Nanophotonic and hydrogel-based diagnostic system for the monitoring of chronic wounds.

Chronic wounds present a major healthcare burden, yet most wounds are only assessed superficially, and treatment is rarely based on the analysis of wound biomarkers. This lack of analysis is based on the fact that sampling of wound biomarkers is typically invasive, leading to a disruption of the wound bed while biomarker detection and quantification is performed in a remote laboratory, away from the point of care. Here, we introduce the diagnostic element of a novel theranostic system that can non-invasively sample biomarkers without disrupting the wound and that can perform biomarker quantification at the point of care, on a short timescale. The system is based on a thermally switchable hydrogel scaffold that enhances wound healing through regeneration of the wound tissue and allows the extraction of wound biomarkers non-destructively. We demonstrate the detection of two major biomarkers of wound health, i.e., IL-6 and TNF-α, in human matrix absorbed into the hydrogel dressing. Quantification of the biomarkers directly in the hydrogel is achieved using a chirped guided mode resonant biosensor and we demonstrate biomarker detection within the clinically relevant range of pg/mL to µg/mL concentrations. We also demonstrate the detection of IL-6 and TNF-α at concentration 1 ng/mL in hydrogel dressing absorbed with clinical wound exudate samples. The high sensitivity and the wide dynamic range we demonstrate are both essential for the clinical relevance of our system. Our test makes a major contribution towards the development of a wound theranostic for guided treatment and management of chronic wounds.

Treatment strategies in patients with gynecological sarcoma: Results of the prospective intergroup real-world registry for gynecological sarcoma in Germany (REGSA-NOGGO RU1).

OBJECTIVE: Gynecological sarcomas account for 3% of all gynecological malignancies and are associated with a poor prognosis. Due to the rarity and heterogeneity of gynecological sarcomas there is still no consensus on optimal therapeutic strategies. This study's objective was to describe the treatment strategies used in patients with gynecological sarcomas in the primary course of disease. METHODS: The German prospective registry for gynecological sarcoma (REGSA) is the largest registry for gynecological sarcomas in Germany, Austria and Switzerland. Primary inclusion criteria for REGSA are histological diagnosis of sarcoma of the female genital tract, sarcoma of the breast or uterine smooth muscle tumors of uncertain malignant potential (STUMP). We evaluated data of the REGSA registry on therapeutic strategies used for primary treatment from August 2015 to February 2021. RESULTS: A total of 723 patients from 120 centers were included. Data on therapeutic strategies for primary treatment were available in 605 cases. Overall, 580 (95.9%) patients underwent primary surgery, 472 (81.4%) of whom underwent only hysterectomy. Morcellation was reported in 11.4% (n=54) of all hysterectomies. A total of 42.8% (n=202) had no further surgical interventions, whereas an additional salpingo-ophorectomy was performed in 54% (n=255) of patients. An additional lymphadenectomy was performed in 12.7% (n=60), an omentectomy in 9.5% (n=45) and intestinal resection in 6.1% (n=29) of all patients. Among 448 patients with available information, 21.4% (n=96) received chemo- or targeted therapies, more commonly as single-agent treatment than as drug combinations. Information about anti-hormonal treatment was available for 423 patients, among which 42 (9.9%) received anti-hormonal treatment, 23 (54.8%) of whom with low-grade endometrial stroma sarcomas. For radiotherapy, data of 437 patients were available, among which 29 (6.6%) patients underwent radiotherapy. CONCLUSION: Our study showed that treatment of patients with gynecologic sarcomas is heterogeneous. Further trials are needed along with more information on treatment modalities, therapy response and patient-reported outcomes to implement new treatment strategies.

Gerenciamento de resíduos em laboratórios de uma universidade pública brasileira: um desafio para a saúde ambiental e a saúde do trabalhador / Waste management in laboratories of a Brazilian public university: a challenge for environmental health and occupational health

RESUMO As instituições de ensino superior, enquanto geradoras e difusoras de conhecimento, precisam cada vez mais assumir seu papel no contexto regional, especialmente na criação de políticas sustentáveis e de preservação do meio ambiente. Neste sentido, o presente artigo objetiva compreender as práticas de gerenciamento de resíduos de serviços de saúde nos laboratórios de ensino-pesquisa do Instituto de Ciências Agrárias da Universidade Federal de Minas Gerais - campus Montes Claros. Trata-se de uma pesquisa com abordagem qualitativa e quantitativa, realizada mediante a aplicação de questionário com os trabalhadores inseridos em atividades dos laboratórios de ensino. Para a análise, foram utilizadas as frequências absolutas e relativas, medidas de posição, tendência central e dispersão. Entre os problemas identificados, ressaltam-se: as não conformidades com a legislação vigente, em relação ao gerenciamento de resíduos nos laboratórios; a ausência relatada pelos trabalhadores, de capacitações para a realização de suas funções, como também de treinamentos para a prevenção de riscos e para o manejo adequado de resíduos; e a cobertura vacinal baixa contra hepatite B e tétano. Apesar de os locais pesquisados realizarem o gerenciamento dos seus resíduos, constata-se que muitas práticas estão em desacordo com a legislação vigente e precisam ser adequadas.

ABSTRACT Higher education institutions, as generators and disseminators of knowledge, are increasingly in need to assume their roles in regional context, especially in the creation of sustainable and environment preservation public policies. In this sense, the aim of this article was to understand the management of health care waste practices in teaching and research laboratories of the Institute of Agrarian Sciences of the Federal University of Minas Gerais - Montes Claros campus. It is a research with quantitative and qualitative approaches, carried out through survey application with workers engaged in the activities of the teaching labs. For the analysis, absolute and relative frequencies, position measurements, central tendency and dispersion were used. Among the problems detected, it should be highlighted: non-compliance with current legislation, concerned to laboratories waste management; absence reported by workers, of training for the accomplishment of their functions, as well as education for risk prevention and proper waste management; insufficient immunization coverage against hepatitis B and tetanus. Although the places researched manage their waste, this work concludes that many practices are at odds with the current legislation and need to be adequate.

Influence of patient and tumor characteristics on therapy persistence with letrozole in postmenopausal women with advanced breast cancer: results of the prospective observational EvAluate-TM study.

BACKGROUND: Treatment of postmenopausal, hormone receptor-positive metastatic breast cancer (MBC) patients varies despite clear therapy guidelines, favoring endocrine treatment (ET). Aim of this study was to analyze persistence of palliative aromatase inhibitor (AI) monotherapy in MBC patients. METHODS: EvAluate-TM is a prospective, multicenter, noninterventional study to evaluate treatment with letrozole in postmenopausal women with hormone receptor-positive breast cancer. To assess therapy persistence, defined as the time from therapy start to the end of the therapy (TTEOT), two pre-specified study visits took place after 6 and 12 months. Competing risk survival analyses were performed to identify patient and tumor characteristics that predict TTEOT. RESULTS: Out of 200 patients, 66 patients terminated treatment prematurely, 26 (13%) of them due to causes other than disease progression. Persistence rate for reasons other than progression at 12 months was 77.7%. Persistence was lower in patients who reported any adverse event (AE) in the first 30 days of ET (89.5% with no AE and 56% with AE). Furthermore, patients had a lower persistence if they reported compliance problems in the past before letrozole treatment. CONCLUSIONS: Despite suffering from a life-threatening disease, AEs of an AI will result in a relevant number of treatment terminations that are not related to progression. Some subgroups of patients have very low persistence rates. Especially with regard to novel endocrine combination therapies, these data imply that some groups of patients will need special attention to guide them through the therapy process. TRIAL REGISTRATION: Clinical Trials Number: CFEM345DDE19.

Quantifying single-cell secretion in real time using resonant hyperspectral imaging.

Cell communication is primarily regulated by secreted proteins, whose inhomogeneous secretion often indicates physiological disorder. Parallel monitoring of innate protein-secretion kinetics from individual cells is thus crucial to unravel systemic malfunctions. Here, we report a label-free, high-throughput method for parallel, in vitro, and real-time analysis of specific single-cell signaling using hyperspectral photonic crystal resonant technology. Heterogeneity in physiological thrombopoietin expression from individual HepG2 liver cells in response to platelet desialylation was quantified demonstrating how mapping real-time protein secretion can provide a simple, yet powerful approach for studying complex physiological systems regulating protein production at single-cell resolution.

Photonic and Plasmonic Nanotweezing of Nano- and Microscale Particles.

The ability to manipulate and sense biological molecules is important in many life science domains, such as single-molecule biophysics, the development of new drugs and cancer detection. Although the manipulation of biological matter at the nanoscale continues to be a challenge, several types of nanotweezers based on different technologies have recently been demonstrated to address this challenge. In particular, photonic and plasmonic nanotweezers are attracting a strong research effort especially because they are efficient and stable, they offer fast response time, and avoid any direct physical contact with the target object to be trapped, thus preventing its disruption or damage. In this paper, we critically review photonic and plasmonic resonant technologies for biomolecule trapping, manipulation, and sensing at the nanoscale, with a special emphasis on hybrid photonic/plasmonic nanodevices allowing a very strong light-matter interaction. The state-of-the-art of competing technologies, e.g., electronic, magnetic, acoustic and carbon nanotube-based nanotweezers, and a description of their applications are also included.

Interest in Integrative Medicine Among Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study.

BACKGROUND: Breast cancer patients often use complementary and alternative medicine, but few prospectively collected data on the topic are available specifically for postmenopausal breast cancer patients. A large prospective study was therefore conducted within a noninterventional study in order to identify the characteristics of patients interested in integrative medicine. METHODS: The EvAluate-TM study is a prospective, multicenter noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive primary breast cancer. Between 2008 and 2009, 5045 postmenopausal patients were enrolled at 339 certified breast centers in Germany. As part of the data collection process, patients were asked at the baseline about their interest in and information needs relating to integrative medicine. RESULTS: Of the 5045 patients recruited, 3411 responded to the questionnaire on integrative medicine and took part in the analysis, 1583 patients expressed an interest in integrative medicine, and 1828 patients declared no interest. Relevant predictors of interest in integrative medicine were age, body mass index, tumor size, previous chemotherapy, and use of concomitant medications for other medical conditions. Interest in integrative medicine declined highly significantly ( P < .001) with age (<50 years, 74.1%; 50-60 years, 54.1%; >65 years, 38.0%). Patients in favor of integrative medicine were significantly less satisfied with the information received about individual treatments and antihormonal therapy. Patients with interest in integrative medicine were more often interested in rehabilitation and fitness, nutritional counseling, and additional support from self-help organizations. These women were mostly interested in receiving information about their disease and integrative medicine from a physician, rather than from other sources. CONCLUSIONS: This study shows that a considerable proportion of postmenopausal breast cancer patients are interested in integrative medicine. Information about integrative medicine should therefore be provided as part of patient care for this group. It was found that receiving concomitant medication for other medical conditions is one of the main predictors for women not being interested in integrative medicine. This group of patients may need special attention and individualized information about integrative medicine. Additionally, most patients were interested in obtaining the relevant information from their doctor.

Factors Influencing Decision-Making for or against Adjuvant and Neoadjuvant Chemotherapy in Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study.

BACKGROUND: Decision-making for or against neoadjuvant or adjuvant chemotherapy in postmenopausal patients with hormone receptor-positive breast cancer does not follow any clear guidelines, and some patients may unnecessarily undergo chemotherapy and be exposed to the associated toxicity. The aim of this study was to identify the patient population for whom this issue may bear relevance. METHODS: Patients being treated with letrozole in the prospective multicenter noninterventional EvAluate-TM study were recruited. The percentage of patients receiving chemotherapy and factors associated with chemotherapy administration were identified. RESULTS: In all, 3,924 (37.4%) patients received chemotherapy before treatment with letrozole. Of these, 293 (20%) underwent neoadjuvant therapy. Younger age was predictive for both adjuvant and neoadjuvant therapy. Overall, decisions in favor of administering chemotherapy are more likely to be made in patients with a higher body mass index (BMI), and neoadjuvant chemotherapy is administered at a higher rate in women with a lower BMI. Concomitant medication influenced the overall decision-making regarding chemotherapy, irrespective of whether it was given on a neoadjuvant or adjuvant basis. CONCLUSION: There is an ongoing debate as to whether all of the many patients who receive chemotherapy actually benefit from it. Neoadjuvant chemotherapy is frequently administered in this patient population, and this should encourage further research to resolve current clinical and research issues.

Organochlorine compound levels in fertile and infertile women from Rio de Janeiro, Brazil / Níveis de substâncias organocloradas em mulheres férteis e inférteis do Rio de Janeiro, Brasil

OBJECTIVE: The aim of the study was quantify organochlorine compounds in women seeking for infertility treatment (n = 15) and in spontaneously pregnant ones (n = 21). MATERIALS AND METHODS: A questionnaire was applied regarding lifestyle, occupational and reproductive history. Blood samples were collected from both groups. RESULTS: From the pesticides studied, pp'DDE was detected in 100% of infertile women, at higher mean levels than in pregnant women (3.02 mcg/L vs. 0.88 mcg/L; p = 0.001; power of 69%), without correlation with the etiology of infertility. Levels of the polychlorinated biphenyls (PCBs) were low, with positive samples in 100% in the infertile women for PCBs 138, 153, 180, while in pregnant women, they were 85.7% for congeners 138 and 153. Only PCB180 showed significance, with frequency of 71.4% (p = 0.019). CONCLUSIONS: The risk factors for female infertility were: age, consumption of untreated water and of canned foods. Exposure to the most prevalent organochlorine compounds described in literature was confirmed in the study, indicating that pp'DDE may adversely influence female fertility.

OBJETIVO: O estudo teve como objetivo quantificar as substâncias organocloradas em mulheres buscando tratamento para infertilidade (n = 15) e que espontaneamente engravidaram (n = 21). MATERIAIS E MÉTODOS: Foi aplicado questionário considerando estilo de vida, história ocupacional e reprodutiva. Amostras de sangue foram obtidas em ambos os grupos. RESULTADOS: Dos pesticidas, pp'DDE foi detectado em 100% das inférteis, com níveis maiores que nas grávidas (3,02 mcg/L vs. 0,88 mcg/L; p = 0,001; poder 69%), sem correlação na etiologia da infertilidade. Os níveis de detecção das bifenilas policloradas (PCBs) foram baixos, com 100% de positividade das amostras nas inférteis para os PCBs 138, 153, 180, e de 85,7% nas grávidas para os congêneres 138 e 153. Apenas PCB180 mostrou significância na frequência de 71,4% (p = 0,019). CONCLUSÕES: Os fatores de risco para infertilidade feminina foram: idade, consumo de água não tratada e alimentos enlatados. A exposição aos organoclorados mais prevalentes descritos na literatura foi confirmada no estudo, indicando que pp'DDE pode influenciar adversamente a fertilidade feminina.

Intra-operative introital ultrasound in Burch colposuspension reduces post-operative complications.

OBJECTIVE: To determine the effect of intra-operative monitoring of bladder neck elevation on cure rate and post-operative complications in patients undergoing colposuspension. DESIGN: Prospective, observational study. SETTING: Urogynaecology units, university hospitals. POPULATION: Ninety women operated on for genuine stress urinary incontinence. METHODS: The topography of the bladder neck and proximal urethra was assessed with pre-, intra- and post-operative introital ultrasound. These measurements were repeated during follow up for up to 48 months after surgery. Burch colposuspension of the bladder neck was performed under intra-operative introital ultrasound control, with reference to the patients' individual pre-operative ultrasound, to achieve a vertical height correction of 1-10 mm. MAIN OUTCOME MEASURES: Mid-term surgical outcome and post-operative complications. RESULTS: Ninety patients underwent colposuspension and 50 (56%) completed 48 months of follow up; 85 women (94%) were objectively continent at 12-month follow up and 42 of 50 (82%) at 48-month follow up. Surgical elevation of the bladder neck resulted in a median intra-operative elevation of 9 mm (7 mm at 48 months). All post-operative measurements demonstrated a significant decrease in linear dorsocaudal movement of the bladder neck during straining (P < 0.001). Funnelling and hypermobility were still decreased 48 months after incontinence surgery (P < 0.001). Voiding difficulty and urgency were uncommon and associated with evidence of funnelling and hypermobility. CONCLUSION: Intra-operative introital ultrasound standardises Burch colposuspension and thus might help to avoid overelevation and associated post-operative complications such as voiding difficulties and de novo urge incontinence without compromising the success of the operation.

Postoperative funneling after anti-incontinence surgery--a prognostic indicator?--Part 1: colposuspension.

AIMS: How does funneling of the bladder neck after open colposuspension affect the postoperative cure rate? METHODS: In a retrospective study, 310 patients who underwent primary colposuspension for urodynamically proven genuine stress urinary incontinence were assessed by introital ultrasound before and immediately after surgery as well as at 6, 12, 24, 36, and 48 months. A total of 152 women completed 48-month follow-up. Objective cure rates at the different follow-up times were calculated and correlated with the presence of postoperative bladder neck funneling. RESULTS: The objective cure rate up to 6 months after colposuspension was 90.0 versus 76.8% up to 48-month follow-up. Urge symptoms occurred in 11.6% (36/310) of the women and de novo urge incontinence in 1.6% (5/310). Bladder neck funneling was significantly reduced after anti-incontinence surgery, from 55.2% before surgery to 12.3% (38/310) at 6-month follow-up (P < 0.0001). Postoperative funneling was associated with a higher recurrence rate. In the funneling group, 58.8 and 40.6% of the patients were continent up to 6 and 48 months, respectively, as opposed to 93.8 and 81.3% in the group without funneling (P < 0.0001). Urgency and de novo urge incontinence were more common in the funneling group (23.5 and 28.3% up to 6 and 48 months, respectively, vs. 12.7 and 13.5%; P < 0.05). CONCLUSIONS: Patients in whom funneling of the bladder neck diagnosed before surgery persists after colposuspension have a higher risk of recurrence and are more likely to develop postoperative complications.

Three-dimensional spheroidal culture of cytotrophoblast cells mimics the phenotype and differentiation of cytotrophoblasts from normal and preeclamptic pregnancies.

Normal placental development is dependent on the orchestrated differentiation of cytotrophoblast (CTB) cells. This study was aimed at studying cytotrophoblast cells from normal and preeclamptic pregnancies in a three-dimensional spheroid-based cell culture model. First trimester cytotrophoblast cells cultured as spheroids maintain their high proliferative and invasive phenotype and respond to different cytokines upon stimulation in a three-dimensional invasion assay. In contrast, third trimester cytotrophoblast spheroids maintain their quiescent nonproliferating phenotype and invasion can only be induced by EGF. Contrasting the regular spheroidal arrangement of cytotrophoblast cells from normal third trimester pregnancies, spheroidal organization of preeclamptic cytotrophoblast cells is disturbed and the cells downregulate CD105 in vivo and in vitro. Furthermore, the invasion of both normal and preeclamptic third trimester, but not first trimester cytotrophoblast cells, is inhibited by pro-inflammatory cytokines. Plasma samples from pregnant women with preeclampsia significantly stimulate the invasion of first trimester cytotrophoblast cells and the sprouting of human umbilical vein endothelial cells (HUVECs) compared to plasma samples from healthy pregnant women. Taken together, the data establish the spheroidal cytotrophoblast model as a powerful system to mimic the in vivo phenotype of first and third trimester and preeclamptic cytotrophoblast cells and demonstrate that plasma-derived factors modulate the differentiation of cytotrophoblast cells.

Conformal radiotherapy planning of cervix carcinoma: differences in the delineation of the clinical target volume. A comparison between gynaecologic and radiation oncologists.

PURPOSE: To assess uncertainties in the definition of the clinical target volume (CTV) for patients scheduled for primary radiotherapy of cervix carcinoma. METHODS AND MATERIALS: Seven physicians (five radiation oncologists and two gynaecologists) independently contoured the CTVs for three patients. All observers were provided with the same clinical information. CTVs were entered directly in the treatment planning system. Differences were analysed qualitatively and quantitatively. RESULTS: The qualitative analysis revealed a good agreement by all observers on anatomical structures identified to be at risk for tumour spread. Quantitatively, however, a large interobserver variability was found. The ratio between largest and smallest volumes ranged between 3.6 and 4.9 for all observers (3.6-4.9 for the radiation oncologists, 1.3-2.8 for the gynaecologists). The median three-dimensional difference in gravity centres ranged between 10.9 and 26.3mm for the respective patients. The ratio of common volumes to encompassing volumes ranged between 0.11 and 0.13 for the radiation oncologists, and between 0.30 and 0.57 for the gynaecologists. CONCLUSIONS: Although there was a good consistency in outlined anatomical structures, for the radiation therapy of carcinomas of the uterine cervix a large interobserver variability in CTV delineation concerning the magnitude and relative location of volumes was observed. Compared to other factors, e.g. set-up and organ motion, interobserver variability in CTV definition seems to have the highest impact on the geometrical accuracy in the radiotherapy of this tumour entity.