Postnatal growth in a cohort of Sardinian intrauterine growth-restricted infants

Recent studies have shown that infants with intrauterine growth restriction (IUGR) undergo catch-up growth during infancy. The aim of our study was to evaluate the postnatal growth in a cohort of IUGR infants born in a tertiary-level Obstetric University Hospital of Northern Sardinia. An observational retrospective study was conducted on 12 IUGR (group A) and 12 control infants (group B) by measuring the anthropometric parameters of weight (W), length (L) and head circumference (HC) from birth to the 3rd postnatal year. At birth, significant differences were found between group A and group B with regard to all the auxological parameters (W, mean 1846.6 versus 3170.8 g, p < 0.0001; HC, 30.1 versus 34.4 cm, p < 0.0001; L, mean 43.4 versus 49.4 cm, p < 0.0001). During the 1st year, 8 of 12 (70%) IUGR infants exhibited a significant catch-up growth in the 3 anthropometric parameters and a regular growth until the 3rd year of follow-up. The majority but not all infants born with IUGR in our series showed significant postnatal catch-up growth essentially during the first 12 months of life. An improved knowledge of the causes of IUGR will help to develop measures for its prevention and individualized treatment

Gender differences in estrogenic compounds effect on human EPCs

Endothelial dysfunction has been defined as an “integrated risk factor”, and several gender difference have been reported in endothelial function. Several evidences suggest that endothelial progenitor cells (EPCs) are an important endogenous system that maintains integrity and vascular homeostasis. Their function is regulated by estrogens and estrogen receptors (ERs), but the effect of estrogenic compounds such as bisphenol A (BPA) and (R,R)-5,11-diethyl-5,6,11,12-tetrahydro-2,8-chrysenediol (THC) on human EPCs is unknown. BPA is used in plastic industry and BPA exposure is associated to abnormalities such as obesity, diabetes, disorders of the reproductive and immune systems, to endothelial dysfunction, and oxidative stress. This endocrine disruptor binds to ERα and ERβ with higher affinity for ERβ. THC is a specific agonist of ERα with a stronger ERβ antagonist activity. Therefore, the present work aimed to analyze if BPA and THC influence in a sex-specific manner the migration of human EPCs, an essential process in endothelial regeneration after vascular injury. EPCs were isolated from healthy adult men and women aged between 18 and 30 years, using a magnetic positive selection with the CD34 MicroBeads, a well-established marker of human progenitor cells. EPCs were also characterized for acetylated LDL Dil- (acLDL) and isothiocyanate (FITC)-conjugated with Ulex europaeus agglutinin I (lectin) uptake. The expression of ERα and ERβ was analysed by Western Blotting, while the migration assay was performed with the transwell chemotaxis assay. Male and female EPCs expressed both classical ERs: ERα was higher, but not significantly, in female cells, while ERβ was similarly expressed in both sexes. Male and female EPCs did not differ in basal migration. 17-β-estradiol (10-9 M e 10-10 M) significantly inhibited migration in female EPCs but not in male ones. Moreover, both 10-5 M THC and BPA (10-8 M) were able to bock migration only in female cells. Considering that BPA has a ERα and a prevalent ERβ agonist activity while THC has ERα agonistic activity and a prevalent ERβ antagonist activity, our data show that the effect on migration observed in female EPCs is mediated by ERα. Our data demonstrate that estrogenic compound have a sexual divergent effect on human EPCs, improving our knowledge on the gender differences observed in the pathophysiology of endothelial function

Autophagic process is sexually different in VSMCs from human male and female neonates

Sex has largely been neglected in cellular studies. Autophagy is a sophisticatedly reg- ulated homeostatic mechanism, which ensures cell’s constituent turnover. Under physiological conditions, autophagy levels are usually low (constitutive autophagy), but can be induced by numerous cellular stresses such as starvation. The influence of sex on autophagy has been studied either in vitro or in vivo, and previous our findings demonstrated the existence of sex differences in rat heart and HUVECs. Vascular smooth muscle cells (VSMCs) are a good experimental model for studying the physiopatholo- gy of the cardiovascular system, in which autophagy plays an important physiological role. Therefore, we investigated the occurrence of sexual dimorphism in constitutive and starvation-induced autophagy between the VSMCs obtained from human umbilical cord arteries (HUASMCs) of male (MHUASMCs) and female (FHUASMCs) neonates. HUASMCs were isolated from the umbilical cord of healthy and normal weight male and female neonates. The expression of oestrogen receptor (ER-α and ER-β) and the primary molecules involved in autophagic process [the mammalian target of rapamycin (mTOR), beclin-1 and microtubule-associated protein 1 light chain 3 (LC3)] were analysed by western blotting. Both cell types expressed both isoforms of the oestrogen receptor (ER): ER-β was higher expressed in the MHUASMCs than the FHUASMCs while ER-α was similarly expressed in both sexes. The level of constitutive autophagy, measured as LC3II/I ratio was higher in FHUASMCs than in MHUASMCs, while male cells had an higher expression of Beclin-1, indicating that constitutive autophagy was at least partly beclin-1-independent. mTOR activity, a regulator of autophagy, did not vary between the sexes, indicating that the observed differences could not be attributed to this central pathway. Starvation promoted autophagy in both MHUASMCs and FHUASMCs, but the increase was more pro- nounced in FHUASMCs. Our results show that sex-differences start in utero and are parameter-specific, suggesting that HUASMCs of both sexes are necessary in in vitro studies to elevate the quality and translational value of research results. The observed differences in the autophagic process could help to emeliorate our knowledge on sex-differences observed in cardiovascular diseases

Red blood cell distribution width in pregnancy: a systematic review

Anisocytosis has been associated with the severity and prognosis of several acute and chronic diseases, as well as physiological conditions such as pregnancy. Anisocytosis is quantified by the red blood cell distribution width (RDW), expressed as the ratio, multiplied by 100, between the standard deviation (SD) of red blood cell volumes and the mean corpuscular volume, or as the SD of erythrocyte volumes (RDW-SD). The aim of the present review was to report the state of the art on the physiological values and the putative diagnostic and prognostic roles of RDW in complicated pregnancy. Literature research for articles published in the last ten years was conducted in Pubmed, Web of Science, ClinicalTrials.gov, and Scopus databases. Abstracts were independently screened by two investigators. If relevant, full articles were retrieved. References, in these articles, citing relevant reviews or original studies were also accessed to identify additional eligible studies. Any disagreement between the reviewers was resolved by a third investigator. A total of 28 studies were included in the review. These studies reported changes in RDW values during physiological pregnancy, and associations between the RDW and several pregnancy complications including anaemia, preeclampsia, gestational diabetes, and recurrent miscarriage. This review provides background information for establishing physiological and pathological RDW values in pregnancy for diagnostic and prognostic use in clinical practice

Human umbilical endothelial cells (HUVECs) and sex differences

HUVECs are worldwide used to study the endothelial physiology and pathology that might be involved in sex and gender differences detected at the cardiovascular level. The present work characterised the phenotype of HUVECs in terms of morphology, proliferative and migratory capacity and in the gene expression of oestrogen and androgen receptors and nitric oxide synthase 3 (NOS3) to evaluated if they are sexually dimorphic. Moreover, autophagic process was analysed in male and female HUVECs (MHUVECs and FHUVECs), as autophagy is influenced by sex. Umbilical cords were obtained from healthy, normal weight, male and female neonates born to healthy non-obese and non-smoking women. HUVECs morphology was analysed by electron microscopy, and their function was investigated by proliferation, viability, wound healing and chemotaxis assays. Real-time PCR was used to evaluate gene expression for oestrogen and androgen receptors and for NOS3, while the expression of the primary molecules involved in autophagic process [(Akt, the mammalian target of rapamycin (mTOR), beclin-1 and microtubule-associated protein 1 light chain 3 (LC3)] and NOS3 were analysed by western blotting. FHUVECs showed significantly higher proliferation and migration rate, and NOS3 mRNA and protein expression than MHUVECs. Conversely, beclin-1 and the LC3-II/LC3-I ratio were higher in MHUVECs than in FHUVECs, indicating a higher autophagy in male cells as also indicated by ultrastructural analysis showing a buildup of autophagic vacuoles at different stages in MHUVECs. The expression of oestrogen and androgen receptor genes, the protein expression of Akt, mTOR, and cellular size and shape were not influenced by sex. Male and female neonates did not differ in body weight, but the weight of male babies was positively associated with the weight of the mother, suggesting that the weight of the mother may exert a different influence on male and female babies. Our findings indicate that sex differences exist from prenatal life and are parameter- specific, suggesting that a better quality of the research on the endothelium in vitro can be obtained by analyzing HUVECs of both sexes as well as its translational value. Moreover, the sex differences observed in HUVECs could help the diseases of adulthood because endothelial dysfunction has a key role in cardiovascular diseases, diabetes mellitus, neurodegeneration and immune diseases

Human umbilical endothelial cells (HUVECs) have a sex: characterisation of the phenotype of male and female cells

Background: Human umbilical endothelial cells (HUVECs) are widely used to study the endothelial physiology and pathology that might be involved in sex and gender differences detected at the cardiovascular level. This study evaluated whether HUVECs are sexually dimorphic in their morphological, proliferative and migratory properties and in the gene and protein expression of oestrogen and androgen receptors and nitric oxide synthase 3 (NOS3). Moreover, because autophagy is influenced by sex, its degree was analysed in male and female HUVECs (MHUVECs and FHUVECs). Methods: Umbilical cords from healthy, normal weight male and female neonates born to healthy non-obese and non-smoking women were studied. HUVEC morphology was analysed by electron microscopy, and their function was investigated by proliferation, viability, wound healing and chemotaxis assays. Gene and protein expression for oestrogen and androgen receptors and for NOS3 were evaluated by real-time PCR and Western blotting, respectively, and the expression of the primary molecules involved in autophagy regulation [protein kinase B (Akt), mammalian target of rapamycin (mTOR), beclin-1 and microtubule-associated protein 1 light chain 3 (LC3)] were detected by Western blotting. Results: Cell proliferation, migration NOS3 mRNA and protein expression were significantly higher in FHUVECs than in MHUVECs. Conversely, beclin-1 and the LC3-II/LC3-I ratio were higher in MHUVECs than in FHUVECs, indicating that male cells are more autophagic than female cells. The expression of oestrogen and androgen receptor genes and proteins, the protein expression of Akt and mTOR and cellular size and shape were not influenced by sex. Body weights of male and female neonates were not significantly different, but the weight of male babies positively correlated with the weight of the mother, suggesting that the mother’s weight may exert a different influence on male and female babies. Conclusions: The results indicate that sex differences exist in prenatal life and are parameter-specific, suggesting that HUVECs of both sexes should be used as an in vitro model to increase the quality and the translational value of research. The sex differences observed in HUVECs could be relevant in explaining the diseases of adulthood because endothelial dysfunction has a crucial role in the pathogenesis of cardiovascular diseases, diabetes mellitus, neurodegeneration and immune disease.</br

Prevalence and type distribution of human papillomavirus infection in women from North Sardinia, Italy

<p>Abstract</p> <p>Background</p> <p>Human papillomavirus (HPV) has been associated with several disorders of the genital tract, skin and oropharynx. The aims of our study were to evaluate the prevalence of HPV infection in women between 15 and 54 years of age in North Sardinia, Italy, to identify the prevalence of High Risk - Human papillomaviruses (HR-HPV) genotypes and to establish a correlation between molecular and cytological results.</p> <p>Methods</p> <p>From 2007 to 2009 we consecutively enrolled women aged 15-54 years admitted to public and private outpatient settings. All the participants filled in a questionnaire about the socio-cultural state, sexual activity and awareness about HPV. 323 cervical specimens were tested for HPV-DNA and HPV genotypes with INNO-LiPA HPV Genotyping CE Amp kit. Samples showing positivity to some HPV genotypes were re-tested using "in house" quantitative Real-Time PCR assays.</p> <p>Results</p> <p>Overall HPV-DNA positivity was detected in 35.9% of the women. The prevalence of HR-HPV infection among HPV positive samples was 93.1% with a specific prevalence of HPV 16, 51, 31, 53 and 18 of 54.3%, 37.9%, 10.3%, 6.9% and 5.2%, respectively. Co-infection with any HPV, HR-HPV, LR-HPV and HR/LR-HPV type was 18.3%, 14.9%, 0.9% and 2.5%, respectively; HPV 16/51 co-infection was detected in 64.6% of the HR-HPV co-infection group. The most frequent HPV-genotypes detected were 16 (32.5%) and 51 (22.7%). Among the 57 patients harboring mono-infection the most prevalent HPV genotypes were 16 (38.6%) and 31(10.5%). A multivariate analysis identified a statistical significant association between HPV infection and age and between HPV infection and previous sexual transmitted diseases. A statistically significant association between cytological cervical lesions and generic HPV exposure was identified.</p> <p>Conclusions</p> <p>To our knowledge, this is the first survey evaluating the prevalence of HPV infection in Northern Sardinia and drawing attention to the unusual high proportion of genotype HPV 51. Given the recent implementation of a widespread immunization program with vaccines not containing HPV 51, it has been relevant to prove the high prevalence of this HPV genotype from the start of the vaccination campaign, in order to avoid in the future attributing to the vaccination program a possible selection effect (HPV replacement).</p

Characteristics and patterns of care of endometrial cancer before and during COVID-19 pandemic

Objective: Coronavirus disease 2019 (COVID-19) outbreak has correlated with the disruption of screening activities and diagnostic assessments. Endometrial cancer (EC) is one of the most common gynecological malignancies and it is often detected at an early stage, because it frequently produces symptoms. Here, we aim to investigate the impact of COVID-19 outbreak on patterns of presentation and treatment of EC patients. Methods: This is a retrospective study involving 54 centers in Italy. We evaluated patterns of presentation and treatment of EC patients before (period 1: March 1, 2019 to February 29, 2020) and during (period 2: April 1, 2020 to March 31, 2021) the COVID-19 outbreak. Results: Medical records of 5,164 EC patients have been retrieved: 2,718 and 2,446 women treated in period 1 and period 2, respectively. Surgery was the mainstay of treatment in both periods (p=0.356). Nodal assessment was omitted in 689 (27.3%) and 484 (21.2%) patients treated in period 1 and 2, respectively (p&lt;0.001). While, the prevalence of patients undergoing sentinel node mapping (with or without backup lymphadenectomy) has increased during the COVID-19 pandemic (46.7% in period 1 vs. 52.8% in period 2; p&lt;0.001). Overall, 1,280 (50.4%) and 1,021 (44.7%) patients had no adjuvant therapy in period 1 and 2, respectively (p&lt;0.001). Adjuvant therapy use has increased during COVID-19 pandemic (p&lt;0.001). Conclusion: Our data suggest that the COVID-19 pandemic had a significant impact on the characteristics and patterns of care of EC patients. These findings highlight the need to implement healthcare services during the pandemic

The use of a decremental dose regimen in patients treated with a chronic low-dose step-up protocol for WHO Group II anovulation: a prospective randomized multicentre study / J.N. Hugues, I. Cédrin-Durnerin, C.M. Howles on behalf of the Recombinant FSH OI Study Group

BACKGROUND: In women with chronic anovulation, the choice of the FSH starting dose and the modality of subsequent dose adjustments are critical in controlling the risk of overstimulation. The aim of this prospective randomized study was to assess the efficacy and safety of a decremental FSH dose regimen applied once the leading follicle was 10–13 mm in diameter in women treated for WHO Group II anovulation according to a chronic low-dose (CLD; 75 IU FSH for 14 days with 37.5 IU increment) step-up protocol. METHODS: Two hundred and nine subfertile women were treated with recombinant human FSH (r-hFSH) (Gonal-f) for ovulation induction according to a CLD step-up regimen. When the leading follicle reached a diameter of 10–13 mm, 158 participants were randomized by means of a computer-generated list to receive either the same FSH dose required to achieve the threshold for follicular development (CLD regimen) or half of this FSH dose [sequential (SQ) regimen]. HCG was administered only if not more than three follicles &#8805;16 mm in diameter were present and/or serum estradiol (E2) values were &lt; 1200 pg/ml. The primary outcome measure was the number of follicles &#8805;16 mm in size at the time of hCG administration. RESULTS: Clinical characteristics and ovarian parameters at the time of randomization were similar in the two groups. Both CLD and SQ protocols achieved similar follicular growth as regards the total number of follicles and medium-sized or mature follicles (&#8805;16 mm: 1.5 &#177; 0.9 versus 1.4 &#177; 0.7, respectively). Furthermore, serum E2 levels were equivalent in the two groups at the time of hCG administration (441 &#177; 360 versus 425 &#177; 480 pg/ml for CLD and SQ protocols, respectively). The rate of mono-follicular development was identical as well as the percentage of patients who ovulated and achieved pregnancy. CONCLUSIONS: The results show that the CLD step-up regimen for FSH administration is efficacious and safe for promoting mono-follicular ovulation in women with WHO Group II anovulation. This study confirms that maintaining the same FSH starting dose for 14 days before increasing the dose in step-up regimen is critical to adequately control the risk of over-response. Strict application of CLD regimen should be recommended in women with WHO Group II anovulation

Effects of intravaginal estriol and pelvic floor rehabilitation on urogenital aging in postmenopausal women

Purpose To assess the effects of the combination of pelvic floor rehabilitation and intravaginal estriol administration on stress urinary incontinence (SUI), urogenital atrophy and recurrent urinary tract infections in postmenopausal women. Methods Two-hundred-six postmenopausal women with urogenital aging symptoms were enrolled in this prospective randomized controlled study. Patients were randomly divided into two groups and each group consisted of 103 women. Subjects in the treatment group received intravaginal estriol ovules, such as 1 ovule (1 mg) once daily for 2 weeks and then 2 ovules once weekly for a total of 6 months as maintenance therapy plus pelvic floor rehabilitation. Subjects in the control group received only intravaginal estriol in a similar regimen. We evaluated urogenital symptomatology, urine cultures, colposcopic findings, urethral cytologic findings, urethral pressure profiles and urethrocystometry before, as well as after 6 months of treatment. Results After therapy, the symptoms and signs of urogenital atrophy significantly improved in both groups. 61/83 (73.49%) of the treated patients, and only 10/103 (9.71%) of the control patients referred a subjective improvement of their incontinence. In the patients treated by combination therapy with estriol plus pelvic floor rehabilitation, we observed significant improvements of colposcopic findings, and there were statistically significant increases in mean maximum urethral pressure (MUP), in mean urethral closure pressure (MUCP), as well as in the abdominal pressure transmission ratio to the proximal urethra (PTR). Conclusions Our results showed that combination therapy with estriol plus pelvic floor rehabilitation was effective and should be considered as a first-line treatment for symptoms of urogenital aging in postmenopausal women.</br