Assessment of quality of life, psychological aspects, and sexual function of women with endometriosis according to pain and infertility: a cross sectional study.

PURPOSE: To evaluate the quality of life, sexual function, anxiety, and depression of women with endometriosis according to pain symptoms and infertility. METHODS: This cross-sectional multicenter study included 229 women with endometriosis followed up at a tertiary hospital in Campinas, a tertiary hospital in São Paulo, and a reproductive medicine clinic in Campinas from 2018 to 2021. The women were divided into four groups according to the presence of pain symptoms and infertility. The Endometriosis Health Profile Questionnaire, Female Sexual Function Index, Beck Depression Inventory, and Beck Anxiety Index were applied to assess quality of life, sexual function, depression, and anxiety of women with endometriosis. RESULTS: The women were grouped as follows: group 1 (45 women without infertility and without pain), group 2 (73 women without infertility and with pain), group 3 (49 women with infertility and without pain), and group 4 (62 women with infertility and pain). Of the women with infertility, the majority had primary infertility. Most women had deep endometriosis (p = 0.608). Women with pain had higher anxiety and depression scores and worse quality of life than women without pain (p < 0.001). Regarding sexual function, all the groups were at risk for sexual dysfunction (p = 0.671). The group of women with pain and infertility have worse anxiety scores (25.31 ± 15.96) and depression (18.81 ± 11.16) than the other groups. CONCLUSION: Pain symptoms worsen anxiety, depression, and quality of life of women with endometriosis and when associated with infertility, greater impairment of psychological aspects may occur.

Pulmonary arteriovenous malformations in Rendu-Osler-Weber syndrome.

Rendu-Osler-Weber syndrome, also known as hereditary hemorrhagic telangiectasia, is an autosomal dominant hereditary disorder. It is characterized by presence of multiple arteriovenous malformations (AVMs) and telangiectasias. This article reports two cases of patients with Rendu-Osler-Weber syndrome who had pulmonary AVMs and underwent successful endovascular treatment. A brief review of the literature shows that up to 50% of patients with the syndrome have pulmonary AVMs and there is usually a positive family history in these patients. These pulmonary AVMs are multiple in 30% of cases and are associated with the most severe disease complications. Most patients are asymptomatic, even in the presence of AVMs with right-left shunts. When these shunts exceed 25% of the total blood volume, dyspnea, cyanosis, digital clubbing, and extracardiac murmurs may occur. Endovascular treatment is safe and offers control of complications from hereditary hemorrhagic telangiectasia and is currently the treatment of choice for these lesions.

Reconsidering the olfactory and brain structures in Kallmann's syndrome: New findings in the analysis of volumetry.

OBJECTIVE: Kallmann's syndrome (KS) is characterized by hypogonadotropic hypogonadism and olfactory disorders. The complementary exams for evaluating of patients with hypogonadotrophic hypogonadism are important for the diagnosis and management of these patients. PATIENTS: We performed a well-established olfactory Sniffin' Stick test (SST) on 17 adult patients with KS and brain magnetic resonance imaging (MRI) to evaluate olfactory structures and further analysis by Freesurfer, a software for segmentation and volumetric evaluation of brain structures. We compared the Freesurfer results with 34 healthy patients matched for age and sex and performed correlations between the data studied. RESULTS: More than half of the patients with KS reported preserved smell but had olfactory disorders in the SST. In the MRI, 16 patients showed changes in the olfactory groove, the olfactory bulb-tract complex was altered in all of them and 52% had symmetrical structural changes. Interestingly, the pituitary gland was normal in only 29%. Regarding correlations, symmetrical changes in the olfactory structures were related to anosmia in 100%, while asymmetric changes induced anosmia in only 50% (p = .0294). In Freesurfer's assessment, patients with KS, compared to controls, had lower brainstem volume. In those with aplastic anterior olfactory sulcus, the brainstem volume was lower than in hypoplasia (p = .0333). CONCLUSIONS: Olfactory assessment and MRI proved to be important auxiliary tools for the diagnosis and management of patients with KS. New studies are needed to confirm the decrease in brainstem volume found by the Freesurfer software in patients with KS. Further studies are needed to confirm the decrease in brainstem volume found by the Freesurfer software in patients with KS.

Assessment of quality of life and psychological repercussions in women with endometriosis according to pain intensity.

The objective is to evaluate quality of life, anxiety, and depression in women with endometriosis, and to correlate these parameters with pain intensity. This multicenter cross-sectional study was conducted on 102 women with endometriosis from 2017 to 2020. The women were divided into two groups according to the pain intensity: group 1 (severe pain, 62 women) and group 2 (mild/moderate pain, 40 women). The Endometriosis Health Profile Questionnaire, Beck Anxiety Inventory, and Beck Depression Inventory were used to assess quality of life and levels of anxiety and depression, respectively. In both groups, mean age and mean body mass index were similar (p˃ 0.5). Most women had deep endometriosis and were on treatment, but group 2 had a longer treatment time (p = 0.044). Group 1 exhibited more depression and anxiety than group 2 (17.1 ± 9.98 vs. 11.15 ± 9.25, p = 0.003 and 23.71 ± 12.92 vs 12.58 ± 10.53, p = 0.001, respectively). Women with high pain had a significantly worse quality of life than those with low pain (48.88 ± 16.02 vs. 23.32 ± 15.93, p < 0.001). Women with endometriosis and high pain intensity have a worse quality of life, and more severe levels of anxiety and depression.

Superficial femoral vein transposition as a solution for hemodialysis vascular access.

The significant growth in the number of individuals dependent on hemodialysis for renal replacement therapy and unrestricted use of short and long-term catheters have challenged vascular surgeons in search of solutions for patients whose options for access via the upper limbs have been exhausted and for the increasing rates of central venous stenosis in these patients. When access via the upper limbs is impossible, exceptional techniques can be used and the lower limbs offer feasible alternative vascular access sites for hemodialysis. This article reports a case of superficial femoral vein transposition to make a loop arteriovenous fistula in a patient with no possibility of access via the upper limbs and presents a literature review on this technique that remains little used.

Body composition in women with premature ovarian insufficiency using hormone therapy and the relation to cardiovascular risk markers: A case-control study.

OBJECTIVE: To compare body composition between women with premature ovarian insufficiency (POI) using hormone therapy and controls with normal ovarian function, and to correlate body composition with cardiovascular risk markers in the POI group. PATIENTS AND DESIGN: A case-control study of 70 women with POI matched by age and body mass index with 70 controls. MEASUREMENTS: All were submitted to whole-body dual-energy X-ray absorptiometry (DXA) to analyse body composition. In the POI group, total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, triglycerides, glucose, insulin, transaminases and C-reactive protein levels were measured, as well as the thickness of the carotid artery intima-media complex. RESULTS: Total mass, fat mass, lean mass (total, percentage and index) and the android/gynoid (A/G) ratio were similar in both groups; however, bone mineral content was lower (P < .001) in the POI group. Lean and fat mass indexes were 14.19 ± 1.63 and 11.04 ± 3.58, respectively, and the percentage of gynoid to android fat was higher (51.17 ± 6.71% versus 47.74 ± 9.19%; A/G ratio = 0.93 ± 0.15) in the POI group. In addition, the increase in total mass correlated positively with glucose and ALT levels and negatively with HDL-cholesterol. Increased A/G ratio was the measurement most frequently associated with cardiovascular risk markers. CONCLUSION: The body composition of women with POI using hormone therapy is similar to that of women with normal ovarian function with regard to lean and fat mass content and fat distribution. In women with POI, the higher the A/G ratio, the worse the cardiovascular risk markers.

Asymptomatic postmenopausal women: what are the risk factors for endometrial malignancies? A multicentric retrospective study.

OBJECTIVE: To evaluate the prevalence and risk factors for endometrial malignancies in asymptomatic postmenopausal women. METHODS: Multicentric retrospective analytical study in two Brazilian Reference Centers. All women without postmenopausal bleeding who were submitted to hysteroscopy with biopsy were included (1665). Excluded women without anatomopathological results (625) and whose medical records were incomplete (37). The variables analyzed were age; parity; body mass index; duration of menopausal status; systemic arterial hypertension; diabetes mellitus; use of hormone replacement therapy; use of tamoxifen; duration of use of tamoxifen; endometrial thickness and biopsy results. RESULTS: The frequency of endometrial malignancies in asymptomatic postmenopausal women was 2.39%. Endometrial thickness ≥8 mm increased the chance of endometrial malignancies, even more, with an endometrial thickness ≥12.55 mm the chance of endometrial malignancies increased by 4.68 times (p < .001 and 95% CI: 1.99-11.03). CONCLUSION: The prevalence of endometrial malignancies was low and the only risk factor for endometrial malignancies in asymptomatic postmenopausal women was endometrial thickness.

Pelvic floor muscle dysfunctions in women with deep infiltrative endometriosis: An underestimated association.

AIMS: Deep infiltrative endometriosis (DIE) may cause pelvic pain and thus negatively affect the function of different structures. We hypothesised that women with DIE may have dysfunctions of the pelvic floor muscles (PFMs) and lower limb muscles (LLMs). METHODS: This cross-sectional study included 160 women (80 with DIE under hormonal treatment and 80 women without DIE), who were assessed to determine the presence of pelvic symptoms (dysmenorrhea, chronic pelvic pain [CPP], deep/penetration dyspareunia, dysuria, dyschezia and vulvodynia), PFM function (PERFECT scheme, presence of hypertonia and trigger points, and muscle contraction and relaxation), abdominal muscle pain (Carnett's test) and muscle shortening in LLM (Thomas, Pace and Ober tests). RESULTS: Women with DIE presented more CPP (30% vs 5%; P < .001), dysuria (12.5% vs 3.75%; P = .043) and dyschezia (47.5% vs 2.5%; P < .001) than the control group. Moreover, they had higher PFM hypertonia (28.75% vs 13.75%; P = .02), weaker PFM contraction (36.35% vs 2.5%; P < .001), and incomplete PFM relaxation (45% vs 13.75%; P < .001). Women with DIE had a higher rate of positive results in the Carnett's test (21.25% vs 2.5%; P < .001) than the control group. Moreover, they had a higher frequency of shortening of the anterior thigh (30% vs 10% in both LLM; P < .001), piriformis (16.25% vs 6.25%; P < .001) and iliotibial band muscles (bilateral; P < .001). Multivariate analysis revealed that the presence of pain increased the risk of PFM hypertonia (OR = 3.73 [1.26-11.07]; P = .018) and caused difficulty in PFM relaxation (OR = 2.98 [1.01-9.37]; P = .049). CONCLUSION: Women with DIE exhibited a greater number of pelvic symptoms and greater PFM/LLM dysfunction than those in the control group. Pain was associated with PFM hypertonia and difficulty in PFM relaxation.

Is Diagnostic Hysteroscopy Safe for the Investigation of Type II Endometrial Cancer? A Retrospective Cohort Analysis.

STUDY OBJECTIVE: Although hysteroscopy (HSC) can be used for assessing the uterine cavity in women with suspected endometrial cancer (EC), it remains controversial as a procedure because it can potentially enhance the metastatic spread of cancer cells. Moreover, it is important to assess this hypothesis for type II EC, a more aggressive phenotype that usually presents with endometrial atrophy and has worse prognosis. Thus, we aimed to assess the prevalence of positive peritoneal cytology result in women with type II EC who underwent HSC as a diagnostic tool and to determine the factors associated with patient relapse/survival. DESIGN: Retrospective cohort analysis (2002-2017). SETTING: Tertiary, academic hospital. PATIENTS: One hundred twenty-seven women with type II EC. INTERVENTIONS: Diagnostic HSC (HSC) (n = 43) or dilation/curettage (D&C) (n = 84). MEASUREMENTS AND MAIN RESULTS: Primary end point was the frequency of positive peritoneal cytology result. Survival curves were projected using the Kaplan-Meier method and compared using the log-rank test. Cox regression analysis with hazard ratio (HR) and 95% confidence intervals (CIs) were calculated to assess the factors related with the disease-free survival (DFS) and the disease-specific survival (DSS). Advanced cancer stage and greater vascular invasion appeared more frequently in the D&C group (p = .008 and p = .04, respectively). Positive peritoneal cytology result was present in 2 of 43 (4.6%) women following HSC and in 9 of 84 (10.7%) following D&C (p = .22). DFS and DSS curves did not statistically differ between the groups. Multivariate analysis for DFS revealed that advanced cancer stage (III and IV) (HR = 4.67; 95% CI, 2.34-9.34; p <.001) and advanced age (HR = 1.08; 95% CI, 1.04-1.13]; p <.001) were the factors associated with relapse. For DSS, advanced age (HR = 1.08; 95% CI, 1.05-1.12; p <.001), cancer stage III/IV (HR = 3.95; 95% CI, 2.18-7.15; p <.001), and vascular invasion (HR = 2.47; 95% CI, 1.34-4.54; p = .004) increased the risk of mortality. CONCLUSION: Diagnostic HSC did not increase the rate of positive peritoneal cytology result at the time of surgical staging in this cohort of women with type II EC and is probably as safe as D&C.

Risk factors for recurrence of deep infiltrating endometriosis after surgical treatment.

AIM: To evaluate the frequency of complications and factors associated with the recurrence of endometriosis in women with deep infiltrating endometriosis (DIE) undergoing surgical treatment. METHODS: A retrospective observational cohort study with 72 women who underwent surgery and followed up by DIE at the University of Campinas from 2007 to 2017. The variables analyzed were clinical characteristics, use and type of drug treatment before and after surgery, operative time and complications inherent to the procedure, as well as the recurrence of lesions on imaging. RESULTS: The mean age of women was 39.7 ± 6.3 years and the mean follow-up was 4.56 ± 2.60 years. Complications were reported in 16.6% of surgeries and recurrence of lesions in 34.7%. The risk of intraoperative complications was higher in the presence of lesions of the bowel and in those who used intramuscular progestin before surgery. A higher risk of recurrence was observed among those who did not use hormonal treatment or used a levonorgestrel-releasing intrauterine device (LNG-IUD) in the postoperative period. CONCLUSION: Women with DIE have a high rate of complications during surgical treatment and a higher risk of recurrence when they did not receive hormonal treatment or when treated with LNG-IUD after surgery.

Iron Regulator Hepcidin Impairs Macrophage-Dependent Cardiac Repair After Injury.

BACKGROUND: Defective systemic and local iron metabolism correlates with cardiac disorders. Hepcidin, a master iron sensor, actively tunes iron trafficking. We hypothesized that hepcidin could play a key role to locally regulate cardiac homeostasis after acute myocardial infarction. METHODS: Cardiac repair was analyzed in mice harboring specific cardiomyocyte or myeloid cell deficiency of hepcidin and challenged with acute myocardial infarction. RESULTS: We found that the expression of hepcidin was elevated after acute myocardial infarction and the specific deletion of hepcidin in cardiomyocytes failed to improve cardiac repair and function. However, transplantation of bone marrow-derived cells from hepcidin-deficient mice ( Hamp-/-) or from mice with specific deletion of hepcidin in myeloid cells (LysMCRE/+/ Hampf/f) improved cardiac function. This effect was associated with a robust reduction in the infarct size and tissue fibrosis in addition to favoring cardiomyocyte renewal. Macrophages lacking hepcidin promoted cardiomyocyte proliferation in a prototypic model of apical resection-induced cardiac regeneration in neonatal mice. Interleukin (IL)-6 increased hepcidin levels in inflammatory macrophages. Hepcidin deficiency enhanced the number of CD45+/CD11b+/F4/80+/CD64+/MHCIILow/chemokine (C-C motif) receptor 2 (CCR2)+ inflammatory macrophages and fostered signal transducer and activator of transcription factor-3 (STAT3) phosphorylation, an instrumental step in the release of IL-4 and IL-13. The combined genetic suppression of hepcidin and IL-4/IL-13 in macrophages failed to improve cardiac function in both adult and neonatal injured hearts. CONCLUSIONS: Hepcidin refrains macrophage-induced cardiac repair and regeneration through modulation of IL-4/IL-13 pathways.

Nonpharmacological Clinical Effective Interventions in Constipation: A Systematic Review.

PURPOSE: To identify nonpharmacological clinically effective interventions for constipation in adults. METHODS: A systematic review of experimental studies of nonpharmacological interventions addressing participants' management of constipation using samples of adults over 18 years of age was conducted. In evaluating the methodological quality of the eligible studies, we used the assumptions of the Cochrane Collaboration, and for the reporting of items in the systematic review we used the Model of Preferential Reporting Items for Systematic Reviews and Meta-Analyses. The protocol of this review was recorded in the International Prospective Register of Systematic Reviews of the University of York under number 43693. RESULTS: This review included 12 randomized controlled trials. Nonpharmacological effective interventions for the resolution of constipation were identified: individualized intervention based on the participant's modifiable risk factors of constipation promoting literacy in health; educational measures in dietary modification and lifestyle; and abdominal massage. CONCLUSIONS: Specific nonpharmacological interventions are crucial for nurses' clinical practice and of major importance for clients and families. Evidence on these interventions in resolving constipation is still scarce and fails to provide evidence-based data to support nursing clinical practice. CLINICAL RELEVANCE: Personal lifestyles, comorbidities, medication, and sedentary habits are likely to be risk factors in constipation. Thus, it is important to invest in nonpharmacological interventions that promote changes in behavior regarding prevention or resolution of constipation. Moreover, nursing researchers worldwide should conduct research for clinical practice regarding the fundamentals of care.

ß-catenin aggregation in models of ALS motor neurons: GSK3ß inhibition effect and neuronal differentiation.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron death. A 20% of familial ALS cases are associated with mutations in the gene coding for superoxide dismutase 1 (SOD1). The accumulation of abnormal aggregates of different proteins is a common feature in motor neurons of patients and transgenic ALS mice models, which are thought to contribute to disease pathogenesis. Developmental morphogens, such as the Wnt family, regulate numerous features of neuronal physiology in the adult brain and have been implicated in neurodegeneration. ß-catenin is a central mediator of both, Wnt signaling activity and cell-cell interactions. We previously reported that the expression of mutant SOD1 in the NSC34 motor neuron cell line decreases basal Wnt pathway activity, which correlates with cytosolic ß-catenin accumulation and impaired neuronal differentiation. In this work, we aimed a deeper characterization of ß-catenin distribution in models of ALS motor neurons. We observed extensive accumulation of ß-catenin supramolecular structures in motor neuron somas of pre-symptomatic mutant SOD1 mice. In cell-cell appositional zones of NSC34 cells expressing mutant SOD1, ß-catenin displays a reduced co-distribution with E-cadherin accompanied by an increased association with the gap junction protein Connexin-43; these findings correlate with impaired intercellular adhesion and exacerbated cell coupling. Remarkably, pharmacological inhibition of the glycogen synthase kinase-3ß (GSK3ß) in both NSC34 cell lines reverted both, ß-catenin aggregation and the adverse effects of mutant SOD1 expression on neuronal differentiation. Our findings suggest that early defects in ß-catenin distribution could be an underlying factor affecting the onset of neurodegeneration in familial ALS.

When Solving Dyspareunia Is Not Enough to Restore Sexual Function in Women With Deep Infiltrating Endometriosis Treated With Dienogest.

The aim of the study was to evaluate dyspareunia and sexual function (SF) in women with deep infiltrating endometriosis (DIE) who were treated with dienogest (DNG) for 12 months. The prospective cohort study took place at the University of Campinas, Brazil, and included 30 women with sonographic diagnosis of DIE and sexual dysfunction treated with 2 mg/daily DNG for 12 months. SF parameters were assessed by the Female Sexual Function Index (FSFI) before and after treatment, and dyspareunia was quantified through the visual analog scale (VAS) during the follow-ups performed every three months. Statistical analysis was performed by ANOVA test and through the use of software SAS, Version 9.4. Women were on average 36.13 ± 6.24 years old, and all of them showed sexual dysfunction (FSFI =17.6 ± 5.7) before DNG; 88.3% had dyspareunia as the main symptom related to DIE (VAS before: 5.3 ± 3.1). At the end of the treatment, dyspareunia showed a decrease of intensity (VAS after: 3.7 ± 3.3; p = .0093) and an improvement on FSFI index was accomplished (p = .0023); however, it did not restore SF completely, considering the FSFI cutoff < 26.55. Long-term treatment for DIE with DNG has provided a decrease in dyspareunia and also an enhancement of SF, although SF has not been restored to normal levels.

Peripheral post-ischemic vascular repair is impaired in a murine model of Alzheimer's disease.

The pathophysiology of sporadic Alzheimer's disease (AD) remains uncertain. Along with brain amyloid-ß (Aß) deposits and neurofibrillary tangles, cerebrovascular dysfunction is increasingly recognized as fundamental to the pathogenesis of AD. Using an experimental model of limb ischemia in transgenic APPPS1 mice, a model of AD (AD mice), we showed that microvascular impairment also extends to the peripheral vasculature in AD. At D70 following femoral ligation, we evidenced a significant decrease in cutaneous blood flow (- 29%, P < 0.001), collateral recruitment (- 24%, P < 0.001), capillary density (- 22%; P < 0.01) and arteriole density (- 28%; P < 0.05) in hind limbs of AD mice compared to control WT littermates. The reactivity of large arteries was not affected in AD mice, as confirmed by unaltered size, and vasoactive responses to pharmacological stimuli of the femoral artery. We identified blood as the only source of Aß in the hind limb; thus, circulating Aß is likely responsible for the impairment of peripheral vasculature repair mechanisms. The levels of the majority of pro-angiogenic mediators were not significantly modified in AD mice compared to WT mice, except for TGF-ß1 and PlGF-2, both of which are involved in vessel stabilization and decreased in AD mice (P = 0.025 and 0.019, respectively). Importantly, endothelin-1 levels were significantly increased, while those of nitric oxide were decreased in the hind limb of AD mice (P < 0.05). Our results suggest that vascular dysfunction is a systemic disorder in AD mice. Assessment of peripheral vascular function may therefore provide additional tools for early diagnosis and management of AD.

Bleomycin-induced flagellate erythema after venous malformation sclerosis-Case report and brief review.

Bleomycin-induced flagellate erythema is a rare but typical skin toxicity of bleomycin. We report the case of a boy with a left foot venous malformation who developed this skin rash after two sessions of bleomycin intralesional injection. We discuss the mechanism and characteristics of this reaction to bleomycin, which is usually benign and self-limited. We conclude that, although rare, flagellate pigmentation can occur when bleomycin is used as a sclerosant in children.

Endovascular treatment of acute gastrointestinal bleeding from a large splenic artery pseudoaneurysm: case report and literature review.

Pseudoaneurysm of the splenic artery is a rare entity, with little more than 150 cases described in the literature. Pancreatitis is the most common etiology, followed by trauma. In contrast with true aneurysms, pseudoaneurysms are frequently symptomatic, with a 47% risk of rupture and 90% mortality if left untreated. We describe the case of a 48-year-old female patient who suffered a gastrointestinal hemorrhage associated with acute-on-chronic pancreatitis. During workup, endoscopy revealed signs of recent bleeding and magnetic resonance angiography of the abdomen showed a large pseudoaneurysm of the splenic artery. The patient underwent endovascular treatment with microcoil embolization and no further bleeding episodes occurred. Endovascular treatment is now an effective option with low morbidity and mortality and success rates in the range of 79-100%, making it a viable technique for patients with active abdominal inflammation. We conducted a review of endovascular techniques and embolization agents used to treat this pathology.

Myeloid-Epithelial-Reproductive Receptor Tyrosine Kinase and Milk Fat Globule Epidermal Growth Factor 8 Coordinately Improve Remodeling After Myocardial Infarction via Local Delivery of Vascular Endothelial Growth Factor.

BACKGROUND: In infarcted heart, improper clearance of dying cells by activated neighboring phagocytes may precipitate the transition to heart failure. We analyzed the coordinated role of 2 major mediators of efferocytosis, the myeloid-epithelial-reproductive protein tyrosine kinase (Mertk) and the milk fat globule epidermal growth factor (Mfge8), in directing cardiac remodeling by skewing the inflammatory response after myocardial infarction. METHODS AND RESULTS: We generated double-deficient mice for Mertk and Mfge8 (Mertk(-/-)/Mfge8(-/-)) and challenged them with acute coronary ligature. Compared with wild-type, Mertk-deficient (Mertk(-/-)), or Mfge8-deficient (Mfge8(-/-)) animals, Mertk(-/-)/Mfge8(-/-) mice displayed greater alteration in cardiac function and remodeling. Mertk and Mfge8 were expressed mainly by cardiac Ly6C(High and Low) monocytes and macrophages. In parallel, Mertk(-/-)/Mfge8(-/-) bone marrow chimeras manifested increased accumulation of apoptotic cells, enhanced fibrotic area, and larger infarct size, as well as reduced angiogenesis. We found that the abrogation of efferocytosis affected neither the ability of circulating monocytes to infiltrate cardiac tissue nor the number of resident Ly6C(High) and Ly6C(How) monocytes/macrophages populating the infarcted milieu. In contrast, combined Mertk and Mfge8 deficiency in Ly6C(High)/Ly6C(Low) monocytes/macrophages either obtained from in vitro differentiation of bone marrow cells or isolated from infarcted hearts altered their capacity of efferocytosis and subsequently blunted vascular endothelial growth factor A (VEGFA) release. Using LysMCre(+)/VEGFA(fl/fl) mice, we further identified an important role for myeloid-derived VEGFA in improving cardiac function and angiogenesis. CONCLUSIONS: After myocardial infarction, Mertk- and Mfge8-expressing monocyte/macrophages synergistically engage the clearance of injured cardiomyocytes, favoring the secretion of VEGFA to locally repair the dysfunctional heart.

Standard hormone therapy is inadequate for bone density in premature ovarian insufficiency.

To assess standard dose hormone therapy (HT) and bone mass in premature ovarian insufficiency (POI), 239 women with POI, 132 using standard estrogen dose HT and 107 women without HT, were evaluated. All underwent bone mineral density (BMD) evaluation in the lumbar spine (LS) and total femur (TF). Mean age, age at last period and body mass index (BMI) for the untreated and for the HT groups were 38.1 ± 6.1 and 36.8 ± 7.3 years; 31.4 ± 7.3 and 30.7 ± 7.2 years; 26.6 ± 7.1 and 25.8 ± 4.6 kg/m2, respectively, (p=NS). The women taking standard dose HT started treatment at the age of 33.8 ± 6.3 years and had been on hormone treatment for 3 years at the time of the bone densitometry examination. The BMD in LS was 1.06 ± 0.15 and 1.00 ± 0.17 g/cm2 (p = 0.003); the BMD in TF was 0.92 ± 0.19 and 0.91 ± 0.13 g/cm2 (p = 0.039), respectively, for the untreated and HT groups. A 45% altered BMD (osteopenia/osteoporosis) in LS was verified in women without treatment and 60.1% in those using the standard dose TH (p = 0.01). The BMD in TF was altered in 32.3% in those without HT and 36.4% in the HT users (p = 0.34). In conclusion, standard dose HT was not adequate to reduce impaired bone mass in the spine and femur of women with POI.