A follow-up on quantitative and qualitative olfactory dysfunction and other symptoms in patients recovering from COVID-19 smell loss.

BACKGROUND: Sudden smell loss is a specific early symptom of COVID-19, which, prior to the emergence of Omicron, had estimated prevalence of ~40% to 75%. Chemosensory impairments affect physical and mental health, and dietary behavior. Thus, it is critical to understand the rate and time course of smell recovery. The aim of this cohort study was to characterize smell function and recovery up to 11 months post COVID-19 infection. METHODS: This longitudinal survey of individuals suffering COVID-19-related smell loss assessed disease symptoms and gustatory and olfactory function. Participants (n=12,313) who completed an initial survey (S1) about respiratory symptoms, chemosensory function and COVID-19 diagnosis between April and September 2020, were invited to complete a follow-up survey (S2). Between September 2020 and February 2021, 27.5% participants responded (n=3,386), with 1,468 being diagnosed with COVID-19 and suffering co-occurring smell and taste loss at the beginning of their illness. RESULTS: At follow-up (median time since COVID-19 onset ~200 days), ~60% of women and ~48% of men reported less than 80% of their pre-illness smell ability. Taste typically recovered faster than smell, and taste loss rarely persisted if smell recovered. Prevalence of parosmia and phantosmia was ~10% of participants in S1 and increased substantially in S2: ~47% for parosmia and ~25% for phantosmia. Persistent smell impairment was associated with more symptoms overall, suggesting it may be a key marker of long-COVID illness. The ability to smell during COVID-19 was rated slightly lower by those who did not eventually recover their pre-illness ability to smell at S2. CONCLUSIONS: While smell ability improves for many individuals who lost it during acute COVID-19, the prevalence of parosmia and phantosmia increases substantially over time. Olfactory dysfunction is associated with broader persistent symptoms of COVID-19, and may last for many months following acute COVID-19. Taste loss in the absence of smell loss is rare. Persistent qualitative smell symptoms are emerging as common long-term sequelae; more research into treatment options is strongly warranted given that even conservative estimates suggest millions of individuals may experience parosmia following COVID-19. Healthcare providers worldwide need to be prepared to treat post COVID-19 secondary effects on physical and mental health.

Consensus paper on postural dysfunction: recommendations for prevention, diagnosis and therapy.

Good fundamentals of posture and balance are essential for the efficient performance of both simple daily tasks and more complex movement patterns. In particular, postural balance is the ability to keep the body in equilibrium and to regain balance after the shift of body segments: postural control mechanisms of integration of the visual, vestibular and foot afferential channels contribute to this. This document provides recommendations based on scientific evidence, clinical practice, and consensus between experts concerning the prevention, diagnosis, and treatment of postural dysfunction at the three stages of life as the developmental age, adult age, and old age > 65 years and follows the "National Guidelines on Classification and Measuring of Posture and its Dysfunctions" per the Italian Ministry of Health (December 2017). The paper answers four main questions: i) "Which measures can be adopted to prevent postural dysfunctions?" ii) "What can we do in order to make a correct diagnosis of postural dysfunction?" iii) "What are the correct treatment programs for postural dysfunctions?" iv) Which professional competencies and experiences are useful for preventing, diagnosing and treating postural dysfunctions? By the Consensus of the Experts and the scientific evidence, emerge that the approach to postural dysfunctions requires a multidisciplinary and interdisciplinary team. Furthermore, rehabilitation treatment interventions must be specific to the age groups that have been indicated, to consider the integration of the main systems and subsystems of postural control that change with age.

Factors associated with relevant olfactory recovery after olfactory training: a retrospective study including 601 participants.

OBJECTIVE: Olfactory training (OT) represents a therapeutic option for multiple etiologies of olfactory dysfunction (OD) that also benefits normosmic subjects. In this retrospective study, we report the effectiveness of OT and factors associated with relevant changes in olfactory function (OF) in large groups of normosmic participants and patients with OD, including a control group that performed no training. METHODS: This was a retrospective pooled analysis including 2 treatment cohorts of 8 previously published studies. Adult participants that either presented with the major complaint of quantitative OD or normosmic volunteers were recruited at various ENT clinics and received OT or no training. The outcome was based on changes in objective olfactory test scores after OT. RESULTS: A total of 601 patients with OD or normosmic subjects were included. OT was more effective compared to no training. No interaction was found between OT and OF. In multivariate analysis, higher baseline OF (adjusted odds ratio, aOR, 0.93) and posttraumatic (aOR, 0.29) or idiopathic OD (aOR, 0.18) compared to postinfectious causes were significantly associated with lower odds of relevant improvements in patients with OD receiving OT. Subgroup analysis of normosmic participants receiving OT further revealed a significant association of lower age and baseline olfactory function with improvements of overall OF. CONCLUSIONS: This study demonstrated that OT was more effective than no training in patients with various causes of OD. Additionally, baseline olfactory performance and etiology of OD were identified as important factors associated with relevant improvements after OT.

Factors associated with relevant olfactory recovery after olfactory training: a retrospective study including 601 participants.

BACKGROUND: Olfactory training (OT) represents a therapeutic option for multiple etiologies of olfactory dysfunction (OD) that also benefits normosmic subjects. In this retrospective study, we report the effectiveness of OT and factors associated with relevant changes in olfactory function (OF) in large groups of normosmic participants and patients with OD, including a control group that performed no training. METHODS: This was a retrospective pooled analysis including 2 treatment cohorts of 8 previously published studies. Adult partici- pants that either presented with the major complaint of quantitative OD or normosmic volunteers were recruited at various ENT clinics and received OT or no training. The outcome was based on changes in objective olfactory test scores after OT. RESULTS: A total of 601 patients with OD or normosmic subjects were included. OT was more effective compared to no training. No interaction was found between OT and OF. In multivariate analysis, higher baseline OF (adjusted odds ratio, aOR, 0.93) and posttraumatic (aOR, 0.29) or idiopathic OD (aOR, 0.18) compared to postinfectious causes were significantly associated with lower odds of relevant improvements in patients with OD receiving OT. Subgroup analysis of normosmic participants receiving OT further revealed a significant association of age and baseline olfactory function with improvements of overall OF. CONCLUSIONS: This study demonstrated that OT was more effective than no training in patients with various causes of OD. Additi- onally, baseline olfactory performance and etiology of OD were identified as important factors associated with relevant improve- ments after OT.

Identification of molecular markers for oocyte competence in bovine cumulus cells.

Cumulus cells (CCs) have an important role during oocyte growth, competence acquisition, maturation, ovulation and fertilization. In an attempt to isolate potential biomarkers for bovine in vitro fertilization, we identified genes differentially expressed in bovine CCs from oocytes with different competence statuses, through microarray analysis. The model of follicle size, in which competent cumulus-oocyte complexes (COCs) were recovered from bigger follicles (≥8.0 mm in diameter) and less competent ones from smaller follicles (1-3 mm), was used. We identified 4178 genes that were differentially expressed (P < 0.05) in the two categories of CCs. The list was further enriched, through the use of a 2.5-fold change in gene expression as a cutoff value, to include 143 up-regulated and 80 down-regulated genes in CCs of competent COCs compared to incompetent COCs. These genes were screened according to their cellular roles, most of which were related to cell cycle, DNA repair, energy metabolism, metabolism of amino acids, cell signaling, meiosis, ovulation and inflammation. Three candidate genes up-regulated (FGF11, IGFBP4, SPRY1) and three down-regulated (ARHGAP22, COL18A1 and GPC4) in CCs from COCs of big follicles (≥8.1 mm) were selected for qPCR analysis. The selected genes showed the same expression patterns by qPCR and microarray analysis. These genes may be potential genetic markers that predict oocyte competence in in vitro fertilization routines.

Olfactory function in patients with hyposmia compared to healthy subjects - An fMRI study.

BACKGROUND: Individuals with hyposmia, or the partial loss of smell, represent a large sector (15 %) of the population that is likely to grow with the current aging population; however, our understanding to how hyposmics centrally process odors is still not clear. One popular non-invasive tool for in vivo imaging of biological activity among human brains has been function magnetic resonance imaging (fMRI) which uses blood-oxygenation level dependent (BOLD) signal as an indirect measurement. Therefore, the aim of this study was to understand differences in olfaction processing between patients with hyposmia and healthy controls using functional magnetic resonance imaging (fMRI). METHODOLOGY: Eleven hyposmic and 12 healthy, normosmic subjects were exposed to two different food-related odors (coffee and peach) during a block-designed fMRI session. Additionally, odor perception qualities were rated for each odor throughout the scanning session. RESULTS: The activations of the normosmic group were localized in typical olfactory areas (insula, orbitofrontal cortex [OFC], limbic system and amygdala). The hyposmic group showed similar regions of activation (insula, OFC, limbic system), however, less activation was found in the amygdala, left anterior cingulate and right OFC, but higher activation was shown in the right parahippocampal and both the left and right posterior cingulate gyrus which are assumed to play an important role in the processing and remembrance of memories. CONCLUSIONS: These results indicate similar central olfactory processing among groups, yet subjects with partial loss may attempt to compensate smell impairment with odor memory or higher motivation to smell.

Pharmacokinetics and residue depletion of erythromycin in gilthead sea bream Sparus aurata L. after oral administration.

Erythromycin (ERY) is an antibiotic effective against Streptococcus iniae, a microorganism responsible for significant losses in aquaculture. No data are available on the pharmacokinetics and residue depletion of ERY in sea bream. The aim of this study was thus to evaluate the pharmacokinetics of ERY in this species after a single oral administration at 75 mg kg(-1) b.w. and to assess its residue depletion from tissues after prolonged treatment for 10 days. ERY was rapidly absorbed in sea bream (Cmax  = 10.04 µg g(-1) and Tmax =1 h), with a half-life of 9.35 h and an AUC0-24 of 56.81 (h µg mL(-1) ). The data obtained and the evaluation of pharmacokinetic/pharmacodynamic parameters allowed us to hypothesize that dosage used in this study should be effective against S. iniae. A rapid reduction in erythromycin concentrations was observed in tissues, with the drug being detectable only during the first day post-treatment. In Europe, the use of ERY in aquaculture is allowed by off-label prescription with a withdrawal time of 500 °C day(-1) . The absence of ERY residues in tissues already at 24 h post-treatment suggests that ERY in sea bream should not pose human food safety issues.

Pharmacokinetics and residue depletion of erythromycin in rainbow trout Oncorhynchus mykiss (Walbaum).

Erythromycin (ERY) is a drug active against Gram-positive bacteria such as Lactococcus garvieae, a pathogen responsible for an important disease that may cause a substantial decrease in rainbow trout Oncorhynchus mykiss (Walbaum) production, the species of fish most commonly produced in Italy. In the literature, studies on the kinetics behaviour of ERY in fish are limited. Therefore, the aim of the present study was to evaluate the pharmacokinetics of ERY in rainbow trout after a single oral treatment with 75 mg kg⁻¹ body weight (b.w.) of ERY and the residue depletion after multiple oral administration of 75 mg kg⁻¹ b.w. day⁻¹ of ERY for 10 days. Blood concentrations of ERY increased up to 20.24 ± 13.32 µg mL⁻¹ at 6 h, then decreased to 5.97 ± 3.89 µg mL⁻¹ at 24 h. The time during which the antibiotic remains in the bloodstream at concentrations exceeding the MIC (T > MIC) and the area under the serum concentration-time curve (AUC)/MIC are both pharmacokinetic-pharmacodynamic (PK/PD) predictors of ERY efficacy, and the data obtained allowed us to hypothesize that a dosage of 75 mg kg⁻¹ b.w. day⁻¹ of ERY could treat the lactococcosis in trout. Regarding the study of ERY depletion, rapid elimination was observed in tissue (muscle plus adherent skin); in fact the concentrations were below the limit of quantification in all samples (except two) by day 10 post-treatment. ERY is not licensed in Europe for use in aquaculture, and its use is possible only by off-label prescription with a precautionary withdrawal time of 500 degree-days, as established by Directive 2004/28/EC. From the data obtained in this study, a withdrawal time of 8.90 days was calculated, corresponding, in our experimental conditions, to 117.5 degree-days, a value significantly lower than that established by the European directive.

Mutations in Cdh23, encoding a new type of cadherin, cause stereocilia disorganization in waltzer, the mouse model for Usher syndrome type 1D.

Mouse chromosome 10 harbors several loci associated with hearing loss, including waltzer (v), modifier-of deaf waddler (mdfw) and Age-related hearing loss (Ahl). The human region that is orthologous to the mouse 'waltzer' region is located at 10q21-q22 and contains the human deafness loci DFNB12 and USH1D). Numerous mutations at the waltzer locus have been documented causing erratic circling and hearing loss. Here we report the identification of a new gene mutated in v. The 10.5-kb Cdh23 cDNA encodes a very large, single-pass transmembrane protein, that we have called otocadherin. It has an extracellular domain that contains 27 repeats; these show significant homology to the cadherin ectodomain. In v(6J), a GT transversion creates a premature stop codon. In v(Alb), a CT exchange generates an ectopic donor splice site, effecting deletion of 119 nucleotides of exonic sequence. In v(2J), a GA transition abolishes the donor splice site, leading to aberrant splice forms. All three alleles are predicted to cause loss of function. We demonstrate Cdh23 expression in the neurosensory epithelium and show that during early hair-cell differentiation, stereocilia organization is disrupted in v(2J) homozygotes. Our data indicate that otocadherin is a critical component of hair bundle formation. Mutations in human CDH23 cause Usher syndrome type 1D and thus, establish waltzer as the mouse model for USH1D.

Whole blood genome-wide gene expression profile in males after prolonged wakefulness and sleep recovery.

Although the specific functions of sleep have not been completely elucidated, the literature has suggested that sleep is essential for proper homeostasis. Sleep loss is associated with changes in behavioral, neurochemical, cellular, and metabolic function as well as impaired immune response. Using high-resolution microarrays we evaluated the gene expression profiles of healthy male volunteers who underwent 60 h of prolonged wakefulness (PW) followed by 12 h of sleep recovery (SR). Peripheral whole blood was collected at 8 am in the morning before the initiation of PW (Baseline), after the second night of PW, and one night after SR. We identified over 500 genes that were differentially expressed. Notably, these genes were related to DNA damage and repair and stress response, as well as diverse immune system responses, such as natural killer pathways including killer cell lectin-like receptors family, as well as granzymes and T-cell receptors, which play important roles in host defense. These results support the idea that sleep loss can lead to alterations in molecular processes that result in perturbation of cellular immunity, induction of inflammatory responses, and homeostatic imbalance. Moreover, expression of multiple genes was downregulated following PW and upregulated after SR compared with PW, suggesting an attempt of the body to re-establish internal homeostasis. In silico validation of alterations in the expression of CETN3, DNAJC, and CEACAM genes confirmed previous findings related to the molecular effects of sleep deprivation. Thus, the present findings confirm that the effects of sleep loss are not restricted to the brain and can occur intensely in peripheral tissues.

Electronic cigarettes: an evaluation of exposure to chemicals and fine particulate matter (PM).

The "electronic (e-)cigarette" generates intense scientific debate about its use. Its popularity is increasing worldwide as a method to reduce/quit smoking, and to smoke indoors when restrictions on smoking tobacco are present. WHO recommends caution, until its effectiveness in helping smokers is clarified, and the possible harm evaluated. The aim of this study was to assess the content of the aromatic liquid mixture and its vapour and the Particulate Matter (PM) emissions of an Italian brand of e-cigarette and to compare its PM emissions with a conventional cigarette. Propylene glycol (66%) and glycerine (24%) were main components in the liquid, while the flavouring substances were less than 0.1%. The same substances were detected in the vapour in similar proportions. Fine and ultrafine PM emissions were higher for the conventional versus the e-cigarette (e.g.: PM10=922 vs 52 microg/m3; PM1=80 vs 14 microg/m3). The e-cigarette seems to give some advantages when used instead of the conventional cigarette, but studies are still scanty: it could help smokers to cope with some of the rituals associated with smoking gestures and to reduce or eliminate tobacco consumption avoiding passive smoking. However, the e-cigarette causes exposure to different chemicals compared with conventional cigarettes and thus there is a need for risk evaluation for both e-cigarettes and passive steam exposure in smokers and non smokers.

Clinical, cytogenetic and molecular study in a case of r(3) with 3p deletion and review of the literature.

Ring chromosome 3 is a rare abnormality with only 10 patients described in the literature. We report a patient with r(3) and ∼6-Mb distal 3p deletion. Single nucleotide polymorphism array, multiplex ligation-dependent probe amplification and fluorescence in situ hybridization techniques revealed that the ring was formed by a break in 3p26.1 and fusion with the subtelomeric region of 3q. The patient presents delayed psychomotor development, growth failure, minor anomalies and other features similar to patients with 3p monosomy. The analysis of 300 metaphase cells using G-banding and fluorescence in situ hybridization with centromeric probe revealed ring instability resulting in cells with secondary aberrations and with ring loss that could also be related to some phenotypic characteristics such as growth delay. This is the first patient with r(3) studied using molecular techniques that determined the exact breakpoints in order to establish a better karyotype-phenotype correlation.

Subjective touch sensitivity leads to behavioral shifts in oral food texture sensitivity and awareness.

Neurotypical individuals have subjective sensitivity differences that may overlap with more heavily studied clinical populations. However, it is not known whether these subjective differences in sensory sensitivity are modality specific, or lead to behavioral shifts. In our experiment, we measured the oral touch sensitivity and food texture awareness differences in two neurotypical groups having either a high or low subjective sensitivity in touch modality. To measure oral touch sensitivity, individuals performed discrimination tasks across three types of stimuli (liquid, semisolid, and solid). Next, they performed two sorting exercises for two texture-centric food products: cookies and crackers. The stimuli that required low oral processing (liquid) were discriminated at higher rates by participants with high subjective sensitivity. Additionally, discrimination strategies between several foods in the same product space were different across the groups, and each group used attributes other than food texture as differentiating characteristics. The results show subjective touch sensitivity influences behavior (sensitivity and awareness). However, we show that the relationship between subjective touch sensitivity and behavior generalizes beyond just touch to other sensory modalities.

Efficacy of ustekinumab in the treatment of patients with Crohn's disease with failure to previous conventional or biologic therapy: a prospective observational real-life study.

Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, was approved by FDA and EMA for the treatment of moderate to severe Crohn's disease (CD). Whether UST is effective in inducing deep remission, including mucosal healing and transmural healing, in patients with CD in a real life setting is not completely clear. This study was performed on 92 subjects with confirmed diagnosis of moderate to severe Crohn's disease and no neoplasia. Before inclusion, all patients had been exposed and had failed to respond to conventional and/or at least one biological therapy. All patients underwent endoscopic examination and bowel MRI and ultrasonography at baseline (T0). At week 52 (T52), patients underwent colonoscopy for assessment of mucosal healing and MRI or ultrasonography for assessment of transmural healing. CDAI was used for the assessment of clinical response and clinical remission. SES-CD was used to assess endoscopic response and remission. Incidence of treatment-related adverse events (TRAEs) was recorded during the study period. Clinical response at week 52 was achieved in 38 (50.5%) patients and clinical remission in 29 (39%). Twenty-six (34%) patients showed mucosal healing, 34 (45%) showed partial endoscopic response. We observed a reduction in SES-CD of at least 50% in 34 (45%) patients as well as an SES-CD ≤ 2 in 26 (35%) patients. All patients with mucosal healing also showed transmural healing. No major TRAEs were observed during treatment. In this multicenter, real life study, we show that UST was well tolerated and effective in inducing clinical response and clinical remission in patients with moderate to severe CD who had previously failed to respond to conventional or biologic therapy. UST showed limited efficacy in inducing deep remission (i.e. mucosal+transmural healing).

Influence of genetic ancestry on the risk of obstructive sleep apnoea syndrome.

The aim of the present study was to evaluate the influence of ethnicity on the risk of developing obstructive sleep apnoea syndrome (OSAS) using genomic analysis methods to estimate ancestry. DNA samples were obtained from 1,010 individuals participating in the São Paulo Epidemiologic Sleep Study, who underwent full-night polysomnography. A total of 31 genetic ancestry-informative markers were selected in order to estimate individual admixture proportions. Of patients with a diagnosis of OSAS, a higher number self-reporting Caucasian ethnicity (65.3%), as well as an increased percentage of European ancestry (78.2±16.7%) and lower percentage of West African ancestry (16.1±15.3%), than among individuals without OSAS (53.6, 73.5±18.1 and 20.1±16.8%, respectively) (p<0.001) was observed. Moreover, after correcting for sex, age, body mass index and socioeconomic status, logistic regression demonstrated that European ancestry was significantly associated with an increased risk of manifesting OSAS (OR 2.80, 95% CI 1.11-7.09). Conversely, West African ancestry was associated with a reduced risk of the OSAS phenotype (OR 0.26, 95% CI 0.09-0.72). This is the first study to incorporate genomic analysis methods to measure the influence of ethnicity on the risk of OSAS. Since genetically determined ancestry may not capture unmeasured cultural and lifestyle differences, the contribution of environmental factors to the current findings should not be disregarded.

Sublingual immunotherapy in polysensitized patients: effect on quality of life.

BACKGROUND: Quality of life (QOL) is an important issue in allergic rhinitis and has been evaluated in a number of studies that have shown how it is impaired in untreated patients and improved by effective treatment. However, there are no data concerning QOL after sublingual immunotherapy (SLIT) in polysensitized patients. OBJECTIVE: To evaluate the effect, in real-life clinical practice, of SLIT on QOL in a population of polysensitized patients with allergic rhinitis. METHODS: We prospectively evaluated 167 consecutively enrolled polysensitized patients with allergic rhinitis. QOL was measured in all cases with the Rhinoconjunctivitis Quality of Life Questionnaire at baseline and after 1 year of SLIT (performed in approximately 70% of cases using single allergen extracts provided by the same manufacturer). RESULTS: The most frequent causes of sensitization were grass pollen, Parietaria, and house dust mites. The mean number of sensitizations per patient was 3.65. SLIT was performed with 1 extract in 123 patients (73.6%), with 2 extracts in 31 patients (18.6%), and with more than 2 extracts in 13 patients (7.8%). The mean values of all the QOL items improved significantly (P < .01 in all cases), with the following reductions noted: activities, 3.96 to 2.89; sleep, 2.07 to 1.56; general problems, 2.16 to 1.5; practical problems, 3.69 to 2.58; nasal symptoms, 3.57 to 2.50; eye symptoms, 2.92 to 1.83; and emotional aspects, 2.2 to 1.44. CONCLUSIONS: This study provides evidence that QOL can be improved in polysensitized patients treated with SLIT, and that the use of just 1 or 2 allergen extracts seems to be sufficient and effective in terms of improving QOL.

Forkhead box M1B is a determinant of rat susceptibility to hepatocarcinogenesis and sustains ERK activity in human HCC.

BACKGROUND AND AIMS: Previous studies indicate unrestrained cell cycle progression in liver lesions from hepatocarcinogenesis-susceptible Fisher 344 (F344) rats and a block of G(1)-S transition in corresponding lesions from resistant Brown Norway (BN) rats. Here, the role of the Forkhead box M1B (FOXM1) gene during hepatocarcinogenesis in both rat models and human hepatocellular carcinoma (HCC) was assessed. METHODS AND RESULTS: Levels of FOXM1 and its targets were determined by immunoprecipitation and real-time PCR analyses in rat and human samples. FOXM1 function was investigated by either FOXM1 silencing or overexpression in human HCC cell lines. Activation of FOXM1 and its targets (Aurora Kinose A, Cdc2, cyclin B1, Nek2) occurred earlier and was most pronounced in liver lesions from F344 than BN rats, leading to the highest number of Cdc2-cyclin B1 complexes (implying the highest G(2)-M transition) in F344 rats. In human HCC, the level of FOXM1 progressively increased from surrounding non-tumorous livers to HCC, reaching the highest levels in tumours with poorer prognosis (as defined by patients' length of survival). Furthermore, expression levels of FOXM1 directly correlated with the proliferation index, genomic instability rate and microvessel density, and inversely with apoptosis. FOXM1 upregulation was due to extracellular signal-regulated kinase (ERK) and glioblastoma-associated oncogene 1 (GLI1) combined activity, and its overexpression resulted in increased proliferation and angiogenesis and reduced apoptosis in human HCC cell lines. Conversely, FOXM1 suppression led to decreased ERK activity, reduced proliferation and angiogenesis, and massive apoptosis of human HCC cell lines. CONCLUSIONS: FOXM1 upregulation is associated with the acquisition of a susceptible phenotype in rats and influences human HCC development and prognosis.

How to interpret reduced forced expiratory volume in 1 s (FEV1)/vital capacity ratio with normal FEV1.

The aim of the present study was to determine whether the combination of low forced expiratory volume in 1 s (FEV(1))/vital capacity (VC) ratio with normal FEV(1) represents a physiological variant or a sign of early airflow obstruction. We studied 40 subjects presenting with low FEV(1)/VC, but FEV(1) within the range of normality predicted by European Respiratory Society reference equations, and 10 healthy controls. All subjects completed two questionnaires and underwent comprehensive pulmonary function testing, which included methacholine challenge and single-breath nitrogen wash-out. According to the questionnaires, the subjects were assigned to three groups, i.e. rhinitis (n = 8), bronchial asthma (n = 13) and chronic obstructive pulmonary disease (COPD; n = 12). Subjects with negative responses to questionnaires were assigned to an asymptomatic group (n = 7). Airway hyperresponsiveness was found in four subjects of the rhinitis group, all of the asthma group, and 10 of the COPD group; in the last two groups, it was associated with signs of increased airway closure and gas trapping. Bronchodilator response to salbutamol was positive in only a few individuals across groups. In the asymptomatic group, no significant functional changes were observed, possibly suggesting dysanaptic lung growth. In subjects with low FEV(1)/VC and normal FEV(1), questionnaires on respiratory symptoms together with additional pulmonary function tests may help to clarify the nature of this pattern of lung function.

The Medical Care Continuity (MCC) project. A pilot study of video-assisted home care within the eTEN European Community program. The Italian experience.

GOALS OF WORK: This study aimed to use an integrated system (Medical Care Continuity (MCC) system) consisting of computer, video telephone, and a high-definition camera to monitor at home chemotherapy side effects in cancer outpatients. PATIENTS AND METHODS: The system allowed 24 h/day video consultation with an intermediate medical call center with possible connection to a specialized hospital if necessary. All patients were provided with internationally validated and project-oriented questionnaires exploring patients' health status and opinions on usefulness and complexity of study devices. The content of each call was recorded on a computer database. An approximate estimate of avoided hospital admissions was calculated. MAIN RESULTS: Median duration of experimentation and frequency of patient/doctor contacts were 2.1 months and 4.2 contact per week, respectively. Overall, a 98% positive opinions on the experimental system was reported at the end of the study by all participants, with a 21% conversion rate with respect to the opinions gathered at study entry. Changes in patient management after a medical call were made in 32% of cases. It was calculated that approximately 2.2 per month unnecessary hospital admissions were avoided. CONCLUSIONS: The MCC system was well managed by both patients and caregivers. These results show that it has the potential to improve medical assistance by virtue of a constant access to medical advice and reduce unnecessary hospital admissions.

Effect of hydrogen bonding interaction on the photophysics of α-amino-orcein.

This paper reports for the first time a detailed spectroscopic investigation into the ground- and excited-state properties of α-amino-orcein (α-AO), one of the main components of the orcein dye, in solvents of different proticity and water at different pHs. In order to gain insight into the nature of the involved transitions and excited state deactivation pathways, the study was carried out by means of UV-Visible steady state and ultrafast spectroscopic techniques with the support of quantum mechanical calculations (DFT and TDDFT). The results highlight that the photophysical and photodynamic behaviour of α-AO are highly sensitive to the solvent proticity and pH. In particular, protic environment induces a red shift (55 nm) of the absorption spectrum together with a relevant decrease of the fluorescence quantum yield (from 0.19 in acetonitrile to 6.6 × 10-3 in methanol) and radiative rate constant (two orders of magnitude). A notable red shift is also caused by increasing the pH leading the molecule from monocationic to neutral and then monoanionic form through two deprotonation steps (pKa = 3.539 ±â€¯0.006 and 11.180 ±â€¯0.006). Following deprotonation, the molecule assumes spectral and photophysical properties very similar to those retrieved in protic media. The observed behaviour has been rationalized through the occurrence of hydrogen bonding, likely involving to a greater extent the carbonyl oxygen of α-AO and the protic solvent, that favours the charge delocalization on the whole chromophore as well as fast non-radiative excited state deactivation. The ultrafast spectroscopic investigation revealed in fact the presence, in protic solvent, of a short living component (tens of picoseconds), assignable to solvent complexed S1 state, alongside the long living component (few nanoseconds) observed in aprotic media and attributed to the solvent free S1 state. The results achieved in this study for α-AO provides an important contribution to the interpretation of absorption and fluorescence features of orcein dye mixture in more complex systems (protein based substrates within the many aspects of the cultural heritage and biomedical field) where hydrogen bonds are expected to play a crucial role in mediating the interaction with the environment.