Dormancy, stemness, and therapy resistance: interconnected players in cancer evolution.

The biological complexity of cancer represents a tremendous clinical challenge, resulting in the frequent failure of current treatment protocols. In the rapidly evolving scenario of a growing tumor, anticancer treatments impose a drastic perturbation not only to cancer cells but also to the tumor microenvironment, killing a portion of the cells and inducing a massive stress response in the survivors. Consequently, treatments can act as a double-edged sword by inducing a temporary response while laying the ground for therapy resistance and subsequent disease progression. Cancer cell dormancy (or quiescence) is a central theme in tumor evolution, being tightly linked to the tumor's ability to survive cytotoxic challenges, metastasize, and resist immune-mediated attack. Accordingly, quiescent cancer cells (QCCs) have been detected in virtually all the stages of tumor development. In recent years, an increasing number of studies have focused on the characterization of quiescent/therapy resistant cancer cells, unveiling QCCs core transcriptional programs, metabolic plasticity, and mechanisms of immune escape. At the same time, our partial understanding of tumor quiescence reflects the difficulty to identify stable QCCs biomarkers/therapeutic targets and to control cancer dormancy in clinical settings. This review focuses on recent discoveries in the interrelated fields of dormancy, stemness, and therapy resistance, discussing experimental evidences in the frame of a nonlinear dynamics approach, and exploring the possibility that tumor quiescence may represent not only a peril but also a potential therapeutic resource.

Assessing ovarian stimulation with letrozole and levonorgestrel intrauterine system after combined fertility-sparing approach for atypical endometrial lesions: a retrospective case-control study.

RESEARCH QUESTION: Is ovarian stimulation with levonorgestrel intrauterine system (LNG-IUS) in situ and co-treatment with letrozole safe and effective in patients undergoing fertility-sparing combined treatment for atypical endometrial hyperplasia (AEH) or early endometrial cancer limited to the endometrium? DESIGN: Retrospective case-control study recruiting women who had undergone fertility-sparing 'combined' treatment and ovarian stimulation with letrozole and LNG-IUS in situ. The 'three steps' hysteroscopic technique was used. Once complete response was achieved, the ovaries were stimulated, and mature oocytes cryopreserved. The LNG-IUS was removed, and embryos transferred. A comparative analysis was conducted between the two control groups of the initial outcomes of ART (number of oocytes and MII oocytes retrieved): healthy infertile women undergoing ovarian stimulation for IVF/ICSI (control group A); and patients diagnosed with breast cancer who underwent ovarian stimulation with letrozole (control group B). RESULTS: Of the 75 patients analysed, 15 underwent oocyte cryopreservation after achieving a complete response to fertility-sparing treatment (study group); 30 patients in control group A and B, respectively. No statistically significant differences were observed in retrieved oocytes and mature oocytes between the study and control groups. In the nine patients who underwent embryo transfer, clinical pregnancy (55.6%), cumulative live birth (44.4%) and miscarriage (20%) rates were reported. In three patients with AEH, recurrence occurred (12%) at 3, 6 and 16 months after removing the LNG-IUS to attempt embryo transfer, respectively. CONCLUSION: Fertility-sparing hysteroscopic combined treatment and subsequent ovarian stimulation with letrozole and LNG-IUS in situ could be suggested to women with AEH or early endometrial cancer who ask for future fertility preservation.

Dynamic microbial and metabolic changes during Apulian Caciocavallo cheese-making and ripening produced according to a standardized protocol.

The cheese microbiota plays a critical role in influencing its sensory and physicochemical properties. In this study, traditional Apulian Caciocavallo cheese coming from 4 different dairies in the same area and produced following standardized procedures have been examined, as well as the different bulk milks and natural whey starter cultures used. Moreover, considering the cheese wheels as the blocks of Caciocavallo cheeses as whole, these were characterized at different layers (i.e., core, under-rind, and rind) of the block using a multi-omics approach. In addition to physical-chemical characterization, culturomics, quantitative PCR, metagenomics, and metabolomics analysis, have been carried out post-salting and throughout ripening time (2 mo) to investigate the major shifts in the succession of the microbiota and flavor development. Culture-dependent and 16S rRNA metataxonomics results clearly clustered samples based on the microbiota biodiversity related to the production dairy plant as the result of the use of different NWS or intrinsic conditions of each production site. At the beginning of the ripening, cheeses were dominated by the Lactobacillus and, in 2 dairies (Art and SdC), Streptococcus genera associated with the NWS. The analysis allowed us to show that, although the diversity of identified genera did not change significantly between the rind, under-rind and core fractions of the same samples, there was an evolution in the relative abundance and absolute quantification, modifying and differentiating profiles during ripening. The qPCR mainly differentiated the temporal adaptation of those species originating from bulk milks and those provided by NWSs. The primary starter detected in NWS and cheese reassured the high relative concentration of 1-butanol, 2-butanol, 2-heptanol, 2-butanone, acetoin, delta-dodecalactone, hexanoic acid ethyl ester, octanoic acid ethyl ester, and VFFA during ripening, while cheeses displaying low abundances of Streptococcus and Lactococcus (dairy Del) have a lower total concentration of acetoin compared with Art and SdC. However, the sub-dominant strains and NSLAB present in cheeses are responsible for the production of secondary metabolites belonging to the chemical classes of ketones, alcohols, and organic acids, reaffirming the importance and relevance of autochthonous strains of each dairy plant although considering a delimited production area.

Uterine cervical stenosis: from classification to advances in management. Overcoming the obstacles to access the uterine cavity.

BACKGROUND: To date hysteroscopy is the gold standard technique for the evaluation and management of intrauterine pathologies. The cervical canal represents the access route to the uterine cavity. The presence of cervical stenosis often makes entry into the uterine cavity difficult and occasionally impossible. Cervical stenosis has a multifactorial etiology. It is the result of adhesion processes that can lead to the narrowing or total obliteration of the cervical canal. PURPOSE: In this review, we summarize the scientific evidence about cervical stenosis, aiming to identify the best strategy to overcome this challenging condition. METHODS: The literature review followed the scale for the quality assessment of narrative review articles (SANRA). All articles describing the hysteroscopic management of cervical stenosis were considered eligible. Only original papers that reported data on the topic were included. RESULTS: Various strategies have been proposed to address cervical stenosis, including surgical and non-surgical methods. Medical treatments such as the preprocedural use of cervical-ripening agents or osmotic dilators have been explored. Surgical options include the use of cervical dilators and hysteroscopic treatments. CONCLUSIONS: Cervical stenosis can present challenges in achieving successful intrauterine procedures. Operative hysteroscopy has been shown to have the highest success rate, particularly in cases of severe cervical stenosis, and is currently considered the gold standard for managing this condition. Despite the availability of miniaturized instruments that have made the management of cervical stenosis more feasible, it remains a complex task, even for experienced hysteroscopists.

Uterine Tumors Resembling Ovarian Sex Cord Tumors (UTROSCTs): A Scoping Review of 511 Cases, Including 2 New Cases.

Uterine Tumors Resembling Ovarian Sex Cord Tumors (UTROSCTs) are rare uterine mesenchymal neoplasms with uncertain biological potential. These tumors, which affect both premenopausal and postmenopausal women, usually have a benign clinical course. Nevertheless, local recurrences and distant metastases have been described. By analyzing 511 cases retrieved from individual reports and cases series, we provide here the most comprehensive overview of UTROSCT cases available in the literature, supplemented by two new cases of UTROSCTs. Case 1 was an asymptomatic 31-year-old woman who underwent a laparoscopic resection of a presumed leiomyoma. Case 2 was a 58-year-old postmenopausal woman with abnormal vaginal bleeding who underwent an outpatient hysteroscopic biopsy of a suspicious endometrial area. In both cases, immunohistochemical positivity for Calretinin and Inhibin was noted, typical for a sex cord differentiation. In both cases, total laparoscopic hysterectomy with bilateral salpingo-oophorectomy was performed. In light of the available literature, no pathognomonic clinical or imaging finding can be attributed to UTROSCT. Patients usually present with abnormal uterine bleeding or pelvic discomfort, but 20% of them are asymptomatic. In most cases, a simple hysterectomy appears to be the appropriate treatment, but for women who wish to become pregnant, uterus-preserving approaches should be discussed after excluding risk factors. Age, tumor size, lymphovascular space invasion, nuclear atypia, and cervical involvement are not reliable prognostic factors in UTROSCT. The current research suggests that aggressive cases (with extrauterine spread or recurrence) can be identified based on a distinct genetic and immunohistochemical phenotype. For instance, UTROSCTs characterized by GREB1::NCOA1-3 fusions and PD-L1 molecule expression appear to be predisposed to more aggressive behaviors and recurrence, with GREB1::NCOA2 being the most common gene fusion in recurrent tumors. Hence, redefining the criteria for UTROSCTs may allow a better selection of women suitable for fertility-sparing treatments or requiring more aggressive treatments in the future.

Divergence Between Clinical Trial Evidence and Actual Practice in Use of Dual Antiplatelet Therapy After Transient Ischemic Attack and Minor Stroke.

BACKGROUND: Randomized controlled trials (RCTs) proved that short-term (21-90 days) dual antiplatelet therapy (DAPT) reduces the risk of early ischemic recurrences after a noncardioembolic minor stroke or high-risk transient ischemic attack (TIA) without substantially increasing the hemorrhagic risk. We aimed at understanding whether and how real-world use of DAPT differs from RCTs. METHODS: READAPT (Real-Life Study on Short-Term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or TIA) is a prospective cohort study including >18-year-old patients treated with DAPT after a noncardioembolic minor ischemic stroke or high-risk TIA from 51 Italian centers. The study comprises a 90-day follow-up from symptom onset. In the present work, we reported descriptive statistics of baseline data of patients recruited up to July 31, 2022, and proportions of patients who would have been excluded from RCTs. We compared categorical data through the χ² test. RESULTS: We evaluated 1070 patients, who had 72 (interquartile range, 62-79) years median age, were mostly Caucasian (1045; 97.7%), and were men (711; 66.4%). Among the 726 (67.9%) patients with ischemic stroke, 226 (31.1%) did not meet the RCT inclusion criteria because of National Institutes of Health Stroke Scale score >3 and 50 (6.9%) because of National Institutes of Health Stroke Scale score >5. Among the 344 (32.1%) patients with TIA, 69 (19.7%) did not meet the RCT criteria because of age, blood pressure, clinical features, duration of TIA, presence of diabetes score <4 and 252 (74.7%) because of age, blood pressure, clinical features, duration of TIA, presence of diabetes score <6 and no symptomatic arterial stenosis. Additionally, 144 (13.5%) patients would have been excluded because of revascularization procedures. Three hundred forty-five patients (32.2%) did not follow the RCT procedures because of late (>24 hours) DAPT initiation; 776 (72.5%) and 676 (63.2%) patients did not take loading doses of aspirin and clopidogrel, respectively. Overall, 84 (7.8%) patients met the RCT inclusion/exclusion criteria. CONCLUSIONS: The real-world use of DAPT is broader than RCTs. Most patients did not meet the RCT criteria because of the severity of ischemic stroke, lower risk of TIA, late DAPT start, or lack of antiplatelet loading dose. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05476081.

Severe Streptococcus equi Subspecies zooepidemicus Outbreak from Unpasteurized Dairy Product Consumption, Italy.

During November 2021-May 2022, we identified 37 clinical cases of Streptococcus equi subspecies zooepidemicus infections in central Italy. Epidemiologic investigations and whole-genome sequencing showed unpasteurized fresh dairy products were the outbreak source. Early diagnosis by using sequencing technology prevented the spread of life-threatening S. equi subsp. zooepidemicus infections.

Hysteroscopic resection vs ultrasound-guided dilation and evacuation for treatment of cesarean scar ectopic pregnancy: a randomized clinical trial.

BACKGROUND: Cesarean scar ectopic pregnancy is a type of ectopic pregnancy in which the fertilized egg is implanted in the muscle or fibrous tissue of the scar after a previous cesarean delivery. The condition can be catastrophic if not managed on time and can lead to significant morbidity and mortality. Several approaches have been studied for the management of cesarean scar ectopic pregnancy in women who opted for termination of pregnancy with no consensus on the best treatment modality reached so far. OBJECTIVE: This study aimed to compare the success rate of hysteroscopic resection vs ultrasound-guided dilation and evacuation for the treatment of cesarean scar ectopic pregnancy. STUDY DESIGN: This was a parallel group, nonblinded, randomized clinical trial conducted at a single center in Italy. Women with singleton gestations at <8 weeks and 6 days of gestation were included in the study. Inclusion criteria were women with a cesarean scar ectopic pregnancy with positive embryonic heart activity who opted for termination of pregnancy. Patients were randomized 1:1 to receive either hysteroscopic resection (ie, intervention group) or ultrasound-guided dilation and evacuation (ie, control group). Both groups received 50 mg/m2 of methotrexate intramuscularly at the time of randomization (day 1) and another dose at day 3. A third dose of methotrexate was planned in case of persistence of positive fetal heart activity at day 5. Participants received either ultrasound-guided dilation and evacuation or hysteroscopic resection from 1 to 5 days after the last dose of methotrexate. Hysteroscopic resection was performed under spinal anesthesia using a 15 Fr bipolar mini-resectoscope. Dilation and evacuation were performed by vacuum aspiration with a Karman cannula, followed by sharp curettage, if necessary, under ultrasound guidance. The primary outcome was the success rate of the treatment protocol, defined as no further treatment required until the complete resolution of the cesarean scar ectopic pregnancy. Resolution of the cesarean scar ectopic pregnancy was evaluated based on decline of beta-hCG and the absence of residual gestational material in the endometrial cavity. Treatment failure was defined as the necessity for further treatment required until the complete resolution of the cesarean scar ectopic pregnancy. A sample size calculation indicated that 54 participants were required to test the hypothesis RESULTS: A total of 54 women were enrolled and randomized. Number of previous cesarean deliveries ranged from 1 to 3. Overall, 10 women received a third dose of methotrexate with 7 of 27 (25.9%) participants in the hysteroscopic resection group and 3 of 27 (11.1%) in the dilation and evacuation group. The success rate was 100% (27/27) in the hysteroscopic resection group and 81.5% (22/27) in the dilation and evacuation group (relative risk, 1.22; 95% confidence interval, 1.01-1.48). Additional procedures were required in 5 cases of the control group, namely 3 hysterectomies, 1 laparotomic uterine segmental resection, and 1 hysteroscopic resection. The length of stay in the hospital was 9.0±2.9 days in the intervention group and 10.0±3.5 days in the control group (mean difference, -1.00 days; 95% confidence interval, -2.71 to 0.71). No cases of admission to intensive care unit or maternal death were reported. CONCLUSION: Hysteroscopic resection was associated with an increased success rate in the treatment of cesarean scar ectopic pregnancy when compared with ultrasound-guided dilation and evacuation.

In silico screening of nanoporous materials for urea removal in hemodialysis applications.

The design of miniaturized hemodialysis devices, such as wearable artificial kidneys, requires regeneration of the dialysate stream to remove uremic toxins from water. Adsorption has the potential to capture such molecules, but conventional adsorbents have low urea/water selectivity. In this work, we performed a comprehensive computational study of 560 porous crystalline adsorbents comprising mainly covalent organic frameworks (COFs), as well as some siliceous zeolites, metal organic frameworks (MOFs) and graphitic materials. An initial screening using Widom insertion method assessed the excess chemical potential at infinite dilution for water and urea at 310 K, providing information on the strength and selectivity of urea adsorption. From such analysis it was observed that urea adsorption and urea/water selectivity increased strongly with fluorine content in COFs, while other compositional or structural parameters did not correlate with material performance. Two COFs, namely COF-F6 and Tf-DHzDPr were explored further through Molecular Dynamics simulations. The results agree with those of the Widom method and allow to identify the urea binding sites, the contribution of electrostatic and van der Waals interactions, and the position of preferential urea-urea and urea-framework interactions. This study paves the way for a well-informed experimental campaign and accelerates the development of novel sorbents for urea removal, ultimately advancing on the path to achieve wearable artificial kidneys.

Simple lattice model explains equilibrium separation phenomena in glassy polymers.

The Robeson bound is a theoretical limit that applies to kinetics-driven membrane separations of gas mixtures. However, this bound does not apply to sorption-driven membrane processes such as CO2/N2 separation, which lacks a theoretical explanation. As a result, we are uncertain about the factors that control the limiting behavior of sorption-driven separations. To address this issue, we employed a simple lattice model and dynamic mean field theory to examine the transport properties of disordered model structures, isolating sorption effects from purely kinetic effects. Our findings indicate that transport effects play a crucial role in sorption-driven processes, and perm-selectivity is consistently lower than sorption selectivity, which is an unattainable limit. We used basic geometric fragments of the structure to explain how transport effects emerge and manifest themselves in sorption-driven processes.

Listeria monocytogenes exposed to antimicrobial peptides displays differential regulation of lipids and proteins associated to stress response.

With the onset of Listeria monocytogenes resistance to the bacteriocin nisin, the search for alternative antimicrobial treatments is of fundamental importance. In this work, we set out to investigate proteins and lipids involved in the resistance mechanisms of L. monocytogenes against the antimicrobial peptides (AMPs) nisin and fengycin. The effect of sub-lethal concentrations of nisin and lipopeptide fengycin secreted by Bacillus velezensis P34 on L. monocytogenes was investigated by mass spectrometry-based lipidomics and proteomics. Both AMPs caused a differential regulation of biofilm formation, confirming the promotion of cell attachment and biofilm assembling after treatment with nisin, whereas growth inhibition was observed after fengycin treatment. Anteiso branched-chain fatty acids were detected in higher amounts in fengycin-treated samples (46.6%) as compared to nisin-treated and control samples (39.4% and 43.4%, respectively). In addition, a higher relative abundance of 30:0, 31:0 and 32:0 phosphatidylglycerol species was detected in fengycin-treated samples. The lipidomics data suggest the inhibition of biofilm formation by the fengycin treatment, while the proteomics data revealed downregulation of important cell wall proteins involved in the building of biofilms, such as the lipoteichoic acid backbone synthesis (Lmo0927) and the flagella-related (Lmo0718) proteins among others. Together, these results provide new insights into the modification of lipid and protein profiles and biofilm formation in L. monocytogenes upon exposure to antimicrobial peptides.

Step-by-Step Hysteroscopic Treatment of Complete Uterine Septum Associated or Not with Cervical Anomalies.

STUDY OBJECTIVE: To demonstrate our hysteroscopic technique using the mini-resectoscope for the treatment of complete uterine septum with or without cervical anomalies. DESIGN: A step-by-step video demonstration of the technique with the use of an educational video. SETTINGS: We present 3 patients diagnosed as having complete uterine septum (U2b according to the ESHRE/ESGE classification) with or without cervical anomalies (C0, normal cervix; C1, septate cervix; C2, double "normal" cervix"), 2 of them with a longitudinal vaginal septum (V1). The first case is a 33-year-old woman with history of primary infertility diagnosed as having a complete uterine septum with normal cervix (class U2bC0V0 according to the ESHRE/ESGE classification). Case 2 is a 34-year-old woman with infertility and abnormal uterine bleeding, diagnosed as having complete uterine and cervical septum and a partial nonobstructive vaginal septum (class U2bC1V1). Case 3 is a 28-year-old woman with infertility and dyspareunia, diagnosed as having a complete uterine septum, double "normal" cervix, and nonobstructive longitudinal vaginal septum (class U2bC2V1) Still 3. The procedures were performed in a tertiary care university hospital. INTERVENTION: The 3 procedures were performed in the operative room using a 15 Fr continuous flow mini-resectoscope and bipolar energy with the patient under general anesthesia Still 1 and Still 2. No complications were encountered in any of the 3 cases. After all procedures, a gel based on hyaluronic acid was applied to minimize postoperative adhesion formation. Patients were discharged home the same day of the procedure after a short period of observation. CONCLUSION: Hysteroscopic treatment of patients with uterine septa associated or not with cervical anomalies using miniaturized instruments is a feasible and effective option for the management of patients with these complex müllerian anomalies.

Restoring Fertility of Patients with Severe Asherman's Syndrome in the Office Setting: A Step-by-Step Recipe for Success.

OBJECTIVE: To describe an effective in-office hysteroscopic strategy to restore fertility of patients with severe Asherman's syndrome. DESIGN: A step-by-step video demonstration of the technique with an emphasis on the key portions of the procedure. A detailed narrated description of the steps is provided. SETTING: Tertiary care University Hospital. INTERVENTIONS: Three patients were managed by hysteroscopy performed in the office setting without anesthesia. Case 1 is a 34-year-old woman with obstetrical history of first-trimester incomplete abortion treated with Dilation and Curettage (D&C), followed by a tubal ectopic pregnancy treated with laparoscopic partial salpingectomy and a subsequent pregnancy on the tubal stump treated with uterine artery embolization. Case 2 is a 40-year-old woman with history of tubal ectopic pregnancy treated with salpingectomy, a surgical first-trimester voluntary termination of pregnancy with D&C and a full term vaginal delivery complicated with retained products of conception that were removed with D&C. Case 3 is a 35-year-old woman with two previous first-trimester spontaneous miscarriages both treated with D&C. Case 1 and 3 were treated using miniaturized mechanical instruments only; in case 2, miniaturized mechanical instruments and the 15 Fr bipolar mini-resectoscope were used. Preoperative 2D and 3D ultrasound were used to predict the complexity of the cases and to guide the surgeon during the procedure. Intrauterine lysis of adhesions was concluded when both tubal ostia were visualized, and the uterine cavity was determined to have adequate shape and volume. At the end of the procedures, hyaluronic acid-based gel was applied to prevent new intrauterine adhesion formation. Two weeks after the initial procedure, a second look diagnostic hysteroscopy was performed. Only one patient (#1) needed additional lysis of adhesions; in this case, at the end of the procedure, a Word catheter was inserted as a barrier method for the prevention of adhesion formation. Eight weeks later, the word catheter was removed, and additional lysis of adhesions was performed. All the surgical procedures were performed without complication, and a healthy endometrium was observed at the second look hysteroscopy, in all the three patients. All 3 patients conceived after the procedure. Pregnancy was achieved after one IVF cycle with the transfer of one frozen embryo in case 1 and spontaneously in cases 2 and 3. Patient 1 was delivered by elective caesarean section due to placenta previa, while the other two patients had normal vaginal deliveries. Patient 1 had Retained Products of Conception requiring hysteroscopic removal using a 27 Fr Resectoscope. CONCLUSION: When using innovative miniaturized instruments and adequate surgical technique, hysteroscopic lysis of adhesions is a feasible and effective in-office strategy to restore fertility in patients with severe Asherman's syndrome. The use of 2D and 3D ultrasound played an important role in the preoperative workup of the patient with Asherman's syndrome.

Gut Microbiota, Metabolome, and Body Composition Signatures of Response to Therapy in Patients with Advanced Melanoma.

Despite the recent breakthroughs in targeted and immunotherapy for melanoma, the overall survival rate remains low. In recent years, considerable attention has been paid to the gut microbiota and other modifiable patient factors (e.g., diet and body composition), though their role in influencing therapeutic responses has yet to be defined. Here, we characterized a cohort of 31 patients with unresectable IIIC-IV-stage cutaneous melanoma prior to initiation of targeted or first-line immunotherapy via the following methods: (i) fecal microbiome and metabolome via 16S rRNA amplicon sequencing and gas chromatography/mass spectrometry, respectively, and (ii) anthropometry, body composition, nutritional status, physical activity, biochemical parameters, and immunoprofiling. According to our data, patients subsequently classified as responders were obese (i.e., with high body mass index and high levels of total, visceral, subcutaneous, and intramuscular adipose tissue), non-sarcopenic, and enriched in certain fecal taxa (e.g., Phascolarctobacterium) and metabolites (e.g., anethole), which were potentially endowed with immunostimulatory and oncoprotective activities. On the other hand, non-response was associated with increased proportions of Streptococcus, Actinomyces, Veillonella, Dorea, Fusobacterium, higher neutrophil levels (and a higher neutrophil-to-lymphocyte ratio), and higher fecal levels of butyric acid and its esters, which also correlated with decreased survival. This exploratory study provides an integrated list of potential early prognostic biomarkers that could improve the clinical management of patients with advanced melanoma, in particular by guiding the design of adjuvant therapeutic strategies to improve treatment response and support long-term health improvement.

Diode laser use in hysteroscopic surgery: current status and future perspectives.

Recent advances in surgical technology and innovative techniques have revolutionized surgical gynecology, including transcervical hysteroscopic procedures. Surgical lasers (Nd-Yag, Argon, diode, and CO2 lasers) have been promoted to remove a variety of gynecological pathologies. For hysteroscopic surgery, the diode laser represents the most versatile and feasible innovation, with simultaneous cut and coagulate action, providing improved hemostasis compared with CO2 laser. The newest diode laser devices exhibit increased power and a dual wavelength, to work precisely with reduced thermal dispersion and minimal damage to surrounding tissues. Their efficacy and safety have been validated both in the hospitals as well as in the office setting. Updated evidence reports that several hysteroscopic procedures, including endometrial polypectomies, myomectomies and metroplasties can be successfully performed with a diode laser. Therefore, this review aimed to give a deeper understanding of the role of laser energy in gynecology and subsequently in hysteroscopy in order to safely incorporate this technology into clinical practice.

The establishment of the gut microbiota in 1-year-aged infants: from birth to family food.

PURPOSE: With the aim of characterizing the gastrointestinal (GI) microbiota and contextually determine how different prenatal, perinatal, and postnatal factors affected its composition in early childhood, infants were enrolled in a longitudinal-prospective study named "A.MA.MI." (Alimentazione MAmma e bambino nei primi MIlle giorni; NCT04122612, October 2019). METHODS: Forty-five fecal samples were collected at 12 months of infants' age, identified as the 3rd follow-up (T3). The evaluated variables were pre-gestational weight and weight gain during pregnancy, delivery mode, feeding, timing of weaning, and presence/absence of older siblings. Fecal alpha and beta-diversities were analyzed. Noteworthy, to determine the impact of the influencing factors, multivariate analyses were conducted. RESULTS: At T3, all prenatal and perinatal variables did not result to be significant whereas, among the postnatal variables, type of milk-feeding and weaning showed the greatest contribution in shaping the microbiota. Although aged 1 year, infants exclusively breastfed until 6 months were mainly colonized by Lactobacillaceae and Enterobacteriaceae. Differently, Bacteroidaceae characterized the microbiota of infants that were never breastfed in an exclusive way. Moreover, although an early introduction of solid foods determined higher values of Faith's PD, high abundances of Ruminococcaceae and Faecalibacterium mainly associated with infants weaned after the 4th month of age. CONCLUSION: The microbial colonization during the first year of life is likely affected by a simultaneous effect of multiple variables playing a significant role at different times. Therefore, these data contribute to add evidence concerning the complex multifactorial interaction between GI microbiota and various stimuli affecting infants during the early stages of life.

Heart rate variability is reduced during the menstrual phase in women with catamenial C1-type temporal lobe epilepsy.

INTRODUCTION: Temporal lobe epilepsy (TLE) is the most frequent focal epilepsy in adulthood. Catamenial C1-type TLE, is characterized by a cyclic seizure exacerbation during the menstrual phase. The heart rate variability (HRV) analysis assesses cardiac autonomic control and may represent a biomarker for Sudden Unexpected Death in Epilepsy (SUDEP). It is plausible that female sex hormones can influence HRV. These changes might be more pronounced in patients suffering from catamenial C1-type TLE where hormonal changes also increase seizure susceptibility. To that aim, we evaluated HRV changes during the menstrual phase of women suffering from catamenial C1-type TLE. METHODS: We enrolled 12 adults with a diagnosis of catamenial C1-type TLE (Catamenial Group) and 12 age-, and seizure-frequency-matched controls with TLE (Non-Catamenial Group). Each patient underwent a 20-minute EEG + EKG recording in resting state during the menstrual phase. HRV parameters were calculated with a short-lasting analysis of EKG records. Time domain-related, frequency domain-related, as well as non-linear analysis parameters, were compared between the two groups. RESULT: Compared to the Non-Catamenial Group, the Catamenial Group showed significant reductions in SDNN (p-value = 0.01), RMSSD (p-value = 0.04), pNN50 (p-value = 0.001), LnLF ms2 (p-value = 0.05), LnHF ms2 (p-value = 0.007), SD1 (p-value = 0.02), and SD2 (p-value = 0.01). These results were independent from age, disease duration, numbers of ASM, and seizure etiology. CONCLUSION: Our data provide experimental evidence that vagal output is reduced during the menstrual phase in patients with catamenial C1-type TLE. These results indicate that, during the menstrual phase, patients with catamenial C1-type TLE may be at a higher risk of developing cardiac dysfunctions and SUDEP.

Cerebral venous thrombosis without thrombocytopenia after a single dose of COVID-19 (Ad26.COV2.S) vaccine injection: a case report.

BACKGROUND: The coronavirus pandemic became the hard challenge for the modern global health system. To date, vaccination is the best strategy against Sars-Cov-2-related illness. About 3 billions of people received at least one of the approved vaccines. The related adverse events were reported during the various experimental phases, but newer and less common side effects are emerging post-marketing. Vaccine-induced thrombocytopenia with thrombosis (VITT) is one of these insidious adverse reactions and it is considered responsible of venous thrombosis, in both the splanchnic and the cerebral circulation. Although its mechanism has been presumably established, resembling that observed in heparin-induced thrombocytopenia, some venous thromboses seem not to recognize this etiology and their pathogenesis remains unknown. Here we described a case of cerebral venous thrombosis after administration of the Ad26.COV2.S, presenting without thrombocytopenia, paving the way for possible novel causes of this vaccine-induced pathological condition. CASE PRESENTATION: A 45-year-old woman came to our observation for bilateral periorbital headache associated with retro-orbital pain started 8 days after administration of COVID vaccine Jannsen. Ophthalmologic exam showing a bilateral papilledema raised the suspicion of intracranial hypertension. Cerebral magnetic resonance imaging revealed signal alteration with T1-positive contrast enhancement in the right temporal and insular lobes suggestive of cerebral venous thrombosis. The absence of thrombocytopenia and platelet factor 4 (PF-4) antibodies led the clinicians to rule out VITT. The patient was treated successfully with warfarin. CONCLUSION: Venous thrombosis occurring after COVID-19 vaccination represents an adverse event of special interest. Patients with thrombosis and thrombocytopenia appear to be affected by a general thrombophilic state, sustained by an autoimmune mechanism, and show a higher mortality. Thrombosis without thrombocytopenia's pathogenesis has not yet been clarified, but laboratory data and good response to vitamin K antagonists help clinicians in the differential diagnosis with VITT. Future research will allow us to discover other possible mechanisms and maybe identify a subgroup of patients with a higher risk of developing this medical complication.

Unicornuate Uterus with Noncommunicating Rudimentary Horn (Class U4aC0V0/ESHRE/ESGE Classification) and a Communicating Bladder Endometriotic Nodule.

STUDY OBJECTIVE: To describe the diagnostic workup and laparoscopic management of a noncommunicating left uterine rudimentary horn (class U4aC0V0 European Society of Human Reproduction and Embryology/European Society of Gastrointestinal Endoscopy Classification) with communicating endometriotic bladder nodule. DESIGN: Step-by-step description of the surgical treatment. PATIENT: A 33-year-old woman with unicornuate uterus and a left-side noncommunicating rudimentary horn affected by primary infertility, mild dysmenorrhea (visual analog scale score 6), severe catamenial dysuria (visual analog scale score 10), and catamenial hematuria. SETTING: Noncommunicating rudimentary horns are rare Müllerian anomalies present in 20% to 25% of women with a unicornuate uterus. It is associated with severe dysmenorrhea, pelvic pain, subfertility, and poor obstetric outcomes and usually presents with cyclic pelvic pain that starts early after the menarche. Endometriotic bladder nodules are present in 1% to 2% of patients with endometriosis. In the literature, there are no reported cases of noncommunicating rudimentary horn with communicating endometriotic bladder nodules. Surgical excision of the rudimentary horn is the treatment of choice. In our case, the 2-dimensional/3-dimensional ultrasound revealed a right unicornuate uterus with a left noncommunicating rudimentary horn with hematometra. The uterine fundus presented «gamma sign¼ vascularization. In addition, a bladder endometriotic nodule (16 × 15 mm) communicating with hematometra was displayed. Magnetic resonance imaging demonstrated no additional malformations. Diagnostic hysteroscopy revealed a single cervix without vaginal malformation and small right uterine cavity with single tubal ostium. At laparoscopy, using hysteroscopic transillumination, a clear plane of dissection was identified between the rudimentary horn and the uterus confirming the presence of a noncommunicating horn. Evaluation of the abdominal cavity showed bilateral normal adnexa with normal ovaries. Chromopertubation showed a patent right Fallopian tube and obstructed left tube. INTERVENTIONS: A left salpingectomy using bipolar and the ultrasonic energy was performed. The utero-ovarian ligament was transected, and the left ovary was preserved. The left ovary was suspended at the pelvic wall, the retroperitoneum was opened, the ureter was identified, and the left uterine artery was temporary occluded. The left round ligament was transected and the left paravesical space was developed. With a lateromedial approach, we opened the vesicouterine septum to dissect the bladder from the rudimentary horn. The endometriotic bladder nodule was gently detached from the uterine horn with a lateromedial approach. The left uterine artery was coagulated and dissected at level of the cervix. A solution of vasopressin was injected between the uterine horn and the uterus. Resection of the rudimentary horn was performed. The peritoneum was closed. The temporary occlusion of the uterine artery was removed. The specimen was placed in a bag and removed using an extracorporeal tissue extraction technique. CONCLUSION: The late clinical presentation of our patient with only mild dysmenorrhea could be explained by the drainage of the hematometra from the noncommunicating horn into the endometriotic bladder nodule. The bladder symptoms in patients with Müllerian anomalies should be carefully investigated. The laparoscopic removal of rudimentary horn with mobilization of communicating bladder nodule when present is a safe and feasible method to improve symptomatology.

Invited review: Fresh pasta filata cheeses: Composition, role, and evolution of the microbiota in their quality and safety.

With a global market of around $55 billion (in US dollars; i.e. around the 57% of the global cheese market), pasta filata cheeses sales are rising approximately 2% per year worldwide and are expected to further increase to $65.01 billion by 2028. Among these groups of cheeses, fresh pasta filata cheeses, such as mozzarella and fior di latte, are the most consumed. Herein, we provide an overview of fresh pasta filata cheeses, their commodity-related and technological aspects, focusing on the composition, the role, and evolution of their microbiota along the dairy chain.