Gestational diabetes mellitus is associated with in vivo platelet activation and platelet hyperreactivity.

BACKGROUND: Gestational diabetes mellitus is associated with obstetrical and long-term cardiovascular complications. Although platelet hyperresponsiveness in type-2 diabetes mellitus has been well characterized and has been shown to play a crucial role in cardiovascular complications, this aspect has been little studied in gestational diabetes mellitus. OBJECTIVE: We aimed to evaluate platelet reactivity, in vivo platelet activation, and endothelial function in gestational diabetes mellitus in comparison with normal pregnancy. STUDY DESIGN: This was a prospective, case-control study of 23 women with gestational diabetes mellitus and 23 healthy pregnant women who were studied at 26 to 28 and 34 to 36 weeks of gestation and at 8 weeks postpartum. Platelet reactivity and in vivo platelet activation, including light transmission aggregometry, PFA-100, platelet activation antigen expression, platelet adhesion under flow, platelet nitric oxide and reactive oxygen species production, and endothelial dysfunction markers, were assessed. RESULTS: The study of platelet function showed a condition of platelet hyperreactivity in cases with gestational diabetes mellitus when compared with healthy pregnant women at enrollment, which was further enhanced at the end of pregnancy and tended to decrease 2 months after delivery, although it still remained higher in gestational diabetes mellitus. In vivo platelet activation was also evident in gestational diabetes mellitus, especially at the end of pregnancy, in part persisting up to 8 weeks after delivery. Finally, women with gestational diabetes mellitus showed defective platelet nitric oxide production and endothelial dysfunction when compared with healthy pregnancies. CONCLUSION: Our data showed that gestational diabetes mellitus generates a condition of platelet hyperreactivity that in part persists up to 2 months after delivery. Impaired platelet sensitivity to nitric oxide and reduced platelet and endothelial nitric oxide production may contribute to the platelet hyperreactivity condition. Platelet hyperreactivity may play a role in the long-term cardiovascular complications of gestational diabetes mellitus women.

Reproductive and Oncologic Outcomes in Young Women with Stage IA and Grade 2 Endometrial Carcinoma Undergoing Fertility-Sparing Treatment: A Systematic Review.

BACKGROUND: Endometrial cancer (EC) is the most common gynecological malignancy in both Europe and the USA. Approximately 3-5% of cases occur in women of reproductive age. Fertility-sparing treatment (FST) options are available, but very limited evidence regarding grade 2 (G2) ECs exists in the current literature. This systematic review aimed to comprehensively evaluate reproductive and oncologic outcomes among young women diagnosed with stage IA or G2EC disease who underwent FST. METHODS: A comprehensive search of the literature was carried out on the following databases: MEDLINE, EMBASE, Global Health, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), the Health Technology Assessment Database, and Web of Science. Only original studies that reported the oncologic and reproductive outcomes of patients with stage IA and G2EC tumors who underwent FST were considered eligible for inclusion in this systematic review (CRD42023484892). Studies describing only the FST for endometrial hyperplasia or G1 EC were excluded. RESULTS: Twenty-two papers that met the abovementioned inclusion criteria were included in the present systematic review. Preliminary analysis suggested encouraging oncologic and reproductive outcomes after FST. CONCLUSIONS: The FST approach may represent a feasible and safe option for women of childbearing age diagnosed with G2EC. Despite these promising findings, cautious interpretation is warranted due to inherent limitations, including heterogeneity in study designs and potential biases. Further research with standardized methodologies and larger sample sizes is imperative for obtaining more robust conclusions.

Health-related quality of life after hysterectomy for endometrial cancer: the impact of enhanced recovery after surgery (ERAS) shifting paradigm.

OBJECTIVES: Enhanced recovery after surgery (ERAS) protocols provide well-known benefits in the immediate recovery with a shorter length of stay (LOS) also in gynecological surgery. However, the impact of ERAS has not been clearly showed yet regarding long-term consequences and health-related quality of life (HRQL). The aim of this study is to investigate the impact of ERAS on HRQL after hysterectomy for endometrial cancer. DESIGN: Observational retrospective study with propensity score matching (PSM). Participants We administered the SF-36 validated questionnaire to women underwent hysterectomy and lymph nodal staging before and after introducing ERAS protocol, getting, respectively, a standard practice (SP) and ERAS group Settings Academic hospital Methods We collected demographic, clinical, surgical and postoperative data and performed a PSM of the baseline coufouders. We administered the questionnaire four weeks after the surgery. The SF-36 measures HRQL using eight scales: physical functioning (PF), role physical (RLP), bodily pain (BP), general health (GH), vitality (Vt), social functioning (SF), role emotional (RLE) and mental health (MH). Results After PSM, we enrolled a total of 154 patients, 77 in each group (SP and ERA). The two groups were similar in terms of age, BMI, anaesthesiologic risk, Charlson comorbidity index (CCI) and surgical technique (minimally invasive versus open access). Median LOS was shorter for ERAS group (5 versus 3 days; p = 0.02), while no significant differences were registered in the rates of postoperative complications (16.9% versus 17.4%; p = 0.66). Response rates to SF-36 questionnaire were 89% and 92%, respectively, in SP and ERAS group. At multivariate analyzes, the mean scores of SF-36 questionnaire, registered at 28 days weeks after surgery (range 26-32 days), were significantly higher in ERAS group for PF (73.3 vs 91.6; p < 0.00), RLP (median 58.3 vs 81.2; p = 0.02) and SF (37.5 versus 58.3; p = 0.01) domains, when compared to SP patients. Limitations Further follow-up was not possible due to the anonymized data derived from clinical audit. Conclusions ERAS significantly increases HRQL of women underwent surgery for endometrial cancer. HRQL assessment should be routinary implemented in the ERAS protocol.

Efficacy, safety, and feasibility of the treatment of intrauterine pathologies with the mini-resectoscope: A systematic review.

BACKGROUND: Hysteroscopy represents the gold standard for the diagnosis and treatment of intrauterine pathologies. The advent of the mini-resectoscope heralded a new era in intrauterine surgery, both in inpatient and outpatient settings. OBJECTIVES: To evaluate the effectiveness, safety, and feasibility of the mini-resectoscope for the treatment of intrauterine pathologies. SEARCH STRATEGY: Electronic databases were searched for English-language trials describing surgical procedures for uterine pathologies performed with a mini-resectoscope until 30 April 2023. SELECTION CRITERIA: Retrospective or prospective original studies reporting the treatment of uterine pathologies with mini-resectoscope were deemed eligible for the inclusion. DATA COLLECTION AND ANALYSIS: Data about study features, characteristics of included populations, surgical procedures, complications, and results/outcomes were collected. RESULTS: Seven papers that met the inclusion criteria were included in this systematic review. Quantitative analysis was not possible due to data heterogeneity. A descriptive synthesis of the results was provided accordingly to the pathology hysteroscopically removed/corrected: polyps and myomas, uterine septum, intrauterine synechiae, and isthmocele. CONCLUSIONS: The mini-resectoscope is poised to play a leading role in hysteroscopic surgery for many pathologies, both in inpatient and outpatient settings. Since some applications of the mini-resectoscope have not yet been thoroughly investigated, future studies should address current knowledge gaps, designing high-quality comparative trials on specific applications.

Use of Diode Laser in Hysteroscopy for the Management of Intrauterine Pathology: A Systematic Review.

Background: Hysteroscopy currently represents the gold standard for the diagnosis and treatment of intrauterine pathologies. Recent technological progress has enabled the integration of diagnostic and operative time, leading to the "see and treat" approach. Diode laser technology is emerging as one of the most innovative and intriguing techniques in this context. Methods: A comprehensive search of the literature was carried out on the main databases. Only original studies reporting the treatment of intrauterine pathologies using diode laser were deemed eligible for inclusion in this systematic review (PROSPERO ID: CRD42023485452). Results: Eight studies were included in the qualitative analysis for a total of 474 patients undergoing laser hysteroscopic surgery. Eighty-three patients had female genital tract abnormalities, 63 had submucosal leiomyomas, 327 had endometrial polyps, and one patient had a scar pregnancy. Except for leiomyomas, whose technique already included two surgical times at the beginning, only seven patients required a second surgical step. Cumulative rates of intraoperative and postoperative complications of 2.7% and 0.6%, respectively, were reported. Conclusions: Diode laser through "see and treat" hysteroscopy appears to be a safe and effective method. However, additional studies with larger sample sizes and improved designs are needed to consolidate the evidence currently available in the literature.

Isthmocele, not cesarean section per se, reduces in vitro fertilization success: a systematic review and meta-analysis of over 10,000 embryo transfer cycles.

IMPORTANCE: Previous reviews have shown that a history of cesarean section (CS) is associated with a worse in vitro fertilization (IVF) prognosis. To date, whether the decline in the IVF chances of success should be attributed to the CS procedure itself or to the presence of isthmocele remains to be clarified. OBJECTIVE: To summarize the available evidence regarding the impact of isthmocele on IVF outcomes. DATA SOURCES: Electronic databases and clinical registers were searched until May 30, 2023. STUDY SELECTION AND SYNTHESIS: Observational studies were included if they assessed the effect of isthmocele on IVF outcomes. Comparators were women with isthmocele and women without isthmocele with a previous CS or vaginal delivery. Study quality was assessed using the modified Newcastle-Ottawa Scale. MAIN OUTCOMES: The primary outcome was the live birth rate (LBR). The effect measures were expressed as adjusted odds ratios (aORs) and unadjusted odds ratios (uORs) with 95% confidence intervals (95% CIs). The body of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation working group methodology. RESULTS: Eight studies (n = 10,873 patients) were included in the analysis. Women with isthmocele showed a lower LBR than both women with a previous CS without isthmocele (aOR, 0.62; 95% CI, 0.53-0.72) and those with a history of vaginal delivery (aOR, 0.55; 95% CI, 0.42-0.71). The LBRs in women with a previous CS without isthmocele and those with a history of vaginal delivery were similar (aOR, 0.74; 95% CI, 0.47-1.15). Subgroup analysis suggested a negative effect of the intracavitary fluid (ICF) in women with isthmocele on the LBR (uOR, 0.36; 95% CI, 0.18-0.75), whereas the LBRs in women without ICF and those without isthmocele were similar (uOR, 0.94; 95% CI, 0.61-1.45). CONCLUSION AND RELEVANCE: We found moderate quality of evidence (Grading of Recommendations Assessment, Development and Evaluation grade 3/4) supporting a negative impact of isthmocele, but not of CS per se, on the LBR in women undergoing IVF. The adverse effect of isthmocele on IVF outcomes appears to be worsened by ICF accumulation before embryo transfer. CLINICAL TRIAL REGISTRATION NUMBER: CRD42023418266.

The challenge of FIGO type 3 leiomyomas and infertility: Exploring therapeutic alternatives amidst limited scientific certainties.

Uterine leiomyomas (ULs) are non-cancerous tumors composed of smooth muscle cells that develop within the myometrium and represent the most prevalent pathological condition affecting the female genital tract. Despite the volume of available research, many aspects of ULs remain unresolved, making it a "paradoxical disease" where the increase in available scientific literature has not been matched by an increase in solid evidence for clinical management. Fertility stands at the top of the list of clinical issues where the role of ULs is still unclear. The leiomyoma subclassification system, released by the International Federaion of Gynecology and Obstetrics (FIGO) in 2008, introduced a new and more effective way of categorizing uterine fibroids. The aim was to go beyond the traditional classification "subserosal, intramural and submucosal", facilitating a detailed examination of individual ULs impact on the female reproductive system. The "type 3 UL" is a special type of myoma, characterized by its complete myometrial development while encroaching the endometrium. It is a unique "hybrid" between a submucous and an intramural UL, that may exert a detrimental "double hit" mechanism, which is of particular interest in patients wishing pregnancy. To date, no robust evidence is available regarding the management of type 3 ULs. The aim of this narrative review is to provide a comprehensive overview of the physiopathological mechanisms that type 3 UL may exert on fertility, and to present new perspectives that may help us to better understand both the need for and the methods of treating this unique type of fibroid.

Chiral high-performance liquid chromatography analysis of mono-, di-, and triacylglycerols with amylose- and cellulose-phenylcarbamate-based stationary phases.

The ever-increasing technological advancement in the (ultra)high-performance liquid chromatography tandem (high-resolution) mass spectrometry platforms have largely contributed to steeply intensify the interest towards lipidomics research. However, mass spectrometers alone are unable to distinguish between enantiomers. This obstacle is especially evident in the case of glycerolipids analysis due the prochiral nature of glycerol. Until a couple of decades ago, the stereoselective analysis of triacylglycerols (TAGs) was performed on the end products generated either from their enzymatic or chemical hydrolysis, namely on mono- or diacyl-sn-glycerols (MAGs and DAGs, respectively). These were then mostly analyzed with Pirkle-type chiral stationary phases (CSPs) after dedicated multi-step derivatization procedures. One of the most significant drawbacks of these traditional methods for enantioselective TAGs analysis (actually of the produced MAGs and DAGs, often investigated as target species per se) was the difficulty to totally abolish the migration of fatty acyls between glycerol positions. This made difficult to control and keep unaltered the stereochemistry of the original molecules. Over the last two decades, it has been widely demonstrated that the enantioselective analysis of intact TAGs as well as of non-derivatized MAGs and DAGs can be efficiently obtained using polysaccharide-based CSPs incorporating either amylose- or cellulose-phenylcarbamate derivatives chiral selectors. In this paper, the enantioselective methods developed with these CSPs for the enantioselective direct LC analysis of MAGs, DAGs and TAGs embedding different types of fatty acid residues are comprehensively reviewed.

Patients' Use of Virtual Reality Technology for Pain Reduction during Outpatient Hysteroscopy: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To summarize evidence from randomized controlled trials (RCTs) on the effectiveness of virtual reality technology (VRT), as used by patients, for reducing pain during outpatient hysteroscopy. DATA SOURCES: Electronic databases and clinical registers were searched until June 21, 2023. The review protocol was registered in PROSPERO before the data extraction (CRD42023434340). METHODS OF STUDY SELECTION: We included RCTs of patients receiving VRT compared with controls receiving routine care during outpatient hysteroscopy. TABULATION, INTEGRATION, AND RESULTS: The primary outcome was average pain during hysteroscopy. Pooled results were expressed as mean differences (MDs) with 95% confidence interval (CI). Sources of heterogeneity were investigated through sensitivity and subgroups analysis. Five RCTs were included (435 participants). The comparison between the intervention and control groups showed a borderline difference in perceived pain during hysteroscopy (MD -0.88, 95% CI -1.77 to 0.01). Subgroup analysis based on the type of VRT (active or passive) indicated that active VRT potentially reduced the perception of pain (MD -1.42, 95% CI -2.21 to -0.62), whereas passive VRT had no effect (MD -0.06, 95% CI -1.15 to 1.03). CONCLUSION: Patients' use of active VRT may be associated with a reduction in pain during outpatient hysteroscopy (evidence Grading of Recommendations Assessment, Development, and Evaluation 2/4). Future research should focus on conducting methodologically robust studies with larger sample sizes and more homogeneous populations.

Systematic Review and Meta-Analysis of the Variants of the Obturatory Artery.

BACKGROUND: Knowledge of vascular anatomy and its possible variations is essential for performing embolization or revascularization procedures and complex surgery in the pelvis. The obturator artery (OA) is a branch of the anterior division of the internal iliac artery (IIA), and it has the highest frequency of variation among branches of the internal iliac artery. Possible anomalies of the origin of the obturator artery (OA) should be known when performing pelvic and groin surgery, where its control or ligation may be required. The purpose of this systematic review and meta-analysis, based on Sanudo's classification, is to analyze the origin of the obturator artery (OA) and its variants. METHODS: Thirteen articles published between 1952 and 2020 were included. RESULTS: The obturator artery (OA) was present in almost all cases (99.8%): the pooled prevalence estimate for the origin from the IIA axis was 77.7% (95% CI 71.8-83.1%) vs. 22.3% (95% CI 16.9-28.2%) for the origin from EIA axis. In most cases, the obturator artery (OA) originated from the anterior division trunk of the internal iliac artery (IIA) (61.6%). CONCLUSIONS: Performing preoperative radiological examination to determine the pelvic vascular pattern and having the awareness to evaluate possible changes in the obturator artery can reduce the risk of iatrogenic injury and complications.

Feasibility and Surgical Outcomes of Hysteroscopic Myomectomy of FIGO Type 3 Myoma: A Systematic Review.

The latest classification from the Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) has reclassified type 3 myomas, changing their classification from intramural to submucosal. While hysteroscopic myomectomy is considered the gold standard treatment for patients experiencing symptoms from submucosal myomas, there are currently no specific guidelines available for managing type 3 myomas, and the optimal surgical approach remains uncertain. Methods: The search for suitable articles published in English was carried out using the following databases (PROSPERO ID CRD42023418602): MEDLINE, EMBASE, Global Health, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), Health Technology Assessment Database, Web of Science and search register. Only original studies reporting data on hysteroscopic myomectomy of type 3 myoma were considered eligible. The main outcomes investigated were the effectiveness and feasibility of hysteroscopic myomectomy and reproductive outcomes after surgical treatment. Results: Two hundred and sixty-one studies were screened and nineteen of these were read for eligibility. Three studies encompassing 56 patients in total were included. Among the overall population studied, three patients needed an additional procedure to completely remove the myoma and five cases of post-surgical synechiae were recorded. No complications were reported. Of 42 patients wishing for pregnancy, the cumulative live birth rates before and after the hysteroscopic myomectomy were 14.3% and 42.9%, respectively. Conclusions: Hysteroscopic myomectomy appears to be a safe and feasible approach. Nevertheless, data reported in the literature are extremely scarce and based on studies with few patients enrolled. New evidence is needed to assess the safety and effectiveness of hysteroscopic treatment for FIGO type 3 myomas.

COVID-19 and Pregnancy: An Updated Review about Evidence-Based Therapeutic Strategies.

The COVID-19 pandemic posed a significant challenge for clinicians in managing pregnant women, who were at high risk of virus transmission and severe illness. While the WHO declared in May 2023 that COVID-19 is no longer a public health emergency, it emphasized that it remains a global health threat. Despite the success of vaccines, the possibility of new pandemic waves due to viral mutations should be considered. Ongoing assessment of the safety and effectiveness of pharmacological therapies is crucial in clinical practice. This narrative review summarizes the evidence-based therapeutic strategies for pregnant women with COVID-19, considering over three years of pandemic experience. The review discusses the safety and effectiveness of various drug regimens (antivirals, anticoagulants, corticosteroids, immunoglobulins, monoclonal antibodies, and therapeutic gases) and procedures (prone positioning and extracorporeal membrane oxygenation). Drugs with contraindications, inefficacy during pregnancy, or unknown adverse effects were excluded from our evaluation. The aim is to provide healthcare professionals with a comprehensive guide for managing pregnant women with COVID-19 based on lessons learned from the pandemic outbreak.

Biochemical and Anthropometric Parameters for the Early Recognition of the Intrauterine Growth Restriction and Preterm Neonates at Risk of Impaired Neurodevelopment.

BACKGROUND: S100B and Tau are implicated with both brain growth and injury. Their urinary levels in 30-to-40-day-old full-term, preterm, IUGR, and preterm-IUGR subjects were measured to investigate their possible relationship with future delayed neurodevelopment. METHODS: Values were related to the neuro-behavioral outcome at two years of age, as well as to brain volumes and urinary NGF assessed at the same postnatal time point. RESULTS: Using the Griffiths III test, cognitive and motor performances were determined to establish subgroups characterized by either normal or impaired neuro-behavior. The latter included preterm, IUGR, and preterm-IUGR individuals who exhibited significantly higher and lower S100B and Tau levels, respectively, along with markedly reduced cerebral volumes and urinary NGF, as previously demonstrated. Contrary to NGF, however, Tau and S100B displayed a weak correlation with brain volumes. CONCLUSIONS: Delayed cognitive and motor performances observed in two-year-old preterm and IUGR-born individuals were also found to be associated with anomalous urinary levels of S100B and Tau, assessed at 30-40 days of the postnatal period, and their changes did not correlate with brain growth. Thus, our data suggests that, in addition to cerebral volumes and NGF, urinary S100B and Tau can also be considered as valuable parameters for the early detection of future neurodevelopmental abnormalities.

Training in Diagnostic Hysteroscopy: The "Arbor Vitae" Method.

Background and Objectives: Diagnostic hysteroscopy is the gold standard in the diagnosis of intrauterine pathology and is becoming an essential tool in the daily practice of gynecology. Training programs for physicians are necessary to ensure adequate preparation and learning curve before approaching patients. The aim of this study was to describe the "Arbor Vitae" method for training in diagnostic hysteroscopy and to test its impact on the knowledge and skills of trainees using a customized questionnaire. Materials and Methods: A three-day hysteroscopy workshop combining theory and practical "hands on "sessions with dry and wet labs has been described. The aim of the course is to teach indications, instruments, the basic principles of the technique by which the procedure should be performed, and how to recognize and manage the pathologies that can be identified by diagnostic hysteroscopy. To test this training method and its impact on the knowledge and skills of the trainees, a customized 10-question questionnaire was administered before and after the course. Results: The questionnaire was administered to 34 participants. All trainees completed the questionnaire, and no missing responses were recorded. Regarding the characteristics of the participants, 76.5% had less than 1 year of experience in performing diagnostic hysteroscopy and 55.9% reported performing fewer than 15 procedures in their career. For 9 of the 10 questions embedded in the questionnaire, there was a significant improvement in the scores between pre- and post-course, demonstrating a perceived significant improvement in theoretical/practical skills by the trainees. Conclusions: The Arbor Vitae training model is a realistic and effective way to improve the theoretical and practical skills required to perform correct diagnostic hysteroscopy. This training model has great potential for novice practitioners to achieve an adequate level of proficiency before performing diagnostic hysteroscopy on live patients.

Impact of FIGO type 3 uterine fibroids on in vitro fertilization outcomes: A systematic review and meta-analysis.

BACKGROUND: The effect of FIGO (the International Federation of Gynecology & Obstetrics) type 3 myomas on in vitro fertilization (IVF) is uncertain. OBJECTIVES: To evaluate whether FIGO type 3 myomas affect IVF outcomes, through a systematic review and meta-analysis (CRD42022379700). SEARCH STRATEGY: Electronic databases were searched until November 15, 2022. SELECTION CRITERIA: Studies evaluating the effects of FIGO type 3 myomas on IVF outcome. DATA COLLECTION AND ANALYSIS: Pooled results were expressed as odds ratios (OR) with 95% confidence intervals (CI). Heterogeneity was assessed using Higgins I2 . Sources of heterogeneity were explored with sensitivity and subgroup analyses. MAIN RESULTS: In total, 1020 patients were included: 324 with FIGO type 3 myomas and 696 controls (without myomas). A pooled data analysis showed a significantly lower live birth rate (OR 2.16, 95% CI 1.55-3.01, I2 = 0%, P < 0.00001), clinical pregnancy rate (OR 2.06, 95% CI 1.52-2.81, I2 = 0%, P < 0.00001), and implantation rate (OR 1.77, 95% CI 1.35-2.32, I2 = 0%, P < 0.00001) in women with untreated myomas compared with controls. The number and size of fibroids correlated with a worsening of IVF outcomes. CONCLUSIONS: FIGO type 3 myomas are significantly associated with a lower implantation rate, cumulative pregnancy rate, and live birth rate. Furthermore, their deleterious effect on the outcome of IVF increases further with increasing size and number. Nevertheless, no firm conclusions could be drawn about the potential benefits of surgery for FIGO type 3 uterine fibroids on IVF outcomes.

Impact of the First and Second Lockdown for COVID-19 Pandemic on Preterm Birth, Low Birth Weight, Stillbirth, Mode of Labor, and of Delivery in Lombardy, Italy.

We investigated the effect of lockdown measures implemented in Lombardy on selected obstetric and perinatal outcomes. Births that occurred during the two lockdowns imposed (i.e., the first from 16 March to 2 June 2020 and the second from 3 November 2020 to 5 April 2021) and the comparison periods (i.e., the first from 16 March to 2 June 2018 and the second from 3 November 2018 to 5 April 2019) were identified using regional healthcare databases. The distribution of births according to the selected outcomes was computed and the Chi-square test was used for testing differences in the periods compared. During the two lockdowns, we observed a lower proportion of low birth weight, from 6.8% in the comparison period to 6.1% in the first lockdown (p = 0.019), and from 6.5% to 6.1% in the second one (p = 0.109). The proportion of preterm births decreased from 6.8% to 6.3% in the first lockdown (p = 0.097), and from 6.2% to 6.0% in the second one (p = 0.172). No differences in stillbirth rate emerged for both lockdowns. Induction of labor was more frequent during both lockdowns, from 28.6% to 32.7% in the first (p < 0.0001), and from 29.9% to 33.2% in the second one (p < 0.0001). Cesarean section was less frequent during the second lockdown.

Preventing Persistence of HPV Infection with Natural Molecules.

Human papillomavirus (HPV) infection is one the most common sexually transmitted infections worldwide. In most cases, the infection is temporary and asymptomatic; however, when persistent, it may lead to lesions that can evolve into cancer in both women and men. Nowadays, prophylactic vaccination is the primary preventive strategy for HPV infections, but vaccines do not cover all types of HPV strains. Scientific research has uncovered the beneficial role of some natural supplements in preventing persistent HPV infections or treating HPV-related lesions. We review the current insight into the roles of natural molecules in HPV infection with a special focus on epigallocatechin gallate (EGCG), folic acid, vitamin B12, and hyaluronic acid (HA). Specifically, EGCG from green tea extracts plays a critical role in suppressing HPV oncogenes and oncoproteins (E6/E7), which are responsible for HPV oncogenic activity and cancer development. Folic acid and vitamin B12 are essential vitamins for multiple functions in the body, and accumulating evidence suggests their importance in maintaining a high degree of methylation of the HPV genome, thus decreasing the likelihood of causing malignant lesions. HA, due to its re-epithelizing property, may prevent HPV virus entry in damaged mucosa and epithelia. Thereby, based on these premises, the combination of EGCG, folic acid, vitamin B12, and HA may be a very promising therapeutic approach to prevent HPV persistence.

Microsampling and enantioselective liquid chromatography coupled to mass spectrometry for chiral bioanalysis of novel psychoactive substances.

In this paper, the development of efficient enantioselective HPLC methods for the analysis of five benzofuran-substituted phenethylamines, two substituted tryptamines, and three substituted cathinones is described. For the first time, reversed-phase (eluents made up with acidic water-methanol solutions) and polar-ionic (eluent made up with an acetonitrile-methanol solution incorporating both an acidic and a basic additive) conditions fully compatible with mass spectrometry (MS) detectors were applied with a chiral stationary phase (CSP) incorporating the (+)-(18-crown-6)-tetracarboxylic acid chiral selector. Enantioresolution was achieved for nine compounds with α and RS factors up to 1.32 and 5.12, respectively. Circular dichroism (CD) detection, CD spectroscopy in stopped-flow mode and quantum mechanical (QM) calculations were successfully employed to investigate the absolute stereochemistry of mephedrone, methylone and butylone and allowed to establish a (R)<(S) enantiomeric elution order for these compounds on the chosen CSP. Whole blood miniaturized samples collected by means of volumetric absorptive microsampling (VAMS) technology and fortified with the target analytes were extracted following an optimized protocol and effectively analysed by means of an ultra-high performance liquid chromatography-MS system. By this way a proof-of-concept procedure was applied, demonstrating the suitability of the method for quali-quantitative enantioselective assessment of the selected psychoactive substances in advanced biological microsamples. VAMS microsamplers including a polypropylene handle topped with a small tip of a polymeric porous material were used and allowed to volumetrically collect small aliquots of whole blood (10 µL) independently from its density. Highly appreciable volumetric accuracy (bias, in the -8.7-8.1% range) and precision (% CV, in the 2.8-5.9% range) turned out.