Controlled mitral valvuloplasty using steerable catheter- waist- formed balloon system: A clinical case series.

As the general population ages, the incidence of degenerative mitral stenosis (MS) among patients has increased. Percutaneous mitral valvuloplasty (PMV) has emerged as a well-established option for mitral rheumatic stenosis with specific characteristics. However, a blank therapeutic space must be filled with the treatment options for degenerative or rheumatic mitral stenosis in patients with many comorbidities and contraindication for valvuloplasty. We here present a comprehensive overview of the current possibilities, despite their scarce success. That is the reason why we propose a case series to facilitate a better understanding of our innovative technique in this challenging clinical context.

Paradoxical GH increase after oral glucose load in subjects with and without acromegaly.

OBJECTIVE: A paradoxical GH rise after the glucose load (GH-Par) is described in about one-third of acromegalic patients. Here, we evaluated the GH profile in subjects with and without acromegaly aiming to refine the definition of GH-Par. DESIGN: Observational case-control study. METHODS: Our cohort consisted of 60 acromegalic patients, and two groups of subjects presenting suppressed GH (< 0.4 µg/L) and high (non-acro↑IGF-1, n = 116) or normal IGF-1 levels (non-acro, n = 55). The distribution of GH peaks ≥ 120% from baseline, insulin, and glucose levels were evaluated over a 180-min time interval after glucose intake. RESULTS: A similar proportion of subjects in all three groups shows a GH ratio of ≥ 120% starting from 120 min. Re-considering the definition of paradoxical increase of GH within 90 min, we observed that the prevalence of GH peaks ≥ 120% was higher in acromegaly than in non-acro↑IGF-1 and non-acro (respectively 42%, 16%, and 7%, both p < 0.001). In patients without GH-Par, a late GH rebound was observed in the second part of the curve. Higher glucose peak (p = 0.038), slower decline after load, 20% higher glucose exposure (p = 0.015), and a higher prevalence of diabetes (p = 0.003) characterized acromegalic patients with GH-Par (with respect to those without). CONCLUSIONS: GH-Par response may be defined as a 20% increase in the first 90 min after glucose challenge. GH-Par, common in acromegaly and associated with an increased prevalence of glucose metabolism abnormalities, is found also in a subset of non-acromegalic subjects with high IGF-1 levels, suggesting its possible involvement in the early phase of the disease.

Molecular study of the presence and transcriptional activity of HPV in semen.

PURPOSE: Human Papillomavirus (HPV) in semen represents a controversial topic. Recent evidence suggests a correlation with poor semen quality, but its detection is still unstandardized in this biological fluid. Thus, the aims of this study were to verify the ability of nested PCR to reveal HPV-DNA in semen; to evaluate association of seminal HPV with sperm parameters and risk factors for infection; to investigate the rate of HPV-DNA positivity in patients with and without risk factors; to assess HPV transcriptional activity. METHODS: We enrolled sexually active men and collected clinical and anamnestic data during andrological and sexually transmitted infections (STIs) evaluation. For each patient, we performed semen analysis and nested PCR to detect HPV-DNA in semen. In positive semen samples, we proceeded with genotyping and RNA quantification to detect HPV transcriptional activity. RESULTS: We enrolled 185 men (36.0 ± 8.3 years), of which 85 with (Group A) and 100 without HPV risk factors (Group B). Nested PCR was able to reveal HPV-DNA in semen, discovering a prevalence of 8.6% (11.8% in Group A and 6% in Group B, respectively). We observed no correlation between sperm quality and seminal HPV. Genital warts and previous anogenital infection were significantly associated with the risk of HPV positivity in semen. Moreover, no viral transcriptional activity was detected in positive semen samples. CONCLUSIONS: Our study suggests that searching for seminal HPV could be important in patients both with and without risk factors, especially in assisted reproduction where the risk of injecting sperm carrying HPV-DNA is possible.

Molecular diagnosis of SARS-CoV-2 in seminal fluid.

PURPOSE: Due to relevant repercussions on reproductive medicine, we aimed to evaluate feasibility of RT-PCR as a detection method of SARS-CoV-2 RNA in seminal fluid. METHODS: A qualitative determination of the RT-PCR assays in semen was performed through different approaches: (1) efficiency of RNA extraction from sperm and seminal plasma was determined using PRM1 and PRM2 mRNA and a heterologous system as control; (2) samples obtained by diluting viral preparation from a SARS-CoV-2 panel (virus cultured in Vero E6 cell lines) were tested; (3) viral presence in different fractions of seminal fluid (whole sample, seminal plasma and post-centrifugation pellet) was evaluated. Semen samples from mild and recovered COVID-19 subjects were collected by patients referring to the Infectious Disease Department of the Policlinico Umberto I Hospital - "Sapienza" University of Rome. Control subjects were recruited at the Laboratory of Seminology-Sperm Bank "Loredana Gandini'' of the same hospital. RESULTS: The control panel using viral preparations diluted in saline and seminal fluid showed the capability to detect viral RNA presence with Ct values depending on the initial viral concentration. All tested semen samples were negative for SARS-CoV-2, regardless of the nasopharyngeal swab result or seminal fluid fraction. CONCLUSION: These preliminary data show that RT-PCR for SARS-CoV-2 RNA testing appears to be a feasible method for the molecular diagnosis of SARS-CoV-2 in seminal fluid, supported by results of the control panel. The ability to detect SARS-CoV-2 in semen is extremely important for reproductive medicine, especially in assisted reproductive technology and sperm cryopreservation.

Hearing and Vision Screening Program for newborns in Italy.

Materials and Methods: Data were collected through a nationwide survey conducted in 2018. All maternity wards active in Italy in 2017 were included. Background: The aims of this paper were to present data on the implementation and coverage of simultane-ous Universal Neonatal Hearing and Vision Screening programmes and to evaluate the organization and management of these healthcare procedures in Italy. Conclusions: Our results show that implementation of simultaneous hearing and vision screening increased the coverage of both screening tests and is a new multi-disciplinary approach to sensorineural disability. The use of both ABR and TEOAE tests in the hearing screening decreases the number of newborns sent for audiological evaluation, with a notable reduction of costs. The consideration that ocular problems are two to three times more common in deaf and hearing impaired children than their in hearing peers, confirms the importance of establishing guidelines for simultaneous hearing and vision screening, that favors the formation of a multi-disciplinary team (pediatrician, audio-logist, ophthalmologist). Results: HEARING SCREENING. Overall 427,365 newborns out of 448,386 (95.3%) received the hearing screening test (first level) in 391 out of the 409 maternity hospitals (95.5%), with a national mean referral rate of 3.63% (SD ± 4.58). A statistically significant increase (p<0.034) of newborns sent to audiological examination was found in maternity hospitals with Neonatal Intensive Care Unit (NICU) with "TEOAE only" protocol (9.32% SD ± 7.57), compared to those with "TEOAE/AABR" (3.0% SD ± 3.29). VISION SCREENING. Overall 335,262 newborns out of 448,386 (74.7%) received vision screening (Red Reflex test) for vision impairment in 302 out of 409 maternity hospitals (73.8%), before nursery discharge. The mean referral rate, recorded in only 22 maternity hospitals out of 302 (7.2%), was 0.48% with a rate of lost to follow up of 0.75 %.

Study of SARS-CoV-2 in semen and urine samples of a volunteer with positive naso-pharyngeal swab.

INTRODUCTION: The recent appearance of SARS-CoV-2 in Wuhan in 2019 has started a pandemic which has involved over a million people worldwide. A matter of debate is the possible viral detection in different body fluids than respiratory droplets. Thus, we evaluated the possible presence of SARS-CoV-2 in semen and urine samples of a volunteer with confirmed COVID-19. MATERIALS AND METHODS: A 31-year-old man with fever, myalgia, anosmia, and ageusia was tested and found positive for SARS-CoV-2 through a pharyngeal swab. Eight days after he provided semen and urine samples in which viral RNA presence was measured using a Real time RT PCR system (RealStar SARS-CoV-2 RT-PCR, Altona Diagnostics) targeting E and S viral genes. RESULTS AND DISCUSSION: Semen and urine samples search for SARS-CoV-2 RNA was negative. Although this should be interpreted cautiously, it may be possible that either the viral clearance kinetics in these matrices matches the progressive clinical recovery of the patient or that the virus was never present in these fluids at the time of the laboratory diagnosis.

Dexamethasone measurement during low-dose suppression test for suspected hypercortisolism: threshold development with and validation.

BACKGROUND AND AIM: Dexamethasone Suppression Test (DST), recommended for Cushing's Syndrome (CS) diagnosis, explores the pituitary feedback to glucocorticoids. Its diagnostic accuracy could be affected by dexamethasone bioavailability, and therefore, we have developed and validated a dexamethasone threshold after 1-mg DST. MATERIALS AND METHODS: We studied 200 subjects: 125 patients were considered retrospectively and 75 were enrolled prospectively as the validation cohort. Serum dexamethasone, Late Night Salivary Cortisol (LNSC), and Urinary Free Cortisol (UFC) were measured with LC-MS/MS. Normal LNSC and UFC levels were used to exclude CS. The lower 2.5th percentile of dexamethasone distribution in non-CS patients with cortisol ≤ 50 nmol/L after 1-mg DST was used as threshold. RESULTS: 16 patients were CS and 184 non-CS (108 adrenal incidentaloma and 76 excluded CS); 4.5 nmol/L resulted the calculated threshold. Cortisol after 1-mg DST confirmed high sensitivity (100% at 50 nmol/L cut-off) and moderate-low specificity (63%, increased to 91% at 138 nmol/L) to diagnose CS in the whole cohort of patients. We could reduce the number of false-positive results (from 10 to 6 and from 7 to 4 in AI and excluded CS) considering adequate dexamethasone levels. Dexamethasone levels were not affected by hypercortisolism, age, gender, smoke, weight, and creatinine. 6% of non-CS patients did not achieve adequate dexamethasone levels (40% of tests with serum cortisol > 138 nmol/L after 1-mg DST). CONCLUSIONS: We developed and validated the routine dexamethasone measurement during 1-mg DST: it is independent from patient's clinical presentation, and it should be used to increase the specificity of serum cortisol levels.

Multimodal surveillance of healthcare associated infections in an intensive care unit of a large teaching hospital

BACKGROUND: Healthcare-associated infections (HAIs), or nosocomial infections, represent a significant burden in terms of mortality, morbidity, length of stay and costs for patients hospitalized in intensive care units (ICUs). Surveillance systems are recommended by national and international institutions to gather data on HAIs in order to develop and evaluate interventions that reduce the risk of HAIs. STUDY DESIGN: Here we describe the methodology and the results of the surveillance system implemented in the ICU of the Policlinico Umberto I, a large teaching hospital in Rome, from April 2016 to October 2018. METHODS: The multimodal infection surveillance system integrates four different approaches: i) active surveillance of inpatients; ii) environmental microbiological surveillance; iii) surveillance of isolated microorganisms; and iv) behavioral surveillance of healthcare personnel. Data were collected on catheter-related bloodstream infections, ventilation-associated pneumonia, catheter-associated urinary tract infections and primary bloodstream infections that developed in patients after 48 h in the ICU. For environmental surveillance 14 points were selected for sampling (i.e. bed edges, medication carts, PC keyboards, sink faucets). The system of active surveillance of HAIs also included surveillance of microorganisms, consisting of the molecular genotyping of bacterial isolates by pulsed-field gel electrophoresis (PFGE). From 1 November 2016, monitoring of compliance with guidelines for hand hygiene (HH) and proper glove or gown use by healthcare personnel was included in the surveillance system. After the first six months (baseline phase), a multimodal intervention to improve adherence to guidelines by healthcare personnel was conducted with the ICU staff. RESULTS: Overall, 773 patients were included in the active surveillance. The overall incidence rate of device-related HAIs was 14.1 (95% CI: 12.2-16.3) per 1000 patient-days. The monthly device-related HAI incident rate showed a decreasing trend over time, with peaks of incidence becoming progressively lower. The most common bacterial isolates were Klebsiella pneumoniae (20.7%), Acinetobacter baumannii (17.2%), Pseudomonas aeruginosa (13.4%) and Staphylococcus aureus (5.4%). Acinetobacter baumannii and Klebsiella pneumoniae showed the highest proportion of isolates with a multidrug-resistant profile. A total of 819 environmental samples were collected, from which 305 bacterial isolates were retrieved. The most frequent bacterial isolates were Acinetobacter baumannii (27.2%), Staphylococcus aureus (12.1%), Enterococcus faecalis (11.1%), Klebsiella pneumoniae (5.2%) and Pseudomonas aeruginosa (4.7%). All Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae environmental isolates were at least multidrug-resistant. Genotyping showed a limited number of major PFGE patterns for both clinical and environmental isolates of Klebsiella pneumoniae and Acinetobacter baumannii. Behavioral compliance rates significantly improved from baseline to post-intervention phase. CONCLUSIONS: By integrating information gathered from active surveillance, environmental microbiological surveillance, surveillance of bacterial isolates and behavioral surveillance of healthcare personnel, the multimodal infection surveillance system returned a precise and detailed view of the infectious risk and microbial ecology of the ICU.

First-line screening tests for Cushing's syndrome in patients with adrenal incidentaloma: the role of urinary free cortisol measured by LC-MS/MS.

INTRODUCTION AND AIM: Patients with adrenal incidentaloma present a wide range of cortisol secretion, which is not always properly defined by first-line screening tests recommended to rule out Cushing's syndrome (CS), such as 1-mg dexamethasone suppression test (1-mg DST), late night salivary cortisol (LNSC), or 24-h urinary free cortisol (UFC). Therefore, we examined the diagnostic performance of each screening test in patients with adrenal incidentaloma. MATERIALS AND METHODS: In a series of 164 consecutive patients with adrenal incidentaloma, we measured serum cortisol after 1-mg DST, LNSC, and UFC (with LC-MS/MS). Medical history was investigated for cardiovascular events (CVE) in a subgroup of 93 patients with at least 2 years of follow-up. RESULTS: Serum cortisol <50 nmol/L after 1-mg DST presented the highest sensitivity (100%) to rule out CS, despite a low specificity (62%). UFC > 170 nmol/24 h achieved the highest diagnostic accuracy (sensitivity 98%, specificity 91%, and negative/positive likelihood ratios of 0.02/10.83, respectively). The prevalence of CVE was higher in patients with non-suppressed cortisol after 1-mg DST and high UFC levels (p = 0.018). Traditional cardiovascular risk factors (hypertension, diabetes mellitus, dyslipidemia, BMI > 30 kg/m2, smoke or high gender-based waist circumference) were not associated with CVE. CONCLUSIONS: The 1-mg DST at its lowest threshold presented high sensitivity in identifying CS, but its low specificity encourages us to consider UFC levels, measured with LC-MS/MS, to reduce false-positive test results. High UFC levels could also be considered as markers to stratify cardiovascular risk in patients with adrenal incidentaloma.

HIV-1 coreceptor usage in paired plasma RNA and proviral DNA from patients with acute and chronic infection never treated with antiretroviral therapy.

Although an independent evolution of viral quasispecies in different body sites might determine a differential compartmentalization of viral variants, the aim of this paper was to establish whether sequences from peripheral blood mononuclear cells (PBMCs) and plasma provide different or complementary information on HIV tropism in patients with acute or chronic infection. Tropism was predicted using genotypic testing combined with geno2pheno (coreceptor) analysis at a 10% false positive rate in paired RNA and DNA samples from 75 antiretroviral-naïve patients (divided on the basis of avidity index into patients with a recent or long-lasting infection). A high prevalence of R5 HIV strains (97%) was observed in both compartments (plasma and PBMCs) in patients infected recently. By contrast, patients with a long-lasting infection showed a quite different situation in the two compartments, revealing more (46%) X4/DM in PBMCs than patients infected recently (3%) (P = 0.008). As- a knowledge of viral strains in different biological compartments might be crucial to establish a therapeutic protocol, it could be extremely useful to detect not only viral strains in plasma, but also viruses hidden or archived in different cell compartments to better understand disease evolution and treatment efficacy in patients infected with HIV.

Detection and quantification of EBV, HHV-6 and CMV DNA in the gastrointestinal tract of HIV-positive patients.

Human herpes viruses (HHVs) have been frequently detected in the gastrointestinal (GI) tract and may contribute to the development of gastric cancer. In the present study, the detection rate and viral load of Epstein Barr virus (EBV), HHV-6 and Cytomegalovirus (CMV) were assessed in the GI tract of human immunodeficiency virus (HIV) positive patients and of uninfected patients. The analysis revealed a significantly higher detection rate of EBV and HHV-6 in HIV-infected individuals than in uninfected subjects (88.5 vs 63%; p = 0.03). Moreover, EBV DNA load was significantly higher in the stomach of HIV patients than in controls. These data suggest that the HIV infection status may increase the persistence of these viruses in the GI compartment. Intriguingly, CMV DNA was undetectable in all biopsy specimens analyzed.

Genotypic testing on HIV-1 DNA as a tool to assess HIV-1 co-receptor usage in clinical practice: results from the DIVA study group.

PURPOSE: We have developed a sequencing assay for determining the usage of the genotypic HIV-1 co-receptor using peripheral blood mononuclear cell (PBMC) DNA in virologically suppressed HIV-1 infected patients. Our specific aims were to (1) evaluate the efficiency of V3 sequences in B versus non-B subtypes, (2) compare the efficiency of V3 sequences and tropism prediction using whole blood and PBMCs for DNA extraction, (3) compare the efficiency of V3 sequences and tropism prediction using a single versus a triplicate round of amplification. RESULTS: The overall rate of successful V3 sequences ranged from 100 % in samples with >3,000 copies HIV-1 DNA/10(6) PBMCs to 60 % in samples with <100 copies total HIV-1 DNA /10(6) PBMCs. Analysis of 143 paired PBMCs and whole-blood samples showed successful V3 sequences rates of 77.6 % for PBMCs and 83.9 % for whole blood. These rates are in agreement with the tropism prediction obtained using the geno2pheno co-receptor algorithm, namely, 92.1 % with a false-positive rate (FPR) of 10 or 20 % and of 96.5 % with an FPR of 5.75 %. The agreement between tropism prediction values using single versus triplicate amplification was 98.2 % (56/57) of patients using an FPR of 20 % and 92.9 % (53/57) using an FPR of 10 or 5.75 %. For 63.0 % (36/57) of patients, the FPR obtained via the single amplification procedure was superimposable to all three FPRs obtained by triplicate amplification. CONCLUSIONS: Our results show the feasibility and consistency of genotypic testing on HIV-1 DNA tropism, supporting its possible use for selecting patients with suppressed plasma HIV-1 RNA as candidates for CCR5-antagonist treatment. The high agreement between tropism prediction by single and triple amplification does not support the use of triplicate amplification in clinical practice.

Rapid spread of the novel respiratory syncytial virus A ON1 genotype, central Italy, 2011 to 2013.

Respiratory infections positive for human respiratory syncytial virus (RSV) subtype A were characterised in children admitted to hospitals in Rome and Ancona (Italy) over the last three epidemic seasons. Different strains of the novel RSV-A genotype ON1, first identified in Ontario (Canada) in December 2010, were detected for the first time in Italy in the following 2011/12 epidemic season. They bear an insertion of 24 amino acids in the G glycoprotein as well as amino acid changes likely to change antigenicity. By early 2013, ON1 strains had spread so efficiently that they had nearly replaced other RSV-A strains. Notably, the RSV peak in the 2012/13 epidemic season occurred earlier and, compared with the previous two seasons, influenza-like illnesses diagnoses were more frequent in younger children; bronchiolitis cases had a less severe clinical course. Nonetheless, the ON1-associated intensive care unit admission rate was similar, if not greater, than that attributable to other RSV-A strains. Improving RSV surveillance would allow timely understanding of the epidemiological and clinicopathological features of the novel RSV-A genotype.

Efficient pump-probe sampling with a single-cavity dual-comb laser: Application in ultrafast photoacoustics.

Ultrafast pump-probe measurements are used to characterize various samples, such as biological cells, bulk, and thin-film structures. However, typical implementations of the pump-probe apparatus are either slow or complex and costly hindering wide deployment. Here we combine a single-cavity dual-comb laser with a simple experimental setup to obtain pump-probe measurements with ultra-high sensitivity, fast acquisition, and high timing precision over long optical delay scan ranges of 12.5 ns that would correspond to a mechanical delay of about 3.75 m. We employ digital signal balancing to obtain shot-noise-limited detection compatible with pump-probe microscopy deployment. Here we demonstrate ultrafast photoacoustics for thin-film sample characterization. We measured a tungsten layer thickness of (700 ± 4) Å with shot-noise-limited detection. Such single-cavity dual-comb lasers can be used for any pump-probe measurements and are especially well-suited for ultrafast photoacoustic studies such as involving ultrasonic echoes, Brillouin oscillations, surface acoustic waves and thermal dynamics.

Genetic diversity and its impact on disease severity in respiratory syncytial virus subtype-A and -B bronchiolitis before and after pandemic restrictions in Rome.

OBJECTIVES: To scrutinize whether the high circulation of respiratory syncytial virus (RSV) observed in 2021-2022 and 2022-2023 was due to viral diversity, we characterized RSV-A and -B strains causing bronchiolitis in Rome, before and after the COVID-19 pandemic. METHODS: RSV-positive samples, prospectively collected from infants hospitalized for bronchiolitis from 2017-2018 to 2022-2023, were sequenced in the G gene; phylogenetic results and amino acid substitutions were analyzed. Subtype-specific data were compared among seasons. RESULTS: Predominance of RSV-A and -B alternated in the pre-pandemic seasons; RSV-A dominated in 2021-2022 whereas RSV-B was predominant in 2022-2023. RSV-A sequences were ON1 genotype but quite distant from the ancestor; two divergent clades included sequences from pre- and post-pandemic seasons. Nearly all RSV-B were BA10 genotype; a divergent clade included only strains from 2021-2022 to 2022-2023. RSV-A cases had lower need of O2 therapy and of intensive care during 2021-2022 with respect to all other seasons. RSV-B infected infants were more frequently admitted to intensive care units and needed O2 in 2022-2023. CONCLUSIONS: The intense RSV peak in 2021-2022, driven by RSV-A phylogenetically related to pre-pandemic strains is attributable to the immune debt created by pandemic restrictions. The RSV-B genetic divergence observed in post-pandemic strains may have increased the RSV-B specific immune debt, being a possible contributor to bronchiolitis severity in 2022-2023.

Deep-Manager: a versatile tool for optimal feature selection in live-cell imaging analysis.

One of the major problems in bioimaging, often highly underestimated, is whether features extracted for a discrimination or regression task will remain valid for a broader set of similar experiments or in the presence of unpredictable perturbations during the image acquisition process. Such an issue is even more important when it is addressed in the context of deep learning features due to the lack of a priori known relationship between the black-box descriptors (deep features) and the phenotypic properties of the biological entities under study. In this regard, the widespread use of descriptors, such as those coming from pre-trained Convolutional Neural Networks (CNNs), is hindered by the fact that they are devoid of apparent physical meaning and strongly subjected to unspecific biases, i.e., features that do not depend on the cell phenotypes, but rather on acquisition artifacts, such as brightness or texture changes, focus shifts, autofluorescence or photobleaching. The proposed Deep-Manager software platform offers the possibility to efficiently select those features having lower sensitivity to unspecific disturbances and, at the same time, a high discriminating power. Deep-Manager can be used in the context of both handcrafted and deep features. The unprecedented performances of the method are proven using five different case studies, ranging from selecting handcrafted green fluorescence protein intensity features in chemotherapy-related breast cancer cell death investigation to addressing problems related to the context of Deep Transfer Learning. Deep-Manager, freely available at https://github.com/BEEuniroma2/Deep-Manager , is suitable for use in many fields of bioimaging and is conceived to be constantly upgraded with novel image acquisition perturbations and modalities.

Rhinovirus bronchiolitis and recurrent wheezing: 1-year follow-up.

The association between bronchiolitis and recurrent wheezing remains controversial. In this prospective study, we assessed risk factors for recurrent wheezing during a 12-month follow-up in 313 infants aged <12 months hospitalised for their first episode of bronchiolitis. Demographic, clinical and laboratory data were obtained with a questionnaire and from medical files. A total of 14 respiratory viruses were concurrently assayed in nasal washings. Parents were interviewed 12 months after hospitalisation to check whether their infants experienced recurrent wheezing. The rate of recurrent wheezing was higher in infants with bronchiolitis than in controls (52.7 versus 10.3%; p<0.001). Multivariate analysis identified rhinovirus (RV) infection (OR 3.3, 95% CI 1.0-11.1) followed by a positive family history for asthma (OR 2.5, 95% CI 1.2-4.9) as major independent risk factors for recurrent wheezing. In conclusion, the virus most likely to be associated with recurrent wheezing at 12 months after initial bronchiolitis is RV, a viral agent that could predict infants prone to the development of recurrent wheezing.

Interleukin-28B (IL-28B) single-nucleotide polymorphisms and interferon plus ribavirin treatment outcome in Italian chronically HCV-infected patients.

To determine the single or combined effect of both rs12979860 and rs8099917 SNPs on HCV treatment response, these variants were genotyped in samples from a cohort of 170 patients infected with different HCV genotypes (HCVGT). The favourable rs12979860 CC genotype was found only in patients with sustained or rapid virological responses (SVR/RVR) and at significantly high proportions in HCVGT1/4 SVR patients. A significant association was also found between the rs8099917 TT genotype and SVR in both HCVGT1/4 and HCVGT2/3 groups of patients. In contrast, we found that there was significantly more of the rs8099917 GG genotype in nonresponders (NR) than in SVR patients which suggests a good association of the minor homozygote GG with the lack of treatment response. The combination of rs12979860/rs8099917 CC/TT favourable genotypes was found only in SVR patients and matched the frequency observed for their rs12979860 CC genotypes alone. By contrast, the inverse unfavourable correlate rs12979860/rs8099917 TT/GG genotype was seen more in NR than in SVR patients as observed for the single GG genotype. This study confirms the impact of both rs12979860 and/or rs8099917 IL-28B SNPs on treatment-induced clearance of HCV-RNA and demonstrates that the rs12979860 CC genotype is stronger than rs8099917 TT genotype in predicting a positive treatment response in HCVGT1/4 patients. The unfavourable rs8099917 GG genotype seems to be more important in predicting the failure of treatment response independently from HCV genotype.

IGF-I/IGFBP system: metabolism outline and physical exercise.

The GH/IGF-I system plays a well-known hormonal role and its effects, mainly anabolic and insulin-sensitizing, are mediated through endocrine as well as paracrine/ autocrine mechanisms. This system includes the binding proteins, namely GH binding proteins and IGF-I binding proteins (IGFBP). As expected, this axis plays a key role in organism modification in consequence of a physical exercise. Physical activity, training, and exercise capacity chiefly involve anabolism process modifications of various tissues, in particular muscular adjustments. Numerous investigators found a correlation among the level of exercise tolerance, muscle strength or walking speed and IGF-I/IGFBP-3 concentrations. However, also inverse and absent correlations between circulating IGF-I concentrations and acute or chronic exercise responses have been reported. IGF-I is generally accepted as an important GH mediator with metabolic effects, through both endocrine and paracrine or autocrine mechanisms. GH is the main regulator of the hepatic synthesis of IGF-I and IGFBP-3, which is the most abundant IGF carrier in human plasma. Recently, it has been shown that the physical exercise stimulatory impact on skeletal muscles is mediated through an increased local IGF-I synthesis with an IGFPB involvement. An absent association of exercise performance and circulating IGF-I may indicate that exercise will exert muscle strength by predominately locally derived paracrine or autocrine mediators rather than endocrine circulating IGF-I. The present review considers the general aspects of the IGF/IGFPB system and the role of the IGF/IGFPB system in relation to physical exercise (type, duration, etc.) taking into account the training aspects.

Machine learning phenomics (MLP) combining deep learning with time-lapse-microscopy for monitoring colorectal adenocarcinoma cells gene expression and drug-response.

High-throughput phenotyping is becoming increasingly available thanks to analytical and bioinformatics approaches that enable the use of very high-dimensional data and to the availability of dynamic models that link phenomena across levels: from genes to cells, from cells to organs, and through the whole organism. The combination of phenomics, deep learning, and machine learning represents a strong potential for the phenotypical investigation, leading the way to a more embracing approach, called machine learning phenomics (MLP). In particular, in this work we present a novel MLP platform for phenomics investigation of cancer-cells response to therapy, exploiting and combining the potential of time-lapse microscopy for cell behavior data acquisition and robust deep learning software architectures for the latent phenotypes extraction. A two-step proof of concepts is designed. First, we demonstrate a strict correlation among gene expression and cell phenotype with the aim to identify new biomarkers and targets for tailored therapy in human colorectal cancer onset and progression. Experiments were conducted on human colorectal adenocarcinoma cells (DLD-1) and their profile was compared with an isogenic line in which the expression of LOX-1 transcript was knocked down. In addition, we also evaluate the phenotypic impact of the administration of different doses of an antineoplastic drug over DLD-1 cells. Under the omics paradigm, proteomics results are used to confirm the findings of the experiments.