Metasurface-assisted Lab-on-fiber optrode for highly sensitive detection of vitamin D.

The increasing demand for vitamin D status assessment has highlighted the need for rapid, sensitive, and user-friendly methods for its detection in biological samples potentially integrated in Point-of-Care (PoC) diagnostic devices. Detection of the major circulating form of vitamin D, 25-hydroxyvitamin D3-25(OH)D3, is particularly challenging due to the laborious procedures for sample preparation and its low molecular weight (∼400 Da), which requires highly sensitive detection methods. In this study, we developed a novel label-free Lab-on-Fiber biosensing platform for highly sensitive detection of 25(OH)D3 based on the integration of plasmonic metasurfaces (MSs) on the tip of a single-mode optical fiber (OF). A dedicated pipeline was carefully designed and developed to optimize the bio-functionalization of the plasmonic sensor tip to specifically detect the target biomolecule. The resulting MS-assisted Lab-on-fiber platform enables direct and highly sensitive detection of 25(OH)D3 in clinically relevant ranges (4-160 ng/mL), both in buffer solution and complex matrix, with limits of detection (LOD) of 1.40 ng/mL in saline buffer and 0.85 ng/mL in complex matrix. Overall, these results demonstrate that our platform can successfully and specifically detect small molecules in label-free configuration, with performances comparable to those of conventional methods used in clinical practice. The high degree of miniaturization combined with its high sensitivity makes our platform an exceptional building block for realizing valid diagnostic alternatives for label-free detection of clinically relevant analytes, which can be transformed into new low-cost, fast, simple, and ready-to-use PoC diagnostic devices with improved processability and performance compared to current methods.

Sexuality in breast cancer survivors: sexual experiences, emotions, and cognitions in a group of women under hormonal therapy.

BACKGROUND: Earlier diagnosis and improved treatments have led to better outcomes in breast cancer, making quality of life a key issue. Sexuality represents a pillar of quality of life, although it is often neglected by both healthcare providers and patients when it comes to cancer. This study aims to explore the differences in sexual functioning, distress, psychopathology, emotions, and cognitions between breast cancer patients under hormonal treatment and controls. METHODS: Seventy-nine women (age range between 24 and 69 years) in hormonal therapy for breast cancer completed a self-reported protocol. A matched control group of 103 women was randomly extracted from an Italian general population database. Eight self-report questionnaires exploring biopsychosocial factors were administered. RESULTS: The current study showed an impaired sexuality in breast cancer patients compared to controls. Breast cancer women under hormonal treatment were characterized by diminished or absent sexual activity (chi2 = 36.16; p < 0.001), lower level of sexual functioning in all areas except for pain (F(1,180) = 8.1; p < 0.01), higher sexual (F(1,180) = 10.08; p < 0.001) and psychological distress (F(1,180) = 6.23; p < 0.05), higher scores in Difficulties in Identifying Feelings (F(1,180) = 7.31; p < 0.01) and Externally Oriented Thinking (F(1,180) = 6.64; p < 0.05), higher level of negative emotions related to sexuality (F(1,180) = 11.13; p < 0.001), and more rigid cognition towards peculiar aspects of sexuality, such as Failure Disengagement Thoughts (F(1,180) = 22.01; p < 0.001) and Age related Beliefs (F(1,180) = 5.7; p < 0.05). CONCLUSIONS: Health care providers do not usually assess those issues in their routine practice, so that sexuality remains an unmet need with remarkable effects on general health and quality of life.

Light-microgel interaction in resonant nanostructures.

Combination of responsive microgels and photonic resonant nanostructures represents an intriguing technological tool for realizing tunable and reconfigurable platforms, especially useful for biochemical sensing applications. Interaction of light with microgel particles during their swelling/shrinking dynamics is not trivial because of the inverse relationships between their size and refractive index. In this work, we propose a reliable analytical model describing the optical properties of closed-packed assembly of surface-attached microgels, as a function of the external stimulus applied. The relationships between the refractive index and thickness of the equivalent microgel slab are derived from experimental observations based on conventional morphological analysis. The model is first validated in the case of temperature responsive microgels integrated on a plasmonic lab-on-fiber optrode, and also implemented in the same case study for an optical responsivity optimization problem. Overall, our model can be extended to other photonic platforms and different kind of microgels, independently from the nature of the stimulus inducing their swelling.

Microgel assisted Lab-on-Fiber Optrode.

Precision medicine is continuously demanding for novel point of care systems, potentially exploitable also for in-vivo analysis. Biosensing probes based on Lab-On-Fiber Technology have been recently developed to meet these challenges. However, devices exploiting standard label-free approaches (based on ligand/target molecule interaction) suffer from low sensitivity in all cases where the detection of small molecules at low concentrations is needed. Here we report on a platform developed through the combination of Lab-On-Fiber probes with microgels, which are directly integrated onto the resonant plasmonic nanostructure realized on the fiber tip. In response to binding events, the microgel network concentrates the target molecule and amplifies the optical response, leading to remarkable sensitivity enhancement. Moreover, by acting on the microgel degrees of freedom such as concentration and operating temperature, it is possible to control the limit of detection, tune the working range as well as the response time of the probe. These unique characteristics pave the way for advanced label-free biosensing platforms, suitably reconfigurable depending on the specific application.

Optical fiber tip templating using direct focused ion beam milling.

We report on a method for integrating sub-wavelength resonant structures on top of optical fiber tip. Our fabrication technique is based on direct milling of the glass on the fiber facet by means of focused ion beam. The patterned fiber tip acts as a structured template for successive depositions of any responsive or functional overlay. The proposed method is validated by depositing on the patterned fiber a high refractive index material layer, to obtain a 'double-layer' photonic crystal slab supporting guided resonances, appearing as peaks in the reflection spectrum. Morphological and optical characterizations are performed to investigate the effects of the fabrication process. Our results show how undesired effects, intrinsic to the fabrication procedure should be taken into account in order to guarantee a successful development of the device. Moreover, to demonstrate the flexibility of our approach and the possibility to engineering the resonances, a thin layer of gold is also deposited on the fiber tip, giving rise to a hybrid photonic-plasmonic structure with a complementary spectral response and different optical field distribution at the resonant wavelengths. Overall, this work represents a significant step forward the consolidation of Lab-on-Fiber Technology.

Simple technique for integrating compact silicon devices within optical fibers.

In this work, we present a simple fabrication process enabling the integration of a subwavelength amorphous silicon layer inside optical fibers by means of the arc discharge technique. To assess our method, we have fabricated a compact in-line Fabry-Perot interferometer consisting of a thin (<1 µm) a-Si:H layer completely embedded within a standard single-mode optical fiber. The device exhibits low loss (1.3 dB) and high interference fringe visibility (~80%) both in reflection and transmission, due to the high refractive index contrast between silica and a-Si:H. A high linear temperature sensitivity up to 106 pm/°C is demonstrated in the range 120°C-400°C. The proposed interferometer is attractive for point monitoring applications as well as for ultrahigh-temperature sensing in harsh environments.

Offspring from endogamic vs. exogamic matings: Absence of anthropometric differences among Sardinian children (Italy).

This study evaluates possible differences in body dimensions among children from matings of different exogamy levels. The cross-sectional sample consisted of 867 children, 435 males, and 432 females, 6-10 years old, attending elementary schools in the metropolitan area of Cagliari, the capital of Sardinia (Italy). The children were divided into two groups according to the level of exogamy. The first group consisted of children of parents born in the same Sardinian municipality and was considered endogamous sensu stricto. The second group included children of parents born in municipalities from different Sardinian linguistic domains and was considered exogamous. The Mann-Whitney test did not reveal significant differences between the two groups of children in the mean rank values of the 36 anthropometric variables considered, with the exception of cephalic circumference in males and chest depth in females. In particular, there were no significant differences for anthropometric variables considered to be indirect indicators of nutritional status: sum of skinfolds, waist/hip ratio, body mass index, total upper arm area, upper arm muscle area, and upper arm fat area. The results indicate that Sardinian children from marriages of different exogamy levels do not differ in body dimensions if they grow up with similar nutritional and socioeconomic conditions.

Urinary endothelin excretion in patients with acute lung injury.

Increase in circulating levels of endothelin (ET), a potent vasoconstrictive and mitogenic endothelium-derived peptide, has been proposed as a marker of endothelium dysfunction in acute lung injury (ALI). In the present study, we have measured levels of immunoreactive ET (irET) by radioimmunoassay, in arterial (irETart), venous (irETven) and urine (irETur) samples obtained from 10 patients with ALI and 10 healthy volunteers. Arterovenous ratio, 24 h urine excretion and renal clearance of the peptide were calculated, to obtain indices of endogenous ET metabolism. The arterovenous ratio of irET was significantly higher in patients with ALI than in healthy volunteers (1.20 +/- 0.20 and 0.85 +/- 0.06, respectively; p < 0.05)). Twenty four hour urinary excretion of the peptide was increased in patients with ALI as compared to healthy volunteers (134.10 +/- 21.0 and 71.70 +/- 9.30 ng.24 h-1, respectively; p < 0.001). Renal clearance of irET was similar in patients with ALI and healthy volunteers, indicating that the increase in excretion as well as in arterovenous gradient observed in patients with ALI was related mainly to pulmonary abnormalities of peptide handling. Urinary excretion of endothelin might be a useful marker of endothelial dysfunction occurring in acute lung injury.

Endothelin abnormalities in patients with pulmonary embolism.

BACKGROUND: Endothelin (ET) is an endothelium-derived multifunctional peptide involved in the local regulation of the vascular tone. STUDY OBJECTIVES: To assess changes of endogenous ET production/excretion in the acute phase (36 h from the event) of pulmonary embolism (PE). PARTICIPANTS: Ten patients with acute PE, nine patients with acute lung injury (ALI), and 12 healthy volunteers (HVs). MEASUREMENTS AND RESULTS: ET was detected by radioimmunoassay in venous and arterial blood as well as in 24-h urine specimens. For each subject, arterial/venous immunoreactive ET (ir-ET) ratio was evaluated as an index of its pulmonary extraction/synthesis. Creatinine clearance was employed in each case to obtain a corrected renal ir-ET clearance. Renal ir-ET clearance was comparable in all three groups. Arterial/venous ir-ET ratio was comparable in PE and in ALI patients (1.31 +/- 0.25 vs 1.24 +/- 0.20; p = 0.7), while it was significantly higher in PE patients than in HV subjects (0.85 +/- 0.07; p = 0.0001). Accordingly, 24-h urine ir-ET excretion was higher in PE (120.50 +/- 27.36 ng/24 h) and ALI patients (135.80 +/- 21.60 ng/24 h) than in HV subjects (68.33 +/- 9.31 ng/24 h; p = 0.0001). CONCLUSIONS: Abnormalities of ET metabolism-mainly related to increased synthesis and/or defective pulmonary handling-occur in the acute phase of PE. The relevance of this finding with respect to the pathogenesis and/or management of pulmonary thromboembolism remains to be elucidated.

Lung volumes and respiratory muscle strength in adult patients with childhood- or adult-onset growth hormone deficiency: effect of 12 months' growth hormone replacement therapy.

We have described impairment of the respiratory function in adult patients with childhood-onset growth hormone (GH) deficiency. The aim of the present study was to evaluate lung volumes and respiratory muscle strength in patients diagnosed as GH deficient before and after 6 and 12 months of recombinant GH treatment. Ten adults diagnosed as GH deficient in childhood, ten adults diagnosed as GH deficient in adulthood and ten healthy subjects entered the study. For each subject, evaluation of respiratory function followed the same standard approach, consisting of respiratory muscle strength assessment, record of flow-volume curves, measurement of static lung volumes and lung diffusing capacity. Childhood-onset GH-deficient patients had a significant reduction of maximal inspiratory (p < 0.01) and maximal expiratory (p < 0.05) mouth pressures. Total lung capacity, vital capacity and functional residual capacity were significantly reduced compared to healthy subjects (p < 0.05). Conversely, residual volume and diffusing lung capacity did not show any significant change. No significant change of the ratio between the percentage forced expiratory volume in 1 s and the forced vital capacity was observed. The decrease of respiratory mouth pressures was not correlated to the decrease of lung volumes. Adult-onset GH-deficient patients had only a significant reduction of maximal expiratory pressure compared to healthy subjects (p < 0.05). After 6 months of treatment no significant differences in any of the evaluated parameters were found. After 12 months of treatment patients with childhood-onset GH deficiency show a significant improvement of lung volumes (p < 0.01) and maximal respiratory mouth pressures (p < 0.005), whereas adult-onset GH-deficient patients show a significant improvement of maximal expiratory pressure (p < 0.05). In conclusion, the results of this study showed that adult patients affected with childhood-onset GH deficiency suffer from an impairment of the ventilatory function due to a reduction of lung volumes and a decrease of respiratory pressures probably due to a reduction of respiratory muscle strength. This impairment was reversed after 12 months of treatment with recombinant GH. Conversely, adult-onset GH-deficient patients had only an impairment of the maximal expiratory pressure, probably due to respiratory muscle weakness re-established after 12 months of GH therapy.

Breathing and brain blood flow during sleep in patients with chronic mountain sickness.

Chronic mountain sickness (CMS) patients have lower arterial O2 saturation (SaO2) during sleep compared with healthy high-altitude residents, but whether nocturnal arterial O2 content (CaO2) and brain O2 delivery are reduced is unknown. We measured SaO2, CaO2, sleep-disordered breathing (SDB), and internal carotid artery flow velocity in 8 CMS patients, 8 age-matched healthy CMS controls, 11 healthy younger-aged Han, and 11 healthy younger-aged Tibetan male residents of Lhasa, Tibet (3,658 m). CMS patients spent a greater portion of the night in SDB (total no. of episodes of apnea, hypopnea, and hypoventilation) than did the CMS controls, young Han, or young Tibetans (15% vs. 5, 1, and 1%, respectively; P < 0.05) because of more frequent apnea and hypoventilation episodes and longer duration of all types of episodes. SDB and unexplained arterial O2 desaturation caused nocturnal SaO2 to be lower and more variable in CMS patients than in CMS controls or in younger-aged Han or Tibetan men. Average CaO2 was similar, but the CMS patients spent 29%, whereas the other groups spent < 4%, of the night at values < 18 ml O2/100 ml whole blood. Internal carotid artery flow velocity during wakefulness was similar in CMS patients and CMS controls despite higher end-tidal PcO2 values in the CMS patients. When contiguous sleep stages are compared, flow velocity rose from stage 2 to rapid-eye-movement sleep in both groups. Whereas flow velocity remained elevated from awake to rapid-eye-movement sleep in the CMS controls, it fell in the CMS patients. During episodes of SDB, internal carotid flow velocity increased in CMS controls but did not change in the CMS patients such that values were lower in the CMS patients than in CMS controls at the end and after SDB episodes. We concluded that SDB and episodes of unexplained desaturation lowered nocturnal SaO2 and CaO2, which, together with a lack of compensatory increase in internal carotid artery flow velocity, likely decreased brain O2 delivery in CMS patients during a considerable portion of the night.

IgA immune response against the mycobacterial antigen A60 in patients with active pulmonary tuberculosis.

Searching for IgG and IgM against the mycobacterial antigen A60 has been recognized as a potential diagnostic tool for pulmonary tuberculosis. The role of detection of anti-A60 IgA in improving diagnostic accuracy of serology is not well known. In this study we measured with ELISA serum levels of both anti-A60 IgG and IgA in 216 subjects. 88 healthy volunteers (44 PPD- and 44 PPD+), 44 patients suffering from nontuberculous lung disease and 15 subjects with healed pulmonary tuberculosis constituted the control population; 69 patients with active pulmonary tuberculosis (35 cavitary forms, 26 productive forms and 8 miliary forms) were examined. The sensitivity of IgG test was 73.9% in pulmonary tuberculosis (77.1% in cavitary forms, 65.4% in productive forms, 87.5% in miliary forms); the specificity of the test was 95.9%. For the IgA test we observed a sensitivity of 72.5% (74.3 in cavitary forms, 69.2% in productive forms, 75.0 in miliary forms) and a specificity of 93.9%. Combination of the two tests increased the sensitivity to 84.0% (+10.1% compared to IgG test, +11.5% compared to IgA test); the specificity decreased to 92.5% (-3.4% vs. IgG test; -1.4 vs. IgA test). In conclusion, the combined use of evaluation of anti-A60 IgG and IgA increases the accuracy of serological diagnosis of pulmonary tuberculosis.

Impairment of lung volumes and respiratory muscle strength in adult patients with growth hormone deficiency.

Little is known of the respiratory function in patients with growth hormone (GH) deficiency. The aim of the present study was to evaluate lung volumes and respiratory muscle strength in patients diagnosed as GH deficient in childhood. Ten patients diagnosed as GH deficient in childhood and ten healthy subjects entered the study. For each subject the evaluation of respiratory function followed the same standard approach, consisting of respiratory muscle strength assessment, recording of flow-volume curves, measurement of static lung volumes and lung diffusing capacity. Both maximal inspiratory and expiratory mouth pressures were decreased in GH deficiency. Vital capacity, N2 functional residual capacity and total lung capacity were significantly reduced when compared to healthy subjects. Conversely, the residual volume and diffusing lung capacity to CO did not show any significant change. No significant change of percentage forced expiratory volume in 1 s/forced vital capacity ratio was observed. The decrease of respiratory mouth pressures was not correlated to the decrease of lung volumes. In conclusion, the results of this study show that adult patients affected with childhood onset GH deficiency suffer from impairment of ventilatory function and a decrease of respiratory muscle pressures, probably due to reduction of respiratory muscle strength.

[Changes of lung volumes and respiratory muscle strength in patients with growth hormone deficiency]. / Modificazioni dei volumi polmonari e della forza muscolare respiratoria in pazienti con deficit dell'ormone della crescita.

The relationship between growth hormone deficiency (GHd) and ventilatory function is not well understood. We studied 7 patients with GHd since childhood who had been adequately treated with replacement therapy until cartilage fusion. Together with 7 well-matched (age and body-type) healthy control subjects, they underwent spirometry including determination of residual volume, and lung diffusing capacity. Also recorded were maximal respiratory muscle pressure during inspiration (PImax) and expiration (PEmax). Patients with GHd showed a significant reduction in total lung capacity and vital capacity while residual volume and lung diffusing capacity remained unchanged. All patients had a significant reduction of both PImax and PEmax. Previously treated adult subjects with GHd present a persistent decrease in lung mobilizing volumes associated with reduced respiratory muscle strength. These alterations may have implications in the management of GHd in adult patients.

Speech-evoked cognitive P300 potentials in cochlear implant recipients.

The cognitive P300 evoked potential was elicited by speech stimuli in successful cochlear implant recipients, and the resulting P300 morphology was remarkably similar to that of normal-hearing individuals. The P300 was elicited by the synthesized speech pair/da/and/di/ presented using an oddball paradigm to nine "good" Nucleus cochlear implant users and nine age-matched normal-hearing subjects (34-81 yr old). There were no significant differences in P300 amplitude and latency between the two groups. Moreover, the N1 and P2 potentials occurred at similar latencies in the two groups, although the N1 amplitude was significantly smaller in the cochlear implant users. The P300 was absent in one "poor" cochlear implant user. The results suggest that the P300 may serve as a useful tool for evaluating the cognitive aspects of auditory processing in cochlear implant recipients, and that it may aid in assessing the success of cochlear implantation.

Case manager attitudes toward client-directed care.

Advocates for individuals with severe and long-term physical disabilities have lobbied aggressively in the U.S. and Canada for the implementation of Independent Provider Care (IPC). In this model of home support service delivery, the client assumes sole responsibility for the management and scheduling of his or her personal care and home support. This article reports on the findings of a Canadian survey that assessed case managers' beliefs regarding the efficacy, benefits, and risks to clients of an IPC program. Survey results indicated that case managers generally believed that IPC would not significantly improve their clients' well-being and quality of care, would pose risks of abuse to both the client and support attendant, and would result in greater job demands for case managers. Possible sources of their apprehension are identified, and measures that may help to alleviate their concerns are discussed.

Spontaneous cerebrospinal fluid leaks in congenital and acquired temporal bone defects-a long-term follow-up.

Twelve patients presenting with tegmen defects and requiring surgical repair were retrospectively reviewed from 1982 to 1993. One half of the patients presented with a cerebrospinal fluid leak at some time in the course of their illness. Nine cases were considered to be acquired, secondary to previous mastoid surgery or trauma. All 9 had encephalocoeles. Three spontaneous leaks were considered congenital; 2 of these patients had encephalocoeles. This report represents a long-term follow-up of these cases, with an average follow-up of 7,6 years. Computed tomography and magnetic resonance imaging technology, as well as contrast studies, have tremendously aided in diagnosis and planning of surgical repair. Nine repairs were done through a dual transmastoid and middle fossa approach, with the other 3 done via a transmastoid approach only. We favored temporalis muscle flaps and temporalis fascia over synthetic materials for defect repairs. The long-term results and complications are discussed.

Speech-evoked cortical potentials in children.

Event-related potentials (ERPs) were obtained to synthesized speech stimuli in 16 school-aged children (7-11 years) and compared to responses in 10 adults. P1, N1, and P2 event-related potentials were elicited by the phoneme /ga/. The mismatch negativity (MMN) was elicited by variants of /da/ and /ga/, which differ in the onset frequency of the second and third formant transitions. In general, the well-defined N1/P2 complex characteristic of the adult response, was not found in children. Waves P1 and N1 had longer peak latencies in children than in adults. Wave P2 amplitude was smaller in children than in adults. In contrast to the often poorly delineated earlier cortical potentials, the MMN was well defined in children. Significant MMNs were obtained in all subjects tested. MMN magnitude (peak amplitude and area) was significantly larger in the children. No significant differences were found in peak latency and duration of the MMN in children compared to the adult response. Another negative wave occurring at 400 msec was also observed in response to the deviant stimuli. This negative wave occurred at a similar latency in adults and children and was significantly larger and more robust in children. Results support the view that development of ERPs does not involve a hierarchical process with respect to latency. That is, earlier occurring waves do not necessarily mature before later occurring waves. The latencies of P1, N1, and P2 and overall morphology of these waves may provide a measure of maturation of central pathways. The early development of the MMN, its apparent robustness in school-aged children, and its reflection of the processing of acoustic differences in speech stimuli suggest its possible use in the assessment of central auditory function.

Mismatch negativity in school-age children to speech stimuli that are just perceptibly different.

The mismatch negativity event-related potential (MMN) was elicited in normal school-age children in response to just perceptibly different variants of the speech phoneme /da/. A significant MMN was measured in each subject tested. Child and adult MMNs were similar with respect to peak latency and duration. Measures of MMN magnitude (peak-to-peak amplitude and area) were significantly larger in children than in adults. The results of the present study indicate that the MMN can be elicited in response to minimal acoustic stimulus differences in complex speech signals in school-age children. The results support the feasibility of using the MMN as a tool in the study of deficient auditory perception in children.