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Chronic stress causes cognitive deficits, such as impairments in episodic-like hippocampus-dependent memory. Stress regulates an opioid-related neuropeptide named Nociceptin/Orphanin FQ (N/OFQ), the ligand of the G protein-coupled receptor NOP. Since this peptide has deleterious effects on memory, we hypothesized that the N/OFQ system could be a mediator of the negative effects of stress on memory. Chronic stress was mimicked by chronic exposure to corticosterone (CORT). The NOP receptor was either acutely blocked using selective antagonists, or knocked-down specifically in the hippocampus using genetic tools. Long-term memory was assessed in the object recognition (OR) and object location (OL) paradigms. Acute injection of NOP antagonists before learning had a negative impact on memory in naive mice whereas it restored memory performances in the chronic stress model. This rescue was associated with a normalization of neuronal cell activity in the CA3 part of the hippocampus. Chronic CORT induced an upregulation of the N/OFQ precursor in the hippocampus. Knock-down of the NOP receptor in the CA3/Dentate Gyrus region prevented memory deficits in the CORT model. These data demonstrate that blocking the N/OFQ system can be beneficial for long-term memory in a neuroendocrine model of chronic stress. We therefore suggest that NOP antagonists could be useful for the treatment of memory deficits in stress-related disorders.

For many decades, cancer treatment has been strongly directed toward the development of cytotoxic and cytostatic drugs, quite often leading to disappointing results due to the inter- and intra-tumoral heterogeneity. Lately, this intra-cellular look has given way to the understanding of the tumor microenvironment, thus enabling modification of the immunological dynamics between tumor cells and their host. An era of new drugs aiming to unlock the host immune system against tumor cells is steadily increasing. Strategies involving adoptive cell therapy, therapeutic vaccines, immune checkpoint inhibitors and so on have provided spectacular clinical responses and increased survival in previously refractory settings and “hard-to-treat” cancers. Based on a comprehensive search in the main scientific databases, annals of recent renowned oncology congresses and platforms of ongoing trials, the clinical pharmacology characteristics of the main classes of immunotherapeutic agents, as well as the new treatment strategies related to immunotherapy in solid tumors, are carefully discussed throughout this review.

The objective of this systematic review was to evaluate the association between a soy-based infant diet and the onset of puberty. We included studies in which children were fed a soy-based diet, and we compared them with those who were not. The primary outcomes were the onset of puberty in girls (thelarche, pubarche, and menarche age), boys (pubarche, voice change, testicular and penis enlargement age), and both (risk of delayed and precocious puberty [PP]). Search strategies were performed in PubMed, Embase, LILACS, and CENTRAL databases. Two reviewers selected eligible studies, assessed the risk of bias, and extracted data from the included studies. The odds ratio (OR) and mean difference (MD) were calculated with a 95% confidence interval (CI) as a measure of the association between soy consumption and outcomes. We used a random-effects model to pool results across studies and the Grading of Recommendations Assessment, Development, and Evaluation to evaluate the certainty of evidence. We included eight studies in which 598 children consumed a soy-based diet but 2957 did not. The primary outcomes that could be plotted in the meta-analysis were the risk of PP and age at menarche. There was no statistical difference between groups for PP (OR: 0.51, 95% CI: 0.09 to 2.94, 3 studies, 206 participants, low certainty of evidence). No between-group difference was observed in menarche age (MD 0.14 years, 95% CI -0.16 to 0.45, 3 studies, 605 children, low certainty of evidence). One study presented this outcome in terms of median and interquartile range, and although the onset of menarche was marginally increased in girls who received a soy-based diet, the reported age was within the normal age range for menarche. We did not find any association between a soy-based infant diet and the onset of puberty in boys or girls. Trial Registration : PROSPERO registration: CRD42018088902 .

Objectives To evaluate the spectrum and frequency of MR findings of the first metatarsophalangeal joint (MTPJ) in asymptomatic volunteers. Methods MR imaging of 30 asymptomatic forefeet was performed with a dedicated extremity 1.5-Tesla system. Participants were between 20 and 49 years of age (mean ± SD: 35.5 ± 8.4 years). Two radiologists assessed cartilage, bone, capsuloligamentous structures, and tendons of first MTPJs on MR images. Results Cartilage defects were observed in 27 % ( n  = 8) of first MTPJs, most frequently located at the base of the proximal phalanx (23 %, n  = 7), whereas cartilage defects of the metatarsal head (13 %, n  = 4) and the metatarsosesamoid compartment were rare (0 %–3 %, n  = 0-1). Bone marrow oedema-like signal changes were present in 37 % ( n  = 11) and subchondral cysts in 20 % ( n  = 6) of first MTPJs. Hyperintense areas on intermediate-weighted sequences (range: 30–43 %, n  = 9–13) and on fluid-sensitive sequences with fat suppression (range: 33–60 %, n  = 10–18) within the medial and lateral collateral ligament complex were common. Plantar recesses (77 %, n  = 23) and distal dorsal recesses (87 %, n  = 26) were frequently observed. Conclusions Cartilage defects, bone marrow oedema-like signal changes, subchondral cysts, plantar recesses, and distal dorsal recesses were common findings on MRI of first MTPJs in asymptomatic volunteers. The collateral ligaments were often heterogeneous in structure and showed increased signal intensity. Key Points • Cartilage defects of asymptomatic first metatarsophalangeal joints were common on MRI. • The collateral ligaments were often heterogeneous in structure and showed increased signal intensity. • Areas of increased signal intensity within the flexor and extensor tendons were rare. • These observations need to be considered in MR examinations of symptomatic cases.

This study evaluates integrated water-saving strategies in two school centres (SC1 and SC2) located in Bragança, Portugal, combining rainwater harvesting systems (RWHS), green roofs (GR), and the replacement of conventional taps with high-efficiency models. Water consumption patterns were analysed, and nine scenarios were simulated to assess their feasibility and economic performance. Scenario 1, which focuses on replacing conventional taps, achieved the highest short-term cost-effectiveness, reducing potable water consumption by approximately 30% and providing a payback period of about one year. Scenario 3, integrating RWHS into conventional roofs with efficient taps, demonstrated the greatest overall benefits, reducing potable water demand by up to 60% and generating annual savings exceeding €7000 + VAT, with payback periods of eight years for SC1 and seven years for SC2. In contrast, scenarios involving extensive GR significantly reduced stormwater runoff but required higher investments and presented longer payback periods, ranging from 17 to 42 years. Overall, the results indicate that combining low-cost efficiency measures with RWHS maximises potable water savings and supports sustainable water management, while GR implementation should be considered selectively, particularly when broader ecological and thermal benefits are prioritised.

This research is focused on the water usage patterns in two student residences—one for male students (Residence I) and the other for female students (Residence II). Surveys and measurements of flushing cisterns, taps, and shower flows were conducted to understand water use behaviors. Scenario 1 proposed replacing washbasin and kitchen taps and installing flow reducers in showers, while Scenario 2 combined Scenario 1 with a rainwater harvesting system for recharging flush cisterns. Showers were found to be the most water-consuming devices, accounting for 46% and 61.41% of water consumption in Residences I and II, respectively, followed by kitchen taps (31.51% in Residence I and 11.52% in Residence II). The flushing cistern consumption was 7.02% in Residence I and 13.22% in Residence II. The implementation of Scenario 1 anticipates a 13% reduction in total water consumption in Residence I and a 10% reduction in Residence II. The reduction in hot water consumption would result in a decrease in annual electricity consumption by 27.8% and 23.06% in Residence I and II, respectively. With the implementation of Scenario 2, the total potential water savings for Residence I could increase to 19.98%, and for Residence II, it could rise to 23.17%. The proposed measures aim to enhance water sustainability in these buildings and can be replicated elsewhere.

Reference flows are important variables for assessing water availability in Brazil, as well as in rural communities in the state of Goiás (Brazil). However, as there is a lack of flowrate data and measurement points, regionalization methods have been used for forecasting the minimum reference flow (Qref) allowed for maintaining water uses. The present research covered 92 hydrographic basins within 46 selected rural communities in the state of Goiás, and 21 basins were selected for carrying out on-site flow measurements, as well as for Qref estimation following three regionalization methodologies. Results show a large variation between the values measured and estimated by the three methodologies, but the statistical analysis found regression equations of one of the methods more suitable for application in rural hydrograph basins of Goiás.

The treatment of endometrial cancer (EC) is challenging. There is no standard of care for patients who progressed after carboplatin and paclitaxel (CT) and all available drugs show a small response and poor long-term survival in this scenario. The objective of this study was to evaluate the efficacy and toxicity profile of palliative doxorubicin after progression to CT therapy in advanced or recurrent EC. A retrospective review of the Brazilian National Cancer Institute database between 2009 and 2013 was performed, and all patients with recurrent and advanced EC treated with palliative doxorubicin after progression on CT were included. Progression-free survival (PFS), overall survival (OS), objective response rates as well as toxicity were evaluated. A total of 33 patients were enrolled, with a median age of 65.7 years. Objective responses were documented in 12.1% (3.0% of complete responses and 9.1% of partial responses). The median PFS was 4.4 months, and the median OS was 8.1 months for patients exposed to doxorubicin. The most common adverse event was anemia observed in 60.6% of patients. This retrospective study suggests that doxorubicin has a modest activity in patients with advanced or recurrent EC after treatment with CT.

This study aimed to determine the water demand of a municipal swimming pool complex to propose water use efficiency measures. Concomitantly, the possibility of recycling and reusing the water from filter backwashing was evaluated. The pools consumed 25.6% of water, the filter backwashing 24.5%, and the showers 34.7%. Despite the current impossibility of reducing water consumption in pools and filter backwashing, it is feasible to promote more efficient use of water through reducing water consumption by adopting simple water-saving initiatives for showers, taps, and flushing cisterns. These were organized into three distinct scenarios: (a) flushing cistern volume adjustment and the replacement of washbasin and kitchen taps; (b) flushing cistern volume adjustment and shower replacement and (c) flushing cistern volume adjustment, shower, washbasin, and kitchen taps replacement. Under scenarios 1, 2, and 3, the water consumption reduction was 8.0, 13.2, and 20.4%, respectively. The initial investment for scenario 1 was €2290.5, €859.0 for scenario 2 and €3149.5 for scenario 3; the annual water bill reduction was €7115.4, €11,518.1, and €17,655.9, respectively. Therefore, the turnover of the investment was four (scenario 1), one (scenario 2), and three months (scenario 3). The filter washings attained the required standard for irrigation after being subjected to 15 h of sedimentation.

This study aimed to determine the water demand of a Municipal Market building to propose water use efficiency measures. The flushing cisterns have the highest water consumption (63.15%), followed by washbasins, restaurant and coffee shop taps, and hairdresser’s showerhead (31.64%). Therefore, the implementation of two main categories of solutions: reducing water consumption through the adoption of efficient devices and installing a rainwater harvesting system (RWHS) when drinking water quality is not required, was evaluated. These solutions were organized in four distinct scenarios: (1) Flushing cistern replacement by dual-flush ones; (2) washbasins, restaurant, coffee shop taps, and hairdresser showerhead replacement; (3) scenario 1 combined to a RWHS for recharging the replaced flushing cisterns and (4) combining scenarios 3 and 4. Under scenarios 1, 2, 3, and 4, the expected water consumption reduction was 28.36%, 17.06%, 57.36%, and 74.41%, respectively. As a result, the annual water bill reduction was €3835.81 (scenario 1), €2307.07 (scenario 2), €7757.65 (scenario 3), and €10,064.73 (scenario 4). Furthermore, to ensure the harvested rainwater attains the required standard for recharge flushing cisterns, it is advisable to dispose of the first-flush rainwater collected after a long dry period.