A prospective, multicenter, randomized, double-blind placebo-controlled trial on purified and specific Cytoplasmic pollen extract for hot flashes in breast cancer survivors.

OBJECTIVE: evaluate the efficacy and tolerability of PureCyTonin against hot flashes (HF) in breast cancer survivors (BCS). METHODS: a prospective, multicenter, randomized, double-blind placebo-controlled trial was conducted in Italy. INTERVENTIONS: administration of PureCyTonin or placebo, for 3 months. Effectiveness was investigated through the compilation of a daily diary for HF and of validated questionnaires (Menopause Rating Scale (MRS), Pittsburgh Sleep Quality Index (PSQI), Visual Analogical Scales (VAS) for HF, sweating, irritability, fatigue, sleep, quality of life), carried out before starting the treatment (T0), after 1 month (T1) and after 3 months (T2). Any side effects and HF diary were recorded at each visit. RESULTS: 19 women were randomized to receive PureCyTonin and 20 to placebo. At T2 compared to T0, in the PureCyTonin group, we found a reduction in the number of HF (p = 0.02) measured by daily diary. An improvement in the subjective perception of women regarding HF intensity (p = 0.04), sweat nuisance (p = 0.02), irritability (p = 0.03) and fatigue (p = 0.04) was observed through VAS scale measurement at T2 compared to T0.The total MRS score was significantly better in the PureCyTonin group at T1 (p = 0.03) compared to T0. CONCLUSIONS: PureCyTonin significantly reduces HF number after 3 months of therapy in BCS and it is well-tolerated.

Hormone Replacement Therapy in Post-Menopause Hormone-Dependent Gynecological Cancer Patients: A Narrative Review.

BACKGROUND: Advances in the treatment of gynecological cancer have led to improvements in survival but also an increase in menopausal symptoms, especially in young women with premature iatrogenic menopause. METHODS: A narrative review was performed to clarify the possibility of prescribing hormone replacement therapy (HRT) after hormone-dependent gynecological cancers (ovarian cancer [OC], cervical adenocarcinoma [AC], and endometrial cancer [EC]). RESULTS: HRT can be prescribed to patients with early-stage, grade I-II OC who experience bothersome menopausal symptoms non-responsive to alternative non-hormone therapy after optimal surgery. Caution should be exercised in administering HRT after serous borderline tumors and endometrioid OC, and HRT is not recommended in low-grade serous OC. HRT is not contraindicated in AC survivors. After surgery for EC, HRT can be prescribed in women with early-stage low-grade EC. There is not enough data to give indications to patients with advanced EC. CONCLUSIONS: HRT can be discussed with patients, evaluating the risks and benefits of hormone-dependent gynecological cancer. Counseling should be performed by gynecologic oncologists experienced in the management of these patients.

Preventing Bone Loss in Breast Cancer Patients: Designing a Personalized Clinical Pathway in a Large-Volume Research Hospital.

BACKGROUND: We assess the impact of bone health clinical management in breast cancer (BC) patients receiving adjuvant endocrine therapy and design a personalized clinical pathway to reduce bone loss in an Italian research hospital. METHODS: The primary endpoint was to assess (through the process improvement organizational method) the clinical pathway that post-surgical BC patients prescribed with endocrine therapy undergo to prevent bone loss. The secondary endpoint was to design a personalized clinical pathway for a prompt implementation of guidelines, to assess and possibly prescribe antiresorptive therapy. RESULTS: During the first year of the execution of the new Diagnostic Therapeutic Assistance Pathway, a 60% increase in Dual-Energy X-ray Absorptiometry evaluations within 30 days and a 39.5% increase in antiresorptive therapy prescription within 90 days (since the prescription of endocrine therapy) were shown, thus increasing patients' compliance. CONCLUSION: Case managers and bone health specialists in this context can improve patients' adherence to therapies and bone health, helping physicians to expand their collaboration.

Vulvovaginal atrophy in women with and without a history of breast cancer: Baseline data from the PatiEnt satisfactiON studY (PEONY) in Italy.

OBJECTIVES: To assess clinical characteristics of postmenopausal women with moderate/severe vulvovaginal atrophy, as well as its impact on sexual function, well-being, and quality of life, and to provide an overview of most used treatments. STUDY DESIGN: Ongoing longitudinal, observational study conducted in 17 Italian gynecology centers, involving women already treated or initiating a local vaginal estrogen therapy or ospemifene. We report baseline data for women with and without a history of breast cancer. Participants filled in self-reported questionnaires at study entry. MAIN OUTCOME MEASURES: Severity of vulvovaginal atrophy; ongoing treatments; patient-reported outcomes, including severity of symptoms, Day-to-Day Impact of Vaginal Aging (DIVA), Female Sexual Function Index (FSFI), Female Sexual Distress Scale-Revised (FSDS-R), and SF-12® Health Survey. RESULTS: Overall, 334 women (20.4 % with a history of breast cancer) started or continued local therapy (61.1 %) or ospemifene (38.8 %) at study entry. Vulvovaginal atrophy was severe in 28.6 %, and was responsible for severe symptoms, particularly vulvar dryness with burning or irritation and pain during sexual intercourse. Both sexual dysfunction (FSFI≤26) (81.5 %) and sexual distress (FSDS-R ≥ 11) (74.4 %) were common. A reduction in the SF-12 mental component score was documented. Women with breast cancer more often had severe vulvovaginal atrophy (41.2 %), had more severe symptoms, and the impact of vaginal symptoms on emotional well-being, sexual functioning and self-concept/body image was greater. The majority of them (83.8 %) received ospemifene as a treatment. CONCLUSIONS: Moderate/severe vulvovaginal atrophy is a common, often neglected condition with an impact on QoL and sexuality, particularly in women with a history of breast cancer. It is important to alleviate the burden associated with the disease.

Bone mineral density and body mass composition measurements in premenopausal anorexic patients: the impact of lean body mass.

INTRODUCTION: Evaluating bone density and body composition by dual-energy x-ray absorptiometry (DXA) and analyzing their relationships among young anorexic women in comparison with normal-lean matched controls. MATERIALS AND METHODS: In this observational cohort study, 98 normal-underweight young females were enrolled (aged more than 16 and less than 24 years). The study group included 68 anorexic patients and 30 healthy age-matched controls. The patients underwent a DXA examination to evaluate bone mineral density and body composition. Several indexes of body composition were used: the FMI (Fat Mass Index), the TLMI (Total Lean Mass Index) and the SMI (Skeletal Muscle mass Index) the last one as a marker of sarcopenia. RESULTS: According to the ISCD (International Society for Clinical Densitometry) criteria, a significantly higher percentage of anorexic patients were found to be below the expected range for age as compared to controls (P < 0.01). According to WHO criteria, 20% of the anorexic patients presented an osteoporotic T-score index at the lumbar level and 18% presented an osteoporotic T-score at the femoral level. As regards the lean body characteristics, the SMI and TLMI were significantly lower in the anorexic population (P < 0.01 and P < 0.001, respectively) and 24% of the anorexic patients presented SMI values that are indicative of pre-sarcopenia. In addition, only the SMI significantly correlated with both the lumbar and the femoral BMD values. CONCLUSION: Anorexic patients have a very high risk of osteoporosis and fractures. Bone density is influenced by fat body mass and also significantly by lean body mass. Special consideration should be given to the sarcopenic condition since it is a worsening factor of bone health.

The impact of glucocorticoids on bone health and growth: endocrine and non-endocrine effects in children and young patients.

Glucocorticoids have numerous applications in short and/or long-term therapy both in pediatric and young adults, based on their significant anti-inflammatory and immunosuppressive effects. Different routes of administration can be provided including topical, inhalatory and oral. Topical treatments are the first choice for many dermatologic conditions. The inhalatory form is widely used in asthma management while systemic pathologies often require oral administration. The risks for adverse effects are related to the dose and duration of therapy as well as the specific agent used. Therefore, long-term treatment has a negative impact on different metabolic systems and can lead to hypertension, dyslipidemia and insulin resistance. In particular, many studies emphasize the direct and indirect effects of glucocorticoids on bone health. Glucocorticoids are the most common iatrogenic cause of osteoporosis and can alter bone development in young adults. These side effects are due to an early and transient increase in bone resorption and a decrease in bone formation. Glucocorticoid-induced changes can act on the bone multicellular unit, bone cells and intracellular signaling pathways. Chronic use can also modify bone mass though indirect endocrine and non-endocrine effects by reducing the anabolic function of sex steroids and GH/IGF-1 axis, interfere with calcium metabolism, as well as muscle atrophy and central fat accumulation. The aim of our review was to revise the available evidence on the impact of glucocorticoid treatment on bone health related to endocrine and non-endocrine effects in Young patients.

Associations between Maternal Dietary Patterns, Biomarkers and Delivery Outcomes in Healthy Singleton Pregnancies: Multicenter Italian GIFt Study.

Background: Maternal nutrition represents a critical risk factor for adverse health outcomes in both mother and offspring. We aimed to investigate associations between maternal nutritional habits, biomarker status, and pregnancy outcome among Italian healthy normal-weight pregnancies. Methods: Multicenter prospective cohort study recruiting Italian healthy normal-weight women with singleton spontaneous pregnancies at 20 ± 2 weeks (T1) in Milan and Naples. All patients underwent nutritional evaluations by our collecting a 7-day weighed dietary record at 25 ± 1 weeks (T2) and a Food Frequency Questionnaire at 29 ± 2 weeks (T3). Maternal venous blood samples were collected at T3 to assess nutritional, inflammatory and oxidative biomarker concentrations (RBCs folate, vitamin D, hepcidin, total antioxidant capacity). Pregnancy outcomes were collected at delivery (T4). General linear models adjusted for confounding factors were estimated to investigate associations between maternal dietary pattern adherence, nutrient intakes, biomarker concentrations and delivery outcomes. Results: 219 healthy normal-weight pregnant women were enrolled. Vitamin D and RBCs folate concentrations, as well as micronutrient intakes, were consistently below the recommended range. In a multi-adjusted model, maternal adherence to the most prevalent 'high meat, animal fats, grains' dietary pattern was positively associated with hepcidin concentrations and negatively associated with gestational age at delivery in pregnancies carrying female fetuses. Hepcidin plasma levels were further negatively associated to placental weight, whereas vitamin D concentrations were positively associated to neonatal weight. Conclusions: A high adherence to an unbalanced 'high meat, animal fats, grains' pattern was detected among Italian normal-weight low-risk pregnancies, further associated with maternal pro-inflammatory status and gestational age at delivery. This evidence underlines the need for a dedicated nutritional counseling even among low-risk pregnancies.

Elephant bones for the Middle Pleistocene toolmaker.

The use of bone as raw material for implements is documented since the Early Pleistocene. Throughout the Early and Middle Pleistocene bone tool shaping was done by percussion flaking, the same technique used for knapping stone artifacts, although bone shaping was rare compared to stone tool flaking. Until recently the generally accepted idea was that early bone technology was essentially immediate and expedient, based on single-stage operations, using available bone fragments of large to medium size animals. Only Upper Paleolithic bone tools would involve several stages of manufacture with clear evidence of primary flaking or breaking of bone to produce the kind of fragments required for different kinds of tools. Our technological and taphonomic analysis of the bone assemblage of Castel di Guido, a Middle Pleistocene site in Italy, now dated by 40Ar/39Ar to about 400 ka, shows that this general idea is inexact. In spite of the fact that the number of bone bifaces at the site had been largely overestimated in previous publications, the number of verified, human-made bone tools is 98. This is the highest number of flaked bone tools made by pre-modern hominids published so far. Moreover the Castel di Guido bone assemblage is characterized by systematic production of standardized blanks (elephant diaphysis fragments) and clear diversity of tool types. Bone smoothers and intermediate pieces prove that some features of Aurignacian technology have roots that go beyond the late Mousterian, back to the Middle Pleistocene. Clearly the Castel di Guido hominids had done the first step in the process of increasing complexity of bone technology. We discuss the reasons why this innovation was not developed. The analysis of the lithic industry is done for comparison with the bone industry.

Recent Insights on the Maternal Microbiota: Impact on Pregnancy Outcomes.

Hormonal changes during and after pregnancy are linked with modifications in the maternal microbiota. We describe the importance of the maternal microbiota in pregnancy and examine whether changes in maternal microbiotic composition at different body sites (gut, vagina, endometrium) are associated with pregnancy complications. We analyze the likely interactions between microbiota and the immune system. During pregnancy, the gastrointestinal (gut) microbiota undergoes profound changes that lead to an increase in lactic acid-producing bacteria and a reduction in butyrate-producing bacteria. The meaning of such changes needs clarification. Additionally, several studies have indicated a possible involvement of the maternal gut microbiota in autoimmune and lifelong diseases. The human vagina has its own microbiota, and changes in vaginal microbiota are related to several pregnancy-related complications. Recent studies show reduced lactobacilli, increased bacterial diversity, and low vaginal levels of beta-defensin 2 in women with preterm births. In contrast, early and healthy pregnancies are characterized by low diversity and low numbers of bacterial communities dominated by Lactobacillus. These observations suggest that early vaginal cultures that show an absence of Lactobacillus and polymicrobial vaginal colonization are risk factors for preterm birth. The endometrium is not a sterile site. Resident endometrial microbiota has only been defined recently. However, questions remain regarding the main components of the endometrial microbiota and their impact on the reproductive tract concerning both fertility and pregnancy outcomes. A classification based on endometrial bacterial patterns could help develop a microbiota-based diagnosis as well as personalized therapies for the prevention of obstetric complications and personalized treatments through nutritional, microbiotic, or pharmaceutical interventions.

No increase in incidence or risk of recurrence of breast cancer in ospemifene-treated patients with vulvovaginal atrophy (VVA).

OBJECTIVE: To estimate the incidence and recurrence of breast cancer (BC) in patients with vulvovaginal atrophy (VVA) treated with ospemifene and matched untreated VVA patients using real-world data. STUDY DESIGN: Retrospective matched cohort study. MAIN OUTCOME MEASURES: VVA patients were identified from the 2011-2018 US MarketScan® insurance claims database. For incidence, ospemifene-treated VVA patients without evidence of BC prior to index treatment were matched to two untreated VVA controls similarly without history of BC on age, index VVA year, geographic region, Charlson Comorbidity categories, and follow-up time. BC after the index treatment was identified by BC diagnosis codes, mastectomy, chemotherapy, or radiation procedure. Incidence rate, rate ratio (RR) and their 95 % confidence intervals (CI) were calculated. The process was repeated to estimate BC recurrence in patients with a history of BC in 1:1, 1:2 and 1:3 matches. RESULTS: 1728 ospemifene users and 3456 untreated patients met the inclusion and matching criteria for assessing incidence. The average number of days for which ospemifene was supplied was 314 (standard deviation [SD] = 340). Average follow-up time from index treatment was 937 days (SD = 392) for treated patients and 915 days (SD = 396) for controls. BC incidence rates per 1000 person-years was 2.03 (95 % CI: 1.06-3.91) for treated patients and 3.53 (95 % CI: 2.49-4.99) for controls (RR = 0.58, 95 % CI: 0.28-1.21). No difference in recurrence was observed between ospemifene-treated and matched untreated patients. Ten (32.3 %) treated vs. 25 (40.3 %) controls in the 1:2 matched analysis had a recurrence. CONCLUSION: No differences were observed in the BC incidence and recurrence rates in ospemifene users compared with matched controls.

Vulvovaginal atrophy (VVA) in breast cancer survivors (BCS) is still an unmet medical need: results of an Italian Delphi Panel.

PURPOSE: VVA is a common disease, with approximately 50% of all postmenopausal women having related symptoms. VVA has a significant impact on the personal and sexual lives and on many aspects of women's self-esteem and emotional well-being. It is particularly frequent and severe in patients treated for BC, where it originates significant economic and social costs. Given the lack of published evidence on this subject, a Delphi Panel was carried out to evaluate:The epidemiology of VVA and of its risk-factors/comorbidities in ItalyThe present standard of care and unmet medical needsThe comparison between recent US epidemiological data and the Italian situationThe health resources used in VVA BC The burden of illnessDespite the considerable negative impact on quality of life, a disparity between the high prevalence of this condition and the infrequent clinical diagnosis is documented in medical practice and in surveys. This inaccuracy is thought to be primarily a consequence of patients' unwillingness and/or reluctance to report symptoms in the clinical setting and of health-care professional's difficulty in approaching this sensitive topic during routine consultations. METHODS: A Delphi Panel methodology was used: a first round of written questionnaires, followed by a plenary meeting with a facilitator and by two additional rounds of telephone interviews. RESULTS: The prevalence of the condition in Italy can be estimated in 115,000 cases out of 380,000 BC survivors. The Panel confirmed that the epidemiological findings of a recent pharmacoeconomic analysis of a US claims database can be applied to Italian patient population. The Panel confirmed also an estimate of 4.25 additional cases/100/yr of UTI (urinary tract infection) in VVA BC patients (vs. a non-VVA-matched population), of 3.68 additional cases of vulvovaginitis, of 6.97 cases of climacteric symptoms, and of 3.64 cases of bone and joint disorders. As far as the resource use is concerned, in the VVA BC populations, 33.4 additional gynecological visits/100/year can be expected, along with 22.8 additional cancer screenings, 7.07 additional outpatient visits and 5.04 screenings for HPV. CONCLUSIONS: Even in Italy, a diagnosis of VVA, especially in a BC population, is associated with a relevant increase in the burden of illness and social costs, compared to a control population matched for age without VVA. This is due essentially to an increase in comorbidities and resource utilization with the consequence that an adequate treatment could reduce the impact of the condition.

Neandertals on the beach: Use of marine resources at Grotta dei Moscerini (Latium, Italy).

Excavated in 1949, Grotta dei Moscerini, dated MIS 5 to early MIS 4, is one of two Italian Neandertal sites with a large assemblage of retouched shells (n = 171) from 21 layers. The other occurrence is from the broadly contemporaneous layer L of Grotta del Cavallo in southern Italy (n = 126). Eight other Mousterian sites in Italy and one in Greece also have shell tools but in a very small number. The shell tools are made on valves of the smooth clam Callista chione. The general idea that the valves of Callista chione were collected by Neandertals on the beach after the death of the mollusk is incomplete. At Moscerini 23.9% of the specimens were gathered directly from the sea floor as live animals by skin diving Neandertals. Archaeological data from sites in Italy, France and Spain confirm that shell fishing and fresh water fishing was a common activity of Neandertals, as indicated by anatomical studies recently published by E. Trinkaus. Lithic analysis provides data to show the relation between stone tools and shell tools. Several layers contain pumices derived from volcanic eruptions in the Ischia Island or the Campi Flegrei (prior to the Campanian Ignimbrite mega-eruption). Their rounded edges indicate that they were transported by sea currents to the beach at the base of the Moscerini sequence. Their presence in the occupation layers above the beach is discussed. The most plausible hypothesis is that they were collected by Neandertals. Incontrovertible evidence that Neandertals collected pumices is provided by a cave in Liguria. Use of pumices as abraders is well documented in the Upper Paleolithic. We prove that the exploitation of submerged aquatic resources and the collection of pumices common in the Upper Paleolithic were part of Neandertal behavior well before the arrival of modern humans in Western Europe.

Local ultra-low-dose estriol gel treatment of vulvo-vaginal atrophy: efficacy and safety of long-term treatment.

Vulvo-vaginal atrophy (VVA) is a chronic condition affecting many postmenopausal women. Local estrogen treatment is recommended. Evaluating efficacy and safety of long-term VVA treatment with ultra-low-dose estriol gel, 120 postmenopausal VVA women were enrolled in a prospective study. They received the first cycle of 1 g/day vaginal gel containing 50 µg estriol for 3 weeks and then twice a week for 12 weeks. Moderate or severe VVA women received a second treatment cycle reaching treatment of 30 weeks. Vaginal pH measurement, subjective symptoms, and objective signs assessment of VVA, endometrial thickness and adverse events (AE) were recorded. Of the 99 women, completing the first phase, 43% experienced a complete VVA symptom relief, and 65% presented a milder VVA degree. After 30 weeks, VVA signs significantly improved (p<.01) compared with baseline and first phase results; total objective symptom evaluation including Schiller's test, flattening of folds and vaginal pH significantly improved (p<.01). At study endpoint, none of the patients had severe VVA, 93% had a positive response, 75% had a complete symptom, and sign resolution. No treatment-related endometrial AE were observed. Postmenopausal VVA long term-treatment with ultra-low-dose estriol vaginal gel is safe and effective.

Cardiovascular Risk/Benefit Profile of MHT.

Background and Objectives: Data emerging from the Women's Health Initiative (WHI) study point toward an association between menopausal hormone therapy (MHT) and cardiovascular (CV) risk. However, post hoc subgroup analyses stratifying participants according to their age and time since menopause, have opened the way to a better understanding of the relationship between estrogen and CV risk. The aim of this review was to revise the current literature and evaluate the CV risk or benefit following administration of MHT considering several factors such as MHT timing, dose, route of administration, and formulation. Materials and Methods: An electronic databases search of MEDLINE (PubMed), Cochrane Central Register of Controlled Trials, Web of Science, SCOPUS, congress abstracts, and Grey literature (Google Scholar; British Library) was performed, with the date range from each database's inception until June 2019. All the studies evaluating MHT and cardiovascular risk, including thromboembolism or stroke, were selected. Results: Timing of MHT initiation was shown to be a critical factor in CV risk assessment. In concordance with the "timing hypothesis", healthy symptomatic women who initiated MHT when aged younger than 60 years, or who were within 10 years of menopause onset, have demonstrated a reduction in both coronary heart disease (CHD) risk and all-cause mortality. In particular, MHT therapy was associated with improvement of subclinical signs of atherosclerosis. Venous thromboembolism (VTE) risk is reduced when low doses of oral estrogen are used. Moreover, transdermal hormonal application significantly reduces CV risk compared with oral administration. MHT impact on the CV system is influenced by either factors inherent to the specific regimen, or factors inherent to the specific patient. Hence, individualization of care is necessary. Conclusion: CV risk calculation should be considered by clinicians in order to exclude patients with high CV risk, in whom MHT is contraindicated. Assessing risks and benefits in a patient-centered approach according to individual's features, health status, and personal preferences is important in order to realize a safe and effective treatment.

Hafting of Middle Paleolithic tools in Latium (central Italy): New data from Fossellone and Sant'Agostino caves.

Hafting of stone tools was an important advance in the technology of the Paleolithic. Evidence of hafting in the Middle Paleolithic is growing and is not limited to points hafted on spears for thrusting or throwing. This article describes the identification of adhesive used for hafting on a variety of stone tools from two Middle Paleolithic caves in Latium, Fossellone Cave and Sant'Agostino Cave. Analysis of the organic residue by gas chromatography/mass spectrometry shows that a conifer resin adhesive was used, in one case mixed with beeswax. Contrary to previous suggestions that the small Middle Paleolithic tools of Latium could be used by hand and that hafting was not needed since it did not improve their functionality, our evidence shows that hafting was used by Neandertals in central Italy. Ethnographic evidence indicates that resin, which dries when exposed to air, is generally warmed by exposure to a small fire thus softened to be molded and pushed in position in the haft. The use of resin at both sites suggests regular fire use, as confirmed by moderate frequencies of burnt lithics in both assemblages. Lithic analysis shows that hafting was applied to a variety of artifacts, irrespective of type, size and technology. Prior to our study evidence of hafting in the Middle Paleolithic of Italy was limited to one case only.

From Neandertals to modern humans: New data on the Uluzzian.

Having thrived in Eurasia for 350,000 years Neandertals disappeared from the record around 40,000-37,000 years ago, after modern humans entered Europe. It was a complex process of population interactions that included cultural exchanges and admixture between Neandertals and dispersing groups of modern humans. In Europe Neandertals are always associated with the Mousterian while the Aurignacian is associated with modern humans only. The onset of the Aurignacian is preceded by "transitional" industries which show some similarities with the Mousterian but also contain modern tool forms. Information on these industries is often incomplete or disputed and this is true of the Uluzzian. We present the results of taphonomic, typological and technological analyses of two Uluzzian sites, Grotta La Fabbrica (Tuscany) and the newly discovered site of Colle Rotondo (Latium). Comparisons with Castelcivita and Grotta del Cavallo show that the Uluzzian is a coherent cultural unit lasting about five millennia, replaced by the Protoaurignacian before the eruption of the Campanian Ignimbrite. The lack of skeletal remains at our two sites and the controversy surrounding the stratigraphic position of modern human teeth at Cavallo makes it difficult to reach agreement about authorship of the Uluzzian, for which alternative hypotheses have been proposed. Pending the discovery of DNA or further human remains, these hypotheses can only be evaluated by archaeological arguments, i.e. evidence of continuities and discontinuities between the Uluzzian and the preceding and succeeding culture units in Italy. However, in the context of "transitional" industries with disputed dates for the arrival of modern humans in Europe, and considering the case of the Châtelperronian, an Upper Paleolithic industry made by Neandertals, typo-technology used as an indicator of hominin authorship has limited predictive value. We corroborate previous suggestions that the Middle-to-Upper Paleolithic transition occurred as steps of rapid changes and geographically uneven rates of spread.

Menopause and hormone replacement therapy: the 2017 Recommendations of the Italian Menopause Society.

Over the last decade, the risk benefits ratio of hormone replacement therapy (HRT) has been reevaluated mainly in tens of cardiovascular risk. Present Consensus Statement is largely inspired by the Global Consensus on Menopausal Hormone Therapy in 2013 and 2016 by leading global menopause societies (The American Society for Reproductive Medicine, The Asia Pacific Menopause Federation, The Endocrine Society, The European Menopause and Andropause Society, The International Menopause Society, The International Osteoporosis Foundation and The North American Menopause Society). The aim of these recommendations is to provide a simple and updated reference on postmenopausal HRT. The term HRT typically includes estrogen replacement therapy (ERT) and estrogen-progestogen therapy (EPT). EPT can be sequential, when progestogen is added to ERT for 10-14 days a month, or continuous combined when progestogen is administered continuously every day along with a fixed amount of estrogen, In the everyday language, HRT includes also tibolone and the tissue-selective estrogen complex.

Early Levallois and the beginning of the Middle Paleolithic in central Italy.

In the second half of the 19th century Pleistocene faunas were discovered in two sites, Sedia del Diavolo and Monte delle Gioie, contained in deposits of the Aniene River in the area of Rome (Latium, Italy). Fieldwork by A.C. Blanc in the late 1930's proved the association of fauna and lithic industry within fluvial deposits interbedded with volcanoclastic layers. A human femoral diaphysis and a metatarsal were later identified in the faunal assemblage from Sedia del Diavolo and evaluated as Neandertal. The lithic assemblages from these two sites were the basis of the definition of the Protopontinian by M. Taschini, which she viewed as a late Middle Pleistocene industry very similar to the later, Upper Pleistocene Pontinian industries, thought to be characteristic of the Latium Mousterian. The chronostratigraphic framework of the Aniene river deposits has been recently updated and the lithic assemblages from these two sites are now confidently dated between 295 and 290 ka, close to the transition from MIS 9 to MIS 8. They fit chronologically between the industries of layers m and d from Torre in Pietra, a site 26 km northwest of Rome. The presence of the Levallois debitage is indisputable yet it occurs within an original technical context, different from what is known in other early occurrences of the Levallois. The date confirms the proposed chronology for the early Levallois in Europe. More importantly these two assemblages demonstrate that this technology can emerge in more diversified contexts than usually described. This suggests that its dispersal in Europe may have been rapid.

The impact of combined nutraceutical supplementation on quality of life and metabolic changes during the menopausal transition: a pilot randomized trial.

PURPOSE: The aim of this study was to assess the efficacy of a combined nutraceutical supplement on symptoms and early metabolic alterations during the menopausal transition. This pilot randomized study was conducted at the service for menopause disorders of the Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy. METHODS: Ninety women in menopausal transition who attended our service with menopausal symptoms were enrolled in the study. Sixty patients, randomly assigned to the treatment group, were prescribed one daily tablet of a combined nutraceutical compound with phytoestrogen substances, vitamins, micronutrients and passion flower herbal medicine for 6 months. Thirty patients did not receive any treatment and comprised the control group. The intensity of perimenopausal symptoms was assessed by the modified Kuppermann Index (KI) at enrollment and at 3 and 6 months of treatment. At baseline and at the end of the study, patients underwent a clinical evaluation, a pelvic ultrasound and analysis of blood samples. RESULTS: In the nutraceutical supplemented group, a significant reduction in menopausal symptoms was demonstrated according to the KI after 3 and 6 months of supplementation (p < 0.01). The within-group analysis of different KI parameters in the treated group showed a significant improvement in hot flushes (p < 0.001), insomnia (p < 0.01), fatigue (p < 0.01) and irritability (p < 0.01). Metabolic parameters did not change significantly in the nutraceutical supplemented group. In the control group, total cholesterol level showed a significant increase (p < 0.05). CONCLUSIONS: Combined nutraceutical supplementation provides an effective and safe solution for early symptoms occurring during menopausal transition.