Combined pulses of light and sound in the retina with nutraceuticals may enhance the recovery of foveal holes.

The present manuscript stems from evidence, which indicates that specific wavelength produce an activation of the autophagy pathway in the retina. These effects were recently reported to synergize with the autophagy-inducing properties of specific phytochemicals. The combined administration of photo-modulation and phytochemicals was recently shown to have a strong potential in eliciting the recovery in the course of retinal degeneration and it was suggested as a non-invasive approach named "Lugano protocol" to treat age-related macular degeneration (AMD). Recent translational findings indicate that the protective role of autophagy may extend also to acute neuronal injuries including traumatic neuronal damage. At the same time, very recent investigations indicate that autophagy activation and retinal anatomical recovery may benefit from sound exposure. Therefore, in the present study, the anatomical rescue of a traumatic neuronal loss at macular level was investigated in a patient with idiopathic macular hole by using a combined approach of physical and chemical non-invasive treatments. In detail, light exposure was administered in combination with sound pulses to the affected retina. This treatment was supplemented by phytochemicals known to act as autophagy inducers, which were administered orally for 6 months. This combined administration of light and sound with nutraceuticals reported here as Advanced Lugano's Protocol (ALP) produced a remarkable effect in the anatomical architecture of the retina affected by the macular hole. The anatomical recovery was almost complete at roughly one year after diagnosis and beginning of treatment. The structural healing of the macular hole was concomitant with a strong improvement of visual acuity and the disappearance of metamorphopsia. The present findings are discussed in the light of a synergism shown at neuronal level between light and sound in the presence of phytochemicals to stimulate autophagy and promote proliferation and neuronal differentiation of retinal stem cells.

Noradrenergic substrates sensing light within brainstem reticular formation as targets for light-induced behavioral and cardiovascular plasticity.

The occurrence of pure light exerts a variety of effects in the human body, which span from behavioral alterations, such as light-driven automatic motor activity, cognition and mood to more archaic vegetative functions, which encompass most organs of the body with remarkable effects on the cardiovascular system. Although empirical evidence clearly indicates occurrence of these widespread effects, the anatomical correlates and long-lasting changes within putatively specific neuronal circuitries remain largely unexplored. A specific role is supposed to take place for catecholamine containing neurons in the core of the brainstem reticular formation, which produces a widespread release of noradrenaline in the forebrain while controlling the vegetative nervous system. An indirect as well as a direct (mono-synaptic) retino-brainstem pathway is hypothesized to rise from a subtype of intrinsically photosensitive retinal ganglion cells (iPRGCs), subtype M1, which do stain for Brn3b, and project to the pre-tectal region (including the olivary pre-tectal nucleus). This pathway provides profuse axon collaterals, which spread to the periacqueductal gray and dorsal raphe nuclei. According to this evidence, a retino-reticular monosynaptic system occurs, which powerfully modulate the noradrenergic hub of reticular nuclei in the lateral column of the brainstem reticular formation. These nuclei, which are evidenced in the present study, provide the anatomical basis to induce behavioral and cardiovascular modulation. The occurrence of a highly interconnected network within these nuclei is responsible for light driven plastic effects, which may alter persistently behavior and vegetative functions as the consequence of long-lasting alterations in the environmental light stimulation of the retina. These changes, which occur within the core of an archaic circuitry such as the noradrenaline-containing neurons of the reticular formation, recapitulate, within the CNS, ancestral effects of light-driven changes, which can be detected already within the retina itself at the level of multipotent photic cells.

The potential effects of nutrients and light on autophagy-mediated visual function and clearance of retinal aggregates.

Increasing findings indicate that a dysfunction in the autophagy machinery is common during retinal degeneration. The present article provides evidence showing that an autophagy defect in the outer retinal layers is commonly described at the onset of retinal degeneration. These findings involve a number of structures placed at the border between the inner choroid and the outer retina encompassing the choriocapillaris, the Bruch's membrane, photoreceptors and Mueller cells. At the center of these anatomical substrates are placed cells forming the retinal pigment epithelium (RPE), where autophagy seems to play most of its effects. In fact, a failure of the autophagy flux is mostly severe at the level of RPE. Among various retinal degenerative disorders, age-related macular degeneration (AMD) is mostly affected by a damage to RPE, which can be reproduced by inhibiting the autophagy machinery and it can be counteracted by the activation of the autophagy pathway. In the present manuscript evidence is provided that such a severe impairment of retinal autophagy may be counteracted by administration of a number of phytochemicals, which possess a strong stimulatory activity on autophagy. Likewise, natural light stimulation administered in the form of pulsatile specific wavelengths is capable of inducing autophagy within the retina. This dual approach to stimulate autophagy is further strengthened by the interaction of light with phytochemicals which is shown to activate the chemical properties of these natural molecules in sustaining retinal integrity. The beneficial effects of photo-biomodulation combined with phytochemicals is based on the removal of toxic lipid, sugar and protein species along with the stimulation of mitochondrial turn-over. Additional effects of autophagy stimulation under the combined effects of nutraceuticals and light pulses are discussed concerning stimulation of retinal stem cells which partly correspond to a subpopulation of RPE cells.

Retinal Degeneration Following Chronic Administration of the Parkinsonism-Inducing Neurotoxin MPTP.

During late stages, retinal degenerative disorders affecting photoreceptors progress independently from the specific disease trigger. In fact, a number of detrimental consequences occur downstream of photoreceptors, which are triggered by the loss of photoreceptors themselves. Such downstream anatomical alterations were originally thought to be compensatory events aimed to restore retinal function. At present, these phenomena are deciphered as detrimental effects and the term retinal degeneration is used to indicate the loss of cells and architecture within the inner retina as a consequence of damage to photoreceptors. In the process of testing a photoreceptor-dependent downstream spreading of neurodegeneration we applied a neurotoxin mimicking Parkinson's disease (PD), 1-methyl, 4-phenyl, 1,2,3,6-tetrahydropyridine (MPTP). Chronic MPTP administration produces degeneration within the mouse retina. This is evident by apoptosis quite circumscribed to photoreceptors, which is reminiscent of most phenotypes of retinal degeneration. Retinal pathology following plain HE histochemistry is more widespread with delamination and loss of neuronal packaging in the inner retina. The retinal damage is characterized by a marked synucleinopathy mostly within retinal ganglion cells. In contrast, dopamine-containing structures are intact while norepinephrine is significantly reduced. Despite the involvement of the retina in PD is documented, no study so far analyzed the onset of a synucleinopathy and a degenerative process mimicking what is now recognized in typical retinal degeneration. The present data provide a novel vista on the reciprocal role of the retina in neurodegenerative disorders.

Exosomes and alpha-synuclein within retina from autophagy to protein spreading in neurodegeneration.

In the course of age-related macular degeneration (AMD) as well as in multiple retinal disorders protein aggregates are described at various levels in the retina. In AMD this fills the space between retinal pigment epithelium (RPE) in the form of drusen, which contains amyloid and other protein aggregates along with lipids. Nonetheless, in very advanced stages of AMD, as well as in other retinal pathologies and early on in retinitis pigmentosa, a number of neuronal inclusions, which stain for α-synuclein spreads all over the retinal layers. Thus, an early or later defect in the clearance of α-synuclein may represent a final common pathway to these phenomena. The physiological clearance of α-synuclein is provided by the autophagy machinery starting at the level of the RPE and occurring throughout the retina. Such a process is also involved in the clearance of melanin-dependent toxic metabolites under the effects of different wavelengths and the stimulatory activity of the sympathetic nervous system. In search for the occurrence of these culprits, here we report the presence of α-synuclein in the retina combined with exosomal detection to document the presence of a α-synuclein spreading apparatus. This was correlated with the occurrence of autophagy markers throughout retinal layers, along with sympathetic innervation, which in turn was related to melanin content.

The neurobiology of nutraceuticals combined with light exposure, a case report in the course of retinal degeneration.

The present article presents a case report and discusses the neurobiology underlying the potential neuro-repair induced by combined administration of phytochemicals in a patient undergoing photo-bio-modulation (PBM), which improves anatomical and clinical abnormalities in the course of age-related macular degeneration (AMD). After combined treatments the patient with nutraceuticals and PBM had noticeable improvement of retinal tissue with excellent vision for her age and no worsening of corneal guttae, which was present at the time of diagnosis. The present treatment was tailored, based on translational evidence, to improve the autophagy pathway, which is a key determinant in the onset and progression of AMD. In fact, treatment with specific patterns of light exposure combined with specific phytochemicals, may synergize in improving the microanatomy of the retina by restoring its neurobiology. The combination of light exposure, at selective wavelengths, with the effects produced by the intake of specific phytochemicals to treat AMD is reported here as "Lugano Protocol". Such a clinical protocol represents an "in progress" development backed up by translational research. In fact, recent evidence indicates that, specific phytochemicals, when administered in combination may promote anatomical and functional integrity within the retina. These in turn synergize with analogous effects produced by specific wavelengths, when administered at specific time intervals. The synergism between specific light and combined phytochemicals is discussed at molecular level, where recent data indicate how these treatments, when delivered according to specific patterns, may enhance autophagy in the retina. The improvement of retinal morphology and visual acuity, observed in this case report is thoroughly discussed in the light of the key role of autophagy in regulating the integrity of the retinal epithelium. Despite exciting, and consistent with translational evidence, the clinical report of a disease modifying effect during AMD owns the inherent limit of a case report, which requires wide validation in large number of patients. The potential effectiveness of "Lugano protocol" may apply to other types of retinal degenerations, where common alterations in the autophagy pathway do occur. Thus, such a therapeutic approach may extend to a common late stage of retinal trans-synaptic degeneration, where maladaptive plasticity during several types of retinal degenerative disorders eventually converge.

Nutraceuticals for dry age-related macular degeneration: a case report based on novel pathogenic and morphological insights.

Age-related macular degeneration represents the main retinal disorder leading to irreversible blindness in people over the age of 50 in the Western World. Here we describe a case report, which suggest that specific nutraceutical compounds may exert beneficial effects on the progression of dry age-related macular degeneration (AMD), an eye disease with no approved treatment or cure. Specific antioxidants, such as lutein, resveratrol and Vaccinium Myrtillus, which are known to reduce the risk of developing AMD, when co-administered alone, were supplemented to diet of an informed patient suffering from dry AMD. The case report indicates an improvement of visual acuity and a long lasting decrease in druse volume and number. The concomitant intake of lutein, resveratrol and Vaccinium Myrtillus when administered for six months produced a marked decrease in the drusen observed at OCT at the 6-month follow-up. At this time interval, the patient experienced a noticeable improvement in visual acuity, a decrease in eye strain, more color contrast, higher visual definition. The case report indicates the potential benefit for a non-invasive treatment with improved quality of vision in dry AMD. A larger population followed over a long-term period is warranted. The support of nutraceuticals could therefore offer a new non-invasive, adverse effect-free which may restore the pathology affecting the cross talk between choroid and retinal cells. The results of this case report are discussed within the frame of molecular mechanisms synergizing site-specifically at the anatomical border between the outer retina and inner choroid.

Measurement of drusen and their correlation with visual symptoms in patients affected by age-related macular degeneration.

Age-related macular degeneration (AMD) is a common retinal disorder, which became more and more prevalent in the last decades. AMD is now the most prevalent cause of blindness in the western world. The disorder is classified into two phenotypes named dry and wet AMD. This is based on the recruitment of novel blood vessels and inflammatory exudates in wet AMD. In both phenotypes, the pathological hallmark is the presence of proteinaceous aggregates called drusen, which mostly accumulate between the choroid and the retinal pigment. Drusen in dry AMD represent the evident pathological finding although they are present, though less defined, in wet AMD. In AMD drusen are supposed to be a pathogenic trigger of the disorder. In fact, drusen may mechanically alter retinal function. A novel hypothesis exists, suggesting that a metabolic defect (systemic or focal within the retinal pigment epithelium) may be the real determinant of visual impairment, while causing the concomitant accumulation of proteinaceous debris and lipids forming the drusen. Here we face such an issue by analyzing the retinal anatomy to correlate visual impairment with the occurrence of drusen number, size and the extent of a drusenoid area in the foveal region. A comparison is made with wet AMD where new vessels and retinal exudates prevail. The study is carried out in 120 patients affected by dry or wet AMD and 21 patients where paradoxical findings are described. The main question consists in inferring whether the occurrence of visual impairment is due, in fact, to a drusen-dependent mechanical damage or drusen just occurs as an independent consequence of an upstream metabolic alteration, which concomitantly impairs the visual process. The present data indicate that, despite a significant difference in visual function between mild and severe AMD patients in the amount of drusen exists, a strong correlation between drusen and visual impairment does not occur. This suggests that drusen and visual deterioration develop as a consequence of similar upstream biochemical alterations but it is likely that drusen do not produce visual deterioration. This is strengthened here by extreme clinical conditions, where visual impairment is severe with a slight alteration in the planar pattern of the retina or, vice versa an extended drusenoid area occurs concomitantly with fair visual acuity, contrast sensitivity and lack of metamorphopsia. A biochemical analysis of key areas in the function of specific domains in the pigment epithelium as described in the accompanying manuscript should help to better disclose the real morpho-functional deficit, which takes place in AMD.

Quality indicators in breast cancer care.

To define a set of quality indicators that should be routinely measured and evaluated to confirm that the clinical outcome reaches the requested standards, Eusoma has organised a workshop during which twenty four experts from different disciplines have reviewed the international literature and selected the main process and outcome indicators available for quality assurance of breast cancer care. A review of the literature for evidence-based recommendations have been performed by the steering committee. The experts have identified the quality indicators also taking into account the usability and feasibility. For each of them it has been reported: definition, minimum and target standard, motivation for selection and level of evidence (graded according to AHRO). In overall 17 main quality indicators have been identified, respectively, 7 on diagnosis, 4 on surgery and loco-regional treatment, 2 on systemic treatment and 4 on staging, counselling, follow-up and rehabilitation. Breast Units in Europe are invited to comply with these indicators and monitor them during their periodic audit meetings.

Does nipple preservation in mastectomy improve satisfaction with cosmetic results, psychological adjustment, body image and sexuality?

We investigated the influence of nipple areolar complex (NAC) sparing in mastectomy, on patient satisfaction with cosmetic results, body-image, sexuality and psychological well-being. We developed a specific questionnaire and compared two groups of women who underwent radical mastectomy with immediate breast reconstruction (IBR). Between 2004 and 2006, 310 women with NAC preservation and 143 patients with successive NAC reconstruction were mailed the questionnaire at follow-up 1 year after definitive complete breast reconstruction surgery. 256 questionnaires was available. Our results showed significant differences in favour of the NAC sparing group regarding body image (difficulty in looking at themselves naked and being seen naked by their partners after surgery, P = 0.001 and P = 0.003, respectively); regarding satisfaction with the appearance of the nipple (P < .0001) and with the sensitivity of the nipple (P = 0.001); regarding the feeling of mutilation (P = 0.003). NAC sparing in mastectomy has a positive impact on patient satisfaction, body image and psychological adjustment.

Assessment of quality of care in an oncology institute using information on patients' satisfaction.

OBJECTIVE: To evaluate the feasibility of conducting a patient satisfaction survey in the oncology hospital setting, using a multidimensional patient satisfaction questionnaire to be completed at home. METHODS: Socio-demographic and clinical data were collected for 133 consecutive patients. Patients were asked to complete the European Organisation for Research and Treatment of Cancer QLQ-C30 (version 2.0) just before hospital discharge and the Comprehensive Assessment of Satisfaction with Care at home 2 weeks after discharge. RESULTS: Respondents (73% of patients approached) were younger, hospitalized for a shorter time and presented less appetite loss, nausea and vomiting and better physical and role functioning than non-responders. The aspects of care for which patients wanted the most improvement were associated with the provision of medical information. In multivariate analyses, longer hospital stay was associated with higher satisfaction with all aspects of medical and nursing care, most probably because patients discharged early were not assured of continuity of care and lacked information regarding self-care at home. Higher global quality of life was associated with higher satisfaction with all aspects of care, suggesting the potential contribution of patient satisfaction to the patients' well-being. CONCLUSIONS: Conducting a patient satisfaction survey in an oncology hospital setting proved feasible; however, further surveys should attempt to obtain the opinion of patients with more severe physical conditions. The assessment of the patients' satisfaction provided indications for improvement of care in a particular hospital. Although the results of this study are specific to one hospital, the methods could be reproduced in other hospital settings, but may possibly lead to other conclusions.

Psychological distress in cancer patients attending the European Institute of Oncology in Milan.

BACKGROUND: The determination of the extent and specific features of the psychological distress to be expected in a cancer centre may influence the choice of interventions to be implemented for addressing these problems. This study was aimed at estimating the prevalence of psychological distress in patients attending a second reference cancer centre in Milan (Italy), and at identifying associated factors. PATIENTS AND METHODS: 190 consecutive patients were assessed within 3 days of hospital discharge using the Hospital Anxiety and Depression Scale. RESULTS: Major depressive disorders or generalised anxiety disorders were estimated in 16% of the patients. Only 2 of these patients were referred to the psycho-oncology unit, hence the psychological distress of many patients was not considered during their hospital stay. In the multiple regression analysis, independent predictors of psychological distress were female gender, experience of disturbance in family and social life due to illness, nausea and vomiting, and perception of being in a poor state of health (R(2) = 0.31, p value < 0.001), while physical functioning, fatigue and pain, significant factors in univariate analysis (p < 0. 05), sociodemographic and clinical factors were not predictors. CONCLUSIONS The psycho-oncology team should focus on helping doctors and nurses identify the patients' psychological problems, dealing with them or making a referral.

A comprehensive assessment of satisfaction with care: preliminary psychometric analysis in an oncology institute in Italy.

BACKGROUND: Little is known about patients' perception of the quality of the care they receive in oncology hospitals. We developed a 61-item comprehensive assessment of satisfaction with care (CASC) to evaluate the competence of hospital physicians and nurses, as well as aspects of care organisation and hospital environment. The aims of this study were to define the structure of the CASC and assess the internal consistency and convergent and discriminant validity of its scales. PATIENTS AND METHODS: Three hundred ninety-five consecutive cancer patients discharged from an oncology institute in Italy were asked to complete the CASC at home and return it in a self-addressed envelope. RESULTS: Two percent of the patients refused to participate and 25% failed to return the questionnaire. Separate factor analyses of the CASC sub-scales disclosed the perceived extent of doctors' and nurses' availability, coordination, human quality, technical competence, provision of psychosocial care and information, as well as the patients' general satisfaction, perception of the organisation of their care, access and comfort. Multi-trait scaling analysis was carried out on item-grouping resulting from factor analyses. High levels of internal consistency and convergent validity were obtained but discriminant validity could be improved. CONCLUSIONS: Results of present psychometric testing of the CASC forecast adequate properties. This will be confirmed by repeating these analyses in a cross-cultural setting.