Liquid to supercooled-liquid crossover from a Boltzmann transport approach to escape and diffusion.

We develop a model describing the motion of a non-Brownian particle in a periodic potential, which we then use to predict the temperature dependence of the diffusivity of a glass-former. In the model, the velocity of the particle is drawn for the equilibrium distribution at rate 1/t c, where t c is the intercollision time in the relaxation time approximation. Solutions within a Boltzmann transport approach show that the diffusivity crossovers from a low-t c regime in which the particle at most crosses a single barrier in between two successive collisions, to a high-t c regime in which the particle may cross several barriers. We then use our model to predict the temperature dependence of the diffusion coefficient of a system of harmonic-spheres, whose energy landscape has features resembling those of the potential considered in our model. We successfully recover a crossover in the temperature dependence of the diffusion coefficient observed through numerical dynamics simulations, as well as the relationship of the diffusivity on the temperature in the high-temperature limit.

The Clean Care Contest: promoting hand hygiene among healthcare and medical students.

INTRODUCTION: Despite continuing efforts, compliance rates and knowledge of best practices in hand hygiene remain disappointing. Recognizing that conventional educational tools seem out of touch with young people and that the med and messages contents need refreshing, the Italian Study Group of Hospital Hygiene of the Italian Society of Hygiene, Preventive Medicine and Public Health devised a novel approach to promote the creation of innovative educational tools for improving knowledge of, and compliance with, hand hygiene rules among healthcare and medical students. METHODS: A contest in creating educational material on hand hygiene practices involved university students of nursing and medicine, and of other healthcare degrees. Students from the universities of the GISIO network were invited to create educational material (e.g., videos, posters, presentations, leaflets, and screensavers) to be presented by May 5th 2019 during the World Hand Hygiene Day / Save Lives: Clean Your Hands Global Annual Initiative of the World Health Organization). A local and a national winners were awarded. RESULTS: Three different local and national contests were performed during 2016, 2017 and 2018. During the three-year period, more than 270 educational tools have been developed: 130 (48%) were judged useful for hand hygiene promotion campaigns. The most frequent projects participating in the contests were videos (39%), posters (29%), leaflets (14%), and others (18%) submitted by more than 1,500 students of nursing (40%), medicine (31%), dentistry (7%), and of other healthcare courses in 14 universities. Products were evaluated by a local committee and, subsequently, local winners represented their University in a national contest. CONCLUSIONS: The contest provided a framework for the creation of innovative and potentially effective educational tools via an engaging approach that leveraged student creativity. Given the need to improve compliance rates, this study suggests that new ways can be advantageously explored to teach hand hygiene procedures and increase awareness of the importance of their consistent use among healthcare and medical students.

Promotion of hand hygiene: the experience of the orthopaedic hospital Gaetano Pini-CTO, Milan, Italy.

BACKGROUND: Hand hygiene is the primary preventive measure against health care-associated infections in terms of cost-effectiveness. In 2005, the WHO proposed the "Global Patient Safety Challenge" campaign, with the aim of reducing the overall incidence of such infections, through multimodal programs and strategies, interactive training tools and standardised methods for monitoring compliance. STUDY DESIGN: On the basis of project "Rimani", sponsored by the Health and Social Care Authority of Emilia-Romagna, the Istituto Ortopedico Gaetano Pini has implemented a project which seeks to increase healthcare staff's compliance with hand hygiene. METHODS: A multidisciplinary working group was created to prepare the project documents. Starting from 5th April 2015, twenty operational units were asked to produce information and training material. On 5th May, during a conference, a committee selected the three best works. The material was distributed on a monthly basis to the various departments. In addition to the training, the specifically trained operators of the Medical Monitoring Department carried out direct hand washing tests, filling out appropriate checklists. Non-compliance relating to the technique recorded in 2014 and 2015 was compared and a statistical analysis was conducted using Student's t-test for paired data. RESULTS: Three tests were carried out in 2014. Ninety-nine cases were monitored and 5 non-compliance cases were reported, concerning the execution of the procedural steps, the running time and closing the tap with one's hands at the end of the wash. In 2015 two tests, involving 30 operational units, were carried out. 60 observations were performed, and no non-conformities emerged concerning the technique. Statistical analysis showed a significant reduction of non-compliances between the 2014 and 2015 P = 0.000). CONCLUSION: The results obtained agree with the main findings in literature. The comparison between the 2014 and 2015 tests shows a trend of improvement in the wash technique. This confirms the effectiveness of a multidisciplinary approach and recognises the active and participatory involvement suggested by the WHO.

Efficacy of the nanoparticle-drug conjugate CRLX101 in combination with bevacizumab in metastatic renal cell carcinoma: results of an investigator-initiated phase I-IIa clinical trial.

BACKGROUND: Anti-angiogenic therapies are effective in metastatic renal cell carcinoma (mRCC), but resistance is inevitable. A dual-inhibition strategy focused on hypoxia-inducible factor (HIF) is hypothesized to be active in this refractory setting. CRLX101 is an investigational camptothecin-containing nanoparticle-drug conjugate (NDC), which durably inhibits HIF1α and HIF2α in preclinical models and in gastric cancer patients. Synergy was observed in the preclinical setting when combining this NDC and anti-angiogenic agents, including bevacizumab. PATIENTS AND METHODS: Patients with refractory mRCC were treated every 2 weeks with bevacizumab (10 mg/kg) and escalating doses of CRLX101 (12, 15 mg/m(2)) in a 3 + 3 phase I design. An expansion cohort of 10 patients was treated at the recommended phase II dose (RP2D). Patients were treated until progressive disease or prohibitive toxicity. Adverse events (AEs) were assessed using CTCAE v4.0 and clinical outcome using RECIST v1.1. RESULTS: Twenty-two patients were response-evaluable in an investigator-initiated trial at two academic medical centers. RCC histologies included clear cell (n = 12), papillary (n = 5), chromophobe (n = 2), and unclassified (n = 3). Patients received a median of two prior therapies, with at least one prior vascular endothelial tyrosine kinase inhibitor therapy (VEGF-TKI). No dose-limiting toxicities were observed. Grade ≥3 AEs related to CRLX101 included non-infectious cystitis (5 events), fatigue (3 events), anemia (2 events), diarrhea (2 events), dizziness (2 events), and 7 other individual events. Five of 22 patients (23%) achieved partial responses, including 3 of 12 patients with clear cell histology and 2 of 10 patients (20%) with non-clear cell histology. Twelve of 22 patients (55%) achieved progression-free survival (PFS) of >4 months. CONCLUSIONS: CRLX101 combined with bevacizumab is safe in mRCC. This combination fulfilled the protocol's predefined threshold for further examination with responses and prolonged PFS in a heavily pretreated population. A randomized phase II clinical trial in mRCC of this combination is ongoing.

Hand and wrist surgery: study of efficacy about a new way for one-day low-complexity surgery.

BACKGROUND: In our Hand Micro-surgery Department surgery procedures identified by some regional legislation as "low-complexity care interventions" (BOCA) are carry out. For this reason, as pilot experience, it has been decided to apply Diagnostic Therapeutic Path (DTP) to this type of surgeries in order to improve the offered service. METHODS: From 2011 to 2012 we collected data about 410 BOCA procedures and we monitored a series of indicators. RESULTS: The patients were classified as ASA score 1-2 (99%) and they had a postoperative observation time less than 24h (95%). They reported a constant reduction of pain in the days after surgery (VAS ≤ 4). In 27 cases were found post-surgical complications. All patients evaluated positively this DTP. CONCLUSIONS: The obtained results were used to improve the activity in others Departments of our Institute.

Phase separation of binary fluids with dynamic temperature.

Phase separation of binary fluids quenched by contact with cold external walls is considered. Navier-Stokes, convection-diffusion, and energy equations are solved by lattice Boltzmann method coupled with finite-difference schemes. At high viscosity, different morphologies are observed by varying the thermal diffusivity. In the range of thermal diffusivities with domains growing parallel to the walls, temperature and phase separation fronts propagate toward the inner of the system with power-law behavior. At low viscosity hydrodynamics favors rounded shapes, and complex patterns with different length scales appear. Off-symmetrical systems behave similarly but with more ordered configurations.

Enalapril: antiproteinuric effect in children with nephrotic syndrome.

AIM: The present study was designed to establish the antiproteinuric effect of ACE-I (enalapril). PATIENTS AND METHODS: Six children with steroid-resistant nephrotic syndrome (SRNS) and one patient affected by Alport syndrome and nephrotic-range proteinuria received enalapril (mean dose 0.3 mg/kg/day) during a mean period of 2 years. Before initiation of therapy, blood pressure was normal in all but one patient, the latter showed normal values with enalapril treatment. RESULTS: Five patients showed a significant increase of albumin levels after the treatment. Creatinine clearance remained stable during the study in all but one patient affected by Alport syndrome. CONCLUSION: In five patients (71.4%) enalapril therapy resulted in an important reduction ofproteinuria, in one patient the treatment was stopped after one year for relapse. In patient with Alport syndrome the fall in creatinine clearance, may simply reflect the natural course of the disease.

Primary vesicoureteric reflux and renal damage in the first year of life.

We retrospectively examined 93 children (47M/46F) with primary vesicoureteric reflux (VUR) followed for a mean period of 3.5 years. They were divided into two groups. Group A included 34 babies (25M/9F) with a prenatal diagnosis of pelvic dilatation. Mean age at presentation was 12 days and no urinary tract infection (UTI) occurred before our first examination. VUR was unilateral in 21 (62%) patients and bilateral in 13 (38%). It was mild (grades I-III) in 12 (25%) refluxing renal units (RRU) and severe (grades IV-V) in 35 (75%). Renal damage (RD) was present, at diagnosis, in 40 (85%) RRU. There was a greater prevalence of abnormal kidneys in male units (88%) than in female units (75%). Group B included 59 infants (22M/37F) less than 1 year old with UTI. The mean age at first examination was 7.6 months. VUR was unilateral in 32 (54%) infants and bilateral in 27 (46%), mild in 60 (70%) RRU and severe in 26 (30%). At diagnosis, 54 (63%) RRU presented RD, which was more common in females (66%) than in males (44%). Our study confirms that primary VUR associated with prenatal hydronephrosis usually affects males and is severe. VUR diagnosed after UTI, instead, is more common in females and is frequently mild. Although in the first type of reflux RD is often present at diagnosis, then probably congenital, it may always progress after UTI; hence the importance of early diagnosis and careful follow-up in each infant with primary VUR.

Prevalence of HNPCC in a series of consecutive patients on the first endoscopic diagnosis of colorectal cancer: a multicenter study. The Italian Collaborative Group.

BACKGROUND AND STUDY AIMS: It is difficult to measure the prevalence of hereditary non-polyposis colorectal cancer (HNPCC) in geographical areas that do not have tumor registers, as is the case in the present study, and it was therefore decided to assess the prevalence in Italy using different methods. PATIENTS AND METHODS: The pedigree was established for 485 of 501 colorectal cancer patients diagnosed with colorectal carcinomas. Patients were included consecutively in 13 gastroenterology centers; they had not taken part in prevention examinations. Information was collected regarding the neoplastic pathology observed in the families, confirmed in 90% of cases among 3515 first-degree relatives and in 79.5% of cases among 7068 second-degree relatives. RESULTS: In the 3515 first-degree relatives (1002 parents, 1560 siblings and 953 children), 61 colorectal carcinomas, 29 carcinomas in the digestive tract outside the colon, and 99 carcinomas in other locations were reported. Only five of the 485 patients (1%) satisfied the Amsterdam criteria (three cancers, two of which were in first-degree relatives in different generations and one in a relative younger than 50). When broadening the criteria that we are proposing (satisfying only two of the three Amsterdam criteria), the prevalence would increase to 3% (15 cases). CONCLUSIONS: Modifying the criteria makes it easier to identify new mutations or confirm the existence of those already known, as well as allowing preventative treatment in relatives who are apparently healthy.

[Chronic renal insufficiency and growth retardation: not an inseparable binomial]. / Insufficienza renale cronica e ritardo di crescita: oggi binomio non più inscindibile.

BACKGROUND: The aim of the study was to evaluate, in children with chronic renal failure and in conservative treatment, the degree to which their growth was compromised, in relation with bone age and with GRF. METHODS: The growth of children (12 F, 14 M) with CRI has been evaluated retrospectively in relation to bone age and GFR. Their mean age at diagnosis was 5.8 years. The pathologies-causing CRI were, in particular, congenital anomalies and hereditary nephropathies. The mean follow-up was 6.1 years. RESULTS: No significant difference was found between bone age (BA) and chronologic age (CA) (4.7 +/- 3.4 vs 5.7 +/- 3.5 years, p < 0.3) at diagnosis, while it was lightly delayed (8.6 +/- 5.2 vs 11 +/- 5.6 years, p < 0.07) at the end of the study. At diagnosis the mean height SDS for CA was 0.64 +/- 1.12, at the end of observation was -1.2 +/- 1. Only in 3 patients height was < -2DS: two of them underwent rhGH treatment; the third patient had a growth potential exhausted. The mean height velocity (HV) was 6 +/- 4.2 cm/y at diagnosis and 4.8 +/- 3 at last observation (p < 0.3). No significant difference at diagnosis was found between the HV cm/y and GRF stratified for range, at follow-up there was light significant difference between HV and light CRF vs severe (p < 0.02). Likewise no significant relationship between HV and CA was observed. Actually 20 patients are in conservative treatment, 6 received renal transplantation: for them the growth has been proportional to reached renal function and age of receiver. CONCLUSIONS: The conservative therapeutic regimens and good compliance allowed to limit growth deficiency.

Antibody responses and persistence in the two years after immunization with two acellular vaccines and one whole-cell vaccine against pertussis.

OBJECTIVE: To evaluate the persistence of specific antibodies induced by primary immunization with three doses of two three-component acellular vaccines against pertussis with an observed efficacy of 84%, and one whole-cell vaccine with an observed efficacy of 36%. STUDY DESIGN: Serum samples were collected from a subsample of 1572 children from the Italian double-blind, placebo-controlled, randomized trial of vaccines used in 15,601 children at three time points: before administration of the first dose of vaccine, and 1 month and approximately 15 months after administration of the third dose. Further evaluation included pooled cross-sectional analysis of serum specimens associated with episodes of cough (which were not laboratory confirmed as pertussis infection) occurring among the entire population enrolled in the trial. RESULTS: With both acellular vaccines there was a fast and steep decrease in geometric mean antibody titers to pertussis toxin, filamentous hemagglutinin, and pertactin after vaccination. Mean titers were close to the limit of detection 15 months after primary immunization. The immunogenicity of the whole-cell study vaccine was poor 1 month after the third dose, and no antibody was detected in nearly all children 15 months after whole-cell vaccination. CONCLUSIONS: Although the study acellular pertussis vaccines induced a strong primary specific antibody response in almost all recipients, the duration of the response was limited. Sustained high-level production of antibody to the antigens tested does not account for the observed efficacy of acellular pertussis vaccines.

Immunogenicity of hepatitis B vaccines among infant recipients of acellular and whole cell pertussis DTP vaccines.

The study was conducted to assess the immunogenicity of three doses of two recombinant hepatitis B virus (HBV) vaccines, administered simultaneously with a DT vaccine or one of three different pertussis vaccines combined with diphtheria and tetanus toxoids. The study population consisted of 1237 children selected from the cohort of 15,601 children enrolled in the Italian trial on pertussis vaccines. HBV vaccination was performed at 2, 4 and 12 months of age, with the first two doses concurrent with OPV and DTP vaccination. The DTP vaccines administered in the pertussis trial included one whole cell DTP, licensed in the USA, and two three-component acellular DTaPs, manufactured in Europe. Immunogenicity to HBV was evaluated on serum samples collected 9 months after the third dose of HBV vaccine. Antibodies against HBsAg were detected by ELISA and expressed in mlU/ml. In 13 children, the antibody response was below the protective level of 10 mlU/ml-1. No statistical difference was found among the various study groups with respect to the proportion of children showing protective response. Higher humoral response was observed in children receiving mixed HBV vaccines in each pertussis study groups.

Cell-mediated and antibody responses to Bordetella pertussis antigens in children vaccinated with acellular or whole-cell pertussis vaccines. The Progetto Pertosse-CMI Working Group.

OBJECTIVE: To examine induction and persistence of cell-mediated immunity (CMI) and antibody responses to Bordetella pertussis antigens in infants receiving antipertussis vaccines. DESIGN AND SETTING: A randomized, blinded study of 142 children receiving acellular pertussis vaccines combined with diphtheria-tetanus toxoids (DTaP) (DTaP manufactured by SmithKline Beecham [DTaP-SB], Rixensart, Belgium, and DTaP manufactured by Chiron Biocin [DTaP-CB], Siena, Italy), or a whole-cell pertussis vaccine (DTwP) (Connaught Laboratories Inc, Swiftwater, Pa), or a diphtheria-tetanus (DT) (Chiron Biocine) only vaccine. Three doses of each vaccine were given at 2, 4, and 6 months of age, and CMI and antibody responses were evaluated before and at 1 and 14 months after vaccination. METHODS AND MAIN OUTCOME MEASURES: Cell-mediated immunity was assessed by proliferation of peripheral blood mononuclear cells stimulated in vitro by B pertussis antigens (pertussis toxin, filamentous hemagglutinin, and pertactin). Antibody titers against pertussis toxin, filamentous hemagglutinin, and pertactin were determined by a standardized enzyme-linked immunosorbent assay. RESULTS: A CMI-positive response to at least 1 B pertussis antigen at 1 or both postvaccination assays was detected in 46%, 55%, and 83% of DTwP, DTaP-SB, and DTaP-CB vaccine recipients, respectively. Frequency of CMI response to individual antigens ranged from less than 4.9% against pertussis toxin in DTwP recipients to 52% against pertactin in DTaP-CB recipients. The postvaccination responses measured at 14 months equalled, or had increased frequency or intensity, that of the 1-month postvaccination responses. Elevated antibody titers against the 3 antigens were present in all DTaP recipients 1 month after vaccination and were higher in CMI-positive children than in CMI-negative children. They fell, however, to low, if not negligible, levels 14 months after vaccination. CONCLUSIONS: Acellular pertussis vaccines were better inducers of CMI response than the whole-cell vaccine, particularly against pertussis toxin. Once acquired, CMI persisted, in contrast with the rapid antibody decline. Thus, CMI responses could be a useful adjunct to serology in the evaluation of pertussis vaccine immunogenicity and a better correlate of long-term immunity to B pertussis than antibody titers.

[Hereditary non polyposis colon cancer (NHP CC) prevalence in South Italy (Campania). Report on a preliminary retrospective study]. / Prevalenza di cancro ereditario del colon non su poliposi (HNPCC) nel sud Italia (Campania). Studio retrospettivo pilota.

The aim of this study was to determine a prevalence of Hereditary Non Polyposis Colo-rectal Cancer (HNPCC) in consecutive one hundred twenty-eight patients living in Campania district and affected by first diagnosed colorectal cancer. Data on 128 patients and their relatives was collected and available for analysys. Our preliminary results seem to demonstrate a low prevalence of HNPCC in Campania and will be verified with a prospective multicentric study in the same area.

Antibody kinetics and long-term sero-prevalence in the Italian clinical trial of acellular pertussis vaccines.

In the Italian Pertussis Vaccine Trial, data were collected to evaluate the persistence of anti-pertussis antibodies. A sub-cohort of 1275 children was followed for this purpose until a mean age of 21 months. An additional evaluation included pooled cross-sectional analysis of serum specimens collected for analysis of cough illnesses. Antibodies to PT, FHA and PRN were measured by ELISA using a standardized technique. With both acellular vaccines in the study (the Chiron Biocine three-component and SmithKline Beecham three-component vaccines) there was a fast and steep decrease of mean geometric titres for PT, FHA and PRN in the months immediately following vaccination. Titres were close to the detection limit 15 months after the end of primary immunization. The immunogenicity of the whole-cell study vaccine (produced by Connaught Laboratories, Inc. Swiftwater, USA) was poor as determined one month after the third dose and no antibody was detected in nearly all children 15 months after the end of vaccination.

Acellular vaccines induce cell-mediated immunity to Bordetella pertussis antigens in infants undergoing primary vaccination against pertussis.

The induction of cell-mediated immunity (CMI) to Bordetella pertussis antigens (whole, heat-inactivated bacterial cells [BPC], pertussis toxin [PT], filamentous haemagglutinin [FHA], pertactin [PRN]) was assessed by a lymphoproliferation assay in vitro in a cohort of children enrolled in a randomized clinical trial of pertussis vaccines efficacy in Italy. Four vaccination groups were compared: children receiving acellular pertussis (aP) vaccines from SmithKline Beecham (SB) or Chiron Biocine (CB) or whole-cell vaccine (wP) from Connaught, each combined with diphtheria and tetanus toxoids (DT), or a DT vaccine only. When the purified antigens were used, statistically significant differences in CMI responses were observed between pre- and post-vaccination samples. In particular, CMI responses to FHA and PRN were detected in the majority of both aP vaccines recipients, whereas DTwP-recipients were CMI-positive in a much lower proportion. Clear-cut differences in PT responses were detected between DTwP and DTaP vaccine recipients, in favour of the latter. These differences were maintained up to 24 months after completion of the primary vaccination schedule. Thus, CMI responses could be a useful adjunct to serology in studying the immune responses to pertussis vaccines.

[Characteristics of surgically removed polyps in the course of follow-up after endoscopic polypectomy from the colon]. / Caratteristiche dei polipi asportati in corso di follow-up successivo a polipectomia endoscopica del colon.

Our experience refers to 188 patients submitted to endoscopic polypectomy, of whom 61 (32.4%) also to subsequent endoscopic controls. The polyps removed during follow-up compared to those previously removed showed the following characteristic: 1) Higher frequency in right colon (p > 0.01); 2) smaller size (p > 0.1); 3) lower frequency of adenomas, not statistically significant; 4) high frequency of relapse in juvenile polyps.

[Cytomegalovirus and herpes simplex virus antibodies in patients with idiopathic ulcerative rectocolitis]. / Anticorpi per il virus citomegalico e per quello dell'herpes simplex in pazienti con rettocolite ulcerosa idiopatica.

The total and fractioned titres of circulating anticytomegalovirus (CMV) and antiherpesvirus (HSV) antibodies were evaluated in 63 idiopathic ulcerative proctocolitis patients in follow-up. The population was disaggregated applying criteria related to the stage of the disease: duration, extension, number of observed relapses over the follow-up. It was noted that just the anti-HSV antibodies were correlated in a statistically significant way to the extension (p less than 0.025) and duration (p less than 0.025) of the disease. We believe that this behaviour is a manifestation of the disease and that the antiHSV titration may be included in a score of evaluation during the follow-up.