Surgical outcomes and complications of sutureless needle-guided intrascleral intraocular lens fixation combined with vitrectomy

Purpose:To analyze the surgical outcomes and complications of sutureless needle-guided intrascleral intraocular lens (IOL) implantation (Yamane technique) combined with pars plana vitrectomy.Methods:Retrospective study of 47 eyes of 46 patients that underwent scleral fixation of IOL by the Yamane technique combined with 3-port pars plana vitrectomy. Demographic data, primary indications for surgery, history of trauma, best corrected visual acuity (BCVA), intraocular pressure (IOP), duration of follow-up, and complications were analyzed.Results:Mean preoperative BCVA was 0.79 logMAR, which improved to 0.39 logMAR at mean 4.21 months (SD: 4.87 D) follow-up. Mean spherical equivalent pre and postoperative was + 7.64 D (SD: 7.74 D) and − 0.47 D (SD: 2.26 D), respectively. Early postoperative complications included hypotony with cyclodialysis cleft (n = 1; 2%), mild vitreous hemorrhage (n = 2; 4%), raised IOP (n = 2; 4%), and transient corneal edema (n = 2; 4%). Late complications included iris optic capture (n = 1; 2%), retinal detachment (n = 1; 2%), cystoid macular edema (CME; n = 2; 4%), IOL decentration (n = 1; 2%), and decentration and tilting of IOL (n = 1; 2%). Management of complications included laser treatment to cyclodialysis cleft, observation for vitreous hemorrhage, topical and oral IOP lowering agents for raised IOP. CME was managed with topical non-steroidal anti-inflammatory drugs. One eye was subjected IOL refixation. The mean number of surgeries per eye was 1.04.Conclusion:Combining needle-guided intrascleral IOL implantation with vitrectomy allows management of other posterior segment complications in the same sitting while obviating the need for the second surgery. It provides satisfactory outcomes that are comparable to published studies. However, a longer follow-up will allow a better understanding of the potential advantages of this approach.     

Role of altered immune cells in liver diseases: a review

Immune cells play an important role in controlling liver tumorigenesis, viral hepatitis, liver fibrosis and contribute to pathogenesis of liver inflammation and injury. Accumulating evidence suggests the effectiveness of natural killer (NK) cells and Kupffer cells (KCs) against viral hepatitis, hepatocellular damage, liver fibrosis, and carcinogenesis. Activation of natural killer cells provides a novel therapeutic strategy to cure liver related diseases. This review discusses the emerging roles of immune cells in liver disorders and it will provide baseline data to scientists to design better therapies for treatment.     

A high methionine,low folate and vitamin B_6/B_(12) containing diet can be associated with memory loss by epigenetic silencing of netrin-1

Memory-epigenetics which is the loss of memory due to epigenetic modifications can be due to the silencing of genes involved in cognitive functions and this is the basis of the current study.We hypothesize that a diet containing high methionine and low vitamins can lead to memory impairment by increasing global DNA methylation and therefore,silencing the netrin-1 gene,which encodes the glycoprotein involved in neurogenesis,axonal guidance and maintenance of the synaptic plasticity.Wild type(C57 BL/6 J) mice were fed with a diet containing excess methionine(1.2%),low-folate(0.08 mg/kg),vitamin B_6(0.01 mg/kg),and B_(12)(10.4 mg/kg) for 6 weeks.Mice were examined weekly for the long-term memory function,using a passive avoidance test,which determined loss of fear-motivated long-term memory starting from the fourth week of diet.Similarly,an increase in brain %5-methyl cytosine was observed starting from the 4 th week of diet in mice.Mice fed with a high methionine,low folate and vitamins containing diet showed a decrease in netrin-1 protein expression and an increase in netrin-1 gene promotor methylation,as determined by methylation-sensitive restriction enzyme-polymerase chain reaction analysis.The increase in methylation of netrin-1 gene was validated by high-resolution melting and sequencing analysis.Furthermore,the association of netrin-1 with memory was established by administering netrin that considerably restored long-term fear motivated memory.Taken together,these results suggest that a diet rich in methionine and lacking in folate and vitamin B_6/B_(12) can induce defects in learning and memory.Furthermore,the data indicates that decrease in netrin-1 expression due to hyper-methylation of its gene can be associated with memory loss.The animal procedures were approved by the Institutional Animal Care and Use Committee,University of Louisville,USA(No.A3586-01) on February 2,2018.     

Reformatted images improve the detection rate of acute traumatic subdural hematomas on brain CT compared with axial images alone

Subdural hematomas (SDHs) comprise a significant percentage of missed intracranial hemorrhage on axial brain CT. SDH detection rates could be improved with the addition of reformatted images. Though performed at some centers, the potential additional diagnostic sensitivity of reformatted images has not yet been investigated. The purpose of our study is to determine if the addition of coronal and sagittal reformatted images to an axial brain CT increases the sensitivity and specificity for detection of acute traumatic SDH. We retrospectively reviewed consecutive brain CTs acquired for acute trauma that contained new SDHs. An equivalent number of normal brain CTs served as control. Paired sets of images were created for each case: (1) axial images only (“axial only”) and (2) axial, coronal, sagittal images (“reformat added”). Three readers interpreted both the axial only and companion reformat added for each case, separated by 1 month. Reading times and SDH detection rates were compared. One hundred SDH and 100 negative examinations were collected. Sensitivity and specificity for the axial-only scans were 75.7 and 94.3 %, respectively, compared with 88.3 and 98.3 % for reformat added. There was a 24.3 % false negative (missed SDH) rate with axial-only scans versus 11.7 % with reformat added (p = <0.001). Median reader interpretation times were longer with the addition of reformatted images (125 versus 89 s), but this difference was not significant (p = 0.23). The addition of coronal and sagittal images in trauma brain CT resulted in improved sensitivity and specificity as well as a reduction in SDH false negatives by greater than 50 %. Reformatted images substantially reduce the number of missed SDHs compared with axial images alone.     

Highly loaded, sustained-release microparticles of curcumin for chemoprevention

Curcumin, a dietary polyphenol, has preventive and therapeutic potential against several diseases. Because of the chronic nature of many of these diseases, sustained-release dosage forms of curcumin could be of significant clinical value. However, extreme lipophilicity and instability of curcumin are significant challenges in its formulation development. The objectives of this study were to fabricate an injectable microparticle formulation that can sustain curcumin release over a 1-month period and to determine its chemopreventive activity in a mouse model. Microparticles were fabricated using poly(D, L-lactide-co-glycolide) polymer. Conventional emulsion solvent evaporation method of preparing microparticles resulted in crystallization of curcumin outside of microparticles and poor entrapment (～1%, w/w loading). Rapid solvent removal using vacuum dramatically increased drug entrapment (～38%, w/w loading; 76% encapsulation efficiency). Microparticles sustained curcumin release over 4 weeks in vitro, and drug release rate could be modulated by varying the polymer molecular weight and/or composition. A single subcutaneous dose of microparticles sustained curcumin liver concentration for nearly a month in mice. Hepatic glutathione-s-transferase and cyclooxygenase-2 activities, biomarkers for chemoprevention, were altered following treatment with curcumin microparticles. The results of these studies suggest that sustained-release microparticles of curcumin could be a novel and effective approach for cancer chemoprevention.     

Poly[3-(3, 4-dihydroxyphenyl) glyceric acid] from Comfrey exerts anti-cancer efficacy against human prostate cancer via targeting androgen receptor, cell cycle arrest and apoptosis

The major obstacles in human prostate cancer (PCA) treatment are the development of resistance to androgen ablation therapy leading to hormone-refractory state and the toxicity associated with chemotherapeutic drugs. Thus, the identification of additional non-toxic agents that are effective against both androgen-dependent and androgen-independent PCA is needed. In the present study, we investigated the efficacy of a novel phytochemical poly[3-(3, 4-dihydroxyphenyl)glyceric acid] (p-DGA) from Caucasian species of comfrey (Symphytum caucasicum) and its synthetic derivative syn-2, 3-dihydroxy-3-(3, 4-dihydroxyphenyl) propionic acid (m-DGA) against PCA LNCaP and 22Rv1 cells. We found that both p-DGA and m-DGA suppressed the growth and induced death in PCA cells, with comparatively lesser cytotoxicity towards non-neoplastic human prostate epithelial cells. Furthermore, we also found that both p-DGA and m-DGA caused G(1) arrest in PCA cells through modulating the expression of cell cycle regulators, especially an increase in CDKIs (p21 and p27). In addition, p-DGA and m-DGA induced apoptotic death by activating caspases, and also strongly decreased AR and PSA expression. Consistent with in vitro results, our in vivo study showed that p-DGA feeding strongly inhibited 22Rv1 tumors growth by 76% and 88% at 2.5 and 5mg/kg body weight doses, respectively, without any toxicity, together with a strong decrease in PSA level in plasma; and a decrease in PCNA, AR and PSA expression but increase in p21/p27 expression and apoptosis in tumor tissues from p-DGA-fed mice. Overall, present study identifies p-DGA as a potent agent against PCA without any toxicity, and supports its clinical application.     

Standardized uptake value by positron emission tomography/computed tomography as a prognostic variable in metastatic breast cancer

BACKGROUND:

In this retrospective, single‐institution study, the authors examine the maximum standardized uptake value (SUVmax) on positron emission tomography/computed tomography (PET/CT) images as a prognostic variable in patients with newly diagnosed metastatic breast cancer (MBC).

METHODS:

Patients with ≥1 metastatic lesion on PET/CT images that were obtained within 60 days of their MBC diagnosis between January 1, 2001 and December 31, 2008 were included. Patients were excluded if they had received chemotherapy ≤30 days before the PET/CT images were obtained. Electronic medical reports were reviewed to determine the SUVmax and overall survival. Because of intraindividual variation in the SUV by body site, separate analyses were conducted by metastatic site. Relationships between site‐specific PET/CT variable tertiles and overall survival were assessed using Cox regression; hazard ratios for the highest tertile versus the lowest tertile were reported.

RESULTS:

In total, 253 patients were identified, and their median age was 57 years (range, 27‐90 years). Of these, 152 patients (60%) died, and the median follow‐up was 40 months. On univariate analysis, SUVmax tertile was strongly associated with overall survival in patients who had bone metastases (N = 141; hazard ratio, 3.13; 95% confidence interval, 1.79‐5.48; P < .001). This effect was maintained on multivariate analysis (HR = 3.19; 95% confidence interval, 1.64‐6.20, P = .002) after correcting for known prognostic variables. A greater risk of death was associated with SUVmax tertile in patients who had metastases to the liver (N = 46; hazard ratio, 2.07; 95% confidence interval, 0.90‐4.76), lymph nodes (N = 149; hazard ratio, 1.1; 95% confidence interval, 0.69‐1.88), and lung (N = 62; hazard ratio, 2.2; 95% confidence interval, 0.97‐4.95), although these results were not significant (P = .18, P = .31, and P = .095, respectively).

CONCLUSIONS:

The current results indicate that PET/CT has value as a prognostic tool in patients with newly diagnosed MBC to bone. Cancer 2012. © 2012 American Cancer Society.     

Results using the OPAL strategy in Mandarin speaking cochlear implant recipients

Abstract

Objective: To evaluate the effectiveness of an experimental pitch-coding strategy for improving recognition of Mandarin lexical tone in cochlear implant (CI) recipients. Design: Adult CI recipients were tested on recognition of Mandarin tones in quiet and speech-shaped noise at a signal-to-noise ratio of?+10?dB; Mandarin sentence speech-reception threshold (SRT) in speech-shaped noise; and pitch discrimination of synthetic complex-harmonic tones in quiet. Two versions of the experimental strategy were examined: (OPAL) linear (1:1) mapping of fundamental frequency (F0) to the coded modulation rate; and (OPAL+) transposed mapping of high F0s to a lower coded rate. Outcomes were compared to results using the clinical ACE? strategy. Study sample: Five Mandarin speaking users of Nucleus® cochlear implants. Results: A small but significant benefit in recognition of lexical tones was observed using OPAL compared to ACE in noise, but not in quiet, and not for OPAL+?compared to ACE or OPAL in quiet or noise. Sentence SRTs were significantly better using OPAL+?and comparable using OPAL to those using ACE. No differences in pitch discrimination thresholds were observed across strategies. Conclusions: OPAL can provide benefits to Mandarin lexical tone recognition in moderately noisy conditions and preserve perception of Mandarin sentences in challenging noise conditions.