One-year glargine treatment can improve the course of lung disease in children and adolescents with cystic fibrosis and early glucose derangements

Background:  Diabetes increases morbidity and mortality in cystic fibrosis (CF) patients, but several studies indicate that also prediabetic status may have a potential impact on both nutrition and lung function.
Objective:  To evaluate the effect of glargine on the clinical course in CF patients with early glucose derangements.
Methods:  CF population was screened for glucose tolerance. CF patients with age >10 yr were screened with fasting hyperglycemia (FH). CF patients with age >10 yr without FH and those with age <10 yr with occasional FH were evaluated for glucose abnormalities on the basis of oral glucose tolerance test and/or continuous glucose monitoring system. All CF patients with glucose derangements were enrolled in an open clinical trial with glargine. Body mass index (BMI) z-score, forced expiratory volume in the first second (FEV₁), number of acute pulmonary exacerbations and hemoglobin A1c, were as outcome measures at baseline and after 1 yr of treatment.
Results:  After 12 months of therapy, BMI z-score improved only in patients with baseline BMI z-score less than −1 (p = 0.017). An 8.8% increase in FEV₁ (p = 0.01) and 42% decrease in the number of pulmonary exacerbations (p = 0.003) were found in the whole group compared with previous 12 months of therapy.
Conclusion:  Glargine could represent an innovative strategy to prevent lung disease progression in CF patients with early glucose derangements. Larger controlled trials are needed to better clarify the effects of insulin on clinical status in CF patients with early glucose derangements.     

Novel Synthetic,Salt-Resistant Analogs of Human Beta-Defensins 1 and 3 Endowed with Enhanced Antimicrobial Activity

Human beta-defensins (hBDs) are antimicrobial peptides of human innate immunity. The antibacterial activities of hBDs 1, 2, and 4 but not the activity of hBD3 are impaired by high salt levels. We have designed and synthesized seven novel hBD analogs, constituted by different domains of hBD1 (which is constitutively expressed in humans) and of hBD3 (which is induced by microorganisms and inflammatory factors in humans), that would maintain and potentially increase the wild-type antimicrobial activities and be salt resistant. We have compared the antibacterial, antiviral, and chemotactic activities of the analogs with those of hBD1 and hBD3. We show that the hBD1 internal region and the hBD3 C-terminal region are critical for antibacterial activity also at high salt concentrations, whereas deletion of the N-terminal region of hBD3 results in an increase in antibacterial activity. All analogs inhibited herpes simplex virus; antiviral activity was enhanced by the hBD1 internal region and the hBD3 C-terminal region. Wild-type and analog peptides were chemotactic for granulocytes and monocytes, irrespective of the salt concentrations. These new peptides may have therapeutic potential.Beta-defensins (BDs) are highly conserved small peptides produced by plants, invertebrates, and vertebrates that developed as part of the primordial immune protective mechanism (19). Four of these peptides, called human BD1 (hBD1; DEFB1), hBD2 (DEFB4), hBD3 (DEFB103A), and hBD4 (DEFB104), are mainly expressed by respiratory, gastrointestinal, and urogenital epithelial cells either constitutively (hBD1) or after induction by microorganisms or inflammatory factors (hBD2 to hBD4) (19). All four hBDs are cationic and 36 to 45 amino acids long and show similar folding and an invariable six-cysteine motif that gives rise to three disulfide bonds (2, 11, 12, 25, 26).Human beta-defensins 1 to 4 exert different bactericidal and antiviral activities against various pathogens (8, 15, 27). The antibacterial effects of hBD1 (9), hBD2 (33), and hBD4 (5) are attenuated by high NaCl concentrations, such as those in the airway surface fluid of patients with cystic fibrosis (CF) (21, 29). Human beta-defensin 3 can withstand NaCl concentrations as high as 150 mM, thanks to its peculiar structural characteristics and charge (10). In the field of viral diseases, hBD2 and -3 inhibit human immunodeficiency virus (HIV) type 1 (HIV-1) replication and virion infectivity (20, 31) and modulate HIV-1 coreceptor expression (20). Human herpes simplex virus (HSV) type 1 (HSV-1), HSV-2, and other viruses preincubated with alpha human neutrophil peptide 1 (hNP1) to hNP3 (6, 28) or theta (37) defensins lose their ability to infect target cells (28). As yet, there are no data on the effect of hBDs on HSV-1 and -2. In addition to direct antimicrobial activity, hBDs also exert chemotactic activity: hBD1, -2, and -3 are chemotactic for monocytes and dendritic and T cells. Human beta-defensin 3 is the only beta-defensin chemotactic for macrophages (4, 18, 19), whereas the chemotactic effect of hBDs on granulocytes has yet to be elucidated (4, 18).The two natural defensins hBD1 and hBD3 were chosen for use in the experiments described in this paper for the following reasons: hBD1 is constitutively expressed but its antibacterial activity is greatly impaired by NaCl, while hBD3 is insensitive to salt. Thus, we designed and synthesized hBD analogs that, in principle, would maintain the antibacterial and antiviral activities of hBD1 and possess a resistance capability in the presence of high NaCl concentrations, like hBD3 does. We then compared the antibacterial, chemotactic, and antiviral activities of the novel synthetic analogs with those of wild-type hBD1 and hBD3. Our data show that some of the synthetic analogs have higher antimicrobial activity than the wild type, also at high NaCl concentrations.     

Vaccines for the Treatment of Non‐Small Cell Lung Cancer: A Renewed Anticancer Strategy

Carcinoma of the lung is the leading cause of cancer death worldwide, with non‐small cell lung cancer (NSCLC) constituting about 85% of all new diagnoses. Standard approaches for each NSCLC stage have reached a plateau in effectiveness. A variety of novel approaches are now being investigated to improve the outcome of this disease. Despite decades of research, no specific active cancer vaccine has, to date, been approved for NSCLC therapy; nevertheless, vaccine therapy has recently re‐emerged as a potential therapeutic approach. In particular, several new paradigms have stemmed from recent clinical findings both in the use of combination therapy approaches with more sophisticated specific vaccines and in clinical trial design and endpoint analyses. Several vaccine therapies have been investigated in NSCLC, including in the early and advanced disease stages. The best results appear to be in the adjuvant settings and in locally advanced NSCLC. In fact, in these two settings, phase III randomized trials are ongoing evaluating the melanoma‐associated antigen A3 vaccine and the liposomal BLP25 vaccine. This paper reviews the main clinical trials involving several different cancer vaccines employed in the treatment of early and advanced stage NSCLC, focusing on those in advanced stages of development.     

Vestibular evoked myogenic potentials in children

OBJECTIVE: The aim of this work is to establish if the vestibular evoked myogenic potentials (VEMPs) could be used as a clinical test of vestibular function in children. MATERIALS AND METHODS: Forty normal hearing children, aged between 3 and 15 years, and classified in preschool and scholar group, have been investigated in order to study normal development of vestibular potentials and to define fundamental parameters of VEMPs, establishing normal data of latencies and amplitude ratio. Electromyographic activity of sternocleidomastoid muscle was recorded while children were laid supine on a bed and asked to raise their head off of the bed in order to activate their neck flexors bilaterally. The saccular receptors were acoustically stimulated with a logon of 500Hz at an intensity of 130dB peSPL presented monaurally through earphones. In each recording, we analysed latencies and amplitudes of the p13 and n23 waves and the amplitude ratio between the two ears. RESULTS: VEMPs were normally detected in all subjects. In preschool group mean p13 and mean n23 latencies were, respectively, 16.13 (+/-2.12)ms and 21.17 (+/-2.77)ms; mean amplitude ratio was 28.49 (+/-18.10). In scholar group mean p13 and n23 were respectively 16.14 (+/-3.48)ms and 21.78 (+/-3.39)ms, while mean amplitude ratio 20.44 (+/-13.24). Comparison of latencies and amplitude ratio between the children groups and control adult group did not showed any significant differences. CONCLUSION: In conclusion, VEMPs could represent a valid and non-invasive technique able to investigate vestibular function in children and, in particular, vestibulo collic reflex.     

Occult lung infarction may induce false interpretation of 18F-FDG PET in primary staging of pulmonary malignancies

Purpose The aim of the present report is to describe abnormal ¹⁸F-fluorodeoxyglucose (FDG) accumulation patterns in the pleura and lung parenchyma in a group of lung cancer patients in whom lung infarction was present at the time of positron emission tomography (PET).Methods Between November 2002 and December 2003, a total of 145 patients (102 males, 43 females; age range 38–85 years) were subjected to whole-body FDG PET for initial staging (n=117) or restaging (n=11) of lung cancer or for evaluation of solitary pulmonary nodules (n=17). Of these patients, 24 displayed abnormal FDG accumulation in the lung parenchyma that was not consistent with the primary lesion under investigation (ipsilateral n=12, contralateral n=9 or bilateral n=3). Without correlative imaging, this additional FDG uptake would have been considered indeterminate in differential diagnosis.Results Of the 24 patients who were identified as having such lesions, six harboured secondary tumour nodules diagnosed as metastases, while in three the diagnosis of a synchronous second primary lung tumour was established. Additionally, nine patients were identified as having post-stenotic pneumonia and/or atelectasis (n=6) or granulomatous lung disease (n=3). In the remaining six (4% of all patients), a diagnosis of recent pulmonary embolism that topographically matched the additional FDG accumulation (SUV_max range 1.4–8.6, mean 3.9) was made. Four of these six patients were known to have pulmonary embolism, and hence false positive interpretation was avoided by correlating the PET findings with those of the pre-existing diagnostic work-up. The remaining two patients were harbouring small occult infarctions that mimicked satellite nodules in the lung periphery. Based on histopathological results, the abnormal FDG accumulation in these two patients was attributed to the inflammatory reaction and tissue repair associated with the pathological cascade of pulmonary embolism.Conclusion In patients with pulmonary malignancies, synchronous lung infarction may induce pathological FDG accumulation that can mimic active tumour manifestations. Identifying this potential pitfall may allow avoidance of false positive FDG PET interpretation.     

Instant in situ formation of a polymer film at the water–oil interface

The water–oil interface is an environment that is often found in many contexts of the natural sciences and technological arenas. This interface has always been considered a special environment as it is rich in different phenomena, thus stimulating numerous studies aimed at understanding the abundance of physico-chemical problems that occur there. The intense research activity and the intriguing results that emerged from these investigations have inspired scientists to consider the water–oil interface even as a suitable setting for bottom-up nanofabrication processes, such as molecular self-assembly, or fabrication of nanofilms or nano-devices. On the other hand, biphasic liquid separation is a key enabling technology in many applications, including water treatment for environmental problems. Here we show for the first time an instant nanofabrication strategy of a thin film of biopolymer at the water–oil interface. The polymer film is fabricated in situ, simply by injecting a drop of polymer solution at the interface. Furthermore, we demonstrate that with an appropriate multiple drop delivery it is also possible to quickly produce a large area film (up to 150 cm²). The film inherently separates the two liquids, thus forming a separation layer between them and remains stable at the interface for a long time. Furthermore, we demonstrate the fabrication with different oils, thus suggesting potential exploitation in different fields (e.g. food, pollution, biotechnology). We believe that the new strategy fabrication could inspire different uses and promote applications among the many scenarios already explored or to be studied in the future at this special interface environment.

A completely new method for easy and quick formation of a thin polymer film at the special setting of a stratified oil/water interface. Morphological SEM and quantitative full-field characterization have been reported using digital holography.     

An Italian Survey on Dietary Habits and Changes during the COVID-19 Lockdown

The World Health Organization has declared the coronavirus outbreak a Public Health Emergency of International Concern; the outbreak has led to lockdowns in several parts of the world, and sudden changes in people’s lifestyles. This study explores the impact of the first coronavirus disease 2019 (COVID-19) pandemic period on dietary habits, lifestyle changes, and adherence to the Mediterranean diet among the Italian population, through an online questionnaire, conducted from April to May 2020, involving 1519 participants. The 14-point Mediterranean Diet Adherence Screener (MEDAS) highlighted a medium Mediterranean diet adherence in 73.5% of responders, which principally included the younger population, aged 18–30 years (p < 0.05). In regards to changes in eating habits, 33.5% of responders declared an influence of the pandemic period on nutritional practice. A decrease in alcohol consumption was reported by 81% of responders, while an increase in frozen food consumption was reported by 81.3% of responders. In addition, 58.8% reported positive weight modification (40.8%, +1–3 kg); physical activity reduction was reported for 70.5% of responders. Our study contributes toward amplifying the investigation on the dietary habits and changes of the Italian population during the COVID-19 lockdown, although the pandemic is ongoing. Similar studies should be performed around the world to understand how the emergency has impacted people’s habits.     

A multimodal approach to treatment in a child care agency

This paper describes the application of the multimodal therapy model to the treatment of children in a child care agency. The model has been adapted to facilitate the team approach to individual assessment and therapy, integrating the work of child care staff, social service personnel, psychiatrists, psychologists, teachers, and others. The approach requires modifying the child's environment, as well as defining specific behavioral, affective, sensory, imagery, cognitive, interpersonal and drug related problems. A comprehensive and systemmatic treatment plan is thereby effected.A short version of this report was published by Psychological Reports, 1980, 47, 250 and a longer version by Microfiche Publications, Document NAPS—03706.     

Activity of Some Plant and Fungal Metabolites towards Aedes albopictus (Diptera,Culicidae)

Aedes albopictus (Skuse) is a widespread mosquito, a vector of important human arboviruses, including Chikungunya, Dengue and Zika. It is an extremely difficult species to control even for the onset of resistances to chemicals insecticides, therefore ecofriendly products are urgently needed. In this study, the activity of Amaryllidaceae alkaloids and some of their semisynthetic derivatives, of 2-methoxy-1,4-naphthoquinone and two analogues, of cyclopaldic acid and epi-epoformin on the survival and development of Ae. albopictus larvae was evaluated. First-instar larval exposure for 24 and 48 h to cyclopaldic acid, resulted in mortality mean per-centage of 82.4 and 96.9 respectively; 1,2-O,O-diacetyllycorine 48h post-treatment caused 84.7% mortality. Larval and pupal duration were proved to decrease significantly when larvae were exposed to cyclopaldic acid, 1,2-O,O-diacetyllycorine and N-methyllycorine iodide. The mean number of third-instar larvae surviving to 2-methyl-1,4-naphthoquinone, 2-hydroxy-1,4-naphthoquinone and 2-methoxy-1,4-naphthoquinone was significantly lower than the number of correspondent control larvae over the time. This study indicated that 1,2-O,O’-diacetyllycorine, N-methyllycorine iodide, cyclopaldic acid and 1,4-naphthoquinone structural derivatives have good potential for developing bioinsecticides for mosquito control programs. The obtained results are of general interest due to the global importance of the seri-ous human diseases such a vector is able to spread.