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Stimulation of the angiotensin II type 2 receptor (AT 2 R) evokes protective effects in various cardiovascular diseases. Thus, this study aimed to investigate the effects of AT 2 R stimulation, with or without AT 1 R blockade, in a model of hypertension with concomitant type 1 diabetes mellitus (T1DM). Spontaneously hypertensive rats (SHRs) were given either citrate or a single dose of streptozotocin (STZ; 55 mg/kg, i.p.) to induce diabetes. After 4 weeks of diabetes, animals were administered either a vehicle (saline), AT 2 R agonist, β-Pro 7 Ang III (0.1 mg/kg/day via osmotic mini-pump), AT 1 R blocker, candesartan (2 mg/kg/day via drinking water), or a combination of both for a further 8 weeks. β-Pro 7 Ang III treatment had no effect on blood pressure, but attenuated the significant increase in cardiac interstitial collagen and protein expression of fibrotic and inflammatory markers, and superoxide levels that was evident in diabetic SHRs. These effects were not observed with candesartan, despite its blood pressure lowering effects. Although β-Pro 7 Ang III had no effect on aortic fibrosis, it significantly attenuated MCP-1 protein expression and superoxide levels when compared to both the non-diabetic and diabetic SHRs, to a similar extent as candesartan. In both the heart and vasculature, the effects of β-Pro 7 Ang III in combination with candesartan were similar to those of β-Pro 7 Ang III alone, and superior to candesartan alone. It was concluded that in hypertension with concomitant diabetes, AT 2 R stimulation with a novel ligand alone, or in combination with AT 1 R blockade, improved the cardiac and vascular structural changes that were strongly associated with inflammation and oxidative stress, independent of blood pressure regulation., Competing Interests: Declaration of Competing Interest Please declare any financial or personal interests that might be potentially viewed to influence the work presented. Interests could include consultancies, honoraria, patent ownership or other. If there are none state ‘there are none’., (Copyright © 2023. Published by Elsevier Masson SAS.)

Background and Purpose: This study investigated the reno-protective effects of a highly selective AT 2 R agonist peptide, β-Pro 7 Ang III in a mouse model of acute kidney injury (AKI)., Methods: C57BL/6 J mice underwent either sham surgery or unilateral kidney ischemia-reperfusion injury (IRI) for 40 min. IRI mice were treated with either β-Pro 7 Ang III or perindopril and at 7 days post-surgery the kidneys analysed for histopathology and the development of fibrosis and matrix metalloproteinase (MMP)-2 and -9 activity. The association of the therapeutic effects of β-Pro 7 Ang III with macrophage number and phenotype was determined in vivo and in vitro., Key Results: Decreased kidney tubular injury, interstitial matrix expansion and reduced interstitial immune cell infiltration in IRI mice receiving β-Pro 7 Ang III treatment was observed at day 7, compared to IRI mice without treatment. This correlated to reduced collagen accumulation and MMP-2 activity in IRI mice following β-Pro 7 Ang III treatment. FACS analysis showed a reduced number and proportion of CD45 + CD11b + F4/80 + macrophages in IRI kidneys in response to β-Pro 7 Ang III, correlating with a significant increase in M2 macrophage markers and decreased M1 markers at day 3 and 7 post-IR injury, respectively. In vitro analysis of cultured THP-1 cells showed that β-Pro 7 Ang III attenuated lipopolysaccharide (LPS)-induced tumour necrosis factor-α (TNF-α) and interleukin (IL)- 6 production but increased IL-10 secretion, compared to LPS alone., Conclusion: Administration of β-Pro 7 Ang III via mini-pump improved kidney structure and reduced interstitial collagen accumulation, in parallel with an alteration of macrophage phenotype and anti-inflammatory cytokine release, therefore mitigating the downstream progression of ischemic AKI., Competing Interests: Conflict of interest statement The authors declare that there are no conflicts of interests., (Copyright © 2023. Published by Elsevier Masson SAS.)

Adhesion formation following gynecological surgery remains a challenge. The adoption of minimally invasive surgical approaches, such as conventional or robotic-assisted laparoscopy combined with meticulous microsurgical principles and the application of adhesion-reducing substances, is able to reduce the risk of de novo adhesion formation but do not eliminate it entirely. Myomectomy is the most adhesiogenic surgical procedure and postoperative adhesions can have a significant impact on the ability to conceive. Therefore, when surgery is performed as infertility treatment, attention should be paid to whether the benefits outweigh the risks. Among several factors, the size and the location of fibroids are the most accountable factors in terms of adhesion development and post surgical infertility; therefore, the search for effective strategies against adhesion formation in this setting is of paramount importance. The purpose of this review is to evaluate the incidence and factors of adhesion formation and the best preventive measures current available., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Mercorio, Della Corte, Boccia, Palumbo, Reppuccia, Buonfantino, Cuomo, Borgo, Zitiello, De Angelis, Laganà, Bifulco and Giampaolino.)

A high salt (HS) diet is associated with an increased risk for cardiovascular diseases (CVDs) and fibrosis is a key contributor to the organ dysfunction involved in CVDs. The activation of the renin angiotensin type 2 receptor (AT 2 R) has been considered as organ protective in many CVDs. However, there are limited AT 2 R-selective agonists available. Our first reported β-substituted angiotensin III peptide, β-Pro 7 -AngIII, showed high selectivity for the AT 2 R. In the current study, we examine the potential anti-fibrotic and anti-inflammatory effects of this novel AT 2 R-selective peptide on HS-induced organ damage. FVB/N mice fed with a 5% HS diet for 8 weeks developed cardiac and renal fibrosis and inflammation, which were associated with increased TGF-β1 levels in heart, kidney and plasma. Four weeks' treatment (from weeks 5-8) with β-Pro 7 -AngIII inhibited the HS-induced cardiac and renal fibrosis and inflammation. These protective effects were accompanied by reduced local and systemic TGF-β1 as well as reduced cardiac myofibroblast differentiation. Importantly, the anti-fibrotic and anti-inflammatory effects caused by β-Pro 7 -AngIII were attenuated by the AT 2 R antagonist PD123319. These results demonstrate, for the first time, the cardio- and reno-protective roles of the AT 2 R-selective β-Pro 7 -AngIII, highlighting it as an important therapeutic that can target the AT 2 R to treat end-organ damage.

Borderline ovarian tumors (BOTs) account for approximately 15% of all epithelial ovarian cancers. In 80% of cases the diagnosis of BOTs is done at stage I and more than a third of BOTs occurs in women younger than 40 years of age wishing to preserve their childbearing potential; the issue of conservative surgical management (fertility-sparing treatment) is thus becoming of paramount importance. At early stages, the modalities of conservative treatment could range from mono-lateral cystectomy to bilateral salpingo-oophorectomy. Although cystectomy is the preferred method to promote fertility it can lead to an elevated risk of recurrence; therefore, an appropriate counseling about the risk of relapse is mandatory before opting for this treatment. Nevertheless, relapses are often benign and can be treated by repeated conservative surgery. Besides the stage of the disease, histological subtype is another essential factor when considering the proper procedure: as most mucinous BOTs (mBOTs) are more commonly unilateral, the risk of an invasive recurrence seems to be higher, compared to serous histotype, therefore unilateral salpingo-oophorectomy is recommended. In the appraisal of current literature, this review aims to gain better insight on the current recommendations to identify the right balance between an accurate staging and an optimal fertility outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Della Corte, Mercorio, Serafino, Viciglione, Palumbo, De Angelis, Borgo, Buonfantino, Tesorone, Bifulco and Giampaolino.)

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disease. The hypothesis that alterations in the microbiome are involved in the genesis of PCOS has been postulated. Aim of this review is to summarize the available literature data about the relationship between microbiome and PCOS. A search on PubMed and Medline databases was performed from inception to November 20Most of evidence has focused on the connection of intestinal bacteria with sex hormones and insulin-resistance: while in the first case, a relationship with hyperandrogenism has been described, although it is still unclear, in the second one, chronic low-grade inflammation by activating the immune system, with increased production of proinflammatory cytokines which interfere with insulin receptor function, causing IR (Insulin Resistance)/hyperinsulinemia has been described, as well as the role of gastrointestinal hormones like Ghrelin and peptide YY (PYY), bile acids, interleukin-22 and Bacteroides vulgatus have been highlighted. The lower genital tract microbiome would be affected by changes in PCOS patients too. The therapeutic opportunities include probiotic, prebiotics and synbiotics, as well as fecal microbiota transplantation and the use of IL-22, to date only in animal models, as a possible future drug. Current evidence has shown the involvement of the gut microbiome in PCOS, seen how humanized mice receiving a fecal transplant from women with PCOS develop ovarian dysfunction, immune changes and insulin resistance and how it is capable of disrupting the secondary bile acid biosynthesis. A future therapeutic approach for PCOS may involve the human administration of IL-22 and bile acid glycodeoxycholic acid.

Aim: Invasive cervical cancer is proceeded by a phase of preinvasive disease that is slow to progress and can be detected, treated, and collectively referred to as cervical intraepithelial neoplasia (CIN). Several excisional and ablative treatments for CIN have been studied, with loop electrosurgical excision procedure (LEEP) and cryotherapy being the two most commonly utilized. The objective of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to compare the compare harms and benefits of LEEP versus cryotherapy in women with CIN., Methods: Electronic databases were searched from their inception until May 2018. We included all RCTs comparing cryotherapy versus LEEP in women with CIN. We included trials evaluating both HIV-seropositive and HIV-seronegative women. The primary outcome was the persistence of the disease at 6-month follow-up. Meta-analysis was performed using the random-effects model to produce summary treatment effects in terms of relative risk (RR) with 95% confidence interval (CI)., Results: Four trials, including 1035 women with CIN, were identified as relevant and included in the meta-analysis. Women who received LEEP for CIN had a significantly lower persistence at 6-month follow-up biopsy (RR: 0.87, 95% CI: 0.76-0.99) and significantly lower recurrence at 12-month follow-up biopsy (RR: 0.91, 95% CI: 0.84-0.99) compared to those who received cryotherapy. No between-group differences were found in the complications rate, but the analyses were not powered for these outcomes., Conclusions: In women with CIN, treatment with LEEP was associated with a significantly lower risk of persistence disease at 6 months and recurrence disease at 12 months compared to treatment with cryotherapy., Competing Interests: There are no conflicts of interest.

There are a number of therapeutic targets to treat organ fibrosis that are under investigation in preclinical models. There is increasing evidence that stimulation of the angiotensin II type 2 receptor (AT 2 R) is a novel anti-fibrotic strategy and we have reviewed the published in vivo preclinical data relating to the effects of compound 21 (C21), which is the only nonpeptide AT 2 R agonist that is currently available for use in chronic preclinical studies. In particular, the differential influence of AT 2 R on extracellular matrix status in various preclinical fibrotic models is discussed. Collectively, these studies demonstrate that pharmacological AT 2 R stimulation using C21 decreases organ fibrosis, which has been most studied in the setting of cardiovascular and renal disease. In addition, AT 2 R-mediated anti-inflammatory effects may contribute to the beneficial AT 2 R-mediated anti-fibrotic effects seen in preclinical models.

Background: Health has improved markedly in Mesoamerica, the region consisting of southern Mexico and Central America, over the past decade. Despite this progress, there remain substantial inequalities in health outcomes, access, and quality of medical care between and within countries. Poor, indigenous, and rural populations have considerably worse health indicators than national or regional averages. In an effort to address these health inequalities, the Salud Mesoamérica 2015 Initiative (SM2015), a results-based financing initiative, was established., Methods: For each of the eight participating countries, health targets were set to measure the progress of improvements in maternal and child health produced by the Initiative. To establish a baseline, we conducted censuses of 90,000 households, completed 20,225 household interviews, and surveyed 479 health facilities in the poorest areas of Mesoamerica. Pairing health facility and household surveys allows us to link barriers to care and health outcomes with health system infrastructure components and quality of health services., Results: Indicators varied significantly within and between countries. Anemia was most prevalent in Panama and least prevalent in Honduras. Anemia varied by age, with the highest levels observed among children aged 0 to 11 months in all settings. Belize had the highest proportion of institutional deliveries (99%), while Guatemala had the lowest (24%). The proportion of women with four antenatal care visits with a skilled attendant was highest in El Salvador (90%) and the lowest in Guatemala (20%). Availability of contraceptives also varied. The availability of condoms ranged from 83% in Nicaragua to 97% in Honduras. Oral contraceptive pills and injectable contraceptives were available in just 75% of facilities in Panama. IUDs were observed in only 21.5% of facilities surveyed in El Salvador., Conclusions: These data provide a baseline of much-needed information for evidence-based action on health throughout Mesoamerica. Our baseline estimates reflect large disparities in health indicators within and between countries and will facilitate the evaluation of interventions and investments deployed in the region over the next three to five years. SM2015's innovative monitoring and evaluation framework will allow health officials with limited resources to identify and target areas of greatest need.

Tamoxifen has been associated with a reduction in the incidence of myocardial infarction. However, the effects of tamoxifen on coronary reactivity have not been fully elucidated. The objective of this study was to determine the effects of chronic treatment with tamoxifen on coronary vascular reactivity in spontaneously hypertensive rats (SHR). Female SHR were divided into four groups (N = 7 each): sham-operated (SHAM), sham-operated and treated with tamoxifen (10 mg/kg) by gavage for 90 days (TAMOX), ovariectomized (OVX), and ovariectomized and treated with tamoxifen (OVX+TAMOX). Mean arterial pressure (MAP), heart rate (HR), coronary perfusion pressure (CPP), and coronary vascular reactivity were measured. MAP and HR were reduced (9.42 and 11.67%, respectively) in the OVX+TAMOX group compared to the OVX group (P < 0.01). The coronary vascular reactivity of the OVX+TAMOX group presented smaller vasoconstrictor responses to acetylcholine (2-64 µg) when compared to the OVX group (P < 0.01) and this response was similar to that of the SHAM group. The adenosine-induced vasodilator response was greater in the TAMOX group compared to the SHAM and OVX groups (P < 0.05). Baseline CPP was higher in OVX+TAMOX and TAMOX groups (136 ± 3.6 and 130 ± 1.5 mmHg) than in OVX and SHAM groups (96 ± 2 and 119 ± 2.3 mmHg; P < 0.01). Tamoxifen, when combined with OVX, attenuated the vasoconstriction induced by acetylcholine and increased the adenosine-induced vasodilatory response, as well as reducing the MAP, suggesting beneficial effects of tamoxifen therapy on coronary vascular reactivity after menopause.

Ochratoxin A (OTA) in wine is linked to contamination by several Aspergillus species. In 2003-2007, grape samples collected in Italy were surveyed for the presence of OTA and OTA-producing fungi. A. niger aggregate was the prevalent species. A. carbonarius, which is considered the main source of OTA in grapes, was mostly found in Southern Italy. The year and the environment had an important influence on the development of the black Aspergillus populations. Testing with ELISA showed OTA to be present in about 30% of the samples. Samples from Southern Italy showed the highest occurrence (45%) and also the highest OTA concentration, sometimes higher than 2 μg/L. The values decreased progressively the further North the samples were taken.

Field tests are useful for the evaluation of the pesticides' impact in realistic use situations. However, the distinction between the direct and indirect effects of a pesticide is not always possible in field, with consequences on the conclusions about pesticides toxicity. Generalist predatory mites belonging to the Phytoseiidae family are widely considered as non-target organisms in pesticide side-effect evaluations. Plant pathogens of several cultivated plants can be of importance as food resources for various phytoseiids. Pesticides with fungicidal activity may have a direct impact on phytoseiids, but they can also have an indirect effect reducing food availability for predatory mites. Here, we present the results of field experiments performed on grapevine, where we investigate whether the availability of the plant pathogen grape downy mildew has an effect on fungicides impact on the predatory mites Typhlodromus pyri Scheuten and Amblyseius andersoni (Chant). In these experiments we used fungicides characterized by differential selectivity to predatory mites in laboratory: copper compounds, folpet, and mancozeb. Results indicated that the abundance of predatory mites was associated with the plant pathogen foliar symptoms presence. The presence of predatory mites was different among treatments in response of the toxicological traits of a pesticide (direct effects), but also as consequences of differential plant pathogen availability induced by fungicide applications (indirect effects). During the investigation, the variable plant pathogen spread on untreated control determined contrasting results on pesticides effect. We segregated the direct effects from the indirect food resource-mediated effects including a non-toxic reference in the experimental protocols., (Copyright 2010 Elsevier Ltd. All rights reserved.)

The study was carried out in a 3,000 m2 area of coastal Atlantic rain forest at Ilha do Mel island (25 degrees 30"S 48 degrees 23'W), on 100 assorted trees separated into 2 meter-high strata starting from the ground. In each stratum all of the occurring epiphytic species were recorded. The sampled species were grouped into three categories: exclusive, preferential, and indifferent, according to their abundance in each strata, and selective, preferential and indifferent, according to abundance on the forophytes. Intermediate strata registered the highest diversity. Six species were considered exclusive to one or two strata, 15 were restricted to some strata and 5 presented a broad distribution. No epiphytic species showed uniform horizontal distribution on the area. The epiphyte richness in a host tree varied from zero to 30. Regarding to fidelity on host tree species, few selective or preferential, and mainly indifferent epiphyte species, were found. A total of 82 epiphyte species were sampled in the surveyed tree, and the Wittaker plot indicate a highly dominant assemblage.