The role of color in transsaccadic object correspondence.

With each saccade, visual information is disrupted, and the visual system is tasked with establishing object correspondence between the presaccadic and postsaccadic representations of the saccade target. There is substantial evidence that the visual system consults spatiotemporal continuity when determining object correspondence across saccades. The evidence for surface feature continuity, however, is mixed. Surface features that are integral to the saccade target object's identity (e.g., shape and contrast polarity) are informative of object continuity, but features that may only imply the state of the object (e.g., orientation) are ignored. The present study tested whether color information is consulted to determine transsaccadic object continuity. We used two variations of the intrasaccadic target displacement task. In Experiments 1 and 2, participants reported the direction of the target displacement. In Experiments 3 and 4, they instead reported whether they detected any target movement. In all experiments, we manipulated the saccade target's continuity by removing it briefly (i.e., blanking) and by changing its color. We found that large color changes can disrupt stability and increase sensitivity to displacements for both direction and movement reports, although not as strongly as long blank durations (250 ms). Interestingly, even smaller color changes, but not blanking, reduced response biases. These results indicate that disrupting surface feature continuity may impact the process of transsaccadic object correspondence more strongly than spatiotemporal disruptions by both increasing the sensitivity and decreasing the response bias.

The effects of subtoxic dose of acetaminophen combined with exercise on the liver of rats.

Regular physical exercise is beneficial to the body. Acute exercise causes oxidant stress in many tissues including the liver by creating an unbalanced status between oxidant and antioxidant levels. Analgesic drugs are commonly consumed to reduce the pain after exercise. Acetaminophen (APAP), commonly used as an over-the-counter analgesic, can cause hepatotoxicity. The aim of this study was to investigate the effect and underlying mechanisms of APAP at subtoxic dose, which is given after the acute and exhaustive exercise on the rat livers. Male Wistar rats weighing 200-250 g were divided into 6 groups each consisting of 7 rats/group; Control, APAP (250 mg/kg, ip), Acute Exercise (AEx), Acute Exhaustive Exercise (AEEx), Acute Exercise and APAP (AEx+APAP) and Acute Exhaustive Exercise and APAP (AEEx+APAP) groups. Rats were exercised at moderate intensity or exhaustive on the treadmill and then received APAP. Tissue MDA levels were significantly increased in AEEx, AEx+APAP and AEEx+APAP groups compared with the control. There was no significant difference in GSH levels between groups. Tissue Sirtuin1 (Sirt1) levels of APAP, AEx and AEEx groups were significantly less than control. There was no significant difference between groups in VEGF levels. Liver damage score was significantly higher in all groups compared with control group. As a result, this study shows that subtoxic dose of APAP treatment alone or in combination with acute or exhaustive treadmill exercise can cause oxidative liver damage by affecting Sirt1 levels and without affecting VEGF levels.

Treatment and outcomes of patients with metastatic spinal cord compression: a double-center study.

OBJECTIVE: Spinal metastases may only affect the bone tissue and result in spinal instability or may additionally result in epidural compression, leading to neurological deficits. Surgery has emerged as a popular method in treating metastatic epidural spinal cord compression (MESCC) due to the advances in surgical techniques and instrumentation. In this study, we evaluated patients with MESCC regarding neurological status, pain status, and survival rates, and presented our experience managing MESCC. PATIENTS AND METHODS: Clinical and radiographic records of 53 patients diagnosed with MESCC between January 2011 and March 2017 were retrospectively evaluated. The study included patients with a pathological diagnosis of primary cancer, those who complained of spinal metastasis, and those who had indications of MESCC on Magnetic Resonance Imaging (MRI). Bone structure and spinal stability were evaluated using assessed Computed Tomography (CT), and metastatic spread was considered using assessed Positron Emission Tomography (PET) in suitable cases. For each patient, the presence of a tumor compressing the spinal cord, age, gender, preoperative, and postoperative American Spinal Injury Association scores (ASIA), Tokuhashi prognostic score (TPS), affected spinal segment, pathological diagnosis, preoperative, and postoperative Visual Analog Scale (VAS), the status of spinal stability, follow-up period, and complications were evaluated. RESULTS: Forty-five patients (82.2% of them were women) underwent surgery with a mean age of 58.29 ± 15.14 years. The most frequent type of primary tumor was multiple myeloma (33.9%), followed by lung (24.6%), gastric (7.5%), and prostate (5.7%). The most common site of metastasis was the thoracic region (43.4%), followed by lumbar (24.5%), multiple (24.5%), and cervical (5.7%). The analysis indicated that a significant difference was found between the survival rates of the TPS categories. CONCLUSIONS: Common symptoms of MESCC include spinal pain and neurological deficit below the level of the injury. Prompt surgical treatment followed by oncological treatment leads to significant neurological recovery, more prolonged survival, pain relief, and improved quality of life in patients with a short survival time. Oncological treatments, including radiotherapy (RT), should be recommended after surgical treatment.

Post-COVID syndrome and pain perception in outpatients with COVID-19.

OBJECTIVE: This study aimed to investigate the prevalence of pain symptoms in outpatients with COVID-19 and to analyze the relationship between pain-related, psychological, and cognitive variables in patients with ongoing pain complaints after COVID-19. PATIENTS AND METHODS: 79 people participated in the research. The focus was on completed demographics (such as age, height, and weight), pain-related (duration and intensity of pain), Modified Medical Research Council (MMRC) Dyspnea Score, and visual analogue scale (VAS) variables. RESULTS: Significant changes were found in some of the post-COVID symptoms after 3 months. From the 3rd month, the VAS pain scale score, EQ-5D-3L quality of life score, and VAS score obtained from EQ-5D-3L quality of life scale, sitting scores decreased compared to the first measurements. Muscle strength, moderate activity, walking, and total scores increased from the third month. CONCLUSIONS: We suggest physical pain and inactivity symptoms in patients with COVID regressed in the 3rd month.

A Multi-Method Approach to Addressing the Toddler Data Desert in Attention Research.

Visual attention skills undergo robust development change during infancy and continue to co-develop with other cognitive processes in early childhood. Despite this, this is a general disconnect between measures of the earliest foundations of attention during infancy and later development of attention in relation to executive functioning during the toddler years. To examine associations between these different measures of attention, the current study administered an oculomotor task (infant orienting with attention, IOWA) and a manual response (Flanker) task with a group of toddlers. We collected simultaneous neural recordings (using functional near-infrared spectroscopy), eye-tracking, and behavioral responses in 2.5- and 3.5-year-olds to examine the neural and behavioral associations between these skills. Results revealed that oculomotor facilitation in the IOWA task was negatively associated with accuracy on neutral trials in the Flanker task. Second, conflict scores between the two tasks were positively associated. At the neural level, however, the tasks showed distinct patterns of activation. Left frontal cortex was engaged during the Flanker task whereas right frontal and parietal cortex was engaged during the IOWA task. Activation during the IOWA task differed based on how well children could control oculomotor behavior during the task. Children with high levels of stimulus reactivity activated parietal cortex more strongly, but children with more controlled oculomotor behavior activated frontal cortex more strongly.

Tracking flanker task dynamics: Evidence for continuous attentional selectivity.

Understanding the dynamics of selective attention has been a central research goal in the cognitive sciences. One account proposes that attention is unitary and increases in selectivity continuously over time. An alternative account proposes that attention switches from a low to a high state of selectivity at a discrete point in time when a distinct selective attention mechanism is engaged. Despite posing fundamentally different theoretical perspectives on selective attention, both accounts have successfully explained outcome-based data, such as reaction time. Here, we used mouse-tracking, which provides high temporal resolution to record movement trajectories in a flanker task. We examined spatial and temporal movement dynamics for characteristics of continuous and discrete shifts in attentional selectivity. Our results showed that attentional selectivity increases gradually over time, rather than abruptly, demonstrating a continuous process of selective attention. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Leptin/Melanocortin pathway hormones in obese patients after laparoscopic sleeve gastrectomy.

OBJECTIVE: The melanocortin system is an important neural system underlying the control of body weight and food intake. This system has recently received great attention as a potential target for obesity treatment. Therefore, the objective of this study was to find out the leptin-melanocortin pathway before and after Laparoscopic Sleeve Gastrectomy (LSG) in obese patients. PATIENTS AND METHODS: The study was carried out with a total of 144 individuals in 3 groups [control, obese group before LSG and obese group after LSG (who underwent LSG one year ago)]. The amount of leptin (LEP), leptin receptor (LEPR), tropomyosin receptor kinase receptor B (TrkB), brain-derived neurotrophic factor (BDNF), pro-opiomelanocortin (POMC) and melanocortin-4 receptors (MC4R) molecules were measured by using Enzyme-Linked Immunosorbent Assays. RESULTS: A statistically significant difference was found between the groups in terms of body mass index (BMI) values (p = 0.001). There was also statistically significant difference present between obese before LSG group and obese after LSG group regarding the levels of LEP, TrkB, BDNF and proteins (p < 0.05). A decline was determined in the LEP and BDNF levels one year follow-up after LSG. CONCLUSIONS: The evidence suggests that the leptin melanocortin pathway strictly regulates food intake and BMI before and after LSG surgery. This pathway should be kept under control for effectively reducing food intake and body weight in the treatment of obesity.

The relationship between serum prolidase activity and histone H3 protein levels and fibromyalgia.

OBJECTIVE: Fibromyalgia (FM) is a clinical syndrome characterized by prominent physical and psychological impairment and widespread pain on both sides of the body, above and below the waist, and along the axial skeleton. It often causes sleep difficulties, memory impairment, mood changes, irritable bowel syndrome, and fatigue. Our study aimed to investigate the relationship between FM and prolidase (peptidase D) and histone H3 protein levels by comparing a patient group with a healthy control group. PATIENTS AND METHODS: In total, 176 people were examined in our study, 88 of whom were healthy and 88 of whom had FM. Serum level was measured by ELISA. Then the results were analyzed using SPSS. All p < 0.05 were considered statistically significant. RESULTS: A significant increase in the levels of prolidase was observed in the patient group compared with the control group (6.28-4.68, p <0.001). Histone H3 protein values were not significantly different between the patient and control groups (p=0.184). The ROC analysis indicated that prolidase was statistically significant in disease prediction (p<0.001, AUC: 0.795 (0.697-0.893), while histone H3 protein was statistically insignificant in predicting disease. CONCLUSIONS: The results of the study show that prolidase activity may play a role in diagnosing FM. In addition, since no study like ours has been performed before, it can bring a new perspective to the literature.

Proflactic effects of rosmarinic acid on spinal cord injury in rats.

PURPOSE: Spinal cord injury (SCI) causes various neurological consequences that disrupt the structure of axons. The C/EBP Homologous Protein (CHOP) acts in neuronal death by apoptosis has been demonstrated in experimental models. Rosmarinic acid (RA) is a phenolic compound used for therapeutic purposes in many diseases. In this study, we investigated the therapeutic effect of Rosmarinic acid application on inflammation and apoptotic development after spinal cord injury. METHODS: Male Wistar albino rats (n: 24) were assigned to three group: control, SCI and SCI+ RA. All rats were fixed on the operating table after anesthesia, the skin of the thoracic region was opened with a midline incision and the paravertebral muscles were dissected and T10-T11 laminas were exposed. A cylindrical tube of 10 cm length was fixed to the area to be laminectomy. A metal weight of 15 grams was left down the tube. Spinal damage was created, skin incisions were sutured. 50 mg/kg rosmarinic acid was given orally for 7 days after the spinal injury. Spinal tissues were fixed in formaldehyde solution and processed for paraffin wax tissue protocol and 4-5 µm sections were taken with microtome for further immunohistochemical examination. Caspase-12 and CHOP antibodies were applied to sections. Remaining tissues were carried out in glutaraldehyde for the first fixation then in osmium tetroxide for the second. Tissues were kept in pure araldite and thin sections were taken for transmission electron microscope. RESULTS: Values of malondialdehyde (MDA), myeloperoxidase (MPO), glutathione peroxidase (GSH), neuronal degeneration, vascular dilation, inflammation, CHOP and Caspase-12 expression were increased in SCI group compared to control group. Only glutathione peroxidase content was decreased in SCI group. In SCI group, disruption of basement membrane structure in canalis ependymalis, degeneration in structures of unipolar bipolar and multipolar neurons, and apoptotic changes were seen with increased inflammation in the piamater region and positive CHOP expression in vascular endothelial cells. In SCI+RA group, reorganization of basement membrane pill in canalis ependymalis were observed with mild Caspase-12 activity in some canalis ependymal and glial cells. Also, moderate CHOP expression in multipolar and bipolar neurons and glia cells were observed. CONCLUSIONS: The application of RA has a significant effect on preventing damage in SCI. It was thought that CHOP and Caspase-12 mediated oxidative stress could be a guide in showing the potential and therapeutic target to stop the apoptotic course after SCI injury.

Audiological evaluation of the cochlear nerve with brainstem evoked response audiometry in patients with COVID-19.

PURPOSE: In this clinical study, it was aimed to prospectively evaluate the cochlear nerve with brainstem evoked response audiometry (BERA) in terms of audiological ailments in patients with COVID-19. Although the relationship of COVID-19 with tinnitus and hearing loss has been investigated since the day this infectious respiratory disease emerged, its relationship with BERA has not been fully demonstrated from a neurological perspective. METHODS: It was carried out on a group of patients who had COVID-19 in the last 6 months between February and August 2021 in Diyarbakir Gazi Yasargil Training and Research Hospital. Patients between the ages of 18-50, who applied to the otorhinolaryngology and neurology clinic and had COVID-19 in the last 6 months, were selected. The COVID-19 group of our study consisted of 30 patients, 18 males and 12 females, who had had COVID-19 disease in the last 6 months, and 30 healthy individuals, 16 males and 14 females, as the control group. RESULTS: In patients with COVID-19, the evaluation of the destruction of the cochlear nerve with BERA showed that there was a statistically significant prolongation in I-III and I-V interpeaks at 70, 80 and 90 db nhl. CONCLUSIONS: Statistically significant prolongation of especially I-III and I-V Interpeaks in BERA showed that COVID-19 has the potential to cause neuropathy. We believe that the BERA test should be considered in the neurological evaluation of cochlear nerve damage in patients with COVID-19 as a differential diagnosis.

Dysphagia, texture modification, the elderly and micronutrient deficiency: a review.

Dysphagia is an underlying symptom of many health issues affecting a person's ability to swallow. Being unable to swallow correctly may limit food intake and subsequently micronutrient status. The elderly may be the most at risk group of suffering dysphagia as well as most likely to be deficient in micronutrients. The use of texture-modified meals is a common approach to increasing dysphagia sufferer's food intake. The modification of food may affect the micronutrient content and currently there is a limited number of studies focusing on micronutrient content of texture-modified meals. This review considers the prevalence of dysphagia within the elderly UK community whilst assessing selected micronutrients. Vitamin B12, C, D, folate, zinc and iron, which are suggested to be most likely deficient in the general elderly UK population, were reviewed. Each micronutrient is considered in terms of prevalence of deficiency, metabolic function, food source and processing stability to provide an overview with respect to elderly dysphagia sufferers.

Rapamycin Improves Vascular Remodelling in a Controlled Rat Model of Monocrotaline-Induced Pulmonary Hypertension

ABSTRACT Background: Pulmonary arterial hypertension (PAH) is a serious disease characterized by the progressive elevation of the pulmonary arterial resistance, leading to the right ventricular failure and death. Objective: To evaluate the effect of rapamycin (RAPA), a potent cell-cycle inhibitor, on exercise capacity, right ventricular hypertrophy and pulmonary vascular remodelling on rats. Methods: A total of 39 nine-week-old male Wistar rats (160-240 g) were divided into three groups: the control (n = 10), PAH control (n = 15) and PAH-RAPA (n = 14) groups. On the 1st day, 60 mg/kg monocrotaline was injected intraperitoneally to induce PAH in the PAH control group and PAH-RAPA groups. On the 21st day, 3 mg/kg/day RAPA was started orally, and the animals were followed for 35 days. On the 35th day, the exercise capacity of the rats was analysed through a modified forced swimming test. After measuring their right ventricular systolic pressure using an open-chest method, their hearts and lungs were excised and analysed histopathologically for right ventricular hypertrophy and pulmonary vascular remodelling. Results: Rapamycin treatment provided limited and insignificant improvements in exercise capacity, right ventricular systolic pressure and right ventricular hypertrophy of the rats. However, there was significant recovery in the rats' pulmonary artery muscular layer thickness with the RAPA treatment (p < 0.049). On the 35th day, the mortality rate was 0% in the control group, 53.1% in the PAH control group and 42.9% in the PAH-RAPA group. No statistically significant decrease was observed in their mortality rates with the RAPA treatment (p > 0.16); however, a significant recovery was noted in terms of the rats' median life span (p < 0.006). Conclusion: Pulmonary artificial hypertension is a progressive disease that is not curable with current therapies. Rapamycin may have the potential to reverse vascular remodelling and prolong life expectancy in cases of pulmonary hypertension.

IL-13 gene polymorphisms (-1112 C/T and -1512 A/C) in patients with chronic and aggressive periodontitis: Effects on GCF and outcome of periodontal therapy.

BACKGROUND: IL-13 is the key cytokine in the regulation of inflammatory with an autoimmune disease and has an anti-inflammatory effect. AIMS: This study aimed to compare IL-13 (-1112 C/T and -1512 A/C) gene polymorphisms in patients with aggressive periodontitis (AgP), chronic periodontitis (CP), and periodontally healthy group (C) and evaluate the effect of nonsurgical periodontal therapy on gingival crevicular fluid (GCF) IL-13 levels in patients. MATERIALS AND METHODS: One hundred thirty patients with AgP, 120 patients with CP, and 70 periodontally healthy subjects were included in this study. Clinical parameters were recorded (plaque and gingival index, probing pocket depth, clinical attachment level), and GCF and blood samples were taken at baseline and 6-week. Nonsurgical periodontal therapy was performed in patients with periodontitis. Gene analyses (IL-13 - 1112C/T (rs1800925) and - 1512 A/C (rs1881457) were performed with real-time polymerase chain reaction (PCR) and cytokine levels were determined by an enzyme-linked immunosorbent assay method. RESULTS: AgP and CP patients showed significant improvement in clinical parameters after periodontal therapy (P < 0.05). According to results, genotype distributions and allele frequencies in IL-13 variants - 1112C/T and - 1512 A/C were found similarly in all groups (P > 0.05). In the AgP group, GCF IL-13 cytokine level is statistically significant and increased in 6 weeks; however, in the CP group, there is no statistically significant difference between baseline and 6 week. In the AgP group, baseline GCF IL-13 cytokine level is lower than those of the CP group and C group (P < 0.05). CONCLUSION: Within the limits of this study, IL-13 -1112 and -1512 gene polymorphisms have not been associated with AgP and CP, and GCF IL-13 cytokine level is increased after treatment in the AgP group.

Object-mediated overwriting across saccades.

How are visual sensory representations that are acquired peripherally from a saccade target related to sensory representations generated foveally after the saccade? We tested the hypothesis that, when the two representations are perceived to belong to the same object, the post-saccadic value tends to overwrite the pre-saccadic value. Participants executed a saccade to a colored target object, which sometimes changed during the saccade by ±15°, 30°, or 45° in color space. They were post-cued to report either the pre-saccadic or post-saccadic color in a continuous report procedure. Substantial overwriting of the pre-saccadic color by the post-saccadic color was observed. Moreover, the introduction of a brief post-saccadic blank interval (which disrupted the perception of object correspondence) led to a substantial reduction in overwriting. The results provide the first direct evidence for an object-mediated overwriting mechanism across saccades, in which post-saccadic values automatically replace pre-saccadic values.

An assessment of nutrition information on front of pack labels and healthiness of foods in the United Kingdom retail market.

BACKGROUND: Front of pack nutrition labelling is part of United Kingdom government's programme of activities aiming to tackle diet-related diseases. There are several front of pack labelling formats available and they differ in the information they deliver. This study assessed the frequency of usage of front of pack food labelling systems on food products in the United Kingdom grocery market. It also measured the healthiness of some foods in the online market by categorising them according to their nutrient contents. METHODS: Five hundred food products in five categories [(1) cereals and cereal products, (2) dairy products, (3) beverages, (4) packaged meats and meat products, and (5) pre-packaged fruits and vegetables] from three main United Kingdom retail websites were investigated. A simple random sampling method was used for product selection according to the categories on the retailers' websites. The healthiness of foods was also assessed by categorising them into 'healthier', 'moderately healthy' and 'least healthy' based on fat, saturated fat, salt and sugar contents. RESULTS: The total number of label types assessed comprises 19.6% of Guideline Daily Amounts or Reference Intakes and 43.8% had a combination of Traffic Light and Reference Intakes (hybrid label). Slightly over a quarter (27.4%) of products included nutritional information in a grid or table, 3.4% of the foods had two of any of the following: Health Logo, Reference Intakes and Traffic Light labels, and 5.8% did not have any Reference Intakes, Traffic Light, Health Logo or Hybrid label. Most of the foods assessed were manufactured in the United Kingdom with only 30.8% imported from 32 countries across four continents. CONCLUSIONS: Traffic Light and Guideline Daily Amounts were the most used front of pack labelling formats on the assessed food product. A higher number of assessed products belonged to the "moderately healthy" and "healthier" categories than the "least healthy". The imported foods that were found in the United Kingdom retail market showed that food choices could be made from the diverse food types.

Age-related decline in visual working memory: The effect of nontarget objects during a delayed estimation task.

Visual working memory (VWM) is an essential aspect of cognitive functioning that becomes compromised in older adults. A canonical probe of VWM is the change detection task in which participants compare a visually presented stimulus with items being maintained in VWM. Older adults show a decreased ability to detect changes between a stimulus and the contents of VWM compared with younger adults. Previously, we used a dynamic neural field (DNF) model to explore changes in neural connectivity that can explain this pattern of decline in performance. These simulations suggest that older adults have cortical interactions that are more diffuse compared to younger adults. In the current article, we examined the precision of representations in VWM using the delayed-estimation task. Participants are first presented with a memory array. After a delay, a location is cued, and participants click on a color wheel to indicate which color was at that location. The model predicted that older adults should show increased guessing rates and decreased precision (defined as the variability of color responses around the target location) relative to younger adults. The model also predicted that presenting the nontarget items during test should improve the precision of responses for older adults but not for younger adults. Results from two experiments supported these predictions of the model. These findings further advance an emerging theory of the neurocognitive decline of VWM and illustrate how older adults' VWM representations are influenced by the context in which information is being recalled. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Temporomandibular arthropathies: A retrospective study with histopathological characteristics.

BACKGROUND: To investigate the incidence of temporomandibular arthropathies diagnosed in a university center and to describe their histopathological characteristics. MATERIAL AND METHODS: Temporomandibular arthropathy cases with corresponding slides were selected from an oral and maxillofacial surgical pathology service. Cases of exclusively articular disc disease were not included. RESULTS: The mean age was 31.3 years with a predominance of females (69.7%). Of these diagnoses, 53.6% were unilateral condylar hyperplasia, 17.8% were bony ankylosis, 14.3% were degenerative joint disease, 10.7% were osteochondroma, and 3.6% were synovial chondromatosis. Condylar hyperplasia presented as thick fibrocartilage and cartilage nests in the cancellous bone. Bony ankylosis exhibited lamellar bone and nests of chondrocytes. Degenerative joint disease presented as an irregular layer of fibrocartilage with areas of clustered chondrocytes and calcified cartilage. Osteochondroma of the condyle exhibited hyaline cartilage and areas of new bone formation. Synovial chondromatosis presented as immature cartilaginous tissue and randomly arranged chondrocytes. CONCLUSIONS: The pathological alterations verified in these arthropathies involved diseases that were predominantly proliferative, i.e., unilateral condylar hyperplasia, osteochondroma and synovial chondromatosis of the tumor or pseudotumor type and bony ankylosis associated with callus formation of the reparative type, and less frequent degenerative changes for which the disease is so named.

Effect on oxidative stress, hepatic chemical metabolizing parameters, and genotoxic damage of mad honey intake in rats.

A total of 66 male Wistar rats were used and six groups (control: 10 animals and experimental: 12 animals) were formed. While a separate control group was established for each study period, mad honey application to the animals in the experimental group was carried out with a single dose (12.5 g kg-1 body weight (b.w.); acute stage), at a dose of 7.5 g kg-1 b.w. for 21 days (subacute stage), and at a dose of 5 g kg-1 b.w. for 60 days (chronic stage). Tissue and blood oxidative stress markers (malondialdehyde (MDA), nitric oxide (NO), 4-hydroxynonenal (HNE), superoxide dismutase, catalase, glutathione (GSH) peroxidase, and glucose-6-phosphate dehydrogenase), hepatic chemical metabolizing parameters in the liver (cytochrome P450 2E1, nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase, nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductase (CYTC), GSH S-transferase (GST), and GSH), and micronucleus and comet test in some samples were examined. Findings from the study showed that single and repeated doses given over the period increased MDA, NO, and HNE levels while decreasing/increasing tissue and blood antioxidant enzyme activities. From hepatic chemical metabolizing parameters, GST activity increased in the subacute and chronic stages and CYTC activity increased in the acute period, whereas GSH level decreased in the subacute stage. Changes in tail and head intensities were found in most of the comet results. Mad honey caused oxidative stresses for each exposure period and made some significant changes on the comet test in certain periods for some samples obtained. In other words, according to the available research results obtained, careless consumption of mad honey for different medical purposes is not appropriate.

The viral capping enzyme nsP1: a novel target for the inhibition of chikungunya virus infection.

The chikungunya virus (CHIKV) has become a substantial global health threat due to its massive re-emergence, the considerable disease burden and the lack of vaccines or therapeutics. We discovered a novel class of small molecules ([1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones) with potent in vitro activity against CHIKV isolates from different geographical regions. Drug-resistant variants were selected and these carried a P34S substitution in non-structural protein 1 (nsP1), the main enzyme involved in alphavirus RNA capping. Biochemical assays using nsP1 of the related Venezuelan equine encephalitis virus revealed that the compounds specifically inhibit the guanylylation of nsP1. This is, to the best of our knowledge, the first report demonstrating that the alphavirus capping machinery is an excellent antiviral drug target. Considering the lack of options to treat CHIKV infections, this series of compounds with their unique (alphavirus-specific) target offers promise for the development of therapy for CHIKV infections.