Primary ovarian cancer after colorectal cancer: a Dutch nationwide population-based study.

BACKGROUND AND PURPOSE: Women with colorectal cancer (CRC) are at risk not only of developing ovarian metastases, but also of developing a primary ovarian malignancy. Several earlier studies have in fact shown a link between the development of primary ovarian cancer and CRC. The purpose of this study was therefore to determine the risk of developing a primary ovarian cancer in women with prior CRC compared to the general population. METHODS: Data from the Netherlands Cancer Registry were used. All women diagnosed with invasive CRC between 1989 and 2017 were included. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) per 10,000 person-years were calculated. RESULTS: During the study period, 410 (0.3%) CRC patients were diagnosed with primary ovarian cancer. Women with CRC had a 20% increased risk of developing ovarian cancer compared to the general population (SIR = 1.2, 95% CI: 1.1-1.3). The AER of ovarian cancer was 0.9 per 10,000 person-years. The risk was especially increased within the first year of a CRC diagnosis (SIR = 3.3, 95% CI: 2.8-3.8) and in women aged ≤ 55 years (SIR = 2.0, 95% CI: 1.6-2.6). CONCLUSION: This study found a slightly increased risk of primary ovarian cancer in women diagnosed with CRC compared to the general population. However, this may be partly attributable to surveillance or detection bias. Nevertheless, our findings could be helpful for patient counseling, as CRC patients do not currently receive information concerning the increased risk of ovarian cancer.

Ovarian metastases in young women with colorectal cancer: a retrospective multicenter cohort study.

BACKGROUND AND PURPOSE: Previous studies indicated that approximately 3.4% of female colorectal cancer (CRC) patients are at increased risk of developing ovarian metastases (OM). It has been suggested that young women more frequently develop this form of metastatic disease. METHODS: This study evaluated, in 6 Dutch hospitals, the proportion of young women with CRC who developed OM. RESULTS: In a cohort of 200 young (age ≤ 55) women with CRC, the proportion of patients diagnosed with synchronous or metachronous OM was calculated. This study revealed that 5% (n = 10) of young female CRC patients developed ovarian metastases resulting in a 5-year overall survival rate of approximately 40%. Furthermore, six patients had concurrent peritoneal metastases, five patients had bilateral ovarian metastases, and five patients had synchronous metastases, while the median time of the occurrence of metachronous metastases (n = 5) was 19 months. CONCLUSION: This retrospective multicenter cohort study indicates that 5% of young women with CRC either present with or develop OM. This result appears to be clinically relevant and demonstrates the need for improved surveillance for young women diagnosed with CRC.

Role Of Ovarian Metastases In Colorectal Cancer (ROMIC): a Dutch study protocol to evaluate the effect of prophylactic salpingo-oophorectomy in postmenopausal women.

BACKGROUND: The mean incidence of ovarian metastases (OM) in patients with colorectal cancer (CRC) is 3.4%. The 5-year survival of these patients, even when operated with curative intent, is remarkably low. The lifetime risk of ovarian cancer is approximately 1.3%. Prophylactic salpingo-oophorectomy (PSO, or surgical removal of the ovaries and fallopian tubes) could reduce the number of CRC patients that develop OM after removal of the primary tumor, as well as preventing the occurrence of primary ovarian cancer. Recently, the care pathway for CRC has been changed in several hospitals in line with the updated Dutch guideline. The possibility of PSO is now discussed with postmenopausal CRC patients in these hospitals. The aims of the current study are firstly to estimate the incidence of OM and primary ovarian cancer in postmenopausal patients with CRC, and secondly to evaluate the effect of PSO in these patients. METHODS: An information bulletin and decision guide on this topic was implemented in several Dutch hospitals in 2020. Post-decision outcomes will be collected prospectively. The study population consists of postmenopausal (≥ 60 years of age) patients that are operated with curative intent for CRC. Based on their own preference, patients will be divided into two groups: those who choose to undergo PSO and those who do not. The main study parameters are the reduction in incidence of ovarian malignancies (metastatic or primary) following PSO, and the number needed to treat (NNT) by PSO to prevent one case of ovarian malignancy. DISCUSSION: This will be the first study to evaluate the effect of PSO in postmenopausal CRC patients that is facilitated by an altered CRC care pathway. The results of this study are expected to provide relevant information on whether PSO adds significant value to postmenopausal patients with CRC. TRIAL REGISTRATION: International Clinical Trials Registry Platform, NL7870. Registered on 2019 July 12. URL of trial registry record: https://trialsearch.who.int/Trial2.aspx?TrialID=NL7870 . PROTOCOL VERSION: 1.0, date 2021 June 8.

Incidence, risk factors, treatment, and survival of ovarian metastases of colorectal origin: a Dutch population-based study.

OBJECTIVE: The aim of this nationwide study was to provide insight in the incidence, risk factors, treatment, and survival of patients with ovarian metastases from colorectal cancer (CRC). METHODS: Data from the Netherlands Cancer Registry were used. All newly diagnosed female CRC patients between 2008 and 2016 were included. Treatment was categorized as follows: cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (CRS-HIPEC); resection of the primary tumor; palliative treatment; and no treatment. Overall survival (OS) was investigated using Kaplan-Meier and multivariable Cox regression analyses. RESULTS: Of 53,883 female CRC patients, 11,343 (21.1%) had metastases at time of diagnosis. Among them, 471 (4.2%) had ovarian metastases. Within latter group, 27.2% received CRS-HIPEC; 38.4% underwent resection of the primary tumor; 25.3% received palliative treatment; and 9.1% received no treatment. Median OS of all patients with ovarian metastases was 17.5 months. In patients receiving CRS-HIPEC, OS was significantly longer than in patients undergoing resection only (median OS 34.1 vs. 17.5 months, adjusted HR 0.44 [0.33-0.66]). Five-year OS was 28.5% for patients having underwent CRS-HIPEC, 11.0% for patients having underwent resection of the primary tumor, 1.2% for patients having underwent palliative treatment, and 0.0% for patients without treatment. CONCLUSIONS: Synchronous ovarian metastases are diagnosed in 4.2% of female colorectal patients presenting with metastatic disease. Risk factors are young age, T4/N+ tumor and histology of signet ring cell carcinoma. Median OS of the entire cohort was 17.5 months, ranging from 3.1 months in patients without treatment to 34.1 months in patients undergoing CRS-HIPEC.

Quantitative margin assessment of radiofrequency ablation of a solitary colorectal hepatic metastasis using MIRADA RTx on CT scans: a feasibility study.

BACKGROUND: Compared to surgery, radiofrequency ablation(RFA) for colorectal liver metastasis(CRLM) is associated with higher local recurrence(LR) rates. A wide margin (at least 5 mm) is generally recommended to prevent LR, but the optimal method to assess ablation margins is yet to be established. The aim of our study was to evaluate the feasibility and reproducibility of CT-CT co-registration, using MIRADA software, in order to assess ablation margins of patients with CRLM. METHODS: In this retrospective study, pre- and post-ablation contrast-enhanced CT scans of 29 patients, treated with percutaneous RFA for a solitary CRLM, were co-registered. Co-registration was performed by two independent radiologist, based on venous structures in proximity to the tumor. Feasibility of CT-CT co-registration and inter-observer agreement for reproducibility and ablation margins was determined. Furthermore, the minimal ablation margin was compared with the occurrence of LR during follow-up. RESULTS: Co-registration was considered feasible in 18 patients (61% male, 63.1(±10.9) year), with a perfect inter-observer agreement for completeness of ablation: κ = 1.0(p < 0.001). And substantial inter-observer agreement for measurement of the minimal margin (≤ 0 mm, 1-5 mm, ≥ 5 mm): κ = 0.723(p-value < 0.001). LR occurred in eight of nine(88.9%) incompletely ablated CRLM and in one of the nine completely ablated CRLM(11.1%). CONCLUSION: Co-registration using MIRADA is reproducible and potentially a valuable tool in defining technical success. Feasibility of co-registration of pre- and post-ablation CT scans is suboptimal if scans are not acquired concordantly. Co-registration may potentially aid in the prediction of LR after percutaneous ablation.

Quality of Life Analysis of Patients Treated with Percutaneous Hepatic Perfusion for Uveal Melanoma Liver Metastases.

PURPOSE: Percutaneous hepatic perfusion with melphalan (M-PHP) is a minimally invasive therapy with proven efficacy in patients with uveal melanoma (UM) liver metastases. M-PHP is associated with a short hospital admission time and limited systemic side effects. In this study, we assessed quality of life (QoL) in UM patients treated with M-PHP. MATERIALS AND METHODS: A prospective, single-center study including 24 patients treated with M-PHP for UM metastases to the liver. QoL questionnaires were collected at baseline, on day 2/3 after M-PHP, and on day 7 and day 21 after M-PHP, according to study protocol. The results were scored according to EORTC-QLQ C30 global health status (GHS), functional scales, and symptom scales. The difference in scores at baseline and subsequent time points was analyzed with the Wilcoxon signed-rank test and multiple testing Bonferroni correction. Adverse events (AE) were registered up to 30 days after M-PHP according to CTCAE v5.0. RESULTS: Twenty-four patients (14 males; median age 63.0 years) completed 96 questionnaires. Most scores on all scales declined on day 2/3 after M-PHP. On day 21 after M-PHP, 12 out of 15 scores returned to baseline, including median GHS scores. Three variables were significantly worse on day 21 compared to baseline: fatigue (6-33; p = 0.002), physical functioning (100 vs 86.7; p = 0.003), and role functioning (100 vs 66.7; p = 0.001). Grade 3/4 AEs consisted mainly of hematological complications, such as leukopenia and thrombopenia. CONCLUSION: M-PHP causes fatigue and a decline in physical and role functioning in the 1st weeks after treatment, but GHS returns to baseline levels within 21 days. LEVEL OF EVIDENCE 3: Cohort study.

Chemotherapy for testicular cancer induces acute alterations in diastolic heart function.

BACKGROUND: After treatment with cisplatin-based chemotherapy for testicular cancer (TC), patients have higher prevalence of cardiovascular complications after long-term follow up. Little is known about acute cardiovascular effects of cisplatin-based chemotherapy. The aim of this study was to explore acute effects of chemotherapy on cardiac function in patients treated for TC. METHODS: Fourteen TC patients (age 34.6 ± 12.3 years) were studied before and 3 months after start with cisplatin-based chemotherapy. Cardiac function was assessed with magnetic resonance imaging. Fasting glucose and insulin levels were measured and insulin sensitivity, reflected by the quantitative insulin sensitivity index (Quicki index), was calculated. RESULTS: Left ventricular (LV) end-diastolic volume and LV stroke volume (SV) significantly decreased from 192 ± 27 to 175 ± 26 ml (P<0.05) and 109 ± 18 to 95 ± 16 ml (P<0.05), respectively. The ratio of early and atrial filling velocities across the mitral valve, a parameter of diastolic heart function, decreased after chemotherapy from 1.87 ± 0.43 to 1.64 ± 0.45 (P<0.01). Metabolic parameters were unfavourably changed, reflected by a decreased Quicki index, which reduced from 0.39 ± 0.05 to 0.36 ± 0.05 (P<0.05). CONCLUSION: Chemotherapy for TC induces acute alterations in diastolic heart function, paralleled by unfavourable metabolic changes. Therefore, early after chemotherapy, metabolic treatment may be indicated to possibly reduce long-term cardiovascular complications.

Extended theory of soft x-ray reflection for realistic lamellar multilayer gratings.

An extended set of coupled wave equations were derived to describe non-idealized lamellar multilayer grating structures with properties as obtained with state-of-the-art fabrication techniques. These generalized equations can include all relevant effects describing the influence of passivation and contamination layers, non-rectangular lamel profiles and sidewall scalloping. The calculations showed that passivation and contamination plays an important role in that it may significantly reduce peak reflectivity. However, we also derived a condition for layer thicknesses having negligible effects. Slightly positive tapered lamel profiles are shown to further reduce the bandwidth as compared to a rectangular lamel profile, whereas negative tapers significantly increased the bandwidth. The influence of intriguing effects, such as the sidewall scalloping caused by Bosch Deep Reactive Ion Etching, are also modeled. We identified the signature of such scalloping as additional side peaks in the reflectivity spectrum and present parameters with which these can be effectively suppressed.

Infrared diffractive filtering for extreme ultraviolet multilayer Bragg reflectors.

We report on the development of a hybrid mirror realized by integrating an EUV-reflecting multilayer coating with a lamellar grating substrate. This hybrid mirror acts as an efficient Bragg reflector for extreme ultraviolet (EUV) radiation at a given wavelength while simultaneously providing spectral-selective suppression of the specular reflectance for unwanted longer-wavelength radiation due to the grating phase-shift resonance. The test structures, designed to suppress infrared (IR) radiation, were fabricated by masked deposition of a Si grating substrate followed by coating of the grating with a Mo/Si multilayer. To give the proof of principle, we developed such a hybrid mirror for the specific case of reflecting 13.5 nm radiation while suppressing 10 µm light, resulting in 61% reflectance at the wavelength of 13.5 nm together with the 70 × suppression rate of the specular reflection at the wavelength of 10 µm, but the considered filtering principle can be used for a variety of applications that are based on utilization of broadband radiation sources.

BRCA1 is secreted and exhibits properties of a granin.

Germline mutations in BRCA1 are responsible for most cases of inherited breast and ovarian cancer. However, the function of the BRCA1 protein has remained elusive. We now show that BRCA1 encodes a 190-kD protein with sequence homology and biochemical analogy to the granin protein family. Interestingly, BRCA2 also includes a motif similar to the granin consensus at the C terminus of the protein. Both BRCA1 and the granins localize to secretory vesicles, are secreted by a regulated pathway, are post-translationally glycosylated and are responsive to hormones. As a regulated secretory protein, BRCA1 appears to function by a mechanism not previously described for tumour suppressor gene products.

Quantum simulation of thermodynamics in an integrated quantum photonic processor.

One of the core questions of quantum physics is how to reconcile the unitary evolution of quantum states, which is information-preserving and time-reversible, with evolution following the second law of thermodynamics, which, in general, is neither. The resolution to this paradox is to recognize that global unitary evolution of a multi-partite quantum state causes the state of local subsystems to evolve towards maximum-entropy states. In this work, we experimentally demonstrate this effect in linear quantum optics by simultaneously showing the convergence of local quantum states to a generalized Gibbs ensemble constituting a maximum-entropy state under precisely controlled conditions, while introducing an efficient certification method to demonstrate that the state retains global purity. Our quantum states are manipulated by a programmable integrated quantum photonic processor, which simulates arbitrary non-interacting Hamiltonians, demonstrating the universality of this phenomenon. Our results show the potential of photonic devices for quantum simulations involving non-Gaussian states.

Combining Melphalan Percutaneous Hepatic Perfusion with Ipilimumab Plus Nivolumab in Advanced Uveal Melanoma: First Safety and Efficacy Data from the Phase Ib Part of the Chopin Trial.

PURPOSE: To define a safe treatment dose of ipilimumab (IPI) and nivolumab (NIVO) when applied in combination with percutaneous hepatic perfusion with melphalan (M-PHP) in metastatic uveal melanoma (mUM) patients (NCT04283890), primary objective was defining a safe treatment dose of IPI/NIVO plus M-PHP. Toxicity was assessed according to Common Terminology Criteria for Adverse Events version 4.03 (CTCAEv4.03). Secondary objective was response rate, PFS and OS. MATERIALS AND METHODS: Patients between 18-75 years with confirmed measurable hepatic mUM according to RECIST 1.1 and WHO performance score 0-1 were included. Intravenous IPI was applied at 1 mg/kg while NIVO dose was increased from 1 mg/kg in cohort 1 to 3 mg/kg in cohort 2. Transarterial melphalan dose for M-PHP was 3 mg/kg (maximum of 220 mg) in both cohorts. Treatment duration was 12 weeks, consisting of four 3-weekly courses IPI/NIVO and two 6-weekly M-PHPs. RESULTS: Seven patients were included with a median age of 63.6 years (range 50-74). Both dose levels were well tolerated without dose-limiting toxicities or deaths. Grade III/IV adverse events (AE) were observed in 2/3 patients in cohort 1 and in 3/4 patients in cohort 2, including Systemic Inflammatory Response Syndrome (SIRS), febrile neutropenia and cholecystitis. Grade I/II immune-related AEs occurred in all patients, including myositis, hypothyroidism, hepatitis and dermatitis. There were no dose-limiting toxicities. The safe IPI/NIVO dose was defined as IPI 1 mg/kg and NIVO 3 mg/kg. There was 1 complete response, 5 partial responses and 1 stable disease (3 ongoing responses with a median FU of 29.1 months). CONCLUSION: Combining M-PHP with IPI/NIVO was safe in this small cohort of patients with mUM at a dose of IPI 1 mg/kg and NIVO 3 mg/kg.

FDA-approved drug screening in patient-derived organoids demonstrates potential of drug repurposing for rare cystic fibrosis genotypes.

BACKGROUND: Preclinical cell-based assays that recapitulate human disease play an important role in drug repurposing. We previously developed a functional forskolin induced swelling (FIS) assay using patient-derived intestinal organoids (PDIOs), allowing functional characterization of CFTR, the gene mutated in people with cystic fibrosis (pwCF). CFTR function-increasing pharmacotherapies have revolutionized treatment for approximately 85% of people with CF who carry the most prevalent F508del-CFTR mutation, but a large unmet need remains to identify new treatments for all pwCF. METHODS: We used 76 PDIOs not homozygous for F508del-CFTR to test the efficacy of 1400 FDA-approved drugs on improving CFTR function, as measured in FIS assays. The most promising hits were verified in a secondary FIS screen. Based on the results of this secondary screen, we further investigated CFTR elevating function of PDE4 inhibitors and currently existing CFTR modulators. RESULTS: In the primary screen, 30 hits were characterized that elevated CFTR function. In the secondary validation screen, 19 hits were confirmed and categorized in three main drug families: CFTR modulators, PDE4 inhibitors and tyrosine kinase inhibitors. We show that PDE4 inhibitors are potent CFTR function inducers in PDIOs where residual CFTR function is either present, or created by additional compound exposure. Additionally, upon CFTR modulator treatment we show rescue of CF genotypes that are currently not eligible for this therapy. CONCLUSION: This study exemplifies the feasibility of high-throughput compound screening using PDIOs. We show the potential of repurposing drugs for pwCF carrying non-F508del genotypes that are currently not eligible for therapies. ONE-SENTENCE SUMMARY: We screened 1400 FDA-approved drugs in CF patient-derived intestinal organoids using the previously established functional FIS assay, and show the potential of repurposing PDE4 inhibitors and CFTR modulators for rare CF genotypes.

Combining Hepatic Percutaneous Perfusion with Ipilimumab plus Nivolumab in advanced uveal melanoma (CHOPIN): study protocol for a phase Ib/randomized phase II trial.

BACKGROUND: While immune checkpoint inhibition (ICI) has revolutionized the treatment of metastatic cutaneous melanoma, no standard treatments are available for patients with metastatic uveal melanoma (UM). Several locoregional therapies are effective in the treatment of liver metastases, such as percutaneous hepatic perfusion with melphalan (M-PHP). The available literature suggests that treatment with ICI following locoregional treatment of liver UM metastases can result in clinical response. We hypothesize that combining M-PHP with ICI will lead to enhanced antigen presentation and increased immunomodulatory effect, improving control of both hepatic and extrahepatic disease. METHODS: Open-label, single-center, phase Ib/randomized phase II trial, evaluating the safety and efficacy of the combination of M-PHP with ipilimumab (anti-CTLA-4 antibody) and nivolumab (anti-PD-1 antibody) in patients with unresectable hepatic metastases of UM in first-line treatment, with or without the limited extrahepatic disease. The primary objective is to determine the safety, toxicity, and efficacy of the combination regimen, defined by maximum tolerated dose (MTD) and progression-free survival (PFS) at 1 year. Secondary objectives include overall survival (OS) and overall response rate (ORR). A maximum of 88 patients will be treated in phase I and phase II combined. Baseline characteristics will be described with descriptive statistics (t-test, chi-square test). To study the association between risk factors and toxicity, a logistic regression model will be applied. PFS and OS will be summarized using Kaplan-Meier curves. DISCUSSION: This is the first trial to evaluate this treatment combination by establishing the maximum tolerated dose and evaluating the efficacy of the combination treatment. M-PHP has shown to be a safe and effective treatment for UM patients with liver metastases and became the standard treatment option in our center. The combination of ICI with M-PHP is investigated in the currently described trial which might lead to a better treatment response both in and outside the liver. TRIAL REGISTRATION: This trial was registered in the US National Library of Medicine with identifier NCT04283890 . Registered as per February 2020 - Retrospectively registered. EudraCT registration number: 2018-004248-49. Local MREC registration number: NL60508.058.19.

Analytic theory of soft x-ray diffraction by Lamellar Multilayer Gratings.

An analytic theory describing soft x-ray diffraction by Lamellar Multilayer Gratings (LMG) has been developed. The theory is derived from a coupled waves approach for LMGs operating in the single-order regime, where an incident plane wave can only excite a single diffraction order. The results from calculations based on these very simple analytic expressions are demonstrated to be in excellent agreement with those obtained using the rigorous coupled-waves approach. The conditions for maximum reflectivity and diffraction efficiency are deduced and discussed. A brief investigation into p-polarized radiation diffraction is also performed.

Happy Hookers: findings from an international study exploring the effects of crochet on wellbeing.

AIMS: With rising rates of mental health disorders being reported globally, it is imperative that we investigate economical and accessible ways to increase relaxation and reduce stress. While there is a plethora of anecdotal evidence as to the positive effects of domestic crafts on mental wellbeing, there is little empirical research in this area. As such, we aimed to explore perceived links between crochet and wellbeing. METHODS: An online survey was developed and piloted, based on an existing tool that explored knitting and wellbeing. The final survey was promoted through social media, over a 6-week period, resulting in valid responses from 8391 individuals. RESULTS: Most respondents were female (99.1%), aged between 41 and 60 years (49.5%) and living in 87 different countries. Many respondents reported crocheting for between 1 and 5 years (42.6%). The three most frequent reasons reported for crocheting were: to be creative (82.1%), to relax (78.5%) and for a sense of accomplishment (75.2%). Respondents reported that crochet made them feel calmer (89.5%), happier (82%) and more useful (74.7%). There was a significant improvement in reported scores for mood before crocheting (M = 4.19, SD = 1.07) and mood after crocheting (M = 5.78, SD = 0.82); z = -69.86, p < .001, r = -0.56. Content analysis of free-text responses identified five major themes: (1) health benefits, (2) process of crochet, (3) personal connection, (4) crochet as contribution and (5) online crochet communities. CONCLUSION: The data suggests that crochet offers positive benefits for personal wellbeing with many respondents actively using crochet to manage mental health conditions and life events such as grief, chronic illness and pain. Crochet is a relatively low-cost, portable activity that can be easily learnt and seems to convey all of the positive benefits provided by knitting. This research suggests that crochet can play a role in promoting positive wellbeing in the general population, adding to the social prescribing evidence base.

Partial Right Atrial Inflow Occlusion for Transient Systemic Hypotension During Deployment of Thoracic Stentgrafts.

PURPOSE: Temporary balloon occlusion of the inferior vena cava to lower cardiac output is a relatively infrequently used technique to induce controlled systemic hypotension. In this technical note, we describe the feasibility, reliability, and safety of partial occlusion of right atrial inflow and the effect on systemic blood pressure during the deployment of a thoracic stentgraft. MATERIALS AND METHODS: Twenty consecutive patients undergoing thoracic endovascular aortic repair, with proximal landing in zone 0-3 of the thoracic aorta, were prospectively included. Right atrial inflow occlusion was performed with a compliant occlusion balloon. RESULTS: Median time to reach a mean arterial pressure of 50 mmHg was 43 s. Median recovery time of blood pressure was 42 s. CONCLUSION: Partial right atrial inflow occlusion with an occlusion balloon is feasible with reliable results and without procedure-related complications.

High-resolution, high-reflectivity operation of lamellar multilayer amplitude gratings: identification of the single-order regime.

High resolution while maintaining high peak reflectivities can be achieved for Lamellar Multilayer Amplitude Gratings (LMAG) in the soft-x-ray (SXR) region. Using the coupled waves approach (CWA), it is derived that for small lamellar widths only the zeroth diffraction order needs to be considered for LMAG performance calculations, referred to as the single-order regime. In this regime, LMAG performance can be calculated by assuming a conventional multilayer mirror with decreased density, which significantly simplifies the calculations. Novel analytic criteria for the design of LMAGs are derived from the CWA and it is shown, for the first time, that the resolution of an LMAG operating in the single-order regime is not limited by absorption as in conventional multilayer mirrors. It is also shown that the peak reflectivity of an LMAG can then still be as high as that of a conventional multilayer mirror (MM). The performance of LMAGs operating in the single-order regime are thus only limited by technological factors.

Dietary cheese whey protein protects rats against mild dextran sulfate sodium-induced colitis: role of mucin and microbiota.

Data from the literature suggest that the availability of the amino acids threonine, cysteine, or both, is limiting for mucin synthesis under conditions of chronic inflammatory bowel disease. Unlike casein, cheese whey protein is rich in these amino acids. The protective effect of cheese whey protein was examined using dextran sulfate sodium (DSS)-induced inflammation of the large intestine in rats that were fed a diet containing casein, cheese whey protein, or casein supplemented with threonine and cysteine. The clinical markers diarrhea and fecal blood were determined using biochemical assays, and gene expression of inflammation markers was used to quantify inflammation. The effect of dairy protein on mucin production was determined by gene expression of rat mucin 2 (MUC2) and by quantifying fecal mucin excretion. Fecal lactobacilli and bifidobacteria were determined using quantitative PCR. Dietary cheese whey protein reduced DSS-induced gene expression of the inflammation markers interleukin 1beta, calprotectin, and inducible nitric oxide synthase, and diminished the clinical symptoms diarrhea and fecal blood loss. Moreover, cheese whey protein increased fecal mucin secretion without affecting gene expression of MUC2, suggesting enhanced mucin synthesis. In addition, cheese whey protein increased fecal lactobacilli and bifidobacteria counts. Supplementation of threonine and cysteine showed comparable effects. In conclusion, cheese whey protein protected rats against DSS-induced gut inflammation. This can most likely be explained by its threonine and cysteine content. Protection can be the result of both the stimulation of intestinal mucin synthesis and modification of microflora composition.