Epistatic Effects Between Amino Acid Insertions and Substitutions Mediate Toxin resistance of Vertebrate Na+,K+-ATPases.

The recurrent evolution of resistance to cardiotonic steroids (CTS) across diverse animals most frequently involves convergent amino acid substitutions in the H1-H2 extracellular loop of Na+,K+-ATPase (NKA). Previous work revealed that hystricognath rodents (e.g., chinchilla) and pterocliform birds (sandgrouse) have convergently evolved amino acid insertions in the H1-H2 loop, but their functional significance was not known. Using protein engineering, we show that these insertions have distinct effects on CTS resistance in homologs of each of the two species that strongly depend on intramolecular interactions with other residues. Removing the insertion in the chinchilla NKA unexpectedly increases CTS resistance and decreases NKA activity. In the sandgrouse NKA, the amino acid insertion and substitution Q111R both contribute to an augmented CTS resistance without compromising ATPase activity levels. Molecular docking simulations provide additional insight into the biophysical mechanisms responsible for the context-specific mutational effects on CTS insensitivity of the enzyme. Our results highlight the diversity of genetic substrates that underlie CTS insensitivity in vertebrate NKA and reveal how amino acid insertions can alter the phenotypic effects of point mutations at key sites in the same protein domain.

COVID-19 radiology CT personnel management.

A new coronavirus outbreak called COVID-19 started in December 2019. In Turkey, the first case was reported on 10 March 2020. In this article, information will be given about the patient and staff management and organization that we have implemented in the Radiology Department of our hospital during the COVID-19 pandemic. The rules we followed were: 1- Performing the examinations of COVID-19 patients and suspects with a CT device isolated from other patients; 2- Reducing the unnecessary workload in imaging modalities other than CT, emergency radiography, and emergency ultrasonography; 3- Directing and managing patients and their relatives in accordance with the mask and distancing rules; 4- Disinfecting the device with an appropriate disinfectant after each patient in order to prevent cross-contamination; 5- Protecting the entire technician team from infection by employing one week work, two weeks off shifts of fixed teams; 6- Ensuring adequate ventilation of the gantry room. Adhering to the above rules, no infection spread was reported from the Radiology department and especially the COVID-19 CT unit.

The structural properties of carotid arteries in carotid artery diseases - a retrospective computed tomography angiography study.

PURPOSE: Aim of the study was to find answers to the following questions: What haemodynamic changes may occur in patients with stenotic, aneurysmal, dissection of the carotid artery and its branches? How do these changes differ in patients with normal and carotid disease? MATERIAL AND METHODS: In order to achieve this aim, the cranio-cervical CT angiography images of patients who were referred to our clinic for any reason and received the diagnosis of carotid stenosis, carotid dissection, and extra or intracranial aneurysm were reviewed retrospectively. RESULTS: Significant differences were detected in the carotid arteries of normal patients and those with aneurysm and dissection. When normal and aneurismal patients were compared, right and left ICA diameters (p = 0.000, p = 0.002, respectively), total ICA diameters (p = 0.000), carotid left Ø diameters (p = 0.026), right and left total Ø diameters (p = 0.024), and Murray's and our cosine values of Ø angles (p = 0.001 and p = 0.022, respectively) were found to be different. Also, in a comparison made between normal patients and patients with dissection, right CCA (p = 0.000), ICA (p = 0.001), ECA (p = 0.004) diameters, total CCA (p = 0.001), ICA (p = 0.009), and ECA (p = 0.003) diameters were also found to be different. CONCLUSIONS: This study showed that the presence of aneurysm plays an important role in the remodelling of the carotid arteries. Also, it is understood that Murray's laws are still valid for the detection of structural deterioration in carotid artery diseases. Hence, it is believed that these data can be used in artificial intelligence studies.

Rationale, design, and methodology of the EPIC (Epidemiology of Polypharmacy and Potential Drug-Drug Interactions in Elderly Cardiac Outpatients) study.

OBJECTIVE: The aim of this study is to assess the prevalence of polypharmacy, inappropriate drug use, and drug-drug interactions (DDIs) in elderly patients presenting at outpatient cardiology clinics in Turkey. METHODS: The EPIC (Epidemiology of Polypharmacy and Potential Drug-Drug Interactions in Elderly Cardiac Outpatients) study will be an observational, real-world, multicenter study conducted to evaluate DDIs and polypharmacy in elderly cardiac outpatients. All consecutive patients (aged ≥65 years) admitted to outpatient cardiology clinics between July 30, 2018 and July 30, 2019 who provide written, informed consent will be enrolled. A total of approximately 5000 patients are to be enrolled in this non-interventional study. All of the data will be collected at one point in time and current clinical practice will be evaluated (ClinicalTrials.gov NCT03370523). RESULTS: Patient demographics, comorbid disease characteristics, laboratory test results, and details of medication use will be collected using self-reports and medical records. The severity of comorbid disease will be recorded and scored according to Charlson Comorbidity Index (CCI) and patients will be divided into 3 groups: mild, those with a CCI score of 1-2; moderate, those with a CCI score of 3-4; and severe, those with a CCI score of ≥5. Polypharmacy will be defined as the use of 5 or more medications at one time. DDIs will be determined using the Lexicomp Online drug interaction screening tool and potentially inappropriate medications will be defined based on the 2015 update of the Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. Severe drug interactions will be defined as those in category D or X. CONCLUSION: EPIC will be the first large-scale study in Turkey to evaluate polypharmacy, potentially inappropriate medications, and DDIs in elderly cardiac outpatients in a real-world clinical setting.

Gray matter changes in patients with deficit schizophrenia and non-deficit schizophrenia.

OBJECTIVES: Reduced gray matter volume is a frequently reported finding in brain imaging studies performed with schizophrenia patients. Some studies suggest a probable link between the negative symptoms of schizophrenia and gray matter loss; however, some of the negative symptoms observed in schizophrenia patients are not primarily linked to the core of schizophrenia. This study aimed to compare gray matter volumes in patients with primary negative symptoms (deficit schizophrenia [DS]), non-DS (NDS) patients, and healthy controls. MATERIALS AND METHODS: The study included 11 DS patients, 18 non-DS patients, and 17 healthy controls. Magnetic resonance imaging (MRI) was performed using a 1.5 Tesla MR unit. The Schedule for Deficit Syndrome (SDS) was used to determine which patients were DS and non-DS. MR images were compared using voxel-based morphometry (VBM) analysis. RESULTS: Contrary to expectations, no evidence to support less gray matter in DS patients than in NDS patients was observed. Furthermore, NDS patients had less gray matter volume in several brain regions (frontal and temporal cortices) than did the DS patients. All patients had perisylvian gray matter volume deficits, though the NDS patients had more widespread volume deficiencies. CONCLUSION: No evidence to support the hypothesis that DS patients have less gray matter volume than those of NDS patients was observed. On the contrary, DS patients had more gray matter volume in some regions; the differences observed in gray matter volume in these brain regions between the 2 patient groups may be responsible for the differences in their clinical manifestations.

Intracranial sewing needles in an adult patient.

A 37-year-old patient is reported with intracranial sewing needles, which were located in the right frontal lobe. Both clinical and radiological findings suggested that these needles must have been introduced in infancy before the closure of anterior fontanelle during an unsuccessful homicide. Usually intracranial foreign objects are placed due to penetrating trauma or surgical procedures. Child abuse has been known for centuries. Many types of physical traumas have been reported, especially in Western countries. In Iran, insertion of sewing needles into the brain aiming to kill the infant have been seen in a lot of cases. This situation takes part in a lot of Persian stories. We reported a 37-year-old man who had 2 intracranial sewing needles with unknown etiology.

The disrupted connection between cerebral hemispheres in schizophrenia patients: a diffusion tensor imaging study.

AIM: In schizophrenia, the disruption of the communication between two brain hemispheres has not been shown clearly in the anatomical aspect despite other studies with different modalities suggested so. In this study, the structural integrity and the variables affecting the structural integrity of the corpus callosum, which is the main connection between two hemispheres, was investigated via diffusion tensor imaging (DTI). METHODS: The participants were evaluated by SCID-I and symptoms of the patients were assessed with PANSS. DT images of 25 schizophrenia patients and 17 healthy volunteers were acquired via 1.5 T MR. Fractioned Anisotropy (FA) values of two groups, measured on the DT images, were compared. RESULTS: It was found that fractioned anisotropy (FA) values were lower in the genu of the patients than the healthy controls; however, there was no difference between the FA values of the patients and the controls in the splenium. Moreover, a significant negative correlation between the splenium FA values and the antipsychotic medication doses; and a trend level negative correlation of splenium FA and PANSS scores were found. CONCLUSION: Corpus callosum is the most important structure that connects two frontal lobes. The hypothesis that posits the fundamental role of the disconnection of frontal lobes in schizophrenia is supported by the findings of this study.