Peripheral Vision in Patients Following Intraocular Lens Implantation: A Systematic Review and Meta-Analysis.

PURPOSE: To update the literature on peripheral optics and vision following intraocular lens (IOLs) implantation. METHODS: We investigated how current IOLs influence peripheral visual function, peripheral optical quality, and visual perception and performance, in patients following cataract surgery. Peripheral vision is described as vision outside the central foveal region of the eye (beyond 4-5° of eccentricity). We systematically searched PubMed, Cochrane Central Register of Controlled Trials, Embase, and gray literature for relevant references. Randomized controlled trials and observational studies were eligible for inclusion. Finally, 47 studies with a total of 5963 participants were eligible for this review, of which 15 were included in the meta-analysis. RESULTS: Regarding visual fields, the meta-analysis showed that the pooled estimate of mean deviation (MD) measured with perimetry tests (standard automated perimetry [SAP], short-wavelength automated perimetry [SWAP], and frequency doubling technology [FDT]) appears to be lower than the mean of healthy age-matched controls, regardless of IOL design. Results for pooled estimate show that localized defects (pattern standard deviation [PSD]) were higher than those in the healthy age-matched controls for FDT. We also collected evidence demonstrating that pseudophakia increases peripheral astigmatism and a myopic shift from 20° onward, leading to decreased peripheral image quality compared with that in phakic eyes. Patient-reported outcomes on peripheral vision showed a pooled score estimate of 95.19, indicating high satisfaction, and for the Steps & Stairs questions, a pooled score estimate at 0.23, indicating no to little difficulty seeing steps and stairs. CONCLUSIONS: Peripheral image quality is degraded in eyes after cataract surgery. Nevertheless, whether this degradation leads to impaired visual function in the periphery requires further investigation.

Comparison of Quality of Life before and after pancreaticoduodenectomy: a prospective study.

BACKGROUND: Pancreatic cancer is an aggressive malignancy, and surgical resection is the only therapeutic option with pancreaticoduodenectomy being considered the standard of care. It is essential to take into account the patients' Quality of Life after the resection, in order to make more informed decisions about treatment options. OBJECTIVE: The aim of the study was to determine perceived Quality of Life levels among patients who undergo pancreaticoduodenectomy, in a period of six months after surgery. METHODS: This prospective study was conducted on all patients (n=40) who underwent pancreaticoduodenectomy in Attikon University General Hospital in Athens, Greece, from January 2013 to June 2015. The Quality of Life was assessed by use of EORTC QLQ-C30 and EORTC QOL-PAN26 questionnaires at four phases: First, after admission at the hospital preoperatively, and then one month, three months, and six months postoperatively. Repeated measurements analysis of variance (ANOVA) was used in order to evaluate changes in Quality of Life measures during the follow-up (postoperative) period. Data analysis was conducted using SPSS version 19. A p-value of less than or equal to 0.05 was set as the level of significance. RESULTS: The study revealed a mixed image. Except for the nausea and vomiting scale, where indeed a symptom increase is initially reported and then gradually decreases below preoperative levels by 6 months, scoring in many symptom scales worsens postoperatively. From first to fourth assessment, fatigue (Mean from 23.61 to 38.72, p=0.005) and financial difficulties scoring (Mean from 5.98 to 42.42, p<0.001) consistently worsen. Functionality scales scoring also tends to get worse between first and fourth assessment, with statistically significant changes for physical (p<0.001), role (p<0.001) and social functioning (p<0.001). However, a slight improvement can be noted in many scales from third to fourth assessment, as in diarrhea (Mean from 32.38 to 29.29), pancreatic pain (Mean from 17.71 to 2.34), global health status (Mean from 50.48 to 52.53) and social functioning (Mean from 43.81 to 48.48) scales. CONCLUSIONS: Quality of Life levels among patients who undergo pancreaticoduodenectomy are getting worse following surgery. However, the longitudinal study of these changes may improve patients' postoperative life by formulating evidence-based interventions concerning symptoms treatment and psychological and social support.

Loss of Lypd6 leads to reduced anxiety-like behaviour and enhanced responses to nicotine.

Nicotine consumption through smoking affects anxious states in humans. However, the precise role of nicotinic acetylcholine receptor (nAChR) circuitry in the regulation of anxiety remains elusive. The Lynx protein Lypd6 is highly enriched in synaptic loci and has been previously identified as an endogenous inhibitor of neuronal nAChR function in vitro. Here, we investigate the effect of Lypd6 in anxiety-related behaviour and examine the molecular underpinnings of its function in the brain. We employ the marble burying (MB) and elevated zero maze (EZM) tests in Lypd6 knock-out (KO) and wild-type (WT) mice and find that loss of Lypd6 leads to decreased digging behaviour in the MB test and increased time spent in the open area in the EZM test. Moreover, we demonstrate that acute nicotine administration reduces digging in the MB test in both KO and WT mice and further accentuates the inherent genotype difference. Using in vitro electrophysiology in dorsal raphe nuclei (DRN) neurons from Lypd6 KO mice, we show that nicotine-evoked whole-cell currents are enhanced in the absence of Lypd6. Collectively, these data are the first to indicate the involvement of Lypd6 in circuits associated with anxiety and suggest that a possible underlying neurobiological mechanism is the modulation of cholinergic responses in the DRN.

Lynx1 and Aß1-42 bind competitively to multiple nicotinic acetylcholine receptor subtypes.

Lynx1 regulates synaptic plasticity in the brain by regulating nicotinic acetylcholine receptors (nAChRs). It is not known to which extent Lynx1 can bind to endogenous nAChR subunits in the brain or how this interaction is affected by Alzheimer's disease pathology. We apply affinity purification to demonstrate that a water-soluble variant of human Lynx1 (Ws-Lynx1) isolates α3, α4, α5, α6, α7, ß2, and ß4 nAChR subunits from human and rat cortical extracts, and rat midbrain and olfactory bulb extracts, suggesting that Lynx1 forms complexes with multiple nAChR subtypes in the human and rodent brain. Incubation with Ws-Lynx1 decreases nicotine-mediated extracellular signal-regulated kinase phosphorylation in PC12 cells and striatal neurons, indicating that binding of Ws-Lynx1 is sufficient to inhibit signaling downstream of nAChRs. The effect of nicotine in PC12 cells is independent of α7 or α4ß2 nAChRs, suggesting that Lynx1 can affect the function of native non-α7, non-α4ß2 nAChR subtypes. We further show that Lynx1 and oligomeric ß-amyloid1-42 compete for binding to several nAChR subunits, that Ws-Lynx1 prevents ß-amyloid1-42-induced cytotoxicity in cortical neurons, and that cortical Lynx1 levels are decreased in a transgenic mouse model with concomitant ß-amyloid and tau pathology. Our data suggest that Lynx1 binds to multiple nAChR subtypes in the brain and that this interaction might have functional and pathophysiological implications in relation to Alzheimer's disease.

Functional interaction between Lypd6 and nicotinic acetylcholine receptors.

Nicotinic acetylcholine receptors (nAChRs) affect multiple physiological functions in the brain and their functions are modulated by regulatory proteins of the Lynx family. Here, we report for the first time a direct interaction of the Lynx protein LY6/PLAUR domain-containing 6 (Lypd6) with nAChRs in human brain extracts, identifying Lypd6 as a novel regulator of nAChR function. Using protein cross-linking and affinity purification from human temporal cortical extracts, we demonstrate that Lypd6 is a synaptically enriched membrane-bound protein that binds to multiple nAChR subtypes in the human brain. Additionally, soluble recombinant Lypd6 protein attenuates nicotine-induced hippocampal inward currents in rat brain slices and decreases nicotine-induced extracellular signal-regulated kinase phosphorylation in PC12 cells, suggesting that binding of Lypd6 is sufficient to inhibit nAChR-mediated intracellular signaling. We further show that perinatal nicotine exposure in rats (4 mg/kg/day through minipumps to dams from embryonic day 7 to post-natal day 21) significantly increases Lypd6 protein levels in the hippocampus in adulthood, which did not occur after exposure to nicotine in adulthood only. Our findings suggest that Lypd6 is a versatile inhibitor of cholinergic signaling in the brain, and that Lypd6 is dysregulated by nicotine exposure during early development. Regulatory proteins of the Lynx family modulate the function of nicotinic receptors (nAChRs). We report for the first time that the Lynx protein Lypd6 binds to nAChRs in human brain extracts, and that recombinant Lypd6 decreases nicotine-induced ERK phosphorylation and attenuates nicotine-induced hippocampal inward currents. Our findings suggest that Lypd6 is a versatile inhibitor of cholinergic signaling in the brain.

Nicotinic Acetylcholine Receptors in the Pathophysiology of Al zheimer's Disease: The Role of Protein-Protein Interactions in Current and Future Treatment.

Nicotinic acetylcholine receptors (nAChRs) have been pursued for decades as potential molecular targets to treat cognitive dysfunction in Alzheimer's disease (AD) due to their positioning within regions of the brain critical in learning and memory, such as the prefrontal cortex and hippocampus, and their demonstrated role in processes underlying cognition such as synaptic facilitation, and theta and gamma wave activity. Historically, activity at these receptors is facilitated in AD by use of drugs that increase the levels of their endogenous agonist acetylcholine, and more recently nAChR selective ligands have undergone clinical trials. Here we discuss recent findings suggesting that the expression and function of nAChRs in AD may be regulated by direct interactions with specific proteins, including Lynx proteins, NMDA-receptors and the Wnt/ß-catenin pathway, as well as ß-amyloid. The ability of protein interactions to modify nAChR function adds a new level of complexity to cholinergic signaling in the brain that may be specifically altered in AD. It is currently not known to what degree current nAChR ligands affect these interactions, and it is possible that the difference in the clinical effect of nAChR ligands in AD is related to differences in their ability to modulate nAChR protein interactions, rather than their effects on ion flow through the receptors. Drugs designed to target these interactions may thus provide a new avenue for drug development to ameliorate cognitive symptoms in AD. Notably, the development of experimental drugs that specifically modulate these interactions may provide the opportunity to selectively affect those aspects of nAChR function that are affected in AD.

Prostate stem cell antigen interacts with nicotinic acetylcholine receptors and is affected in Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder involving impaired cholinergic neurotransmission and dysregulation of nicotinic acetylcholine receptors (nAChRs). Ly-6/neurotoxin (Lynx) proteins have been shown to modulate cognition and neural plasticity by binding to nAChR subtypes and modulating their function. Hence, changes in nAChR regulatory proteins such as Lynx proteins could underlie the dysregulation of nAChRs in AD. Using Western blotting, we detected bands corresponding to the Lynx proteins prostate stem cell antigen (PSCA) and Lypd6 in human cortex indicating that both proteins are present in the human brain. We further showed that PSCA forms stable complexes with the α4 nAChR subunit and decreases nicotine-induced extracellular-signal regulated kinase phosphorylation in PC12 cells. In addition, we analyzed protein levels of PSCA and Lypd6 in postmortem tissue of medial frontal gyrus from AD patients and found significantly increased PSCA levels (approximately 70%). In contrast, no changes in Lypd6 levels were detected. In concordance with our findings in AD patients, PSCA levels were increased in the frontal cortex of triple transgenic mice with an AD-like pathology harboring human transgenes that cause both age-dependent ß-amyloidosis and tauopathy, whereas Tg2576 mice, which display ß-amyloidosis only, had unchanged PSCA levels compared to wild-type animals. These findings identify PSCA as a nAChR-binding protein in the human brain that is affected in AD, suggesting that PSCA-nAChR interactions may be involved in the cognitive dysfunction observed in AD.

Quality of Life Variables Assessment, Before and After Pancreatoduodenectomy (PD): Prospective Study.

INTRODUCTION: The treatment of pancreatic cancer is a complex problem, due to late diagnosis, the need for specialized surgical treatment, the large number of relapses and poor survival. OBJECTIVE: To evaluate the quality of life of patients with periampulary pancreatic cancer before and after pancreatoduodenectomy (PD). MATERIAL & METHOD: The sample was collected in the "Attikon" University General Hospital (Chaidari). It consists of 20 subjects with a mean age of 65.9 years (SD = 10,2 years). For the quality of life measurement, we used the (EORTC) QLQ-C30 version 3.0., as well as the EORTC QOL-PAN26. RESULTS: From the sample of 20 patients who participated, full data were collected for 18 of them during the first month, 17 during the third month and 16 during the sixth month.Regarding symptoms, as they were recorded with the QLQ-30 questionnaire, there was a significant increase of fatigue, a significant reduction of pain and constipation, while economic difficulties increased.  As for the mean and median values for the dimensions of the PAN-26 questionnaire during monitoring, there was a significant decrease in pancreatic and liver pain symptoms during follow-up, while the gastrointestinal symptoms increased in frequency. In addition, the body image and sexuality worsened. CONCLUSIONS: The surgical treatment of pancreatic cancer with pancreatoduodenectomy (PD), according to the early survey data using the (EORTC) QLQ-C30 version3.0, and the EORTC QOL-PAN26 questionnaires, seems to have a favorable impact on quality of life, as evidenced by the improvement of most parameters evaluated during the study period.

Type II autosomal dominant osteopetrosis: radiological features in two families containing five members with asymptomatic and uncomplicated disease.

In this study we analysed the imaging patterns in two families containing five members with asymptomatic and uncomplicated autosomal dominant osteopetrosis (ADO II), and we report new and uncommon radiological manifestations. These findings might be useful in the context of reducing the incidence of fractures and other orthopaedic complications. Diffuse pelvic sclerosis on radiographs was observed incidentally in two patients. Both cases were asymptomatic, and the patients had never suffered a fracture. The suggestion of ADO II was raised. A detailed medical history, an imaging survey, and a haematological study were obtained so that other rare causes of osteosclerosis could be ruled out. No genetic study was conducted. All their first-degree relatives were also examined. Bony sclerosis was observed in five patients, and the radiological findings were analysed. A not previously reported thickening of the skull base without cranial nerve palsy or optic nerve atrophy was revealed in all patients. Scoliosis was present in three of them. This has been reported previously only once in ADO II. No lower limb deformity was detected. This study provided information on the pattern of radiological features in familial asymptomatic ADO II. These data on new and rare imaging findings will increase the diagnostic awareness of physicians and will guide a thorough investigation of the entire family. This might result in a consequent decrease in the incidence of fractures and other orthopaedic complications.