.

Resumo Parasitas de importância veterinária têm se concentrado fortemente em animais domésticos que foram introduzidos na região neotrópica. O texto usado no ensino de parasitologia para estudantes de veterinária em Trinidad investigou apenas os parasitas de espécies domesticadas. No texto de parasitologia veterinária revisado, nenhuma menção foi feita sobre os parasitas que afetam os animais selvagens neotropicais. As informações sobre animais selvagens neotropicais tiveram que ser obtidas a partir de textos sobre o manejo de animais selvagens nos Neotrópicos. Os textos revisados neste documento vão de meados da década de 1950 até 2020. As informações apresentadas nesta revisão revelam o trabalho exaustivo realizado sobre os parasitas de espécies domesticadas, mas também revelaram poucas informações sobre animais neotropicais com potencial para domesticação. Em conclusão, esta revisão revela a lacuna de informação que existe nos textos de parasitologia utilizados no ensino de estudantes de veterinária. No futuro, esses textos de parasitologia podem ser revisados para incluir capítulos sobre os parasitas de animais neotropicais com potencial para domesticação. Atualmente, os alunos que se formam no curso de parasitologia veterinária têm poucas informações sobre os parasitas de animais que estão presentes em seus quintais.

A robust experimental and computational analysis framework at multiple resolutions, modalities and coverages.

The ability to study cancer-immune cell communication across the whole tumor section without tissue dissociation is needed, especially for cancer immunotherapy development, which requires understanding of molecular mechanisms and discovery of more druggable targets. In this work, we assembled and evaluated an integrated experimental framework and analytical process to enable genome-wide scale discovery of ligand-receptors potentially used for cellular crosstalks, followed by targeted validation. We assessed the complementarity of four different technologies: single-cell RNA sequencing and Spatial transcriptomic (measuring over >20,000 genes), RNA In Situ Hybridization (RNAscope, measuring 4-12 genes) and Opal Polaris multiplex protein staining (4-9 proteins). To utilize the multimodal data, we implemented existing methods and also developed STRISH (Spatial TRanscriptomic In Situ Hybridization), a computational method that can automatically scan across the whole tissue section for local expression of gene (e.g. RNAscope data) and/or protein markers (e.g. Polaris data) to recapitulate an interaction landscape across the whole tissue. We evaluated the approach to discover and validate cell-cell interaction in situ through in-depth analysis of two types of cancer, basal cell carcinoma and squamous cell carcinoma, which account for over 70% of cancer cases. We showed that inference of cell-cell interactions using scRNA-seq data can misdetect or detect false positive interactions. Spatial transcriptomics still suffers from misdetecting lowly expressed ligand-receptor interactions, but reduces false discovery. RNAscope and Polaris are sensitive methods for defining the location of potential ligand receptor interactions, and the STRISH program can determine the probability that local gene co-expression reflects true cell-cell interaction. We expect that the approach described here will be widely applied to discover and validate ligand receptor interaction in different types of solid cancer tumors.

Mapping Local Failure Following Bladder Radiotherapy According to Dose.

AIMS: To determine the relationship between local relapse following radical radiotherapy for muscle-invasive bladder cancer (MIBC) and radiation dose. MATERIALS AND METHODS: Patients with T2-4N0-3M0 MIBC were recruited to a phase II study assessing the feasibility of intensity-modulated radiotherapy to the bladder and pelvic lymph nodes. Patients were planned to receive 64 Gy/32 fractions to the bladder tumour, 60 Gy/32 fractions to the involved pelvic nodes and 52 Gy/32 fractions to the uninvolved bladder and pelvic nodes. Pre-treatment set-up was informed by cone-beam CT. For patients who experienced local relapse, cystoscopy and imaging (CT/MRI) was used to reconstruct the relapse gross tumour volume (GTVrelapse) on the original planning CT . GTVrelapse D98% and D95% was determined by co-registering the relapse image to the planning CT utilising deformable image registration (DIR) and rigid image registration (RIR). Failure was classified into five types based on spatial and dosimetric criteria as follows: A (central high-dose failure), B (peripheral high-dose failure), C (central elective dose failure), D (peripheral elective dose failure) and E (extraneous dose failure). RESULTS: Between June 2009 and November 2012, 38 patients were recruited. Following treatment, 18/38 (47%) patients experienced local relapse within the bladder. The median time to local relapse was 9.0 months (95% confidence interval 6.3-11.7). Seventeen of 18 patients were evaluable based on the availability of cross-sectional relapse imaging. A significant difference between DIR and RIR methods was seen. With the DIR approach, the median GTVrelapse D98% and D95% was 97% and 98% of prescribed dose, respectively. Eleven of 17 (65%) patients experienced type A failure and 6/17 (35%) patients type B failure. No patients had type C, D or E failure. MIBC failure occurred in 10/17 (59%) relapsed patients; of those, 7/11 (64%) had type A failure and 3/6 (50%) had type B failure. Non-MIBC failure occurred in 7/17 (41%) patients; 4/11 (36%) with type A failure and 3/6 (50%) with type B failure. CONCLUSION: Relapse following radiotherapy occurred within close proximity to the original bladder tumour volume and within the planned high-dose region, suggesting possible biological causes for failure. We advise caution when considering margin reduction for future reduced high-dose radiation volume or partial bladder radiotherapy protocols.

Assessing Bladder Radiotherapy Response With Quantitative Diffusion-Weighted Magnetic Resonance Imaging Analysis.

AIMS: Radiotherapy with radiosensitisation offers opportunity for cure with organ preservation in muscle-invasive bladder cancer (MIBC). Treatment response assessment and follow-up are reliant on regular endoscopic evaluation of the retained bladder. In this study we aim to determine the role of diffusion-weighted magnetic resonance imaging (DWI) and apparent diffusion coefficient (ADC) analysis to assess bladder radiotherapy response. MATERIALS AND METHODS: Patients with T2-T4aN0-3M0 MIBC suitable for radical radiotherapy were recruited prospectively to an ethics approved protocol. Following transurethral resection of the bladder tumour and prior to any treatment, magnetic resonance imaging including DWI was performed on a 1.5T system using b values of 0, 100, 150, 250, 500, 750 s/mm2. DWI was repeated 3 months after completing radiotherapy. Cystoscopy and tumour site biopsy were undertaken following this. The response was dichotomised into response (0.9, P < 0.01). ΔADCall mean of 0.16 × 10-3 mm2/s and ΔADCb100 mean 0.12 × 10-3 mm2/s predicted radiotherapy response with sensitivity/specificity/positive predictive value/negative predictive value of 92.9%/100.0%/100.0%/75.0% and 89.3%/100.0%/100.0%/66.7%, respectively. CONCLUSIONS: Quantitative DWI analysis can successfully provide non-invasive assessment of bladder radiotherapy response. Multicentre validation is required before prospective testing to inform MIBC radiotherapy follow-up schedules and decision making.

Examination of Genetic Susceptibility in Radiation-Associated Meningioma.

Previous epidemiological studies have demonstrated elevated susceptibility to ionizing radiation in some families, thus suggesting the presence of genetic components that conferred increased rate of radiation-associated meningioma (RAM). In this study, we exome-sequenced and investigated the segregation pattern of rare deleterious variants in 11 RAM pedigrees. In addition, we performed a rare-variant association analysis in 92 unrelated familial cases of RAM that were ancestry-matched with 88 meningioma-free controls. In the pedigree analysis, we found that each family carried mostly a unique set of rare deleterious variants. A follow-up pathway analysis of the union of the genes that segregated within each of the 11 pedigrees identified a single statistically significant (q value = 7.90E-04) "ECM receptor interaction" set. In the case-control association analysis, we observed no statistically significant variants or genes after multiple testing correction; however, examination of ontological categories of the genes that associated with RAM at nominal P values <0.01 identified biologically relevant pathways such as DNA repair, cell cycle and apoptosis. These results suggest that it is unlikely that a small number of highly penetrant genes are involved in the pathogenesis of RAM. Substantially larger studies are needed to identify genetic risk variants and genes in RAM.

Radionuclide ventriculography phase analysis for risk stratification of patients undergoing cardiotoxic cancer therapy.

BACKGROUND: Accurate diagnostic tools to identify patients at risk of cancer therapy-related cardiac dysfunction (CTRCD) are critical. For patients undergoing cardiotoxic cancer therapy, ejection fraction assessment using radionuclide ventriculography (RNVG) is commonly used for serial assessment of left ventricular (LV) function. METHODS: In this retrospective study, approximate entropy (ApEn), synchrony, entropy, and standard deviation from the phase histogram (phase SD) were investigated as potential early markers of LV dysfunction to predict CTRCD. These phase parameters were calculated from the baseline RNVG phase image for 177 breast cancer patients before commencing cardiotoxic therapy. RESULTS: Of the 177 patients, 11 had a decline in left ventricular ejection fraction (LVEF) of over 10% to an LVEF below 50% after treatment had commenced. This patient group had a significantly higher ApEn at baseline to those who maintained a normal LVEF throughout treatment. Of the parameters investigated, ApEn was superior for predicting the risk of CTRCD. Combining ApEn with the baseline LVEF further improved the discrimination between the groups. CONCLUSIONS: The results suggest that RNVG phase analysis using approximate entropy may aid in the detection of sub-clinical LV contraction abnormalities, not detectable by baseline LVEF measurement, predicting a subsequent decline in LVEF.

Reproductive diseases in captive Agoutis (Dasyprocta leporina) / Doenças reprodutivas em cutias em cativeiro (Dasyprocta leporina)

Reproductive diseases have been well documented in domestic livestock such as sheep, goat, cattle and pigs. However, there is very little information on these diseases in the agouti (Dasyprocta leporina). The agouti is used for its meat in South America and the Caribbean. More recently, intensive farming of this animal is being practiced in the Neotropics. There is dearth of information on dystocia and vaginal prolapses in the agouti. This document reports on three cases of reproductive diseases in captive reared agoutis in Trinidad and Tobago. The first case was a female agouti weighing approximately 3 kg that was in the last stage of pregnancy, which was found dead in its cage. The vulva of the mother had the protruding hind-limbs of the fetus. Necroscopic evaluation of carcass revealed little fat tissue and the mother had two fetuses in the right horn of the uterus. Each fetus weighed approximately 200 g. The fetuses were well formed with fur, teeth and eyes. The placenta was attached to each fetus. The pathological findings suggested that dystocia resulted from secondary uterine inertia which was the cause of death of the adult female agouti. The second case was that of an adult female agouti weighing 2.5 kg. This female had given birth to an offspring three weeks prior and was observed to have had a vaginal prolapse. Surgery was performed and the prolapsed vagina was placed back into the pelvic cavity. Further to this intervention, the vagina prolapsed twice. Subsequent to the re-insertion of the vaginal tissue the agouti was euthanized. The third case was also that of a dystocia. However, the fetuses weighed 235 g and 165 g respectively and were in normal presentation, posture and positioning. The fetus however was unable to pass via the vagina and was trapped in the pelvic cavity. This caused secondary uterine inertia which was the cause of death. The causes of reproductive diseases in these cases are unknown but the feeding management and space allowance given to the agouti in late gestation may be contributing factors.

As doenças reprodutivas têm sido bem documentadas em rebanhos domésticos, como ovinos, caprinos, bovinos e suínos. Porém, há muito pouca informação sobre essas doenças na cutia (Dasyprocta leporina). A cutia é usada como carne na América do Sul e no Caribe. Mais recentemente, a criação intensiva desse animal está sendo praticada na região neotropical., Há escassez de informações sobre distocia e prolapsos vaginais na cutia. Este documento relata três casos de doenças reprodutivas em cutias criadas em cativeiro em Trinidad e Tobago. O primeiro caso foi de uma cutia de aproximadamente 3 kg que estava na última fase de gestação, encontrada morta em sua gaiola. A vulva da mãe tinha as patas traseiras salientes do feto. A avaliação necroscópica da carcaça revelou pouco tecido adiposo e a mãe tinha dois fetos no corno direito do útero. Cada feto pesava aproximadamente 200 g. Os fetos eram bem formados com pelos, dentes e olhos. A placenta foi presa a cada feto. Os achados patológicos sugeriram que a distocia resultou de inércia uterina secundária, que foi a causa da morte da cutia adulta. O segundo caso foi o de uma cutia adulta pesando 2,5 kg. Essa fêmea deu à luz uma cria três semanas antes e foi observado que tinha prolapso vaginal., A cirurgia foi realizada e a vagina prolapsada foi colocada de volta na cavidade pélvica. Após essa intervenção, a vagina prolapsou duas vezes. Após a reinserção do tecido vaginal, a cutia foi eutanasiada. O terceiro caso também foi de distocia. No entanto, os fetos pesavam 235 g e 165 g e estavam em apresentação, postura e posicionamento normais. O feto, entretanto, não conseguiu passar pela vagina e ficou preso na cavidade pélvica. Isso causou inércia uterina secundária, que foi a causa da morte. As causas das doenças reprodutivas nesses casos são desconhecidas, mas o manejo da alimentação e o espaço concedido à cutia no final da gestação podem ser fatores contribuintes.

Reproductive diseases in captive Agoutis (Dasyprocta leporina) / Doenças reprodutivas em cutias em cativeiro (Dasyprocta leporina)

Reproductive diseases have been well documented in domestic livestock such as sheep, goat, cattle and pigs. However, there is very little information on these diseases in the agouti (Dasyprocta leporina). The agouti is used for its meat in South America and the Caribbean. More recently, intensive farming of this animal is being practiced in the Neotropics. There is dearth of information on dystocia and vaginal prolapses in the agouti. This document reports on three cases of reproductive diseases in captive reared agoutis in Trinidad and Tobago. The first case was a female agouti weighing approximately 3 kg that was in the last stage of pregnancy, which was found dead in its cage. The vulva of the mother had the protruding hind-limbs of the fetus. Necroscopic evaluation of carcass revealed little fat tissue and the mother had two fetuses in the right horn of the uterus. Each fetus weighed approximately 200 g. The fetuses were well formed with fur, teeth and eyes. The placenta was attached to each fetus. The pathological findings suggested that dystocia resulted from secondary uterine inertia which was the cause of death of the adult female agouti. The second case was that of an adult female agouti weighing 2.5 kg. This female had given birth to an offspring three weeks prior and was observed to have had a vaginal prolapse. Surgery was performed and the prolapsed vagina was placed back into the pelvic cavity. Further to this intervention, the vagina prolapsed twice. Subsequent to the re-insertion of the vaginal tissue the agouti was euthanized. The third case was also that of a dystocia. However, the fetuses weighed 235 g and 165 g respectively and were in normalpresentation, posture and positioning. The fetus however was unable to pass via the vagina and was trapped in the pelvic cavity. This caused secondary uterine inertia which was the cause of death. The causes of reproductive diseases in these cases are unknown but the feeding [...].

As doenças reprodutivas têm sido bem documentadas em rebanhos domésticos, como ovinos, caprinos, bovinos e suínos. Porém, há muito pouca informação sobre essas doenças na cutia (Dasyprocta leporina). A cutia é usada como carne na América do Sul e no Caribe. Mais recentemente, a criação intensiva desse animal está sendo praticada na região neotropical. Há escassez de informações sobre distocia e prolapsos vaginais na cutia. Este documento relata três casos de doenças reprodutivas em cutias criadas em cativeiro em Trinidad e Tobago. O primeiro caso foi de uma cutia de aproximadamente 3 kg que estava na última fase de gestação, encontrada morta em sua gaiola. A vulva da mãe tinha as patas traseiras salientes do feto. A avaliação necroscópica da carcaça revelou pouco tecido adiposo e a mãe tinha dois fetos no corno direito do útero. Cada feto pesava aproximadamente 200 g. Os fetos eram bem formados com pelos, dentes e olhos. A placenta foi presa a cada feto. Os achados patológicos sugeriram que a distocia resultou de inércia uterina secundária, que foi a causa da morte da cutia adulta. O segundo caso foi ode uma cutia adulta pesando 2,5 kg. Essa fêmea deu à luz uma cria três semanas antes e foi observado que tinha prolapso vaginal. A cirurgia foi realizada e a vagina prolapsada foi colocada de volta na cavidade pélvica. Após essa intervenção, a vagina prolapsou duas vezes. Após a reinserção do tecido vaginal, a cutia foi eutanasiada. O terceiro caso também foi de distocia. No entanto, os fetos pesavam 235 g e 165 g e estavam em apresentação, postura e posicionamento normais. O feto, entretanto, não conseguiu passar pela vagina e ficou preso na cavidade pélvica. Isso causou inércia uterina secundária, que foi a causa da morte. As causas das doenças reprodutivas nesses casos são desconhecidas, mas o manejo da alimentação e o espaço concedido à cutia no final da gestação podem ser fatores contribuintes.

Reproductive diseases in captive Agoutis (Dasyprocta leporina)

Abstract Reproductive diseases have been well documented in domestic livestock such as sheep, goat, cattle and pigs. However, there is very little information on these diseases in the agouti (Dasyprocta leporina). The agouti is used for its meat in South America and the Caribbean. More recently, intensive farming of this animal is being practiced in the Neotropics. There is dearth of information on dystocia and vaginal prolapses in the agouti. This document reports on three cases of reproductive diseases in captive reared agoutis in Trinidad and Tobago. The first case was a female agouti weighing approximately 3 kg that was in the last stage of pregnancy, which was found dead in its cage. The vulva of the mother had the protruding hind-limbs of the fetus. Necroscopic evaluation of carcass revealed little fat tissue and the mother had two fetuses in the right horn of the uterus. Each fetus weighed approximately 200 g. The fetuses were well formed with fur, teeth and eyes. The placenta was attached to each fetus. The pathological findings suggested that dystocia resulted from secondary uterine inertia which was the cause of death of the adult female agouti. The second case was that of an adult female agouti weighing 2.5 kg. This female had given birth to an offspring three weeks prior and was observed to have had a vaginal prolapse. Surgery was performed and the prolapsed vagina was placed back into the pelvic cavity. Further to this intervention, the vagina prolapsed twice. Subsequent to the re-insertion of the vaginal tissue the agouti was euthanized. The third case was also that of a dystocia. However, the fetuses weighed 235 g and 165 g respectively and were in normal presentation, posture and positioning. The fetus however was unable to pass via the vagina and was trapped in the pelvic cavity. This caused secondary uterine inertia which was the cause of death. The causes of reproductive diseases in these cases are unknown but the feeding management and space allowance given to the agouti in late gestation may be contributing factors.

Resumo As doenças reprodutivas têm sido bem documentadas em rebanhos domésticos, como ovinos, caprinos, bovinos e suínos. Porém, há muito pouca informação sobre essas doenças na cutia (Dasyprocta leporina). A cutia é usada como carne na América do Sul e no Caribe. Mais recentemente, a criação intensiva desse animal está sendo praticada na região neotropical., Há escassez de informações sobre distocia e prolapsos vaginais na cutia. Este documento relata três casos de doenças reprodutivas em cutias criadas em cativeiro em Trinidad e Tobago. O primeiro caso foi de uma cutia de aproximadamente 3 kg que estava na última fase de gestação, encontrada morta em sua gaiola. A vulva da mãe tinha as patas traseiras salientes do feto. A avaliação necroscópica da carcaça revelou pouco tecido adiposo e a mãe tinha dois fetos no corno direito do útero. Cada feto pesava aproximadamente 200 g. Os fetos eram bem formados com pelos, dentes e olhos. A placenta foi presa a cada feto. Os achados patológicos sugeriram que a distocia resultou de inércia uterina secundária, que foi a causa da morte da cutia adulta. O segundo caso foi o de uma cutia adulta pesando 2,5 kg. Essa fêmea deu à luz uma cria três semanas antes e foi observado que tinha prolapso vaginal., A cirurgia foi realizada e a vagina prolapsada foi colocada de volta na cavidade pélvica. Após essa intervenção, a vagina prolapsou duas vezes. Após a reinserção do tecido vaginal, a cutia foi eutanasiada. O terceiro caso também foi de distocia. No entanto, os fetos pesavam 235 g e 165 g e estavam em apresentação, postura e posicionamento normais. O feto, entretanto, não conseguiu passar pela vagina e ficou preso na cavidade pélvica. Isso causou inércia uterina secundária, que foi a causa da morte. As causas das doenças reprodutivas nesses casos são desconhecidas, mas o manejo da alimentação e o espaço concedido à cutia no final da gestação podem ser fatores contribuintes.