The effect of trifocal and extended-depth-of-focus intraocular lenses on optical coherence tomography parameters.

PURPOSE: Optical properties of commonly used multifocal and extended-depth-of-focus (EDOF) intraocular lenses (IOLs) can induce artifacts or changes in optical coherence tomography (OCT) measurements. Our purpose was to investigate the possible effects of different IOLs on peripapillary and macular OCT parameters. METHODS: The preoperative and postoperative third-month peripapillary OCT and ganglion cell analysis (GCA) parameters of patients having monofocal (Alcon IQ), multifocal (PanOptix), or EDOF (Vivity) IOL implanted during cataract surgery were compared. RESULTS: Sixty-four eyes of 64 patients were included (21 monofocal, 24 multifocal, and 19 EDOF). Although all OCT image qualities increased postoperatively, only GCA image quality changes in the monofocal and multifocal groups reached statistical significance. Most peripapillary retinal nerve fiber layer (RNFL) and GCA parameters were similar preoperatively and postoperatively. The superior RNFL thickness in the monofocal group and the temporal RNFL thickness in the EDOF group were higher postoperatively ( P = 0.04 and P = 0.02, respectively). Most GCA and RNFL value changes between preoperative and postoperative measurements were similar between groups. In the parameters that changed, postoperative values were higher in the monofocal group ( P = 0.02 for minimum ganglion cell layer and inner plexiform layer, P = 0.04 for average RNFL). CONCLUSION: Trifocal and EDOF IOLs do not seem to have a negative effect on OCT parameters.

Ocular Symptoms in Kidney, Liver, and Heart Transplant Patients.

OBJECTIVES: The purpose of this study was to report the ocular manifestations in kidney, liver, and heart transplant recipients. MATERIALS AND METHODS: We reviewed the medical records of kidney, liver, and heart transplant recipients who were examined at the ophthalmology clinic of a tertiary hospital between October 2021 and October 2022. We evaluated the ocular complaints of the patients, ophthalmological examination findings, the etiology of the underlying disease, comorbidities, posttransplant duration, and the medications used. Ocular pathologies were classified as corneal, conjunctival, lens, vitreoretinal, and optic disc pathologies for the analysis. RESULTS: Our study included 233 patients (191 kidney, 40 liver, 2 heart transplant patients). Mean age of patients was 42.94 ± 17.45 years. Among the patient group, 80.3% had at least 1 pathological ocular finding. In subgroup analysis, 12.4% of the patients had corneal pathologies, 19.3% had conjunctival pathologies, 33.0% had lens pathologies, 33.5% had vitreoretinal pathologies, and 18.9% had optic disc-related pathologies. The most common finding was dry eye, followed by cataract and vitreoretinal pathologies. The most common vitreoretinal pathology was diabetic retinopathy, followed by hypertensive retinopathy. The ocular pathology incidence in kidney and liver transplant patients was similar (P = .05). The 2 heart transplant patients did not have any ocular pathologies except refractive errors. In addition, no significant correlation was observed between posttransplant duration and ocular pathologies (P = .28). CONCLUSIONS: Ocular findings were seen in most of the kidney and liver transplant recipients. Therefore, it is required that these patients undergo routine ocular screenings in order to facilitate early diagnosis and prompt treatment when needed.

Comparison of visual performance and quality of life with a new nondiffractive EDOF intraocular lens and a trifocal intraocular lens.

PURPOSE: To compare visual performance and quality of life (QoL) following bilateral implantation of a new nondiffractive extended depth-of-focus (EDOF) intraocular lens (IOL) and a trifocal IOL. SETTING: Department of Ophthalmology, Baskent University Faculty of Medicine, Ankara, Turkey. DESIGN: Prospective comparative interventional case series. METHODS: 104 eyes of 52 patients with cataract, bilaterally implanted with a nondiffractive EDOF IOL or a trifocal IOL, were included. Outcome measures were uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), distance corrected intermediate visual acuity and distance corrected near visual acuity, defocus curves, QoL (Visual Function Index 14), quality of vision (Quality of Vision [QoV] index), contrast sensitivity (Pelli-Robson chart), and binocular reading speed. RESULTS: Twenty-six patients were included in each group. The UDVA and CDVA were better in the EDOF group (0.05 ± 0.04 and 0.01 ± 0.04) than the trifocal group (0.13 ± 0.06 and 0.11 ± 0.07) ( P = .02 and .01). Defocus curves showed that visual acuity was better with the EDOF IOL for vergences at 0.00, -0.50, and -1.00 and better with the trifocal IOL for vergences at -2.50, -3.00, -3.50, and -4.00. Contrast sensitivity scores were similar with both IOLs ( P = .12). The overall mean QoL scores were lower in the EDOF group, indicating a better QoL ( P = .04). The QoV was better in the EDOF group with significantly less glare, halos, and blurry vision ( P < .01). CONCLUSIONS: The EDOF IOL performed better at distance, and the trifocal IOL performed better at near. Overall QoL and quality of vision were better with the EDOF IOL.

Abdominal Massage in Functional Chronic Constipation: A Randomized Placebo-Controlled Trial.

OBJECTIVE: The aim of this study was to investigate the effects of abdominal massage on the severity of constipation, bowel function, and quality of life (QoL) in patients with functional chronic constipation in a randomized placebo-controlled design. METHODS: Seventy-four patients diagnosed with functional constipation according to the Rome IV diagnostic criteria were included. Patients were randomly assigned to the intervention group (abdominal massage plus lifestyle advice) or the control group (placebo therapeutic ultrasound plus lifestyle advice). Abdominal massage or placebo ultrasound was applied for 4 weeks. The primary outcome measure was the Constipation Severity Instrument score. Bowel diary data and the Patient Assessment of Constipation Quality of Life Questionnaire score were used as secondary outcome measures. Differences in outcome measures within and between groups were analyzed by repeated-measures analysis of variance. RESULTS: Although constipation severity, bowel function indicators (defecation frequency and duration and stool consistency), and QoL were found to improve significantly over time in both groups, improvements in both primary and secondary outcomes were much more significant in the abdominal massage group. In addition, group × time interaction effects were found to be significant for constipation severity, bowel function findings, and QoL. There were approximately 70% and 28% reductions in constipation severity, 56% and 38% improvement rates in QoL, and 70% and 43% increases in defecation frequency in the intervention and placebo groups, respectively. CONCLUSION: Abdominal massage should be one of the first-line conservative approaches in the management of functional chronic constipation. Further randomized placebo-controlled studies with long-term follow-up are needed. IMPACT: For functional constipation, which is a common gastrointestinal problem, abdominal massage should be considered as an option in first-line therapy because of its effect beyond the placebo effect. LAY SUMMARY: If you have functional constipation, your physical therapist may be able to provide abdominal massage to help reduce your symptoms.

Health-related quality of life in non-paraplegic (ambulatory) children with myelomeningocele.

PURPOSE: Evaluation of the effects of ventriculoperitoenal shunt and incontinence presence on health-related quality of life of ambulatory myelomeningocele patients. METHODS: The study group included 35 myelomeningocele patients, between 5 and 18 years old (mean age = 9.6), who were neonatally operated. All patients were ambulatory. The Child Edition of the Child Health and Illness Profile (CHIP-CE) used to evaluate the patient group. Seventeen patients were using clean intermittent catheterization and nine patients had ventriculoperitoneal shunt. RESULTS: The CHIP-CE has five domains, and in satisfaction, resilience and achievement domains, significant lower scores were obtained from our study group. In terms of clean intermittent catheterization use, we got significantly lower scores on satisfaction, resilience and achievement domains (p < 0.05). According to the presence of ventriculoperitoneal shunt, we found lower scores in satisfaction, resilience, risk avoidance and achievement domains but the differences were not significant (p > 0.05). No significant difference was spotted according to gender and age. CONCLUSIONS: Continence problems have important effects on life quality of myelomeningocele patients. Incontinency should always be considered as a major variable in health-related quality of life evaluations.

SOX2 expression is an early event in a murine model of EGFR mutant lung cancer and promotes proliferation of a subset of EGFR mutant lung adenocarcinoma cell lines.

OBJECTIVES: Primary and acquired resistance to EGFR TKIs in EGFR mutant lung cancer occurs primarily through secondary mutations in EGFR or Met amplification. Drug resistance can also be mediated by expression of pluripotency transcription factors, such as OCT4, SOX2 and NANOG that decrease terminal differentiation. In this study, we investigated the expression and role of SOX2 in model systems of EGFR mutant tumors. MATERIALS AND METHODS: Immunoblotting or immunohistochemistry was used to assess expression of pluripotency transcription factors in lungs of transgenic mice or in human NSCLC cell lines. Expression of SOX2 was reduced by shRNA knockdown, and response to erlotinib and cellular proliferation were assessed. RESULTS AND CONCLUSION: Induction of mutant EGFR in transgenic CCSP-rtTA/TetO-EGFR(L858R/T790M) mice correlated with increased OCT4 and SOX2 expression in lung tissue prior to tumor development. Established lung tumors retained SOX2 expression. To assess a role for SOX2 in tumorigenesis, a panel of NSCLC cell lines with activating EGFR mutations was assessed for SOX2 expression. Two of six cell lines with mutant EGFR showed detectable SOX2 levels, suggesting SOX2 expression did not correlate with EGFR mutation status. To assess the role of SOX2 in these cell lines, HCC827 and H1975 cells were infected with lentivirus containing SOX2 shRNA. Knockdown of SOX2 decreased proliferation in both cell lines and increased sensitivity to erlotinib in HCC827 cells. Because constitutive activation of the PI3K/Akt pathway is associated with EGFR TKI resistance, cells were treated with PI3K/AKT inhibitors and expression of SOX2 was examined. PI3K/Akt inhibitors decreased SOX2 expression in a time-dependent manner. These data suggest targeting SOX2 may provide therapeutic benefit in the subset of EGFR-mutant tumors with high constitutive levels of SOX2, and that until more direct means of inhibiting SOX2 are developed, PI3K/Akt inhibitors might be useful to inhibit SOX2 in EGFR TKI resistant tumors.

Investigation of ocular neovascularization-related genes and oxidative stress in diabetic rat eye tissues after resveratrol treatment.

Changes in vascular endothelial growth factor (VEGF), angiotensin-converting enzyme (ACE), matrix metalloproteinase (MMP)-9, and endothelial nitric oxide synthase (eNOS) mRNA expression profiles and oxidative stress in the eye tissue microenviroment may have important roles in ocular neovascularization and permeability in proliferative diabetic retinopathy. The present study investigated the effects of resveratrol (RSV) treatment on the mRNA expression profile of VEGF, ACE, MMP-9, and eNOS, which are associated with vascular neovascularization, and glutathione, protein carbonyl, and nitrite-nitrate levels, which are markers of oxidative stress in eyes of diabetic rats. Twenty-four Wistar albino male rats were divided into four groups. After diabetes induction with streptozotocin (10 mg/kg/day) RSV was administered to the RSV and diabetes mellitus (DM) + RSV groups for 4 weeks. The mRNA levels were measured by quantitative real-time polymerase chain reaction assay, and biochemical estimations were determined with spectrophotometric assays in eye homogenates. The mRNA expression levels of VEGF, ACE, and MMP-9 were increased in the DM group compared with the control group, and RSV treatment decreased their mRNA levels. Expression of eNOS mRNA was increased in the RSV and DM groups and decreased in the DM + RSV group. Nitrite-nitrate levels and protein carbonyl content were increased and glutathione levels were decreased in the DM group compared with controls. Consequently, these data suggest that RSV suppressed the expression of eNOS, which is actively involved in the inflammation and healing process in chronic diabetes. Although oxidative stress was increased in eye tissue from diabetic rats, mRNA levels of VEGF, MMP-9, and ACE genes associated with vascular remodeling did not change in diabetic eyes.

Nicotine does not enhance tumorigenesis in mutant K-ras-driven mouse models of lung cancer.

Smoking is the leading cause of preventable cancer deaths in the United States. Nicotine replacement therapies (NRT) have been developed to aid in smoking cessation, which decreases lung cancer incidence. However, the safety of NRT is controversial because numerous preclinical studies have shown that nicotine enhances tumor cell growth in vitro and in vivo. We modeled NRT in mice to determine the effects of physiologic levels of nicotine on lung tumor formation, tumor growth, or metastasis. Nicotine administered in drinking water did not enhance lung tumorigenesis after treatment with the tobacco carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Tumors that develop in this model have mutations in K-ras, which is commonly observed in smoking-related, human lung adenocarcinomas. In a transgenic model of mutant K-ras-driven lung cancer, nicotine did not increase tumor number or size and did not affect overall survival. Likewise, in a syngeneic model using lung cancer cell lines derived from NNK-treated mice, oral nicotine did not enhance tumor growth or metastasis. These data show that nicotine does not enhance lung tumorigenesis when given to achieve levels comparable with those of NRT, suggesting that nicotine has a dose threshold, below which it has no appreciable effect. These studies are consistent with epidemiologic data showing that NRT does not enhance lung cancer risk in former smokers.

Inhibition of ErbB2 by herceptin reduces viability and survival, induces apoptosis and oxidative stress in Calu-3 cell line.

Human epidermal growth factor receptor 2 (ErbB2) amplification and overexpression has been seen in many cancer types including non-small cell lung cancer (NSCLC). Thus, ErbB2 is an important target for cancer therapies. Increased ErbB2 expression has been associated with drug resistance in cancer cells. Herceptin is a humanized monoclonal antibody that targets the extracellular domain of ErbB2. In this study, we aimed to block ErbB2 signaling with Herceptin and assess cytotoxicity and effects on apoptosis, oxidative stress, nuclear factor kappa-B (NF-kB), and Survivin expression in Calu-3 cell line. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay were used to assess cell viability as a marker of proliferation. Acridine orange/ethidium bromide (AO/EB) staining and caspase 3/7 activity were measured as the markers of apoptosis. The relative expressions of NF-kB-p50 and Survivin mRNAs were evaluated. Activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT), and the levels of glutathione (GSH) and reactive oxygen species (ROS) were determined in a time- and dose-dependent manner. Our results show that Herceptin treatment inhibits cell proliferation and activates apoptosis but without effects on Survivin and NF-kB expression in Calu-3 cell line. Intracellular glutathione levels and SOD and CAT activities were decreased in a time- and dose-dependent manner associated with oxidative stress. Also, ROS were increased at 24 h. These results provide evidence that Herceptin can be used as a cytotoxic and apoptotic agent in NSCLC.

Polymorphisms in the vitamin D receptor gene and risk of lung cancer.

BACKGROUND: Differences between the individual variations in DNA may modulate lung cancer process. Many studies reported that Vitamin D Receptor (VDR) gene polymorphisms may influence the cancer risk due to their antiproliferative, antiangiogenic, antimetastatic and apoptotic effects. MATERIAL/METHODS: The genotype and haplotype frequencies of three polymorphisms of VDR, i.e. TaqI (rs731236), BsmI (rs1544410), and ApaI (rs7975232), were studied using PCR-RFLP in 137 patients with lung cancer and 156 controls. RESULTS: Differences were observed in genotype (P=0.024) and allele (P=0.011) frequencies of TaqI polymorphism due to the "T" allele. Furthermore, compared with the "tt" genotype, the odds ratio for the "TT" genotype increased 2.24 times (95%CI=1.05-4.77, P=0.037). Comparing cases and controls, smoking habit (P=0.012) and gender distribution (P=0.005) were found to increase the risk of lung cancer in patients with "TT" homozygotes, demonstrating the role of gene-environment interaction in lung cancer. In addition, when age and gender within the case group only were evaluated in relation to genotype, the adjusted odds ratios for the "TT" genotype increased 2.20 times (95%CI=1.01-4.78, P=0.047) for age and 2.24 times (95%CI=1.05-4.80, P=0.037) for gender. However, no differences were observed for the distribution of variant genotypes of the BsmI and ApaI polymorphisms (P>0.05). To evaluate the joint effects of these polymorphisms, haplotype analysis was performed which showed that the haplotype baT was associated with higher lung cancer risk compared with the most common haplotype BAt (P=0.026). CONCLUSIONS: This is perhaps the first study suggesting that TaqI polymorphism of the VDR gene might be a risk factor for lung cancer and that age, gender, and smoking habit could have an impact on lung cancer risk.

Genetic variations in the hypoxia-inducible factor-1alpha gene and lung cancer.

Hypoxia-inducible factor-1 (HIF-1), an important genetic component of angiogenesis, becomes stable as a response to tumor hypoxia and facilitates tumor survival. The polymorphisms of the HIF-1alphagene may cause changes in the activity of this protein, which serves as a transcription factor for many genes in tumorigenesis. In this study, we have investigated the relationship between seven HIF-1alphapolymorphisms [C > T substitution in intron 8 (rs10873142), T418I (rs41508050) in exon 10, P564P (rs41492849), L580L (rs34005929), P582S (rs11549465), A588T (rs11549467) in exon 12 and dinucleotide GT repeats in intron 13 (rs10645014)] among lung cancer patients in the Turkish population. Genomic DNA was isolated from 141 lung cancer cases and 156 controls and subjected to PCR for amplification. Genotyping was carried out with RFLP and DNA sequencing methods. There was no significant difference between the lung cancer cases and controls in terms of the distribution of genotyping frequencies of seven HIF-1alphapolymorphisms (P > 0.05). No significant relationship was found between the C > T substitution in intron 8 and P582S haplotypes and development of lung cancer. In addition, there were no significant associations between the genotypes and clinopathological characteristics of the cases examined. These findings show that polymorphisms in the HIF-1alphagene do not confer susceptibility to lung cancer.

Polymorphisms in the aurora-A gene is not associated with lung cancer in the Turkish population.

Lung cancer, a complex neoplasm of lung tissue, is influenced by several environmental and genetic factors which could be changed in each individual. Aurora-A gene is related to mitotic events such as: chromosome instability, cell cycle regulation, spindle formation, and kinetechore-microtubule connections. This centrosomic serine/threonine kinase provides a strong connection between mitotic errors and carcinogenesis. The genomic alterations such as single nucleotide polymorphisms (SNPs) can exist in molecular pathways of lung cancer. Therefore, we evaluated the role of genetic polymorphisms of Aurora-A gene in the lung cancer in the Turkish population. Genotypes of five Aurora-A polymorphisms (F31I, V57I, 6328G/A, P50L, and S104L) were determined in 102 healty controls and 102 new diagnosed lung cancer cases. All samples were genotyped with DNA sequence technique. There were not any genotype variations in P50L, S104L, and 6328G/A polymorphisms. The frequencies of both genotypes F31I and V57I in lung cancer patients were not significantly different from those in controls (p > 0.05). A multivariable logistic regression analysis including patient characteristics, such as age and gender, did not change the results.