Pediatric lung function testing during a pandemic: An international perspective.

The COVID pandemic has passed its first peak for now in many countries while some are still on the rise, with some facing a second wave of cases. Precautions and infection control measures for both pediatric and adult pulmonary function testing (PFT) have been a topic of debate during the pandemic. Many centers had to close their PFT laboratories during the initial periods of the pandemic and are reopening as the numbers of new cases are decreasing. This review aims to summarize different practices of PFT laboratory management in different countries, including patient appointments, personal protective equipment, testing room requirements and telemedicine during and immediately following the COVID pandemic.

Influence of Relativistic Effects on the Contact Formation of Transition Metals.

Our analysis of the contact formation processes undergone by Au, Ag, and Cu nanojunctions reveals that the distance at which the two closest atoms on a pair of opposing electrodes jump into contact is, on average, 2 times longer for Au than either Ag or Cu. This suggests the existence of a longer-range interaction between those two atoms in the case of Au, a result of the significant relativistic energy contributions to the electronic structure of this metal, as confirmed by ab initio calculations. Once in the contact regime, the differences between Au, Ag, and Cu are subtle, and the conductance of single-atom contacts for metals of similar chemical valence is mostly determined by geometry and coordination.

Evidence of an Off-Resonant Electronic Transport Mechanism in Helicenes.

Helical molecules have been proposed as candidates for producing spin-polarized currents, even at room conditions, due to their chiral asymmetry. However, describing their transport mechanism in single molecular junctions is not straightforward. In this work, we show the synthesis of two novel kinds of dithia[11]helicenes to study their electronic transport in break junctions among a series of three helical molecules: dithia[n]helicenes, with n = 7, 9, and 11 molecular units. Our experimental measurements and clustering-based analysis demonstrate low conductance values that remain similar across different applied voltages and molecules. Additionally, we assess the length dependence of the conductance for each helicene, revealing an exponential decay characteristic of off-resonant transport. This behavior is primarily attributed to the misalignment between the energy levels of the molecule-electrodes system. The length dependence trend described above is supported by ab initio calculations, further confirming an off-resonant transport mechanism.

A Group-Theoretic Approach to the Origin of Chirality-Induced Spin-Selectivity in Nonmagnetic Molecular Junctions.

Spin-orbit coupling gives rise to a range of spin-charge interconversion phenomena in nonmagnetic systems where certain spatial symmetries are reduced or absent. Chirality-induced spin-selectivity (CISS), a term that generically refers to a spin-dependent electron transfer in nonmagnetic chiral systems, is one such case, appearing in a variety of seemingly unrelated situations ranging from inorganic materials to molecular devices. In particular, the origin of CISS in molecular junctions is a matter of an intense current debate. Here, we derive a set of geometrical conditions for this effect to appear, hinting at the fundamental role of symmetries beyond otherwise relevant quantitative issues. Our approach, which draws on the use of point-group symmetries within the scattering formalism for transport, shows that electrode symmetries are as important as those of the molecule when it comes to the emergence of a spin-polarization and, by extension, to the possible appearance of CISS. It turns out that standalone metallic nanocontacts can exhibit spin-polarization when relative rotations which reduce the symmetry are introduced. As a corollary, molecular junctions with achiral molecules can also exhibit spin-polarization along the direction of transport, provided that the whole junction is chiral in a specific way. This formalism also allows the prediction of qualitative changes of the spin-polarization upon substitution of a chiral molecule in the junction with its enantiomeric partner. Quantum transport calculations based on density functional theory corroborate all of our predictions and provide further quantitative insight within the single-particle framework.

Unraveling the Interplay between Quantum Transport and Geometrical Conformations in Monocyclic Hydrocarbons' Molecular Junctions.

In the field of molecular electronics, especially in quantum transport experiments, determining the geometrical configurations of a single molecule trapped between two electrodes can be challenging. To address this challenge, we employed a combination of molecular dynamics (MD) simulations and electronic transport calculations based on density functional theory to determine the molecular orientation in our break-junction experiments under ambient conditions. The molecules used in this study are common solvents used in molecular electronics, such as benzene, toluene (aromatic), and cyclohexane (aliphatic). Furthermore, we introduced a novel criterion based on the normal vector of the surface formed by the cavity of these ring-shaped monocyclic hydrocarbon molecules to clearly define the orientation of the molecules with respect to the electrodes. By comparing the results obtained through MD simulations and density functional theory with experimental data, we observed that both are in good agreement. This agreement helps us to uncover the different geometrical configurations that these molecules adopt in break-junction experiments. This approach can significantly improve our understanding of molecular electronics, especially when using more complex cyclic hydrocarbons.

Antibiotic allergy.

Antibiotics are commonly injected during the perioperative period and are responsible of 15 percent of the anaphylactic reactions. Anaphylaxis triggered by antibiotics primarily involves penicillin and cephalosporin. The management of patients with histories of allergic reactions to antibiotics is a common situation in clinical practice. The confirmation or invalidation of the allergic nature of the reported reaction is not based on in vitro tests, but on a rigorous allergological work-up based on detailed analysis of clinical history, skin tests and drug provocation test. Considering a possible cross-reactivity between penicillins, once an immediate penicillin allergy has been diagnosed, skin testing with the alternative molecule (cephalosporin, carbapenem, aztreonam) is mandatory and, if negative, the relevant drug should be given in an appropriate setting at increasing doses.

Reference ranges for interrupter resistance technique: the Asthma UK Initiative.

Measuring interrupter resistance (R(int)) is an increasingly popular lung function technique and especially suitable for preschool children because it is simple, quick and requires only passive cooperation. A European Respiratory Society (ERS)/American Thoracic Society (ATS) Task Force recently published empirical recommendations related to procedures, limitations and interpretation of the technique. However, for valid interpretation, high-quality reference equations are required and these have been lacking. The aim of the present study was to collate R(int) data from healthy children in order to produce more robust reference equations. A further aim was to examine the influence of methodological differences on predicted R(int) values. R(int) data from healthy children were collected from published and unpublished sources. Reference equations for expiratory and inspiratory R(int) were developed using the LMS (lambda, mu, sigma) method. Data from 1,090 children (51% males) aged 3-13 yrs were collated to construct sex-specific reference equations for expiratory R(int) and data from 629 children (51% males) were collated for inspiratory R(int). Height was the best independent predictor of both expiratory and inspiratory R(int). Differences between centres were clinically irrelevant, and differences between ethnic groups could not be examined. The availability of a large and generalisable sample and the use of modern statistical techniques enabled the development of more appropriate reference equations for R(int) in young children.

Timing of oral feeding changes in premature infants who underwent osteopathic manipulative treatment.

BACKGROUND: The delayed transition from gavage-to-nipple feeding is one of the most significant factors that may prolong hospital length of stay (LOS). Osteopathic manipulative treatment (OMT) has been demonstrated to be effective regarding LOS reduction, but no investigations have documented its clinical validity for attaining oral feeding. OBJECTIVES: To assess OMT utility regarding the timing of oral feeding in healthy preterm infants. DESIGN: Preliminary propensity score-matched retrospective cohort study. SETTING: Data were extrapolated from the neonatal intensive care unit (NICU) of Del Ponte Hospital in Varese, Italy, during the period between March 2012 and December 2013. INTERVENTIONS: Two propensity score-matched groups of healthy preterm infants aged 28+0 to 33+6 were compared, observing those supported with OMT until hospital discharge and control subjects. MAIN OUTCOME MEASURES: Days from birth to the attainment of oral feeding was the primary endpoint. Body weight, body length, head circumference and LOS were considered as secondary endpoints. RESULTS: Seventy premature infants were included in the study as the control group (n = 35; body weight (BW) = 1457.9 ± 316.2 g; gestational age (GA) = 31.5 ± 1.73 wk) and the osteopathic group (n = 35; BW = 1509.6 ± 250.8 g; GA = 31.8 ± 1.64 wk). The two groups had analogous characteristics at study entry. In this cohort, we observed a significant reduction in TOF (-5.00 days; p = 0.042) in the osteopathic group with a greater effect in very low birth weight infants. CONCLUSIONS: These data demonstrate the utility and potential efficacy of OMT for the attainment of oral feeding. Further adequately powered clinical trials are recommended.

Allergen specific nasal challenge to latex in children with latex allergy: clinical and immunological evaluation.

There are no data concerning the significance of allergen specific nasal challenge to latex (ASNCL) in the pediatric population and the effect of mometasone furoate nasal spray (MFNS), topic corticosteroid exerting a potent anti-inflammatory activity in children with latex allergic rhinitis. The aims of this study are: to investigate the clinical and immune pathological effects of ASNCL in children with latex allergy; to study the effects of MFNS pre-medication on the clinical and immune pathological effects of ASNCL in children with latex allergy. Thirteen children: 6 male and 7 female, mean (SD) age 9.6 (2.9) years, with latex allergy and seven children: 3 male and 4 female, mean (SD) age 9.9 (3.8) years, without latex allergy underwent ASNCL. Nasal symptoms were recorded, nasal lavage fluid was collected to measure tryptase, eosinophil cationic protein (ECP), interleukin-5, interferon-gamma levels, and spirometric test was performed for each patient without or with premedication with MFNS. ASNCL induced a clinical allergic response and increased tryptase levels only in children with latex allergy. No serious adverse events occurred after ASNCL. MFNS premedication reduced both tryptase and ECP levels only in children with latex allergy. ASNCL is a simple, reliable and useful tool to make or confirm the diagnosis of nasal symptoms due to latex; it allows us to study both clinical symptoms and local immunological changes. MFNS premedication before an ASNCL may prevent some immunological responses induced by ASNCL without clinical allergic modifications.

Diagnostic value of three different latex extracts.

The diagnosis of latex allergy is made on clinical history, but a confirmatory skin prick test (SPT) or a serological assay based on a commercial latex extract is always recommendable. Different raw materials can be used in the preparation of commercial latex extracts. Such extracts can consequently show both different qualitative profiles and a different diagnostic potential. Therefore, the selection of a proper latex extract is essential for in vitro and in vivo diagnosis of latex allergy. In the present study three different latex extracts, prepared from different raw materials (ammoniated -AL-, serum -SL-, or rubber particles -RPE- latex), are compared by in vitro techniques using sera from twenty patients with latex allergy. SDS-PAGE technique was used to compare the antigenic profile of the three latex extracts. Subsequently, their allergenic profiles were evaluated by immunoblotting technique using the individual sera from the twenty latex allergic patients. The diagnostic potential of the three latex extracts was also evaluated using direct Radio-Allergo-Sorbent Test (RAST) as well as skin prick tests (SPTs). In order to establish the more appropriate latex extract in a perspective of in vivo diagnosis of latex sensitization, the same latex extracts were subsequently compared by an in vivo SPT involving ten of the above subjects. The SDS-PAGE profiles of the three latex extracts examined were quite different. SL extract showed numerous bands comprised between 10-100 kDa. RPE extract was characterized by two intense bands at 14 and 20 kDa while AL extract showed the poorer antigenic composition. Analogously, immunoblotting analysis evidenced a different profile in relation to both different patients and extracts. For only two out of the twenty sera, direct RAST results showed a same positive class in relation to the different latex extracts used. SPT with SL extract showed, in respect to the other extracts (AL, RPE), a significantly higher wheal. This study showed that SL extract is able to express the best in vitro and in vivo diagnostic potential. Thus, its use should be preferred for the diagnosis of patients affected by latex allergy.

Nitric oxide (NO) inhibits prostaglandin E2 9-ketoreductase (9-KPR) activity in human fetal membranes.

Nitric oxide (NO) synthesized by fetal membranes may act either directly inhibiting myometrium contractility or indirectly interacting with tocolytic agents as prostaglandins (PGs). Here we examined if NO could modulate prostaglandin E(2) 9-ketoreductase (9-KPR) activity in human fetal membranes (HFM). 9-KPR is the enzyme that converts PGE(2) into PGF(2alpha), the main PGs known to induce uterine contractility at term. Chorioamnion explants obtained from elective caesareans were incubated with aminoguanidine (AG), an iNOS inhibitor, or NOC-18, a NO donor. NOC-18 (2mM) increased PGE(2) production and diminished PGF(2alpha) synthesis in HFM. AG presented the opposite effect. When we evaluated the activity of 9-KPR by the conversion of [(3)H]-PGE(2) into [(3)H]-PGF(2alpha) and 13,14-dihidro-15-keto prostaglandin F(2alpha) (the PGF(2alpha) metabolite), we found that NOC-18 inhibited 9-KPR activity. Interestingly, AG did not elicit any effect on 9-KPR but l-NAME, a non-selective NOS inhibitor, significantly increased its activity. Our data suggests that exogenous NO inhibits 9-KPR activity in HFM, thus modulating the synthesis of important labor mediators as PGF(2alpha).

Cross-reactivity between IgE-binding proteins from Anisakis simplex and Dermatophagoides pteronyssinus.

An association was found between Anisakis simplex (As) and Dermatophagoides pteronyssinus (Dp) sensitization. One recent study shows a cross-reactivity between As and Dp and tropomyosin (tr)is suspected as being one of the proteins responsible of this cross-reaction. The aim of our study was: 1) to confirm the cross-reactivity between Dp and As; 2) to determine the importance of tr in this cross reaction. SDS-PAGE analysis of Dp and As (metabolic and somatic) extracts was carried out. Then an IgE immunoblotting test using serum from a patient who had specific IgE only to Dp and As and immunoblotting inhibition experiments using Dp extract and tr as inhibitors were performed. We found that patients serum reacted: 1) against larval As antigens with a molecular weight (mw) of 25 kilodalton (kD) and a mw > than 100 kD, 2) against various metabolic As antigens with a mw > than 100 kD, a mw ranging approximately from 35 to 50 kD, and a mw around 20 kD, and 3) against Dp proteins with mw between 35 and 55 kD. Preincubation of patient's serum with Dp extract caused the disappearance of reactivity against antigens with a mw > than 100 kD in both larval and metabolic As extracts and against proteins with mw ranging approximately from 35 to 50 kD in the metabolic As extract. Preincubation of patients serum with As extract caused the disappearance of reactivity against antigens with mw between 35 and 55 kD in the Dp extract. Pre-incubation of patients serum with tr did not induce any change in the immunoblotting profile. The results show that 1) cross-reactive components between Dp and As are some proteins with a mw ranging approximately from 35 to 50 kD and with a mw > than 100 kD, and 2) tr is not involved in cross-reactivity between As and Dp.

Mould/dampness exposure at home is associated with respiratory disorders in Italian children and adolescents: the SIDRIA-2 Study.

AIMS: To report on the relation between home mould and/or dampness exposure and respiratory disorders in a large sample of children and adolescents in Italy, accounting for age at time of exposure. METHODS: 20,016 children (mean age 7 years) and 13,266 adolescents (mean age 13 years) completed questionnaires on indoor exposures and respiratory symptoms/diseases. Statistical analyses were adjusted for sex, age, questionnaire's compiler, area of residence, season of interview, parental educational status, family history of asthma, rhinitis, eczema, chronic obstructive pulmonary disease, presence of gas water heaters, passive smoking, pets, and active smoking (only for adolescents). Population attributable risk % (PAR) was also computed. RESULTS: Asthma was more strongly related to only early than to only current exposure, both in children (OR 1.80, 95% CI 1.41 to 2.30) and adolescents (OR 1.89, 95% CI 1.38 to 2.59). The same result was found for rhino-conjunctivitis (OR 1.46, 95% CI 1.17 to 1.82), in children, and for wheeze among adolescents (OR 1.56, 95% CI 1.15 to 2.11). In children, wheeze (OR 1.98, 95% CI 1.47 to 2.66) and eczema (OR 1.44, 95% CI 1.09 to 1.91) were more strongly related to mould/dampness when exposed both early and currently; the same occurred in adolescents for rhino-conjunctivitis (1.78, 95% CI 1.30 to 2.45). Although persistent cough/phlegm was significantly related to mould/dampness exposure in children, regardless of exposure timing, no significant association between mould/dampness exposure and eczema or cough/phlegm was found among adolescents. PAR estimates were higher for only early than only current exposures. Avoiding early only exposure would abate wheeze by 6%, asthma or cough/phlegm by 7%, rhino-conjunctivitis in children by 4%, and in adolescents, asthma by 6%, and wheeze by 4%. CONCLUSIONS: Respiratory disorders such as wheeze and asthma can often be explained by exposure to home mould/dampness, especially early in life. The association seems more evident in children than in adolescents. These findings may suggest the need for environmental prevention strategies.

Induction of a novel conformation in the progesterone receptor by ZK299 involves a defined region of the carboxyl-terminal tail.

Progesterone receptor antagonists are a promising class of therapeutic drugs indicated for the treatment of a variety of reproductive conditions. Understanding their mechanism of action at the molecular level is an important prerequisite for the development of future generations of these drugs. Using limited proteolytic analysis to monitor conformational changes in the progesterone receptor, we can detect three distinct classes of progestin antagonist. The effect of the first, RU486, on the conformation of the carboxyl terminus of the receptor has been previously described. The second, exemplified by RWJ 47626, a nonsteroidal compound with in vitro antiprogestin activity, induces a proteolytic fragment pattern indistinguishable from that induced by the agonist R5020. Finally, ZK299 induces a fragment pattern intermediate between that induced by R5020 and RU486. Site-directed mutagenesis of the carboxyl-terminal tail of the progesterone receptor indicates that the region containing the putative activation function AF-2 is differentially exposed to proteolytic attack depending on the nature of the antagonist bound. The differentially exposed region is most accessible when the antagonist RU486 is bound, less accessible when the antagonist ZK299 is bound, and least accessible when the antagonist RWJ47626 or agonist R5020 is bound. The results suggest that multiple types of antiprogestin can be defined in terms of their effects on the conformation of the carboxyl-terminal activation function of the progesterone receptor.

Iginio Tansini revisited.

The origin of the muscolocutaneous latissimus dorsi flap dates back to 1906 when Igino Tansini, an Italian surgeon, described a procedure to reconstruct the mastectomy defect. After a detailed study of Tansini's original description and drawings, new insights about the pedicle of its compound flap have been found, showing that it has the same pedicle of the scapular flap. In the end, Tansini's flap should be more correctly considered as a compound musculocutaneous scapular flap.

Fractionated stereotactic radiosurgery and concurrent taxol in recurrent glioblastoma multiforme: a preliminary report.

PURPOSE: Surgery and systemic chemotherapy offer modest benefit to patients with recurrent glioblastoma multiforme. These tumors are associated with rapid growth and progressive neurological deterioration. Radiosurgery offers a rational alternative treatment, delivering intensive local therapy. A pilot protocol to treat recurrent glioblastoma was developed using fractionated stereotactic radiosurgery with concurrent intravenous (i.v.) Taxol as a radiation sensitizer. METHODS AND MATERIALS: The treatment outcome was analyzed in 14 patients with recurrent glioblastoma treated with fractionated stereotactic radiosurgery and concurrent Taxol. Median tumor volume was 15.7 cc and patients received a mean radiation dose of 6.2 Gy at 90% isodose line, 4 times weekly. The median dose of Taxol was 120 mg/m2. RESULTS: The median survival was 14.2 months, 1-year survival was 50%. CONCLUSIONS: Survival for this small group of patients was similar to or better than historical controls or patients treated with single-fraction radiosurgery alone. This data should stimulate the investigation of both fractionated radiosurgery and the development of radiation sensitizers to further enhance treatment.

Nonsteroidal progesterone receptor ligands with unprecedented receptor selectivity.

We have characterized a series of nonsteroidal progesterone receptor ligands, the tetrahydropyridazines. Compounds in this series, exemplified by RWJ 26819, demonstrate high affinity and unprecedented specificity for the progesterone receptor relative to other steroid hormone receptors. Like steroidal progestins, RWJ 26819 induces binding of the receptor to a progesterone response element in vitro, and stimulates gene expression in and proliferation of T47D human breast cancer cells. When administered to rabbits orally or subcutaneously, the compound induces histological changes in the uterine lining comparable to those induced by levonorgestrel. It also inhibits ovulation in monkeys. Though less potent in cells and in animal models than would be predicted from binding affinity alone, their enhanced selectivity suggests that they could be effectively used in a clinical setting. Most of the tetrahydropyridazines synthesized are progestin agonists or mixed agonists and antagonists in vitro; however, one compound with antagonist activity in the rabbit uterine transformation assay has been identified.

The relation between physician-diagnosed sinusitis, asthma, and skin test reactivity to allergens in 8-year-old children.

The purpose of this study was to assess the prevalence of sinusitis in a nonselected sample of children, and the relation of sinusitis to allergic rhinitis (AR), atopy, asthma, and cough in the same population sample. Of 1246 children enrolled at birth in the Tucson Children's Respiratory Study, 835 were studied at a mean age +/-SD of 8.6 +/- 0.7 years. Questionnaires asking about MD-Sinusitis, MD-AR, MD-Asthma, and cough were completed by parents. Skin tests for seven common aeroallergens in the Tucson area had been performed in 630 of the participating children at the mean age +/-SD of 6.3 +/- 0.9 years. Prevalence of MD-Sinusitis was 13.1%; 78% of subjects with MD-Sinusitis also had MD-AR. Detailed analysis of the relation between MD-Sinusitis and individual environmental allergens tested for showed that only a response to Bermuda grass pollen was significantly associated with MD-Sinusitis after controlling for MD-AR [adjusted odds ratio 2.3 (95% CI 1.2-4.3)]. Having MD-Sinusitis was also significantly associated with MD-Asthma and cough [odds ratios 3.0 (95% CI 1.8-5.2)] and 2.5 (95% CI 1.6-3.8), respectively]. However, logistic regression demonstrated that, after controlling for MD-AR and skin test reactivity, MD-Sinusitis was no longer significantly associated with MD-Asthma or cough. We conclude that MD-Sinusitis is a common condition in childhood. The main independent risk factors in our community for MD-Sinusitis were grass pollen and current MD-AR. MD-Sinusitis was not associated with MD-Asthma or with cough after controlling for skin test reactivity and for MD-AR.

Airway resistance and spirometry in children with perinatally acquired human immunodeficiency virus-type 1 infection.

Airway resistance was measured by the interrupter technique in 54 children [aged 63.8 months (range: 9.1-131.6 months)], with perinatal human immunodeficiency virus-type 1 (HIV-1) infection and in a control group of 315 gender, height, and race-matched healthy children. In addition, 14 HIV-infected children, aged 75-131 months, had spirometry performed. Resistance was significantly higher in infected children than in controls (0.84 +/- 0.3 vs 0.64 +/- 0.08 kPa x l(-1) x s; t = 9.991; P < 0.0001). Resistance decreased with age in controls (r = -0.95; P < 0.001), but not in infected children (r= -0.22; P = 0.105). Resistance did not correlate with mothers' intravenous drug addiction, perinatal data, T-cell subset numbers, treatment, clinical course, or presence of respiratory complications. Resistance was higher (t = 3.103; P < 0.003) in p24 antigen-positive than in negative children. Thirty-nine children underwent a second evaluation 12.3 months (range 11.1-14 months) after the first. Resistance was higher (t = 3.960; P < 0.0001) at the second evaluation compared to the first. Eight of 14 children had abnormal spirometric measurements. We conclude that perinatal HIV-1 infection is associated with increased airway resistance and often abnormal spirometry. The degree of abnormalities in resistance depends on the duration of the infection rather than on HIV-1-related respiratory complications.

Treatment of recurrent glioblastoma multiforme using fractionated stereotactic radiosurgery and concurrent paclitaxel.

Despite the progress in neurosurgery and radiotherapy, almost all patients treated with malignant gliomas develop recurrent tumors and die of their disease. Eighty-eight patients (median age 56 years) with recurrent glioblastoma (median tumor volume 32.7 cm3) were treated with noninvasive fractionated stereotactic radiosurgery and concurrent paclitaxel used as a sensitizer. The median interval between diagnosis of primary glioblastoma and salvage radiosurgery was 7.8 months. Four weekly treatments (median dose: 6.0 Gy) were delivered after the 3-hour paclitaxel infusion (median dose: 120 mg/m2). Survival was calculated by the Kaplan-Meier method from radiosurgery treatment. Overall median survival was 7.0 months, and the 1-year and 2-year actuarial survival rates were 17% and 3.4%, respectively. When grouped by performance status, there was no difference in survival between the patients with low and high Karnofsky score. Patients with tumor volume less than 30 cm3 survived significantly longer than those with tumor greater than 30 cm3 (9.4 vs. 5.7 months, p = 0.0001). Their 1-year survival rate was 40% and 8%, respectively. Eleven patients (11%) had reoperation because of expanding mass. Stable disease was seen in 40% of patients (n = 34), and increase in radiographically detected mass was observed in 41 patients (48.8%). Although the treatment of recurrent GBM is mostly palliative, the fractionated radiosurgery offers a chance for prolonged survival, especially in patients with a smaller tumor volume.