Clinical manifestations of a new alpha-1 antitrypsin genetic variant: Q0parma

Alpha-1 antitrypsin deficiency is an autosomal, codominant disorder caused by mutations of the SERPINA1 gene. Several mutations of SERPINA1 have been described associated with the development of pulmonary emphysema and/or chronic liver disease and cirrhosis. Here, we report a very rare PI*Q0parma variant identified for the first time in an Italian family originally from the city of Parma in Northern Italy

Swept-Source Optical Coherence Tomography Biometer as Screening Strategy for Macular Disease in Patients Scheduled for Cataract Surgery

The aim of this study was to assess the central macular imaging captured with an optical biometer based on full-eye-length Swept-Source OCT (SS-OCT) scan as a screening strategy for identifying macular diseases in patients scheduled for cataract surgery. 1,114 eyes of 749 consecutive patients underwent a biometrical examination with IOLMaster 700 SS-OCT technology (Carl Zeiss) and conventional Spectral-Domain OCT (SD-OCT) (Spectralis OCT, Heidelberg) device analysis on the same day. Seven examiners graded the scans individually in a full-masked mode. Twenty-five eyes were excluded for media opacities. Among the 1,089 included eyes, statistical analysis revealed a mean Kendall\u2019s Coefficient of 0.83 (range 0.76\u20130.89). A logistic regression model demonstrated a highly significant correlation (p < 0.001) between the coefficient of concordance and SD-OCT imaging. Intraobserver reproducibility was 0.89 (range 0.86\u20130.91). Optical biometer SS-OCT scans showed a mean sensitivity of 0.81 and a mean specificity of 0.84. The positive and negative predictive value detected was 0.78 and 0.86, respectively. In order to predict the risk of reduced visual recovery, especially in cases of retinal pathology, optical biometer with SS-OCT scan has proven to be a useful modality for detecting macular structural abnormalities in patients undergoing cataract surgery. Conventional SD-OCT remains mandatory to confirm the presumed diagnosis

Functional and structural reliability of optic nerve head measurements in healthy eyes by means of optical coherence tomography angiography

Background and Objectives: the aim of the study was to evaluate the repeatability and reproducibility of optical microangiography (OMAG)-based optical coherence tomography angiography (OCTA) in the optic nerve head (ONH) and radial peripapillary capillary (RPC) perfusion assessment of healthy eyes. Materials and Methods: in this observational study, a total of 40 healthy subjects underwent ONH evaluation, using an OMAG-based OCTA system at baseline (T0), after 30 min (T1), and after 7 days (T2). The main outcome measures were the vessel density (VD) and flux index (FI) of the RPCs, as well as peri-papillary retinal nerve fibre layer (pRNFL) thickness. The analysis was performed by two observers independently. The coefficient of repeatability (CR), within the subject coefficient of variation (CVw) and intrasession correlation coefficient (ICC), to evaluate intrasession repeatability of measurements was calculated for each observer. Results: the high intrasession and intersession repeatability and reproducibility were assessed in the two observers for all three outcome measures. Of note, the CRs for the first and the second observer were 0.011 (95% confidence interval (CI) 0.009–0.014) and 0.016 (95% CI 0.013–0.020) for FI, 0.016 (95% CI 0.013–0.021) and 0.017 (95% CI 0.014–0.021) for VD, and 2.400 (95% CI 1.948–3.092) and 3.732 (95% CI 3.064–4.775) for pRNFL thickness, respectively. The agreement between them was excellent for pRNFL assessment and very good for FI and VD. Conclusion: OCTA has a great potential in the accurate assessment of ONH and peri-papillary microcirculation. It allows for repeated and reproducible measurements without multiple scans-related bias, thus guaranteeing an independent operator analysis with good reproducibility and repeatability

Anatomical and functional changes after dexamethasone implant and ranibizumab in diabetic macular edema: A retrospective cohort study

AIM: To investigate the efficacy and safety of ranibizumab (RZB group) and dexamethasone implant (DEX group) intravitreal treatments in patients with treatment-na\uefve center involved diabetic macular edema (DME) by means of functional and morphological assessments. METHODS: This retrospective cohort study included 50 eyes of 50 patients with DME treated either with RBZ or DEX. Best-corrected visual acuity (BCVA) and microperimetry were evaluated at baseline and during a 6-month follow-up. In addition, central macular thickness (CMT) by means of structural optical coherence tomography (OCT) and retinal capillary plexus density and choriocapillary density by means of OCT angiography were assessed in all cases. RESULTS: Functional and morphological parameters significantly improved during the study period in both groups. BCVA improved significantly in both groups with a greater increase in the DEX group compared to the RBZ group (P=0.030). Microperimetry significantly differed during follow-up between the two treatments (P=0.031). In both groups CMT significantly decreased (P<0.001) without statistically significant differences between the two groups. A statistically significant increase of deep capillary plexus density was detected in both groups at 30d after therapy. The retreatment rate was 0.70\ub10.10 and 0.65\ub10.10 in the RBZ group and 0.65\ub10.10 and 0.50\ub10.11 in DEX group at 120 and 180d respectively. Two out of 25 patients in DEX group showed intraocular pressure increase requiring hypotonic eye drops. CONCLUSION: Both treatments are very effective for DME treatment during 6mo of follow-up with a lower retreatment rate in DEX group

A CGRP receptor antagonist peptide formulated for nasal administration to treat migraine

Objectives: To investigate the formulation of the peptide‐based antagonist (34Pro,35Phe)CGRP27–37, of the human calcitonin gene‐related peptide (CGRP) receptor as a potential nasally delivered migraine treatment. Methods: Peptide sequences were prepared using automated methods and purified by preparative HPLC. Their structure and stability were determined by LC‐MS. Antagonist potency was assessed by measuring CGRP‐stimulated cAMP accumulation in SK‐N‐MC, cells and in CHO cells overexpressing the human CGRP receptor. In vivo activity was tested in plasma protein extravasation (PPE) studies using Evans blue dye accumulation. Peptide‐containing chitosan microparticles were prepared by spray drying. Key findings: (34Pro,35Phe)CGRP27–37 exhibited a 10‐fold increased affinity compared to αCGRP27–37. Administration of (34Pro,35Phe)CGRP27–37 to mice led to a significant decrease in CGRP‐induced PPE confirming antagonistic properties in vivo . There was no degradation of (34Pro,35Phe)CGRP27–37 and no loss of antagonist potency during formulation and release from chitosan microparticles. Conclusions: (34Pro,35Phe)CGRP27–37 is a potent CGRP receptor antagonist both in vitro and in vivo, and it can be formulated as a dry powder with no loss of activity indicating its potential as a nasally formulated anti‐migraine medicine

Hypoactive Sexual Desire Disorder in Postmenopausal Women: Quality of Life and Health Burden

Abstract Objectives To describe the health-related quality of life (HRQOL) implications of hypoactive sexual desire disorder (HSDD) in a national sample of postmenopausal women ages 30–70. Methods The Nationwide Survey of Female Sexual Health, a random-digit telephone survey of US households, collected information on female sexual function, demographic characteristics, HRQOL, and the presence of specific medical disorders from 1189 naturally or surgically postmenopausal women in stable relationships of ≥3 months duration. HSDD was defined as Results HSDD was associated with significant HRQOL decrements, with the largest SF-12 score differences in mental health (HSDD: 45.4 [standard error 1.9] vs. no HSDD: 51.0 [0.6], P < 0.01), vitality (HSDD: 47.7 [1.3] vs. no HSDD: 52.0 [0.7], P < 0.01), social function (HSDD: 47.3 [1.4] vs. no HSDD: 50.9 [0.7], P < 0.05), and bodily pain (HSDD: 41.4 [2.2] vs. no HSDD: 46.7 [0.9], P < 0.05). EQ-5D index was 0.08 points lower (HSDD: 0.76 [0.03] vs. no HSDD: 0.84 [0.02], P < 0.05) for those with HSDD compared with those without. HSDD was associated with a 0.1-point decrement in naturally menopausal women (HSDD: 0.78 [0.03] vs. no HSDD 0.88 [0.01], P < 0.01). Women with HSDD showed more HRQOL impairment than healthy population norms but were similar to adults with other chronic conditions such as diabetes and back pain. Conclusions Women with HSDD showed substantial impairment in HRQOL. Given a prevalence of 6.6% to 12.5% among US women, HSDD represents an important burden on quality of life

IGF-I and IGFBP-3 Polymorphisms in Relation to Circulating Levels among African American and Caucasian Women

Circulating insulin-like growth factor-one (IGF-I) and IGF binding protein-3 (IGFBP-3) levels have been associated with common diseases. Although family-based studies suggest that genetic variation contributes to circulating IGF-I and IGFBP-3 levels, analyses of associations with multiple IGF-I and IGFBP-3 single nucleotide polymorphisms (SNPs) have been limited, especially among African Americans. We evaluated 30 IGF-I and 15 IGFBP-3 SNPs and estimated diplotypes in association with plasma IGF-I and IGFBP-3 among 984 premenopausal African American and Caucasian women. In both races, IGFBP-3 rs2854746 (Ala32Gly) was positively associated with plasma IGFBP-3 (CC versus GG mean difference among Caucasians = 631 ng/ml, 95% confidence interval: 398, 864; African Americans = 897 ng/ml, 95% confidence interval: 656, 1138), and IGFBP-3 diplotypes with the rs2854746 GG genotype had lower mean IGFBP-3 levels than referent diplotypes with the CG genotype, while IGFBP-3 diplotypes with the CC genotype had higher mean IGFBP-3 levels. IGFBP-3 rs2854744 (−202 A/C) was in strong linkage disequilibrium with rs2854746 in Caucasians only, but was associated with plasma IGFBP-3 in both races. Eight additional IGFBP-3 SNPs were associated with 5% or greater differences in mean IGFBP-3 levels, with generally consistent associations between races. Twelve IGF-I SNPs were associated with 10% or greater differences in mean IGF-I levels, but associations were generally discordant between races. Diplotype associations with plasma IGF-I did not parallel IGF-I SNP associations. Our study supports that common IGFBP-3 SNPs, especially rs2854746, influence plasma IGFBP-3 levels among African Americans and Caucasians, but provides less evidence that IGF-I SNPs affect plasma IGF-I levels

Use of hormones in doping and cancer risk

Hormones with anabolic properties such as growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are commonly abused among professional and recreational athletes to enhance physical ability. Despite their adverse effects are well-documented, the use of GH and IGF-1 has recently grown. This article highlights the anabolic activity related to mechanisms of cancer development and progression. GH/IGF-1 axis is able to activate cellular mechanisms that modulate every key stage of cancer formation and progression, such as inhibition of apoptosis, resistance to treatments, and induction of angiogenesis, metastatic process and cell proliferation. Results from pre-clinical studies and epidemiological observations in patients with an excess of GH and IGF-1 production or treated with these hormones showed a positive association with the risk to develop several types of cancer. In conclusion, athletes should be made aware that long-term treatment with doping agents might increase the risk of developing cancer, especially if associated with other licit or illicit drugs and/or high-protein diet