Ovarian stimulation and endometriosis progression or recurrence: a systematic review

Available evidence on the impact of ovarian stimulation on the progression of endometriosis or its recurrence was systematically reviewed. Data from ovarian stimulation alone, or associated with intrauterine insemination (IUI) or IVF, were included. Sixteen studies were selected. Initial case reports (n = 11) documented some severe clinical complications. However, subsequent observational studies were more reassuring. Overall, five conclusions can be drawn: (i) IVF does not worsen endometriosis-related pain symptoms (moderate quality evidence); (ii) IVF does not increase the risk of endometriosis recurrence (moderate quality evidence); (iii) the impact of IVF on ovarian endometriomas, if present at all, is mild (low quality evidence); (iv) IUI may increase the risk of endometriosis recurrence (low quality evidence); (v) deep invasive endometriosis might progress with ovarian stimulation (very low quality evidence). In conclusion, available evidence is generally reassuring (at least for IVF) and does not justify aggressive clinical approaches such as prophylactic surgery before assisted reproductive technology treatment to prevent endometriosis progression or recurrence. However, further evidence is required before being able to reach definitive conclusions. In particular, the potential effects on deep invasive endometriosis and the possible synergistic effect of stimulation and pregnancy are two areas that need to be explored further

Time to redefine endometriosis including its pro-fibrotic nature

Endometriosis is currently defined as presence of endometrial epithelial and stromal cells at ectopic sites. This simple and straightforward definition has served us well since its original introduction. However, with advances in disease knowledge, endometrial stromal and glands have been shown to represent only a minor component of endometriotic lesions and they are often absent in some disease forms. In rectovaginal nodules, the glandular epithelium is often not surrounded by stroma and frequently no epithelium can be identified in the wall of ovarian endometriomas. On the other hand, a smooth muscle component and fibrosis represent consistent features of all disease forms. Based on these observations, we believe that the definition of endometriosis should be reconsidered and reworded as 'A fibrotic condition in which endometrial stroma and epithelium can be identified'. The main reasons for this change are: (1) to foster the evaluation of fibrosis in studies on endometriosis pathogenesis using animal models; (2) to limit potential false negative diagnoses if pathologists stick stringently to the current definition of endometriosis requiring the demonstration of endometrial stromal and glands; (3) to consider fibrosis as a potential target for treatment in endometriosis. This opinion article is aimed at boosting the attention paid to a largely neglected aspect of the disease. We hope that targeting the fibrotic process might increase success in developing new therapeutic approaches

Design of additively manufactured moulds for expanded polymers

The traditional tools used in steam-chest moulding technologies for the shaping of expanded polymers can be replaced today by lighter moulds, accurately designed and produced exploiting the additive manufacturing technology. New paradigms have to be considered for mould design, assuming that additive manufacturing enables the definition of different architectures that are able to improve the performance of the moulding process. This work describes the strategies adopted for the design and manufacturing by Laser powder bed fusion of the moulds, taking into specific consideration their functional surfaces, which rule the heat transfer to the moulded material, hence the quality of the products and the overall performance of the steamchest process. The description of a case study and the comparison between the performance of the traditional solution and the new moulds are also presented to demonstrate the effectiveness of the new approach. This study demonstrates that the redesign and optimization of the mould shape can lead to a significant reduction of the energy demand of the process, thanks to a homogeneous delivery of the heating steam throughout the part volume, which also results in a remarkable cutting of the cycle time

Eddy covariance methane measurements at a Ponderosa pine plantation in California

Long term methane flux measurements have been mostly performed with plant or soil enclosure techniques on specific components of an ecosystem. New fast response methane analyzers make it possible to use the eddy covariance (EC) technique instead. The EC technique is advantageous because it allows continuous flux measurements integrating over a larger and more representative area including the complete ecosystem, and allows fluxes to be observed as environmental conditions change naturally without disturbance. We deployed the closed-path Fast Methane analyzer (FMA) from Los Gatos Research Ltd and demonstrate its performance for EC measurements at a Ponderosa pine plantation at the Blodgett Forest site in central California. The fluctuations of the CH<sub>4</sub> concentration measured at 10 Hz appear to be small and their standard deviation is comparable to the magnitude of the signal noise (±5 ppbv). Consequently, the power spectra typically have a white noise signature at the high frequency end (a slope of +1). Nevertheless, in the frequency range important for turbulent exchange, the cospectra of CH<sub>4</sub> compare very well with all other scalar cospectra confirming the quality of the FMA measurements are good for the EC technique. We furthermore evaluate the complications of combined open and closed-path measurements when applying the Webb-Pearman-Leuning (WPL) corrections (Webb et al., 1980) and the consequences of a phase lag between the water vapor and methane signal inside the closed path system. The results of diurnal variations of CH<sub>4</sub> concentrations and fluxes are summarized and compared to the monthly results of process-based model calculations

Autologous Microfragmented Adipose Tissue Reduces the Catabolic and Fibrosis Response in an in Vitro Model of Tendon Cell Inflammation

Background. Mesenchymal stem cells (MSCs) emerged as a promising therapy for tendon pathologies. Microfragmented adipose tissue (\u3bcFAT) represents a convenient autologous product for the application of MSC-based therapies in the clinical setting. In the present study, the ability of \u3bcFAT to counteract inflammatory processes induced by IL-1\u3b2 on human tendon cells (TCs) was evaluated. Methods. Cell viability and proliferation were evaluated after 48 hours of transwell coculture of TCs and autologous \u3bcFAT in the presence or absence of IL-1\u3b2. Gene expression of scleraxis, collagen type I and type III, metalloproteinases-1 and -3, and cyclooxygenase-2 was evaluated by real-time RT-PCR. The content of VEGF, IL-1Ra, TNF\u3b1, and IL-6 was evaluated by ELISA. Results. IL-1\u3b2-treated TCs showed augmented collagen type III, metalloproteases, and cyclooxygenase-2 expression. \u3bcFAT was able to reduce the expression of collagen type III and metalloproteases-1 in a significant manner, and at the same time, it enhanced the production of VEGF, IL-1Ra, and IL-6. Conclusions. In this in vitro model of tendon cell inflammation, the paracrine action of \u3bcFAT, exerted by anti-inflammatory molecules and growth factors, was able to inhibit the expression of fibrosis and catabolic markers. Then, these results suggest that the application of \u3bcFAT may represent an effective conservative or adjuvant therapy for the treatment of tendon disorders

Disarming the guarded prognosis: predicting survival in newly referred patients with incurable cancer

People affected by cancer want information about their prognosis but clinicians have trouble estimating and talking about it. We sought to determine the nature and accuracy of medical oncologists' estimates of life expectancy in newly referred patients with incurable cancer. With reference to each patient, medical oncologists estimated how long they thought 90, 50, and 10% of similar patients would live. These proportions were chosen to reflect worst case, predicted, and best case scenarios suitable for discussions. After a median follow-up of 35 months, 86 of the 102 patients had died with an observed median survival of 12 months. Oncologists' estimates of each patient's worst case, predicted and best case scenarios were well-calibrated: 10% of patients lived for fewer months than estimated for the worst 10% of similar patients; 50% lived for at least as long as estimated for 50% of similar patients (predicted survival), and 17% lived for more months than estimated for the best 10% of similar patients. Oncologists' estimates of each patient's predicted survival were imprecise: 29% were within 0.67–1.33 times the patient's actual survival, 35% were too optimistic (>1.33 times the actual survival), and 39% were too pessimistic (<0.67 times the actual survival). The proportions of patients with actual survival times bounded by simple multiples of their predicted survival were as follows: 61% between half to double their predicted, 6% at least three to four times their predicted, and 4% no more than 1/6 of their predicted; similar to the proportions in an exponential distribution (about 50%, 10% and 10% respectively). Ranges based on simple multiples of the predicted survival time appropriately convey prognosis and its uncertainty in newly referred people with incurable cancer

CD73 expression and clinical significance in human metastatic melanoma.

CD73 is an ectoenzyme involved in the production of adenosine. It exerts immunosuppressive and protumoral roles and has emerged as a potential immuno-oncology target. CD73 expression was detected in TC in 54% of melanoma metastases, involving &lt; 50% TC in the majority of the cases, with variable intensity. CD73 expression was significantly associated with a lower Breslow's depth of the primary lesion and was more frequent in patients having received prior non-surgical therapies. In an adjusted analysis, CD73 expression in TC (H-score &gt; 37.5 or intensity &gt; 1) significantly correlated to decreased overall survival (OS) from biopsy. Of the samples containing TIMC, 35% presented CD73+ TIMC. Highly infiltrated tumors were more likely to contain CD73+ TIMC. CD73 expression in TIMC (percentage ≥1%) significantly correlated with improved OS from biopsy. Immunohistochemistry detected CD73 expression in more than half of metastatic melanomas. While CD73 expression in TC significantly correlated with decreased OS, CD73 expression in TIMC significantly associated with improved OS. These results encourage the study of anti-CD73 therapies for metastatic melanoma patients. CD73 expression was assessed by immunohistochemistry in metastatic melanomas from 114 patients. Immunostainings were evaluated in tumor cells (TC) (percentage, intensity (1-3) and H-score) and in tumor-infiltrating mononuclear cells (TIMC) (percentage)

The X-ray outburst of the Galactic Center magnetar over six years of Chandra observations

The magnetar SGR J1745-2900 discovered at parsecs distance from the Milky Way central black hole, Sagittarius A*, represents the closest pulsar to a supermassive black hole ever detected. Furthermore, its intriguing radio emission has been used to study the environment of the black hole, as well as to derive a precise position and proper motion for this object. The discovery of SGR J1745-2900 has opened interesting debates about the number, age and nature of pulsars expected in the Galactic center region. In this work, we present extensive X-ray monitoring of the outburst of SGR J1745-2900 using the Chandra X-ray Observatory, the only instrument with the spatial resolution to distinguish the magnetar from the supermassive black hole (2.4" angular distance). It was monitored from its outburst onset in April 2013 until August 2019, collecting more than fifty Chandra observations for a total of more than 2.3 Ms of data. Soon after the outburst onset, the magnetar emission settled onto a purely thermal emission state that cooled from a temperature of about 0.9 to 0.6 keV over 6 years. The pulsar timing properties showed at least two changes in the period derivative, increasing by a factor of about 4 during the outburst decay. We find that the long-term properties of this outburst challenge current models for the magnetar outbursts.Comment: 11 pages, 6 figures. Accepted by Ap

Repeated implantation failure at the crossroad between statistics, clinics and over-diagnosis

The most common definition of repeated implantation failure (RIF) is the failure to obtain a clinical pregnancy after three completed IVF cycles. This definition, however, may lead to misuse of the diagnosis. To disentangle this, we set up a mathematical model based on the following main assumptions: rate of success of IVF constant and set at 30%; and RIF postulated to be a dichotomous condition (yes or no) with a prevalence of 10%. On this basis, the expected cumulative chance of pregnancy after three and six cycles was 59% and 79%, respectively. Consequently, the false\u2013positive rate of a diagnosis of RIF is 75% and 51%, respectively. Increasing the rate of success of IVF or the prevalence of RIF lowers but does not make unremarkable the rate of false\u2013 positive diagnoses. Overall, this model shows that the commonly used definition of RIF based on three failed attempts in a standard population with good prognosis leads to over-diagnosis and, potentially, to over-treatments