Enhancing chlamydospore production in Duddingtonia flagrans on solid substrate: The impact of mannitol and varied cultivation conditions.

Duddingtonia flagrans is a nematophagous fungus which has shown promising results as a non-chemical parasitic control tool. The fungus disrupts the parasite's life cycle by trapping larvae in the environment through the networks generated from chlamydospores, thus preventing the reinfection of animals. One barrier to the development of a commercial product using this tool is the need to increase chlamydospore production in the laboratory for its administration to livestock. The purpose of this study was to evaluate the addition of mannitol to an enriched culture medium and the effect of adverse cultivation conditions on chlamydospore production. D. flagrans was cultivated on Petri dishes with corn agar for 4 weeks at 27 °C and 70% relative humidity (RH). Four groups were then formed, all with Sabouraud agar as a base, to which different growth inducers were added: GSA (glucose Sabouraud agar), GSA-MI (glucose Sabouraud agar + meso inositol), GSA-E (enriched glucose Sabouraud agar), and AE-M (enriched agar + mannitol). After 4 weeks, chlamydospores were recovered by washing the surface of each plate with distilled water and then quantified. The medium that yielded the highest amount of chlamydospores was subjected to different cultivation conditions: NC (normal conditions): 70% RH and 27 °C, AC (adverse conditions) 1: 20% RH and 40 °C, CA2: 60% RH and 27 °C, and CA3: 55% RH and 24 °C. It was determined that mannitol increases chlamydospore production (65x106 chlamydospores/plate), and when reducing humidity by 10% under cultivation conditions it resulted in an approximately 10% increase in chlamydospore production compared to the control group. These results suggest that the addition of polyols, as well as its cultivation under certain environmental conditions, can improve chlamydospore production on a laboratory scale.

Analysis of connectivity between the world's banking markets: The COVID-19 global pandemic shock.

We contribute to the literature on financial networks by presenting empirical evidence that the global shock of the COVID-19 pandemic caused changes in the forms and intensity of banking sector connections between different countries. These changes include providing the highest level of connectivity observed in the timeline initiated in 2005. We used a comprehensive set of information containing data from 35 countries (developed and emerging economies) and showed the change in the classification of transmitting and receiving spillover during the COVID-19 crisis. Our results provide relevant insights into systemic integration between countries' banking markets, especially during difficult times. Our results are significant to Central Banks, banking sector investors, and governments seeking assistance from banks in the solutions for the resumption of the economy in the face of the COVID-19 shock.

Comparison of the AllplexTM Respiratory Panel Assays and the automated Fast Track Diagnostics Respiratory pathogens 21 assay for the diagnosis of pediatric respiratory viral infections.

Acute respiratory tract infections frequently occur in children and represent one of the leading causes of morbidity and mortality worldwide. Quick and accurate pathogen detection can lead to a more appropriate use of antimicrobial treatment as well as timely implementation of isolation precautions. In the last decade, several commercial assays have been developed for the simultaneous diagnosis of respiratory pathogens, which substantially vary in formulation and performance characteristics. The aim of this study was to compare the performance of the "AllplexTM Respiratory Panel Assays" (Seegene) with that of the automated "Fast Track Diagnostics Respiratory pathogens 21" assay (Siemens) for the diagnosis of pediatric respiratory viral infections. One hundred forty-five nasopharyngeal wash samples, collected at the Bambino Gesù Pediatric Hospital in Rome during the fall-winter 2017-2018 season, were processed and analyzed with both workflows. Our results suggest a high concordance between the two methods for positive and negative samples. Sensitivity and specificity were calculated with both tests as a reference method. For the AllplexTM Respiratory Panel Assays, they were 98% and 100%, respectively, and for the Fast Track Diagnostics Respiratory pathogens 21 assay, they were both 100%. This comparative study allowed us to highlight the characteristics of the two assays to evaluate the best solution, on the basis of diagnostic routine and laboratory workflows, keeping in mind local epidemiology.

The 'brick diet' and postprandial insulin: a practical method to balance carbohydrates ingested and prandial insulin to prevent hypoglycaemia in hospitalized persons with diabetes.

AIM: Insulin is the preferred treatment for the control of diabetes in hospital, but it raises the risk of hypoglycaemia, often because oral intake of carbohydrates in hospitalized persons is lower than planned. Our aim was to assess the effect on the incidence of hypoglycaemia of giving prandial insulin immediately after a meal depending on the amount of carbohydrate ingested. METHODS: A prospective pre-post intervention study in hospitalized persons with diabetes eating meals with stable doses of carbohydrates present in a few fixed foods. Foods were easily identifiable on the tray and contained fixed doses of carbohydrates that were easily quantifiable by nurses as multiples of 10 g (a 'brick'). Prandial insulin was given immediately after meals in proportion to the amount of carbohydrates eaten. RESULTS: In 83 of the first 100 people treated with the 'brick diet', the oral carbohydrate intake was lower than planned on at least one occasion (median: 3 times; Q1-Q3: 2-6 times) over a median of 5 days. Compared with the last 100 people treated with standard procedures, postprandial insulin given on the basis of ingested carbohydrate significantly reduced the incidence of hypoglycaemic events per day, from 0.11 ± 0.03 to 0.04 ± 0.02 (P < 0.001) with an adjusted incidence rate ratio of 0.70 (95% confidence interval 0.54-0.92; P = 0.011). CONCLUSIONS: In hospitalized persons with diabetes treated with subcutaneous insulin, the 'brick diet' offers a practical method to count the amount of carbohydrates ingested, which is often less than planned. Prandial insulin given immediately after a meal, in doses balanced with actual carbohydrate intake reduces the risk of hypoglycaemia.

Mental performance in 8-year-old children fed reduced protein content formula during the 1st year of life: safety analysis of a randomised clinical trial.

In humans, maximum brain development occurs between the third trimester of gestation and 2 years of life. Nutrition during these critical windows of rapid brain development might be essential for later cognitive functioning and behaviour. In the last few years, trends on protein recommendations during infancy and childhood have tended to be lower than that in the past. It remains to be demonstrated that lower protein intakes among healthy infants, a part of being able to reduce obesity risk, is safe in terms of mental performance achievement. Secondary analyses of the EU CHOP, a clinical trial in which infants from five European countries were randomised to be fed a higher or a lower protein content formula during the 1st year of life. Children were assessed at the age of 8 years with a neuropsychological battery of tests that included assessments of memory (visual and verbal), attention (visual, selective, focused and sustained), visual-perceptual integration, processing speed, visual-motor coordination, verbal fluency and comprehension, impulsivity/inhibition, flexibility/shifting, working memory, reasoning, visual-spatial skills and decision making. Internalising, externalising and total behaviour problems were assessed using the Child Behaviour Checklist 4-18. Adjusted analyses considering factors that could influence neurodevelopment, such as parental education level, maternal smoking, child's gestational age at birth and head circumference, showed no differences between feeding groups in any of the assessed neuropsychological domains and behaviour. In summary, herewith we report on the safety of lower protein content in infant formulae (closer to the content of human milk) according to long-term mental performance.

From guidelines to real world: results from the National Multiple Myeloma Registry in Uruguay on 222 newly diagnosed multiple myeloma patients from 2012 to 2015.

Introduction: In the last decade, substantial improvements in the understanding of the biology of multiple myeloma and the development of novel therapeutic options have led to increased response rates, progression free survival and overall survival. In underdeveloped countries, it is a huge challenge to adapt for this evolution, both in diagnostic and therapeutic aspects. Methods: We conducted a retrospective, national analysis of all patients with newly diagnosed multiple myeloma in a recent period. Diagnostic and prognostic evaluation is carried out according to international recommendations in the majority of patients. Results: The clinical presentation at diagnosis is similar to those reported internationally, although with higher rates of anemia and severe renal failure. Most patients were diagnosed in advanced Durie-Salmon stage (80%), with high ISS score (48% ISS 3). Treatment, both in candidates and non-candidates for transplantation, is conditioned by a limited supply of possibilities, scarce availability of new drugs and absence of clinical trials. This determines lower results in response depth and survival. At 32 months, overall survival was 61.8%, with a statistical difference in favor of younger patients, standard-risk MM and those treated with novel drugs. No patient received antibacterial or antifungal prophylaxis while the majority received adequate antiviral prophylaxis. Infections were the main cause of death (29.7%), overcoming the disease itself. Conclusions: This analysis allows us to raise awareness about strengths and weaknesses in our management of MM patients. There is a need to promote earlier detection, improve supportive care and reduce infection mortality. Greater availability of evidence-based recommended treatment options is required. Access to clinical trials is warranted if care is to be improved.

An acute febrile outbreak in a refugee community of an Italian asylum seeker center: lessons learned.

OBJECTIVES: The management of infectious outbreaks in closed settings represents an important public health issue. An outbreak of acute febrile syndrome affecting 22 refugees resident at the Asylum Seekers Centre of Castelnuovo di Porto in Rome has been reported, and the preventive and control measures adopted have been described as an example of public health safety. METHODS: Pharyngeal swab and whole-blood samples were collected from 22 cases observed and analyzed for standard bacterial cultures and respiratory and herpesviruses by qualitative CLART PneumoVir2 and Entherpex microarray. RESULTS: A possible respiratory-transmitted etiology and a concomitant reactivation of multiple herpesviruses have been evidenced. The epidemiological investigation showed that the spread of the epidemic was promoted because patients were hosted in neighboring rooms or in the same room, facilitating the rapid spread of infectious disease. CONCLUSIONS: The potential way of transmission was supposed, and preventive measures for infection control were adopted. The measures adopted are an example of best practice for outbreak management, and the microbiological surveillance is recommended for public health improvement.

An attempt to replace an ivermectin-resistant Cooperia spp. population by a susceptible one on grazing pastures based on epidemiological principles and refugia management.

The maintenance of anthelmintic-susceptible parasite refugia to delay the onset of anthelmintic resistance is an almost impossible effort in many grazing livestock production countries given that current refugia consist of already resistant parasites. Rather, efforts could be focused on replacing the resistant parasite refugia by susceptible parasite ones and implementing sustainable parasite control measures from then on. To this purpose, a trial was conducted to attempt to establish a new population of ivermectin-susceptible Cooperia sp. on a beef cattle farm with proven problems of ivermectin-resistant Cooperia. During two consecutive years, 82 (Year 1) and 100 (Year 2) recently weaned and parasite-free heifers were inoculated with 40,000 or 30,000 susceptible Cooperia L3, respectively, at a time when levels of resistant parasite refugia were normally low. The animals were subsequently allowed to graze on the problem pastures during autumn until the end of spring. Levels of parasitism in the animals and on pasture were monitored monthly and animals were treated with levamisole when needed. The combination of parasitological monitoring and local epidemiological knowledge was essential to determine when treatments were to be administered. No clinical signs of gastrointestinal parasitosis in the herd were observed throughout the study and unnecessary treatments were avoided. Faecal egg counts reduction tests (FECRT) and controlled efficacy tests (CET) employing worm counts were carried out at different times throughout the study to determine the clinical efficacy (FECRT) and the absolute efficacy (CET) of ivermectin, respectively. The clinical efficacy of ivermectin increased from an initial 73% to 99.4%, while the absolute efficacy increased from 54.1% to 87.5% after just two animal production cycles. The switch from a resistant parasite population to a susceptible one requires knowledge of parasitological epidemiology, especially in relation to seasonal variations of parasite populations in both the host and in refugia.

Second primary malignancies in multiple myeloma: an overview and IMWG consensus.

Background: Therapeutic advancements following the introduction of autologous stem cell transplantation and 'novel' agents have significantly improved clinical outcomes for patients with multiple myeloma (MM). Increased life expectancy, however, has led to renewed concerns about the long-term risk of second primary malignancies (SPMs). This review outlines the most up-to-date knowledge of possible host-, disease-, and treatment-related risk factors for the development of SPMs in patients with MM, and provides practical recommendations to assist physicians. Design: A Panel of International Myeloma Working Group members reviewed the most relevant data published in the literature as full papers, or presented at meetings of the American Society of Clinical Oncology, American Society of Hematology, European Hematology Association, or International Myeloma Workshops, up to June 2016. Here, we present the recommendations of the Panel, based on this literature review. Results: Overall, the risk of SPMs in MM is low, multifactorial, and partially related to the length of patients' survival and MM intrinsic susceptibility. Studies suggest a significantly increased incidence of SPMs when lenalidomide is administered either following, or concurrently with, oral melphalan. Increased SPM incidence has also been reported with lenalidomide maintenance following high-dose melphalan, albeit to a lesser degree. In both cases, the risk of death from MM was significantly higher than the risk of death from SPMs, with lenalidomide possibly providing a survival benefit. No increase in SPM incidence was reported with lenalidomide plus dexamethasone (without melphalan), or with bortezomib plus oral melphalan, dexamethasone, or thalidomide. Conclusion: In general, the risk of SPMs should not alter the current therapeutic decision-making process in MM. However, regimens such as lenalidomide plus dexamethasone should be preferred to prolonged exposure to lenalidomide plus oral melphalan. SPM risk should be carefully discussed with the patient in the context of benefits and risks of different treatment options.

Association of early protein intake and pre-peritoneal fat at five years of age: Follow-up of a randomized clinical trial.

BACKGROUND AND AIMS: The double-blind randomized European Childhood Obesity Project (CHOP) demonstrated that reduced protein content in infant formula leads to a lower body mass index (BMI) up to six years of age. Here we aimed at assessing pre-peritoneal fat, a marker of visceral fat, in children participating in the CHOP trial. METHODS AND RESULTS: Healthy term formula-fed infants in five European countries were randomized either to higher (n = 550) or lower (n = 540) protein formulas in the first year of life. Infants who were exclusively breastfed for at least three months (n = 588) were enrolled as an observational (non randomized) group. At age 5 years, subcutaneous fat (SC) and pre-peritoneal fat (PP) were measured by ultrasound in a subgroup of 275 children. The PP fat layer was thicker in the higher compared to the lower protein group (adjusted estimated difference: 0.058 cm, 95%CI 0.002; 0.115; p = 0.043), while SC fat was not different. Girls showed a thicker SC fat layer than boys. CONCLUSIONS: Higher protein intake in formula-fed infants appears to enhance pre-peritoneal fat tissue accumulation at the age of 5 years, but not of subcutaneous fat, which may trigger adverse metabolic and health consequences.

A multicenter observational study on the management of hyperglycemia in patients with acute coronary syndrome.

AIM: To assess the prevalence, risk and management of hyperglycemia in patients with acute coronary syndrome (ACS). DESIGN: a multicenter prospective observational study of a representative sample of patients with ACS consecutively admitted to intensive cardiac care units (ICCU). SETTING: 31 out of 61 ICCUs in Lombardy, the most heavily populated Italian region. From May 2009 to April 2010 1260 patients (69.4% male; mean age 68 ± 13 years) were included in the study: 301 (23.9%) were known diabetic patients (D) and 265 (21.0%) had hyperglycemia (H) (blood glucose >180 mg/dL) at hospital admission, 174 with a history of diabetes (D+H+) and 91 without (D-H+). On the first day after admission intravenous insulin infusion was prescribed to 72 D+H+ (41.4%) and 10 D-H+ (11.0%), according to different protocols. Approximately one third of D+H+ patients (59) and one fifth (17) of D-H+ maintained mean blood glucose higher than 180 mg/dL during the first day in the ICCU. Patients with diabetes or hyperglycemia had a higher incidence of major adverse cardiovascular events or death in hospital. However, at multivariable analysis neither diabetes nor blood glucose at admission was associated with a poor prognosis whereas mean blood glucose on the first day was an independent negative prognostic predictor (OR 1.010, 95% CI 1.002-1.018, p = 0.016). CONCLUSION: Hyperglycemia is frequent in patients with ACS and is independently associated with a poor in-hospital prognosis if it persists in first day. Unfortunately, however, this condition is still poorly treated, with far from optimal blood glucose control.

Hepatitis C virus and interferon type III (interferon-λ3/interleukin-28B and interferon-λ4): genetic basis of susceptibility to infection and response to antiviral treatment.

There has been a significant increase in our understanding of the host genetic determinants of susceptibility to viral infections in recent years. Recently, two single-nucleotide polymorphisms (SNPs), rs12979860 T/C and rs8099917 T/G, upstream of the interleukin (IL)-28B/interferon (IFN)-λ3 gene have been clearly associated with spontaneous and treatment-induced viral clearance in hepatitis C virus (HCV) infection. Because of their power in predicting the response to IFN/ribavirin therapy, the above SNPs have been used as a diagnostic tool, even though their relevance in the management of HCV infection will be blunt in the era of IFN-free regimens. The recent discovery of a new genetic variant, ss469415590 TT/ΔG, upstream of the IL-28B gene, which generates the novel IFN-λ4 protein, has opened up a new and alternative scenario to understand the functional architecture of type III IFN genomic regions and to improve our knowledge of the pathogenetic mechanism of HCV infection. A role of ss469415590 in predicting responsiveness to antiviral therapy has also been observed in HCV-infected patients receiving direct antiviral agents. The underlying biological mechanism that links the above IL-28B polymorphisms (in both IFN-λ3 and IFN-λ4) to spontaneous and treatment-induced clearance of HCV infection remains to be discovered. Despite this, shedding some light on this issue, which is the main aim of this review, may provide new insights into the general topic of 'host genetics and viral infections'.

Search for solar axions by the CERN axion solar telescope with 3He buffer gas: closing the hot dark matter gap.

The CERN Axion Solar Telescope has finished its search for solar axions with (3)He buffer gas, covering the search range 0.64 eV ≲ ma ≲ 1.17 eV. This closes the gap to the cosmological hot dark matter limit and actually overlaps with it. From the absence of excess x rays when the magnet was pointing to the Sun we set a typical upper limit on the axion-photon coupling of gaγ ≲ 3.3 × 10(-10) GeV(-1) at 95% C.L., with the exact value depending on the pressure setting. Future direct solar axion searches will focus on increasing the sensitivity to smaller values of gaγ, for example by the currently discussed next generation helioscope International AXion Observatory.

Elevated risk of death and major cardiovascular events in subjects with newly diagnosed diabetes: findings from an administrative database.

AIMS: To investigate the incidence of major cardiovascular complications and mortality in the first years of follow-up in patients with newly diagnosed diabetes. METHODS AND RESULTS: We examined incidence rates of hospitalization for cardiovascular reasons and death among new patients with diabetes using the administrative health database of the nine million inhabitants of Lombardy followed from 2002 to 2007. Age and sex-adjusted rates were calculated and hazard ratios (HR) were estimated with a matched population without diabetes of the same sex, age (± 1 year) and general practitioner. There were 158,426 patients with newly diagnosed diabetes and 314,115 subjects without diabetes. Mean follow-up was 33.0 months (SD ± 17.5). 9.7% of patients with diabetes were hospitalized for cardiovascular events vs. 5.4% of subjects without diabetes; mortality rate was higher in patients with diabetes (7.7% vs. 4.4%). The estimated probability of hospitalization during the follow up was higher in patients with diabetes than in subjects without for coronary heart disease (HR 1.4, 95% CI 1.3-1.4), cerebrovascular disease (HR 1.3.95% CI 1.2-1.3), heart failure (HR 1.4, 95% CI 1.3-1.4) as was mortality (HR 1.4, 95% CI 1.4-1.4). Younger patients with diabetes had a risk of death or hospital admission for cardio-cerebrovascular events similar to subjects without diabetes ten years older. CONCLUSIONS: The elevated morbidity and mortality risks were clear since the onset of diabetes and rose over time. These data highlight the importance of prompt and comprehensive patients care in addition to anti-diabetic therapy in patients with newly diagnosed diabetes.

Methodology for quantifying the behavioral activity of dairy cows in freestall barns.

The objectives of this study were to 1) evaluate the validity of automated monitoring systems as assessment method for the behavioral activity of dairy cows compared with video recording, and 2) determine the sampling intervals required to obtain reliable estimates of the daily behavior. To determine lying, standing, and walking, 12 cows were equipped with automatic recording devices (IceTag = 12 cows, HOBO Pendant G = 5 cows), and their behavior was simultaneously recorded using a video recording system. The correspondence between the IceTag, HOBO logger, and video recording data was analyzed using 2 × 2 contingency tables, and we determined the sensitivity, specificity, and predictive value (positive and negative). Both types of loggers demonstrated high sensitivity (Sen ≥ 0.961) and specificity (Sp ≥ 0.951) for lying and standing behaviors with predictive values near 1.00. The HOBO logger can accurately describe the laterality of lying behavior, whereas the IceTag device inadequately recorded walking, with probability predictive values ≤ 0.303. Daily behaviors of the dairy cows were compared for 10 different sampling intervals (1 s, and 1, 2, 3, 4, 5, 10, 15, 30, and 60 min) collected by the IceTag, using linear regression. A strong relationship (R(2) ≥ 0.978) was found between the total lying times from data on a per-second basis and estimates obtained by 1, 2, 3, 4, 5, 10, and 15 min sampling intervals. The sampling intervals of 1 and 2 min were comparable for all aspects of lying behavior (R(2) ≥ 0.813; P > 0.05 for slope = 1, intercept = 0). Long sampling intervals (30 and 60 min) showed positive relationship for estimating time spent lying and standing (R(2) ≥ 0.774), but were inappropriate for predicting these behaviors, because they lacked accuracy and precision. Both the IceTag and HOBO logger accurately measured all aspects of lying and standing behavior. Reliable estimates of lying and standing time can be generated using relatively short interval lengths (e.g., 3, 4, 5, 10, or 15 min). Shorter sampling intervals (≤ 2 min) are required to accurately measure aspects of lying behavior such as number of lying bouts per day. The automated monitoring systems are time- and labor-saving tools that can be used by research or on farm to assess cow comfort related to lying behavior.

[Primary ciliary dyskinesia: clinical and genetic aspects]. / Discinesia ciliare primitiva: aspetti clinici e genetici.

Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous disease, characterized by ciliary disfunction and impaired mucociliary clearance, resulting in a range of clinical manifestations such as chronic bronchitis, bronchiectasis, chronic rhino-sinusitis, chronic otitis media, situs viscerum inversus in almost 40-50% of cases and male infertility. The triad situs viscerum inversus, bronchiectasis and sinusitis is known as Kartagener syndrome. Up to now little is known about genetic, diagnostic and therapeutic aspects of primary motile ciliary diseases in children: for this reason, diagnosis is generally delayed and almost all treatments for PCD are not based on randomized studies but extrapolated from cystic fibrosis guidelines. The aim of this review is to propose to pediatricians a summary of current clinical and diagnostic evidence to obtain better knoledwge of this condition. The earlier diagnosis and the right treatment are both crucial to improve the prognosis of PCD.

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.