Measuring gravitational attraction with a lattice atom interferometer.

Despite being the dominant force of nature on large scales, gravity remains relatively elusive to precision laboratory experiments. Atom interferometers are powerful tools for investigating, for example, Earth's gravity1, the gravitational constant2, deviations from Newtonian gravity3-6 and general relativity7. However, using atoms in free fall limits measurement time to a few seconds8, and much less when measuring interactions with a small source mass2,5,6,9. Recently, interferometers with atoms suspended for 70 s in an optical-lattice mode filtered by an optical cavity have been demonstrated10-14. However, the optical lattice must balance Earth's gravity by applying forces that are a billionfold stronger than the putative signals, so even tiny imperfections may generate complex systematic effects. Thus, lattice interferometers have yet to be used for precision tests of gravity. Here we optimize the gravitational sensitivity of a lattice interferometer and use a system of signal inversions to suppress and quantify systematic effects. We measure the attraction of a miniature source mass to be amass = 33.3 ± 5.6stat ± 2.7syst nm s-2, consistent with Newtonian gravity, ruling out 'screened fifth force' theories3,15,16 over their natural parameter space. The overall accuracy of 6.2 nm s-2 surpasses by more than a factor of four the best similar measurements with atoms in free fall5,6. Improved atom cooling and tilt-noise suppression may further increase sensitivity for investigating forces at sub-millimetre ranges17,18, compact gravimetry19-22, measuring the gravitational Aharonov-Bohm effect9,23 and the gravitational constant2, and testing whether the gravitational field has quantum properties24.

Sperm donation: an alternative to improve post-ICSI live birth rates in advanced maternal age patients.

STUDY QUESTION: Can sperm donation increase live birth rates following ICSI in advanced maternal age (AMA) patients? SUMMARY ANSWER: Sperm donation increases the live birth rate in AMA ICSI cycles. WHAT IS KNOWN ALREADY: In ICSI practice, sperm donation has been predominantly applied to overcome male infertility. The involvement of paternal age and lower sperm quality in the severe reduction in fertility observed in AMA patients remains to be clarified. STUDY DESIGN, SIZE, DURATION: Retrospective multicenter cohort study including data generated between 2015 and 2019 from 755 ICSI cycles achieving a fresh embryo transfer, of which 337 were first homologous cycles (normozoospermic partner sperm and homologous oocytes) and 418 were first sperm donation cycles (donor sperm and homologous oocytes). The association of sperm origin (partner vs donor) with live birth was assessed by multivariate analysis in non-AMA (<37 years, n = 278) and AMA (≥37 years, n = 477) patients, separately, including in the model all variables previously found to be associated with live birth in a univariate analysis (number of MII oocytes recovered, number of embryos transferred, and maternal age). ICSI outcomes were compared between sperm donation and homologous cycles in overall, non-AMA and AMA patients. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted in three fertility clinics and included 755 Caucasian patients aged 24-42 years undergoing their first homologous or sperm donation ICSI cycle achieving a fresh embryo transfer. MAIN RESULTS AND THE ROLE OF CHANCE: The multivariate analysis revealed that sperm donation was positively associated with the likelihood of a live birth independently of all other variables tested in AMA (P = 0.02), but not in non-AMA patients. Live birth, delivery, and miscarriage rates differed substantially between sperm donation and homologous AMA cycles; live birth and delivery rates were 70-75% higher (25.4% vs 14.5% and 22.5% vs 13.5%, respectively; P < 0.01), while miscarriage occurrence was less than half (18.0% vs 39.5%; P < 0.01) in sperm donation compared to homologous AMA cycles. LIMITATIONS, REASONS FOR CAUTION: This study is limited by its retrospective nature, differences in patients profiles between sperm donation and homologous-control groups and varying proportion of donor cycles between fertility centers, although these variations have been controlled for in the statistical analysis. WIDER IMPLICATIONS OF THE FINDINGS: The findings suggest that sperm donation increases live birth rates while reducing miscarriage occurrence in AMA patients, and thus may be a valid strategy to improve ICSI outcomes in this growing and challenging patient group. STUDY FUNDING/COMPETING INTEREST(S): N/A. TRIAL REGISTRATION NUMBER: N/A.

From COVID-19 or because COVID-19?

Infections and pandemics will condition us in an increasingly predominant way regarding diagnostic, medical, and surgical activities in all specialist areas. Particularly cardiovascular disease represents an important field also during other health crisis like COV19 pandemia. A common strategy in the future, to cohabit with pandemic events and to be able to continue an elective and not only emergency cardiac surgery program represents an imperative.

Comparison of three therapeutic regimens for genotype-3 hepatitis C virus infection in a large real-life multicentre cohort.

BACKGROUND & AIMS: In the direct-acting antiviral era, treatment of genotype-3 HCV (HCV-GT3) is still challenging. Real-life comparisons between recommended regimens, sofosbuvir (SOF)+daclatasvir (DAC), SOF/velpatasvir (VEL), glecaprevir/pibrentasvir (GLE/PIB), are scarce. We aimed at filling this data gap. METHODS: Sustained virological response 12 weeks after treatment completion (SVR12) was assessed for all HCV-GT3 patients consecutively treated within the Lombardia web-based Navigatore HCV-Network; differences in SVR12 across regimens were evaluated by logistic regression. RESULTS: Of the 2082 subjects with HCV-GT3, 1544 were evaluable for comparisons between regimens: SOF + DAC (1023, 66.2%), SOF/VEL (369, 23.9%), GLE/PIB (152, 9.8%). Patients treated with former regimens were more frequently male, cirrhotic, HIV-positive, pretreated, used ribavirin in their regimen, and had lower baseline HCV-RNA. SVR12 was similar across groups: 94.8% in SOF + DAC, 97.6% in SOF/VEL, 96.7% in GLE/PIB (P = .065). At univariate analysis, SVR12 was associated with female gender (97.9% vs 94.8%, P = .007) and lower median pretreatment Log10 HCV-RNA (5.87 vs 6.20, P = .001). At multivariate logistic regression analysis, treatment with SOF/VEL was associated with a higher likelihood of SVR12 than SOF + DAC, but only in the absence of ribavirin (98% vs 90.3%). Female gender and lower pretreatment HCV-RNA were independently associated with SVR12. CONCLUSIONS: In a large real-life setting of HCV-GT3-infected patients with a high proportion of cirrhosis, the success rate was remarkable. The slight advantage of SOF/VEL on SOF + DAC was significant only without ribavirin. The current prescription shift towards novel regimens (ie SOF/VEL and GLE/PIB) in easier-to-treat patients allows ribavirin-free and shorter schedules without mining SVR12 in this <> genotype.

Squeezing on Momentum States for Atom Interferometry.

We propose and analyze a method that allows for the production of squeezed states of the atomic center-of-mass motion that can be injected into an atom interferometer. Our scheme employs dispersive probing in a ring resonator on a narrow transition in order to provide a collective measurement of the relative population of two momentum states. We show that this method is applicable to a Bragg diffraction-based strontium atom interferometer with large diffraction orders. This technique can be extended also to small diffraction orders and large atom numbers N by inducing atomic transparency at the frequency of the probe field, reaching an interferometer phase resolution scaling Δϕ∼N^{-3/4}. We show that for realistic parameters it is possible to obtain a 20 dB gain in interferometer phase estimation compared to the standard quantum limit. Our method is applicable to other atomic species where a narrow transition is available or can be synthesized.

Atom Interferometry with the Sr Optical Clock Transition.

We report on the realization of a matter-wave interferometer based on single-photon interaction on the ultranarrow optical clock transition of strontium atoms. We experimentally demonstrate its operation as a gravimeter and as a gravity gradiometer. No reduction of interferometric contrast was observed for a total interferometer time up to ∼10 ms, limited by geometric constraints of the apparatus. Single-photon interferometers represent a new class of high-precision sensors that could be used for the detection of gravitational waves in so far unexplored frequency ranges and to enlighten the boundary between quantum mechanics and general relativity.

Fatty liver disease and lifestyle in youngsters: diet, food intake frequency, exercise, sleep shortage and fashion.

BACKGROUND & AIMS: Fatty liver is associated with alcohol habits and/or overweight/obesity. We challenged several lifestyle features associated with fatty liver and, particularly, with non-alcoholic fatty liver disease (NAFLD). Among them, sleep shortage as a result of nightlife habits and a preference for plus-size fashion were assessed. The latter consists of fashionable plus-sized clothing for actual individuals' size and reflects a frequent attitude of some social or age groups, conceivably indicating more global and widespread trend and behaviour. METHODS: We studied a group of 708 non-diabetic youngsters, 458 women and 250 men, 21.72 ± 3.71 years old (range 15-35 years), referred for minor digestive ailments for clinical assessment, ultrasound detection of fatty liver and nutritional counselling. Details of personal history regarding lifestyle, food intake frequency and alcohol intake, dietary and physical exercise profile, sleep duration and clothing preferences were recorded. RESULTS: The prevalence of NAFLD in this cohort of youngsters is 67/708 (9.4%). Even if it is quantitatively very low in both groups, the average alcohol intake, always below 20 g/day, is greater in NAFLD subjects (5.83 ± 4.32 g) vs. subjects with normal liver (2.02 ± 3.20 g). The number of meals/day and adherence to a Mediterranean diet profile are smaller in NAFLD subjects. By multiple regression, BMI, sedentary life, plus-sized clothing for their actual size, sleep shortage and lower frequency of daily food intake are associated with the presence of NAFLD. CONCLUSIONS: Onset and continuation of fatty liver disease, beyond food and exercise quantity and quality, with their effects on obesity, may also be associated with other aspects of lifestyle.

Regulatory B cell (B10 Cell) expansion during Listeria infection governs innate and cellular immune responses in mice.

Pathogens use numerous methods to subvert host immune responses, including the modulation of host IL-10 production by diverse cell types. However, the B cell sources of IL-10 and their overall influence on innate and cellular immune responses have not been well characterized during infections. Using Listeria as a model pathogen, infection drove the acute expansion of a small subset of regulatory B cells (B10 cells) that potently suppress inflammation and autoimmunity through the production of IL-10. Unexpectedly, spleen bacteria loads were 92-97% lower in B10 cell-deficient CD19(-/-) mice, in mice depleted of mature B cells, and in mice treated with CD22 mAb to preferentially deplete B10 cells before infection. By contrast, the adoptive transfer of wild-type B10 cells reduced bacterial clearance by 38-fold in CD19(-/-) mice through IL-10-dependent pathways. B10 cell depletion using CD22 mAb significantly enhanced macrophage phagocytosis of Listeria and their production of IFN-γ, TNF-α, and NO ex vivo. Accelerated bacteria clearance following B10 cell depletion significantly reduced Ag-specific CD4(+) T cell proliferation and cytokine production, but did not alter CD8(+) T cell responses. B10 cell regulatory function during innate immune responses was nonetheless dependent on cognate interactions with CD4(+) T cells because B10 cells deficient in IL-10, MHC-II, or IL-21R expression did not influence Listeria clearance. Thus, Listeria manipulates immune responses through a strategy of immune evasion that involves the preferential expansion of endogenous B10 cells that regulate the magnitude and duration of both innate and cellular immune responses.

Lung transthoracic ultrasound elastography imaging and guided biopsies of subpleural cancer: a preliminary report.

BACKGROUND: Despite the usefulness of elastography in assessing the stiffness/elasticity of tissues, and its proven diagnostic accuracy in thyroid, breast, and prostate cancers, among others, it is not yet applied in transthoracic ultrasound (TUS) scans to investigate lung nodules. PURPOSE: To investigate the potential clinical utility of TUS elastography in diagnosing lung cancer proven by fine-needle aspiration biopsy (FNAB). MATERIAL AND METHODS: TUS elastography was performed in 95 consecutive patients (71 men, 24 women; age, 62.84 ± 7.37 years) with lesions suspected of involving the chest wall or the pleura detected on chest X-ray or computed tomography (CT). Patients with pleural effusions were not enrolled, but were further evaluated by pleural fluid cytology. Patients were excluded from the study if a diagnosis had already been made based on sputum cytology and/or bronchoscopic histology (making TUS biopsy unnecessary) or if their lung lesions could not be visualized under standard US. Under FNAB, 34 consolidations were ascribed to pneumonia and 65 to cancer. Under TUS, tissue stiffness, detected using a convex multifrequency 2-8-mHz probe and a MyLab™Twice - ElaXto, was scored from 1 (greatest elasticity) to 5 (no elasticity). Subpleural solid masses (2-5 cm) were initially detected by TUS and subsequently assessed by FNAB. RESULTS: Histological diagnoses were: small cell lung cancer (4/61), adenocarcinoma (29/61), squamous cell carcinoma (SCC) (12/61), large cell lung carcinoma (12/61), and lymphomas (4/61). Patients' age and mass sizes (3.06 ± 0.88 cm) were not significantly associated with any histological type. A significant lower elasticity of SCC (4.67 ± 0.492) was observed versus other types of lung cancer (P < 0.005), and versus pneumonia (2.35 ± 0.48). CONCLUSION: Since only squamous cell lung carcinoma displays the feature of significantly reduced elasticity, and since no clear-cut diagnostic key is yet available, the clinical usefulness of TUS elastography is currently limited with a view to characterizing tumors. Nevertheless, it does enable good non-invasive imaging of lung nodules, providing information on their stiffness, and can improve the accuracy and yield of FNAB.

Transthoracic ultrasound in the assessment of pleural and pulmonary diseases: use and limitations.

Interest in transthoracic ultrasound (US) procedures increased after the availability of portable US equipment suitable for use at the patient's bedside. It is possible to detect space-occupying lesions of the pleura, pleural effusion, focal or diffuse pleural thickening and subpleural lesions of the lung, even in emergency settings. Transthoracic US is useful as a guidance system for thoracentesis and peripheral lesion biopsy, where it minimises the occurrence of pneumothorax and haemorrhage. Transthoracic US imaging is strongly influenced by physical interaction of the ultrasonic beam at the tissue/air interface, which gives rise to reverberations classified as simple (A-line), "comet tail" and "ring down"(B-line) artifacts. Although these artifacts can be suggestive of a disease condition, they are essentially imaging errors present even in normal subjects and in empty-pleura post-pneumonectomy patients. In order to clarify some confusion and to report on the state of the art, we present a review of the literature on transthoracic US in diseases of the pleura and peripheral lung regions and our own clinical experience over 3 decades. The review focuses on quality assurance procedures and their value in diagnostic imaging and patient monitoring and warns against possible inappropriate indications and misleading information. Thoracic US is much more than "fishing for the moon in the well".

Correlation between vegetarian diet and oral health: a systematic review.

OBJECTIVE: Nutrition plays a significant role in preserving the balance of the human body. Considering each person's particular characteristics, diet can directly and indirectly alter the body's immune response. The purpose of this study is to draw attention to the connection between a vegetarian diet and its impact on oral health. MATERIALS AND METHODS: To determine the connection between a vegetarian diet and dental health, a search of the literature was conducted on the PubMed, Scopus, and Web of Science databases. English language and a publication year between January 1, 2013, and March 1, 2023, were the inclusion criteria for the search. RESULTS: There were 167 articles in total that addressed the subject of interest, and 18 of them were chosen for qualitative analysis. CONCLUSIONS: This study suggests that a vegetarian diet may alter oral health, namely periodontal health, tooth erosion, and oral microbiome. Even if the data collected prevents the effect of a vegetarian diet on oral health from being confirmed, this study acts as a starting point for future, more focused research.

Maternal immunity shapes biomarkers of germinal center development in HIV-exposed uninfected infants.

Introduction: HIV-exposed uninfected (HEU) infants exhibit elevated pro-inflammatory biomarkers that persist after birth. However, comprehensive assessments of bioprofiles associated with immune regulation and development in pregnant women with HIV (PWH) and HEU infants has not been performed. Maternal immunity in PWH may be imprinted on their HEU newborns, altering immune bioprofiles during early immune development. Methods: Cryopreserved paired plasma samples from 46 HEU infants and their mothers enrolled in PACTG 316, a clinical trial to prevent perinatal HIV-1 transmission were analyzed. PWH received antiretrovirals (ARV) and had either fully suppressed or unsuppressed viral replication. Maternal blood samples obtained during labor and infant samples at birth and 6 months were measured for 21 biomarkers associated with germinal centers (GC), macrophage activation, T-cell activation, interferon gamma (IFN-γ)-inducible chemokines, and immune regulatory cytokines using Mesoscale assays. Pregnant women without HIV (PWOH) and their HIV unexposed uninfected (HUU) newborns and non-pregnant women without HIV (NPWOH) served as reference groups. Linear regression analysis fitted for comparison among groups and adjusted for covariant(s) along with principal component analysis performed to assess differences among groups. Results: Compared with NPWOH, PWOH displayed higher levels of GC, macrophage, and regulatory biomarkers. PWH compared to PWOH displayed elevated GC, T cell activation, and IFN-γ-inducible chemokines biomarkers at delivery. Similar to their mothers, HEU infants had elevated GC, macrophage, and IFN-γ-inducible chemokines, as well as elevated anti-inflammatory cytokines, IL-10 and IL-1RA. Across all mother/newborn dyads, multiple biomarkers positively correlated, providing further evidence that maternal inflammation imprints on newborn bioprofiles. By 6 months, many HEU biomarkers normalized to levels similar to HUU infants, but some GC and inflammatory biomarkers remained perturbed. Bioprofiles in PWH and HEU infants were similar regardless of the extent of maternal viral suppression by ARV. Conclusions: GC immune pathways are perturbed in HEU newborns, but immune regulatory responses down regulate inflammation during early infancy, indicating a transient inflammatory effect. However, several GC biomarkers that may alter immune development remain perturbed.

Mitral annular disjunction in idiopathic ventricular fibrillation patients: just a bystander or a potential cause?

AIMS: Previously, we demonstrated that inferolateral mitral annular disjunction (MAD) is more prevalent in patients with idiopathic ventricular fibrillation (IVF) than in healthy controls. In the present study, we advanced the insights into the prevalence and ventricular arrhythmogenicity by inferolateral MAD in an even larger IVF cohort. METHODS AND RESULTS: This retrospective multi-centre study included 185 IVF patients [median age 39 (27, 52) years, 40% female]. Cardiac magnetic resonance images were analyzed for mitral valve and annular abnormalities and late gadolinium enhancement. Clinical characteristics were compared between patients with and without MAD. MAD in any of the 4 locations was present in 112 (61%) IVF patients and inferolateral MAD was identified in 24 (13%) IVF patients. Mitral valve prolapse (MVP) was found in 13 (7%) IVF patients. MVP was more prevalent in patients with inferolateral MAD compared with patients without inferolateral MAD (42 vs. 2%, P < 0.001). Pro-arrhythmic characteristics in terms of a high burden of premature ventricular complexes (PVCs) and non-sustained ventricular tachycardia (VT) were more prevalent in patients with inferolateral MAD compared to patients without inferolateral MAD (67 vs. 23%, P < 0.001 and 63 vs. 41%, P = 0.046, respectively). Appropriate implantable cardioverter defibrillator therapy during follow-up was comparable for IVF patients with or without inferolateral MAD (13 vs. 18%, P = 0.579). CONCLUSION: A high prevalence of inferolateral MAD and MVP is a consistent finding in this large IVF cohort. The presence of inferolateral MAD is associated with a higher PVC burden and non-sustained VTs. Further research is needed to explain this potential interplay.

Characterization of a rare IL-10-competent B-cell subset in humans that parallels mouse regulatory B10 cells.

Regulatory B cells control inflammation and autoimmunity in mice, including the recently identified IL-10-competent B10 cell subset that represents 1% to 3% of spleen B cells. In this study, a comparable IL-10-competent B10 cell subset was characterized in human blood. B10 cells were functionally identified by their ability to express cytoplasmic IL-10 after 5 hours of ex vivo stimulation, whereas progenitor B10 (B10pro) cells required 48 hours of in vitro stimulation before they acquired the ability to express IL-10. B10 and B10pro cells represented 0.6% and approximately 5% of blood B cells, respectively. Ex vivo B10 and B10pro cells were predominantly found within the CD24(hi)CD27(+) B-cell subpopulation that was able to negatively regulate monocyte cytokine production through IL-10-dependent pathways during in vitro functional assays. Blood B10 cells were present in 91 patients with rheumatoid arthritis, systemic lupus erythematosus, primary Sjögren syndrome, autoimmune vesiculobullous skin disease, or multiple sclerosis, and were expanded in some cases as occurs in mice with autoimmune disease. Mean B10 + B10pro-cell frequencies were also significantly higher in patients with autoimmune disease compared with healthy controls. The characterization of human B10 cells will facilitate their identification and the study of their regulatory activities during human disease.

Renal insufficiency in non-diabetic subjects: relationship of MTHFR C677t gene polymorphism and left ventricular hypertrophy.

BACKGROUND: Association of methylenetetrahydrofolate reductase (MTHFR) 677C>T gene polymorphism with hyperhomocysteinemia, renal failure, and cardiovascular events is controversial. We investigated the relationship of MTHFR 677C>T polymorphisms with left ventricular hypertrophy (LVH) and renal insufficiency. METHODS: Glomerular filtration rate (GFR) and left myocardial ventricular mass/m2 were assessed in 138 non-diabetic subjects (age, 50.93 ± 14.85 years; body mass index, 27.95 ± 5.98 kg/m(2)), 38 no-mutation wild MTHFR C677CC, 52 heterozygous MTHFR C677CT, and 48 homozygous MTHFR C677TT, all with adequate adherence to current international healthy dietary guidelines. Serum homocysteine, insulin resistance, high-sensitivity C-reactive-protein (hsCRP), parathyroid hormone, and renal artery resistive index (RRI) were challenged by odds ratio analysis and multiple linear regression models. RESULTS: MTHFR 677C>T polymorphism showed higher GFR (73.8 ± 27.99 vs. 58.64 ± 29.95; p= 0.001) and lower renal failure odds (OR, 0.443; 95% confidence interval, 0.141-1.387) in comparison with wild MTHFR genotype. A favorable effect on GFR of MTHFR polymorphism is presented independently by the negative effects of LVH, increased intra-renal arterial resistance, and hyperparathyroidism; GFR is the significant predictive factor to LVH. CONCLUSIONS: Renal insufficiency in non-diabetic subjects is explained by interactions of MTHFR C677T polymorphism mutation with LVH, hsCRP, intact parathyroid hormone (iPTH), and RRI. Sign of these predictive effects is opposite: subjects with MTHFR 677C>T polymorphism have lower likelihood of renal insufficiency; differently, wild-type MTHFR genotype subjects have lower GFR and greater hsCRP, iPTH, RRI, and LVH.