Post-diagnosis serum 25-hydroxyvitamin D concentrations in women treated for breast cancer participating in a lifestyle trial in Italy.

OBJECTIVE: To report cross-sectionally serum levels of 25-hydroxyvitamin D [25(OH)D] in women living in Italy within 12 months from breast cancer (BC) diagnosis. METHODS: Baseline data were obtained from 394 women diagnosed with primary BC, enrolled from 2016 to 2019 in a lifestyle trial conducted in Italy. Subjects' characteristics were compared between two 25(OH)D concentrations (hypovitaminosis D<20 and ≥20 ng/mL) with the Chi-squared test or Fisher's exact test for small-expected counts. Using multiple logistic regression-adjusted models, we estimated odds ratios (ORs) of hypovitaminosis D with 95% confidence intervals (CIs) in the total sample and in the unsupplemented subgroup. RESULTS: Hypovitaminosis D was found in 39% of all subjects, 60% in unsupplemented subjects, and 10% in supplemented subjects. Increasing ORs of hypovitaminosis D were found with increasing body mass index, 25-30, >30, and ≥35 versus <25 kg/m2 (ORs: 2.50, 4.64, and 5.81, respectively, in the total cohort and ORs: 2.68, 5.38, and 7.08 in the unsupplemented); living in the most southern Italian region (OR 2.50, 95%CI 1.22-5.13); and with hypertriglyceridemia (OR 2.46; 95%CI 1.16-5.22), chemotherapy history (OR 1.86, 95%CI 1.03-3.38), and inversely with anti-estrogenic therapy (OR 0.43, 95%CI 0.24-0.75) in the total sample. CONCLUSIONS: Hypovitaminosis D in women recently diagnosed with BC and participating in a lifestyle trial in Italy was widespread and highest with obesity, hypertriglyceridemia, and chemotherapy use. Considering that hypovitaminosis D is a risk factor for lower efficacy of bone density treatments and possibly BC mortality, our results suggest the need to promptly address and treat vitamin D deficiency.

Human remains from Arma di Nasino (Liguria) provide novel insights into the paleoecology of early Holocene foragers in northwestern Italy.

We report the discovery and analysis of new Mesolithic human remains-dated to ca. 10,200-9000 cal. BP-from Arma di Nasino in Liguria, northwestern Italy, an area rich in Upper Paleolithic and Neolithic attestations, but for which little information on Early Holocene occupation was available. The multi-proxy isotopic profile of the two individuals reveals that-despite the proximity of the site to the Mediterranean seashore and the use of shellfish as decorative elements in burials-the ecology of these foragers was based on the exploitation of high-altitude resources, presumably in the nearby western Alps. This constitutes the first direct evidence in northwestern Italy of a significant ecological shift towards higher altitudes following deglaciation, especially when compared to isotopic data of the Late Pleistocene hunter-gatherers from the nearby site of Arene Candide Cave, who exploited terrestrial resources nearer to the coast and at lower altitudes. While the biochemistry of Nasino's skeletal assemblage revealed new details on Early Holocene lifeways in the area, the osteobiography of one individual offers glimpses into the life experience of a specific female forager, depicting a scenario of early skeletal trauma, developmental disturbances, long-term impairments, and resilience amongst the last European hunter-gatherers.

Hysteroscopic laser ablation of symptomatic uterine fibroids: insights from a prospective study.

OBJECTIVE: This study aimed to evaluate the feasibility and efficacy of in-office hysteroscopic ablation of submucous uterine fibroids using a diode laser. METHOD: A pilot study was conducted between January 2018 and January 2019 in a tertiary care university hospital. Patients with at least one symptomatic, class 0-2 FIGO classification, uterine fibroid ≤7 cm in size were eligible for inclusion. Evaluation of the changes in fibroid size and vascularity was performed using three-dimensional Doppler ultrasonography. Vaporization of the fibroid core was conducted using a 980-1470 nm wavelength diode laser inserted through the hysteroscope's working channel. The primary outcome was evaluation of the fibroid volume before and at 2 months after the procedure. RESULTS: Twenty women were enrolled in the study. At 2-month follow-up, the volume of the fibroids was significantly reduced (51.6 ± 22.5 vs. 33.4 ± 17.1 mm3; p < 0.001). A major reduction of three-dimensional sonographic color Doppler vascularity (observed by the same operator and confirmed by four blind reviewers) was also achieved in 12/20 patients (60%; p = 0.03) while a reported symptom of heavy menstrual bleeding decreased from 18/20 (90%) to 2/18 (10%; p < 0.01). CONCLUSION: Hysteroscopic laser ablation represents a feasible and effective alternative for treating women with symptomatic submucous fibroids in the office setting. Further studies with larger sample size and longer follow-up periods are needed to validate this promising technique.Key messageThis pilot study shows that in-office hysteroscopic laser ablation (HLA) could be a feasible alternative to treat symptomatic submucous uterine fibroids by coagulating their core, reducing their size and vascularization.

Unilateral cleft nose deformities at adulthood.

Secondary rhinoplasty is a challenging procedure, requiring a precise preoperative diagnosis of nasal deformities before correcting them. As there is currently no accepted outcome measurement tool available to assess unilateral cleft lip and palate (UCLP) nose sequelae before secondary rhinoplasty. The goal of this retrospective study is to identify the nose deformities and rate them in an evaluation scale that allows collecting and analyzing cleft nose data. Our retrospective cohort is composed of 29 patients with UCLP, who underwent secondary rhinoplasty between 2010 and 2021 in a cleft center, with a mean age of 23years old. Evaluation of deformities is made from preoperative two-dimensional photography. The assessment photographic tool is a custom-designed scale of 16 items. A binary scoring system is used by two experts to assess nasolabial deformities. The most encountered sequelaes are the alar foot displacement (93%), the enlarged tip (90%) and the nostril horizontalization (86%). The inter-examiner ICC for total rating was calculated at 0.911 and indicated a strong level of reliability that was highly significant (P<0.05). The simplicity, reliability and reproducibility of the proposed assessment system could be interesting for clinicians, in order to diagnose the nasal deformities before surgery, but also to assess postoperative success of a secondary rhinoplasty and thus to compare several surgical techniques.

Satisfaction survey of secondary rhinoplasty among unilateral cleft lip and palate patients.

Secondary rhinoplasty on patients with cleft is a challenging procedure, and the most important criterion for evaluating the surgery success is patient satisfaction even if it's subjective. OBJECTIVES: To evaluate patient satisfaction following secondary cleft rhinoplasty with a specific assessment for patients with Unilateral Cleft Lip and Palate (UCLP). PATIENTS AND METHODS: Our retrospective cross-sectional study is composed of 29 patients with UCLP with a mean age of 23years old, who underwent secondary rhinoplasty between 2010 and 2021 in our department. The survey was conducted postoperatively using a cleft-nose specific custom designed questionnaire based on the Byrne questionnaire, over the phone. This satisfaction questionnaire comprises six questions about physical appearance and one question about functional aspect. Patients were asked to answer "yes" or "no" or to rate from 0 (no improvement) to 10 (perfect result) depending on the question. RESULTS: Twenty out of 29 people responded to the questionnaire, representing an answer rate of 69%. The average score given by the patient for nasolabial scar improvement was 7.2/10, and the one concerning global improvement was 8.2/10. All patients would be ready to undergo the same procedure again, knowing the final result. A functional improvement concerning breathing or snoring was reported in 45% of cases. All dorsum or tip issues were improved after surgery (P=0,07). CONCLUSIONS: Our results demonstrate high patient satisfaction after cleft rhinoplasty, which encourages the continuation of this surgery. We would recommend the use of this simple questionnaire to allow a more accurate evaluation of patient outcomes.

Organic synthesis associated with serpentinization and carbonation on early Mars.

Water-rock interactions are relevant to planetary habitability, influencing mineralogical diversity and the production of organic molecules. We examine carbonates and silicates in the martian meteorite Allan Hills 84001 (ALH 84001), using colocated nanoscale analyses, to characterize the nature of water-rock reactions on early Mars. We find complex refractory organic material associated with mineral assemblages that formed by mineral carbonation and serpentinization reactions. The organic molecules are colocated with nanophase magnetite; both formed in situ during water-rock interactions on Mars. Two potentially distinct mechanisms of abiotic organic synthesis operated on early Mars during the late Noachian period (3.9 to 4.1 billion years ago).

Complex mortuary dynamics in the Upper Paleolithic of the decorated Grotte de Cussac, France.

The Mid-Upper Paleolithic (Gravettian) karstic Grotte de Cussac (France) contains two areas of human remains in the context of abundant (and spectacular) parietal engravings. The first area (loci 1 and 2) includes the skeleton of a young adult male in a bear nest, rearranged by postdecomposition inundation, and the variably fragmentary remains of at least two individuals distributed across two bear nests, sorted anatomically and with most of the elements constrained to one side of one nest. The second area (locus 3) retains remains of two adults and an adolescent, in upper hollows and variably distributed down the slope, largely segregated into upper versus lower body groups. The only decoration associated with the human remains is red pigment on some of the bones or underlying sediment. The human remains indicate variable nonnatural deposition and manipulation of human bodies, body portions, and skeletal elements of at least six individuals. Moreover, Cussac is unusual in the association of these remains with exceptional parietal art. The complex Cussac mortuary pattern joins growing evidence from other Gravettian sites of variable treatment of individuals after death, within and across sites, in terms of formal deposition of the body versus postmortem manipulation versus surface abandonment. It provides a window onto the social diversity and the complex interactions of the living and the dead among these successful Late Pleistocene foragers.

Office hysteroscopy in the management of women with postmenopausal bleeding.

Postmenopausal bleeding (PMB) is a relevant aspect for health-care providers in clinical practice: the first objective is to rule out potential gynecological cancer. The purpose of this narrative review is to evaluate the role of office hysteroscopy in the management of PMB. Office hysteroscopy is a minimally invasive procedure allowing direct visualization of uterine pathology without the need for general anesthesia and the use of an operating room, generating cost savings and greater compliance among patients. Here, we focus on major intrauterine diseases (polyps, submucosal myomas, endometrial hyperplasia, and cancer) as causes of PMB. Office hysteroscopy appears to be safe and feasible, and could allow accurate diagnosis of intrauterine pathologies, especially that with a focal growth pattern, otherwise misdiagnosed with blinded procedures. However, studies focusing exclusively on postmenopausal women are still few, so further research, especially randomized controlled trials, is needed.

Pharmacological and non-pharmacological pain relief for office hysteroscopy: an up-to-date review.

In-office hysteroscopy is considered the standard technique for visualization of the uterine cavity and the diagnosis of intrauterine pathologies. Moreover, nowadays, it is possible to treat a vast number of intracavitary diseases in the office, without the need for the inpatient setting. However, in some cases, pain might occur, and this is the most common reason for not completing the procedure. Over the last 20 years, many efforts have been carried out to miniaturize the instrumentation and to improve the techniques in order to avoid discomfort. Nonetheless, hysteroscopy still provokes distress for many patients. For this reason, pharmacological and non-pharmacological treatments for intraoperative and postoperative pain relief have been widely used for in-office hysteroscopy, with different results in various groups of women. The purpose of this review was to analyze the current literature on pharmacological aids (non-steroidal anti inflammatory drugs, cyclooxygenase-2 inhibitors, antispasmodics, local anesthetics, prostaglandins, opioids) and non-pharmacological interventions (transcutaneous electrical nerve stimulation, uterine stretching, uterine pressure, warming of distension medium, hypnosis, music, vocal-local) and to evaluate their impact on the relief from pain experienced during in-office hysteroscopy.

Hysteroscopic treatment of submucosal fibroids in perimenopausal women: when, why, and how?

Uterine fibroids are a common finding in premenopausal women. They considerably reduce the quality of life by provoking abnormal uterine bleeding and consequent anemia and pelvic pain. Over the past 20 years, radical surgery (hysterectomy) for symptomatic fibroids has been partially replaced with minimally invasive surgical procedures that spare the uterus, with lower costs and reduced morbidity. Outpatient and inpatient operative hysteroscopy have been validated as safe and effective minimally invasive treatment options for both submucosal and intramural fibroids. In such a scenario, several technological innovations and the possibility of pharmacological pretreatment have enhanced the hysteroscopic approach. However, the counseling and treatment of perimenopausal women remain a challenge for the gynecologist. The main purpose of this review is to provide an updated guide to the management of submucosal fibroids in perimenopausal women, depicting how, when, and why hysteroscopic treatment is a valuable choice to eliminate symptoms and satisfy the patient's wish to improve their overall quality of life.

Publisher Correction: Deep Electrical Resistivity Tomography for a 3D picture of the most active sector of Campi Flegrei caldera.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Deep Electrical Resistivity Tomography for a 3D picture of the most active sector of Campi Flegrei caldera.

The central sector of the Campi Flegrei volcano, including the Solfatara maar and Pisciarelli fumarole field, is currently the most active area of the caldera as regards seismicity and gaseous emissions and it plays a significant role in the ongoing unrest. However, a general volcano-tectonic reconstruction of the entire sector is still missing. This work aims to depict, for the first time, the architecture of the area through the application of deep Electrical Resistivity Tomography. We reconstructed a three-dimensional resistivity model for the entire sector. Results provide useful elements to understand the present state of the system and the possible evolution of the volcanic activity and shed solid bases for any attempt to develop physical-mathematical models investigating the ongoing phenomena.

Maternal nutritional restriction during late gestation impairs development of the reproductive organs in both male and female lambs.

Maternal nutritional restrictions during late gestation could lead to fetal hypoglycemia. Glucose levels in the fetal sheep regulate circulating insulin-like growth factor 1 (IGF1) levels, which stimulate cell proliferation and differentiation of reproductive organs after binding to its own receptor or estrogen receptors. The objective of this study was to determine the effects of subnutrition of ewes during the last trimester of gestation on the serum glucose/IGF1 levels and development of reproductive organs in their lambs. Pregnant ewes carrying singletons were randomly assigned to restricted (R ewes, n = 8) or control (C ewes, n = 8) groups (4 lambs of each gender/group) and fed with 50% or 100% of metabolic energy requirements from ∼100 days of gestation to term (∼147 days), respectively. Blood samples from lambs were taken on the first day after born and once at week for serum glucose and IGF1 determination. Lambs were euthanatized at 2 months of age, reproductive organs were weighted and tissue samples were collected from them for histology and to measure mRNA expression of IGF1 and its receptor (IGF1R) by qRT-PCR. Pre-partum glucose levels in R ewes were significantly lower compared to C ewes (p < .05). Compared to lambs born from C ewes, lambs born from R ewes showed lower serum levels of glucose and IGF1 during the first week of age (p < .05). At 2 month of age, these lambs had significant lower uterine and testicular weight and lower ovarian, uterine and testicular mRNA expressions of IGF1 and its receptor (p < .05). Histological findings showed that diameter of secondary and tertiary follicles in ovaries and number of endometrial glands in uterus of females, or number of Sertoli cells and seminiferous tubules and diameter, perimeter and tubular area in testicles of males were significantly lower in lambs born from R ewes compared to the respective organs of lambs born from the C ewes (p < .05). In conclusion, these results demonstrate that maternal subnutrition during late gestation affects IGF1 levels during fetal life and impairs reproductive development in the neonatal lamb, which could have permanent negative consequences in the future reproductive performance of the offspring.

Vitamin D in human reproduction: the more, the better? An evidence-based critical appraisal.

OBJECTIVE: Vitamin D is a fat-soluble secosteroid hormone that regulates calcium, magnesium, and phosphate homeostasis and plays a pivotal role as antiproliferative and immunomodulatory mediator. Considering the different sources of synthesis and dietary intake as well as the pleiotropic actions in extremely diverse (micro)environments of the body, the supplementation of this Vitamin should be carefully evaluated taking into account the several pathways that it regulates. In the current brief review, we aimed to summarize the available evidence about the topic, in order to suggest the best evidence-based supplementation strategy for human reproduction, avoiding the unuseful (and sometimes hazardous) empiric supplementation. MATERIALS AND METHODS: Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases. RESULTS: Accumulating evidence from in vitro fertilization (IVF) trials suggests that fertilization rate decreases significantly with increasing levels of 25OH-D in follicular fluid; in addition, Vitamin D levels in the follicular fluid are negatively correlated to the quality of embryos and the higher values of Vitamin D are associated with lower possibility to achieve pregnancy. Both low and high Vitamin D serum concentrations decrease not only spermatozoa count, but their progressive motility as well as increase morphological abnormalities. Finally, studies in animal models found that severe hypervitaminosis D can reduce the total skeletal calcium store in embryos and may compromise the postnatal survival. CONCLUSIONS: Based on the retrieved data, we solicit to be extremely selective in deciding for Vitamin D supplementation, since its excess may play a detrimental role in fertility.

Papillomavirus genotyping on formaldehyde fixed paraffin-embedded tissues in vulvar intraepithelial neoplasia.

PURPOSE: Few studies have described the epidemiology of human papillomavirus (HPV) in vulvar intraepithelial neoplasia (VIN). The aim of this study was to genotype HPV on formalin fixed paraffin-embedded tissues in VIN lesions. METHODS: A 5-year retrospective study was conducted by including all patients attending the teaching hospital of Nice with a diagnosis of VIN between 1st January 2010 and 31st December 2014. For all patients, HPV genotyping was performed with the PapilloCheck® microarray kit, routinely used on cervical cytology samples, and optimized for formaldehyde fixed paraffin-embedded tissues in VIN. RESULTS: Forty patients were included in the study: 39 patients had usual VIN and one presented with differentiated VIN. Among the 39 patients with usual VIN, the prevalence of HPV was 90% (35/39). Thirty-two patients had high grade VIN (82%) and seven low grade VIN (18%). In high grade VIN, the most represented HPV types were: HPV 16 (21/32 66%), HPV 56 (3/32 9%) and HPV 33 (2/32 6%). In low grade VIN, the most represented HPV types were: HPV 16 (4/7 57%) and HPV 6 (3/7 43%). Interestingly, 5/39 (13%) of patients diagnosed with usual VIN also had co-existing lichen sclerosus. CONCLUSIONS: We have optimized a HPV genotyping technique, routinely used on cervical cytology samples, and on paraffin fixed embedded tissue showing VIN. Moreover, we have identified five patients with lichen sclerosus co-existing with usual VIN. This association has rarely been reported and proves that these two entities can coexist.

Myo-inositol as a male fertility molecule: speed them up!

Myo-inositol (MYO) usually represents a therapeutic option for female infertility associated with insulin resistance. Recently, several evidences are accumulating about the potential use of MYO for the treatment of male infertility. This article summarizes the rationale for MYO in the treatment of male infertility. In particular, it illustrates the potential antioxidant and prokinetic role of MYO, and its importance for the modulation of hormonal regulation. In the final part of the manuscript has been added a proposal for a clinical algorithm reserved for patients with asthenozoospermia, where probably MYO could exert specific pharmacological effects.

A 6500-year-old Middle Neolithic child from Pollera Cave (Liguria, Italy) with probable multifocal osteoarticular tuberculosis.

Clear skeletal evidence of prehistoric tuberculosis (TB) is rare, especially in children. We describe and differentially diagnose the pathological changes displayed by a five-year-old child, Pollera 21 (PO21) dated to the Middle Neolithic of Liguria (Italy), or 5740±30 BP (Beta-409341; 6635-6453cal BP, 2σ, OxCal 4.2). PO21 shows a number of osteoarticular lesions, mainly of a lytic nature with very little bone proliferation: the vertebral column, the shoulder and pelvic girdles, and the ribcage are involved. Given the nature and pattern of the lesions, we propose a diagnosis of multifocal (or multiple) bone TB. Attempts to detect TB aDNA through molecular analysis gave negative results, but this alone is not sufficient to prove that PO21 was not infected with TB. The lesions observed in PO21 share similarities with other published evidence, such as spinal and joint involvement, and disseminated cyst-like lesions. Conversely, PO21 does not show diffuse bone deposition, such as hypertrophic osteoarthropathy (HOA) or endocranial modifications such as serpens endocrania symmetrica (SES). PO21 adds to our knowledge of patterns of TB manifestation in archaeological skeletal remains, which is especially important considering the variability in types and patterns of osteoarticular lesions seen today in people with TB.

Digging Deeper: Observing Primordial Gravitational Waves below the Binary-Black-Hole-Produced Stochastic Background.

The merger rate of black hole binaries inferred from the detections in the first Advanced LIGO science run implies that a stochastic background produced by a cosmological population of mergers will likely mask the primordial gravitational wave background. Here we demonstrate that the next generation of ground-based detectors, such as the Einstein Telescope and Cosmic Explorer, will be able to observe binary black hole mergers throughout the Universe with sufficient efficiency that the confusion background can potentially be subtracted to observe the primordial background at the level of Ω_{GW}≃10^{-13} after 5 years of observation.

Hormonal treatment with transdermal testosterone in patients with male accessory gland inflammation (MAGI): Effects on sperm parameters.

Recently, it has been reported that treatment with testosterone (T) could have favourable effects on prostate inflammation; however, the data appear inconsistent. The main evidences concern experimental studies, and there is lower information obtainable from clinical studies. This study was conducted on patients with diagnosis of male accessory gland infection (MAGI) and a concomitant hormonal condition of acquired hypergonadotropic hypogonadism and has evaluated the effects on sperm parameters of the administration of a transdermal formulation of T gel for 3 months. The treated patients showed a significantly increased percentage of spermatozoa with normal form and progressive motility (p < .05 vs baseline), a significant reduction of CD45pos leucocytes in the semen (p < .05 vs baseline) and finally a significant increase of the seminal concentrations of zinc, fructose and alpha-glucosidase (p < .05 vs baseline) identified as key parameters associated to secretory function of the male accessory glands. The results of this study suggest the use of transdermal T in hypogonadal patients with MAGI for favourable effects on sperm parameters.