Central tolerance shapes the neutralizing B cell repertoire against a persisting virus in its natural host.

Viral mimicry of host cell structures has been postulated to curtail the B cell receptor (BCR) repertoire against persisting viruses through tolerance mechanisms. This concept awaits, however, experimental testing in a setting of natural virus-host relationship. We engineered mouse models expressing a monoclonal BCR specific for the envelope glycoprotein of lymphocytic choriomeningitis virus (LCMV), a naturally persisting mouse pathogen. When the heavy chain of the LCMV-neutralizing antibody KL25 was paired with its unmutated ancestor light chain, most B cells underwent receptor editing, a behavior reminiscent of autoreactive clones. In contrast, monoclonal B cells expressing the same heavy chain in conjunction with the hypermutated KL25 light chain did not undergo receptor editing but exhibited low levels of surface IgM, suggesting that light chain hypermutation had lessened KL25 autoreactivity. Upon viral challenge, these IgMlow cells were not anergic but up-regulated IgM, participated in germinal center reactions, produced antiviral antibodies, and underwent immunoglobulin class switch as well as further affinity maturation. These studies on a persisting virus in its natural host species suggest that central tolerance mechanisms prune the protective antiviral B cell repertoire.

Stopping Microfluidic Flow.

A cross-comparison of three stop-flow configurations-such as low-pressure (LSF), high-pressure open-circuit (OC-HSF), and high-pressure short-circuit (SC-HSF) stop-flow-is presented to rapidly bring a high velocity flow O(m s-1) within a microchannel to a standstill O(µm s-1). The performance of three stop-flow configurations is assessed by measuring residual flow velocities within microchannels having three orders of magnitude different flow resistances. The LSF configuration outperforms the OC-HSF and SC-HSF configurations within a high flow resistance microchannel and results in a residual velocity of <10 µm s-1. The OC-HSF configuration results in a residual velocity of <150 µm s-1 within a low flow resistance microchannel. The SC-HSF configuration results in a residual velocity of <200 µm s-1 across the three orders-of-magnitude different flow resistance microchannels, and <100 µm s-1 for the low flow resistance channel. It is hypothesized that residual velocity results from compliance in fluidic circuits, which is further investigated by varying the elasticity of microchannel walls and connecting tubing. A numerical model is developed to estimate the expanded volumes of the compliant microchannel and connecting tubings under a pressure gradient and to calculate the distance traveled by the sample fluid. A comparison of the numerically and experimentally obtained traveling distances confirms the hypothesis that the residual velocities are an outcome of the compliance in the fluidic circuit.

Coumarin-Phosphazenes: Enhanced Photophysical Properties from Hybrid Materials.

Phosphazenes have drawn a great deal of interest over the past 20 years as a potentially useful building block for the fabrication of fluorescent materials. The main objective of this work is to explore novel derivatives produced by coumarins, a class of chemicals well-known for their photophysical importance, and cyclophosphazenes. UV absorbance, fluorescence emission, quantum yield, and lifetime measurements were conducted to comprehend the optical properties. Furthermore, single-crystal X-ray analysis and theoretical calculations were carried out to confirm the structure of the molecule. The obtained findings collectively confirm the commendable optical properties exhibited by the studied compounds. Moreover, a detailed study of the crystal packing arrangement of DPP-Et-Kum-Et compound crystallized in the P21/n monoclinic space group revealed the presence of stacking interactions between the nonplanar conjugated benzene rings of the coumarins and the rigid diphenyl groups attached to the phosphazene ring. The crystal structure of the DPP-Kum-Me-Me compound is mainly based on classical C-H···O intermolecular hydrogen bonding interactions with an average distance of 2.52 Å. Importantly, the calculated absorption spectra of the compounds are in close agreement with the experimental data, further supporting their interesting electronic properties. Given that the DPP-Et-Kum-Et and DPP-Kum-Et compounds have the theoretically lowest band gaps (4.31 and 4.30 eV, respectively), the activation energies of these compounds were determined by an impedance analyzer using dc conductance values measured at different temperatures. The calculated activation energies for DPP-Et-Kum-Et and DPP-Kum-Et are 104.49 and 100.92 meV, respectively. The results demonstrate that both theoretical and experimental calculations are in agreement with each other and that the DPP-Kum-Et compound has the lowest conductivity.

A Novel and Simple Method for a Differentiation of Alcohol Types.

BACKGROUND: Alcohol poisoning is a significant global problem that has become an epidemic. The determination of the alcohol type is hereby essential as it may affect the course of the treatment; however, there is no routine laboratory diagnostic method for alcohol types other than for ethanol. In this study, we aimed to define a simple method for alcohol type differentiation by utilizing a combination of breathalyzer and spectrophotometrically measured serum ethanol results. METHODS: A breathalyzer and spectrophotometry were used to measure four different types of alcohol: ethanol, isopropanol, methanol, and ethylene glycol. To conduct serum alcohol analysis, four serum pools were created, each containing a different type of alcohol. The pools were analyzed using the spectrophotometric method with an enzymatic ethanol test kit. An experiment was conducted to measure the different types of alcohol using impreg-nated cotton and a balloon, simulating a breathalyzer test. An algorithm was created based on the measurements. RESULTS: Based on the results, the substance consumed could be methanol or isopropanol if the breathalyzer test indicates a positive reading and if the blood ethanol measurement is negative. If both the breathalyzer and the blood measurements are negative, the substance in question may be ethylene glycol. CONCLUSIONS: This simple method may determine methanol or isopropanol intake. This straightforward and innovative approach could assist healthcare professionals in different fields with diagnosing alcohol intoxication and, more precisely, help reducing related morbidity and mortality.

Predictive Value of the Naples Prognostic Score on Long-Term Outcomes in Patients with Peripheral Artery Disease Revascularized via Percutaneous Intervention.

BACKGROUND: Lower extremity peripheral artery disease (PAD) is the third most common clinical manifestation of atherosclerosis after coronary artery disease and stroke. Despite successful endovascular treatment (EVT), mortality and morbidity rates still remain higher in patients with PAD. Naples prognostic score (NPS) is a novel scoring system, reflects the patient's nutritional and immunological statuses as well as systemic inflammatory responses. In this study, we aimed to investigate the relationship between NPS and long-term outcomes in patients with PAD. METHODS: The population of this retrospective study consisted of 629 PAD patients who underwent EVT at Kafkas University Hospital between 2020 and 2023. For each patient, the NPS was calculated and then patients were divided into 3 groups based on their NPS. The primary end point of the study was the rate of major adverse cardiovascular (MACEs) and limb events (MALEs), that is, all-cause death or development of critical limb ischemia with consequent amputation. RESULTS: Of a total of 629 patients, 62 were classified into group 0 (NPS 0), 315 into group 1 (NPS 1 or 2), and 252 into group 2 (NPS 3 or 4). The distribution of patients' baseline characteristics, angiographic features and MACEs and MALEs according to the NPS groups was analyzed. Significant adverse outcomes differences were observed among the 3 groups (P < 0.001). Multivariate logistic regression analysis revealed that age, diabetes mellitus, chronic kidney disease, lowest preprocedure ankle-brachial index, left ventricular ejection fraction and NPS (hazard ratio 1.916, 95% confidence interval [CI] 1.530-2.398, P < 0.001) were independent predictors of MACE whereas diabetes mellitus, presence of previous PAD, hemoglobin level, in-hospital acute thrombotic occlusion and NPS (odds ratio 1.963, 95% CI 1.489-2.588, P < 0.001) were independent predictors of MALE. CONCLUSIONS: The inflammatory and nutritional state reflected by NPS levels was strongly associated with all-cause mortality and amputation after EVT in patients with PAD. Furthermore, NPS was found to be an independent predictor of these clinical outcomes.

The Efficacy and Safety of Retrograde Intrarenal Surgery in Elderly Patients: A Propensity Score Matching Study by the RIRSearch Group.

INTRODUCTION: To evaluate the efficacy and safety of retrograde intrarenal surgery (RIRS) in elderly patients by comparing them with propensity score-matched age groups. METHODS: Patients who underwent RIRS to treat upper urinary tract stone disease at seven centers were included in the study and were divided into four groups. The age intervals of the patients in Group 1, Group 2, Group 3, and Group 4 were 18-29 years old, 30-49 years old, 50-64 years old, and over 65 years old, respectively. Propensity score matching analysis was used to homogenize the groups in terms of demographic and clinical properties. Operative results, preoperative complications, peroperative complications, postoperative complications, duration of hospitalization time, and stone-free status were compared between groups. RESULTS: A total of 1,017 patients were included in the study. There were 69 (9.9%) patients in Group 1, 324 (46.5%) in Group 2, 217 (31.1%) in Group 3, and 87 (12.5%) in Group 4 after propensity score matching. The operation time and postoperative complication rates were significantly different among groups, whereas the hospitalization time, peroperative complication rates, and stone-free status were similar. The operation time was significantly higher in patients over 65 years old (p=0.001). The postoperative complication rates were significantly higher in Group 1 with Clavien I-II complication predominance (p=0.003). CONCLUSION: The efficacy and safety of RIRS did not change with aging, and RIRS was an effective option for the treatment of upper urinary system stones in elderly patients.

Responses of Five Different Artificial Intelligence Chatbots to the Top Searched Queries About Erectile Dysfunction: A Comparative Analysis.

The aim of the study is to evaluate and compare the quality and readability of responses generated by five different artificial intelligence (AI) chatbots-ChatGPT, Bard, Bing, Ernie, and Copilot-to the top searched queries of erectile dysfunction (ED). Google Trends was used to identify ED-related relevant phrases. Each AI chatbot received a specific sequence of 25 frequently searched terms as input. Responses were evaluated using DISCERN, Ensuring Quality Information for Patients (EQIP), and Flesch-Kincaid Grade Level (FKGL) and Reading Ease (FKRE) metrics. The top three most frequently searched phrases were "erectile dysfunction cause", "how to erectile dysfunction," and "erectile dysfunction treatment." Zimbabwe, Zambia, and Ghana exhibited the highest level of interest in ED. None of the AI chatbots achieved the necessary degree of readability. However, Bard exhibited significantly higher FKRE and FKGL ratings (p = 0.001), and Copilot achieved better EQIP and DISCERN ratings than the other chatbots (p = 0.001). Bard exhibited the simplest linguistic framework and posed the least challenge in terms of readability and comprehension, and Copilot's text quality on ED was superior to the other chatbots. As new chatbots are introduced, their understandability and text quality increase, providing better guidance to patients.

Single hybrid population but multiple parental individuals at the origin of parthenogenetic rock lizards Darevskia sapphirina and D. bendimahiensis Schmidtler, & Eiselt Darevsky (1994) endemic to the area of Lake Van in East Turkey.

Among vertebrates, obligate parthenogenesis is only found in Squamata, where it always has a hybrid origin and a few lizard genera contain most of the known hybridogenous parthenogenetic taxa. Parthenogenesis thus seems to be pre-conditioned at the genus level, but it is not clear how often the encounter between two parental sexually reproducing species can result in the parthenogenetic offspring, nor whether the success of such hybridization event requires certain conditions or the specific time frame. To address this question, we studied the rock lizards of genus Darevskia, where a pair of parental species, D. valentini and D. raddei, as well as their parthenogenetic daughter species D. bendimahiensis and D. sapphirina, are found in close proximity NE of the Lake Van in East Anatolia. Using ddRAD-seq genotyping on 19 parental and 18 hybrid individuals, we found that (i) all parthenogenetic individuals from both D. bendimahiensis and D. sapphirina have a monophyletic origin tracing back to a single initial hybrid population, but their current genetic variation is geographically structured; (ii) unlike the most probable paternal ancestor, the genetically closest extant population of the maternal ancestor is not the geographically nearest one; and (iii) in the parthenogens, about 1% of loci carry multiple haplotypes, frequently differentiated by multiple substitutions. This pattern, in addition to biases in the relative frequency of haplotypes of maternal and paternal origin, does not appear compatible with a scenario of the entire parthenogenic clonal population having descended from a single pair of parental individuals. Instead, the data suggest that multiple parental individual ancestries still persist in the parthenogenetic gene pool. This supports the notion that although hybridization leading to parthenogenesis is generally rare at the level of species, it may be more common at the individual/population level once the right conditions are met.

From Nose to Lumbar Spinal Cord - Reduced Sperm Numbers Occur by Olfactory Bulbectomy-Related Onuf's Nucleus Degeneration: New Experimental Evidence for Kallmann Syndrome.

INTRODUCTION: Olfaction and its relation to human health is an area of growing interest. Although olfaction disorders have been considered a part of Kallmann syndrome, the role of olfactory dysfunction on spermatogenesis has not been studied yet. We studied if olfactory bulbectomy (OBX) causes dysfunction in spermatogenesis as a result of Onuf's nucleus damage. METHODS: Twenty-eight male rats were divided into three groups: six as the control (G-1; n = 6), six as the only frontal burr hole applied animals SHAM (G-2; n = 6), and 16 as the study group (G-3; n = 16) in which OBX was performed. The animals were followed for 2 months. After the decapitation of the animals, olfactory bulb (OB) volumes (mm3), the neuron density of the Onuf's nucleus (n/mm3), and sperm density (n/mm3) were estimated stereologically and analyzed. RESULTS: OB volumes (mm3), degenerated neuron density of Onuf's nucleus (n/mm3), and sperm numbers of control, SHAM, and study groups were estimated as: 4 ± 0.5; 6 ± 2 and 103.245 ± 10.841 in G-1; 3.5 ± 0.7; 14 ± 4 and 96.891 ± 9.569 in G-2; and 1.3 ± 0.3; 91 ± 17 and 73.561 ± 6.324 in G-3. The statistical results of degenerated neuron density of Onuf's nucleus and sperm numbers between groups are p < 0.005 for G-1/G-2; p < 0.0005 for G-2/G-3; and p < 0.00001 for G-1/G-3. DISCUSSION: This study first time indicates that Onuf's nucleus degeneration secondary to OBX seems to be responsible for reduced sperm numbers.

The Predictive Factors for the Longer Survival of the Reusable Flexible Ureterorenoscopy.

PURPOSE: The flexible ureterorenoscopy (FURS) is expensive and fragile equipment which easily break down during the surgery. f-URS have yet some problems with their durability that affect survival. One of the most important ways to increase the survival of a device is to improve its use in the right indications. We aimed to investigate whether the durability of the f-URS will be affected due to the volume and location of the stone and some anatomical features of the including infundibulopelvic angle (IPA), and location anomalies. MATERIALS AND METHODS: The collected data from 705 patients' data including their age, sex, stone location, and stone volume, S-ReSC score, Hounsfield unit (HU) as stone density, IPA, BMI, and the usage time of f-URS using 10f-URS were included to study. Exp(B) values and confidence intervals (95% CIs) of parameters were calculated with COX regression and Roc curve analysis was also used to determine the cut-off value. RESULTS: Renal malformation, DJstent use, previous ESL application, and UAS use did not affect contrary to expectations stone volume, HU, IPA, and S-ReSC score were among the factors statistically significant affecting the durability of the device. It was observed, Exp(B) values of the affecting factors to be 0.984, 0.268, 0.894, and 0.607, respectively. We found the most appropriate cutoff value for IPA as 41.25 degrees. CONCLUSION: The mean stone volume broken by each of the subsequent f-URS may increase, while the mean operative time may decrease as time progresses. This result shows us the importance of mastery of the device, such as the deflection maneuver, and the correct use distance of the laser, which improves with the increase in user experience, and makes us interpret that the operation time is shortened with this self-confidence. Factors including stone volume, HU, IPA, S-ReSC score affect the durability of the f-URS device and the as well as manufacturing features.

Overexpression of POFUT1 promotes malignant phenotype and mediates perineural invasion in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive neoplasms, which requires more effective prevention and treatment modalities. Previous studies found that protein O-fucosyltransferase 1 (POFUT1) upregulation promotes carcinogenesis, although the potential roles, underlying molecular mechanisms, and biological implications of POFUT1 in HNSCC were not investigated. In this study, in silico analyses referred POFUT1 as a potential oncogene in HNSCC. Further analysis of tumor and normal tissue samples as well as HNSCC cells with quantitative real-time polymerase chain reaction, Western blot analysis, and immunohistochemistry showed significant overexpression of POFUT1 in HNSCC clinical tumor tissue specimens and cell lines compared to corresponding controls. In vitro investigations revealed that overexpression of POFUT1 promoted phenotypes associated with cancer aggressiveness and its knockdown in HNSCC cells suppressed those phenotypes. Further xenograft experiments demonstrated that POFUT1 is an oncogene in vivo for HNSCC. Immunohistochemical analysis with human clinical samples and cancer cell-dorsal root ganglion ex-vivo coculture model showed that deregulation of POFUT1 is involved in the perineural invasion of HNSCC cells. These results suggest POFUT1 expression as a potential prognostic marker for patients with head and neck cancer and highlight its potential as a target for HNSCC therapy, although more molecular clues are needed to better define the functions of POFUT1 related to HNSCC carcinogenesis.

Low relapse rate in patients with giant cell arteritis in a multi-centre retrospective Turkish Registry.

OBJECTIVES: Glucocorticoids (GC) are widely accepted as the standard first-line treatment for giant cell arteritis (GCA). However, relapse rates are reported up to 80% on GC-only protocol arms in controlled trials of tocilizumab and abatacept in 12-24 months. Herein, we aimed to assess the real-life relapse rates retrospectively in patients with GCA from Turkey. METHODS: We assembled a retrospective cohort of patients with GCA diagnosed according to ACR 1990 criteria from tertiary rheumatology centres in Turkey. All clinical data were abstracted from medical records. Relapse was defined as any new manifestation or increased acutephase response leading to the change of the GC dose or use of a new therapeutic agent by the treating physician. RESULTS: The study included 330 (F/M: 196/134) patients with GCA. The mean age at disease onset was 68.9±9 years. The most frequent symptom was headache. Polymyalgia rheumatica was also present in 81 (24.5%) patients. Elevation of acute phase reactants (ESR>50 mm/h or CRP>5 mg/l) was absent in 25 (7.6%) patients at diagnosis. Temporal artery biopsy was available in 241 (73%) patients, and 180 of them had positive histopathological findings for GCA. For remission induction, GC pulses (250-1000 methylprednisolone mg/3-7 days) were given to 69 (20.9%) patients, with further 0.5-1 mg/kg/day prednisolone continued in the whole group. Immunosuppressives as GC-sparing agents were used in 252 (76.4%) patients. During a follow-up of a median 26.5 (6-190) months, relapses occurred in 49 (18.8%) patients. No confounding factor was observed in relapse rates. GC treatment could be stopped in only 62 (23.8%) patients. Additionally, GC-related side effects developed in 64 (24.6%) patients, and 141 (66.2%) had at least one Vasculitis Damage Index (VDI) damage item present during follow-up. CONCLUSIONS: In this first multi-centre series of GCA from Turkey, we observed that only one-fifth of patients had relapses during a mean follow-up of 26 months, with 76.4% given a GC-sparing IS agent at diagnosis. At the end of follow-up, GC-related side effects developed in one-fourth of patients. Our results suggest that patients with GCA had a low relapse rate in real-life experience of a multi-centre retrospective Turkish registry, however with a significant presence of GC-associated side effects during follow-up.

The effect of the pandemic period on Bladder Pain Syndrome patients under amitriptyline treatment.

INTRODUCTION: COVID-19 is a disease that may cause anxiety, depression, and stress. Bladder pain syndrome (BPS) is a disease in which stress and psychological factors might negatively affect its course. In this study, we aimed to examine the possible clinical aggregation of the pandemic period on BPS patients. MATERIALS AND METHODS: A total of 35 BPS patients diagnosed between 2010 and 2018 were included. All patients were using medical treatment, and the follow-up period was at least 6 months. According to our clinical follow-up protocol, the BPS patients were given the King's Health Questionnaire (KHQ), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Overactive Bladder Form V8 (OAB-V8), and Visual Analog Score (VAS) in every visit. In the sixth month of the pandemic, the clinical course of the patients was questioned by telephone or video interview, and their treatment continuities were questioned. Information was received about the delays in their follow-up and the difficulties in accessing healthcare opportunities. The same questionnaires were filled out and compared with pre-pandemic scores. RESULTS: The mean age of the patients included in the study was 50.2 ± 13.32 (min:20, max:74), 11 were males and 24 were females. The mean follow-up periods were 71.8 ± 35.6 months. All questionnaire scores showed an increase compared to the pre-pandemic period. A statistically significant increase was detected during the pandemic in all sub-units of the KHQ. The VAS and OAB-V8 scores of 16 patients who requested hospital admission were significantly higher than before the pandemic. However, there was no statistically significant difference in the increase in VAS and OAB-V8 scores of the 19 patients who refused to come to the hospital. CONCLUSION: BPS patients have been negatively affected by the emotional effects of the COVID-19 pandemic. Due to the fear, stress, anxiety, and depression, the symptoms of BPS patients exacerbated, and the patients could not receive the necessary support due to a lack of regular follow-ups.

Enterococcus gallinarum group meningitis after transanal migration of the ventriculoperitoneal shunt: a pediatric case report.

In the literature, only 11 Enterococcus gallinarum group meningitis has been reported so far. The Enterococcus gallinarum group was shown for the first time in a pediatric patient presenting with meningitis after bowel perforation, a complication of a ventriculoperitoneal shunt. A 30-month-old male patient presented with vomiting and fever, with the ventriculoperitoneal shunt distal catheter protruding from the anal orifice. The patient was diagnosed with intestinal perforation and meningitis. Enterococcus gallinarum group bacterial yield in cerebrospinal fluid culture. A total of 6 weeks of intravenous antibiotic treatment was given in the hospital. After the treatment, the patient was re-ventriculoperitoneal shunt and was discharged. Among the shunt complications, meningitis with intestinal perforation is rare. It should be kept in mind that meningitis in such patients may be caused by very rare microbiological factors such as Enterococcus gallinarum group. Antibiotherapy should be given according to the culture result. Then planning should be made for a permanent shunt.

New surgical technique for non-missile trauma hemostasis as a result of sewing needle.

Traumas are the most important cause of mortality in the pediatric population. Bleeding is an important complication, especially in traumatic brain injuries with coagulation problem addition. Low-velocity penetrating brain injuries may be caused by sewing needles, nails, and knives. There are few studies in the literature for this injury type. This study presented a surgical technique and treatment to increase hemostasis in a 2-year-old patient after a sewing needle injury.

Retrograde Intrarenal Surgery Learning Curves of Urology Residents Supervised by an Experienced Endourologist: An RIRSearch Study.

INTRODUCTION: Although retrograde intrarenal surgery (RIRS) is being performed with increasing frequency, there are only a limited number of studies about the learning curve (LC). This study aimed to analyze the LC of RIRS for five surgeons who underwent the same training. MATERIALS AND METHODS: The data of the 410 patients who underwent RIRS between April 2017 and 2022 in a single institution, which were performed consecutively by five surgeons, were analyzed. All 50 cases performed by each surgeon were included and numbered consecutively and separately, according to the date of the operation. The combined stone-free rate (SFR) was calculated for each surgeon's cases in the same row, and the LCs were created using moving average and cumulative sum (CUSUM) analyses. Separate multivariable analyses identified each period's (LC vs. beyond) characteristics. RESULTS: The LCs from the combined SFRs reached a plateau after approximately 50 cases for both the CUSUM and the moving average. The effect of stone burden on SFR was more evident in the first 50 cases compared to subsequent cases in the multivariable analyses (p = 0.001 and p = 0.047, respectively). Case order and stone density were independent factors in the first 50 cases (OR: 1.02 [95% CI 1.00-1.04], p = 0.04 and OR: 0.99 [95% CI 0.99-1.00], p = 0.04) but not significant in subsequent cases (OR: 0.97 [95% CI 0.94-1.00], p = 0.1 and OR: 1.00 [95% CI 0.99-1.00], p = 0.7, respectively). Compared to single locations except the lower calyx, the unfavorable effect of the multiple-stone localization on SFR grew in strength after the 50th case (OR: 0.42 [95% CI 0.23-0.78], p = 0.01 and OR: 0.20 [95% CI 0.09-0.46], p < 0.001, respectively). CONCLUSIONS: This is the first study reporting on the RIRS LCs of urology residents. While stone burden, density, and multiple-stone localization were the factors determining SFR in the learning period, after completing the LC, the effect of stone burden weakened and multiple-stone localization became stronger.

Combined Pulsed Magnetic Field and Radiofrequency Electromagnetic Field Enhances MMP-9, Collagen-4, VEGF Synthesis to Improve Wound Healing Via Hif-1α/eNOS Pathway.

BACKGROUND: The blood supply of the tissue is very important in the acceleration of wound healing. Radiofrequency electromagnetic field (RF) and the pulsed magnetic field (PMF) increase vasodilation to contribute wound healing. The aim of this study was to evaluate the effects of RF and PMF on wound healing via hypoxia-inducible factor-1 alpha (Hif-1α)/endothelial nitric oxide synthase (eNOS) pathway. METHODS: Forty-eight rats were divided into 4 groups as sham (wound created only), PMF (27.12 MHz, 12 times a day at 30-min intervals), RF (0.5 mT, continuously) and PMF + RF groups. Wounds were created at 1.5 × 1.5 cm size to the dorsal region, and animals were put into unit. Six animals were killed on days 4 and 7; wound tissues were collected for histopathological, immunohistochemical as collagen-4, cytokeratin, matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF) staining and Hif-1α/eNOS/VEGF expressions. RESULTS: On day 4, in addition to increasing VEGF and MMP-9 stainings, connection between intact tissue and scar tissue which was stronger in the RF- and PMF-applied groups was observed. On day 7, epithelization started; inflammatory reaction decreased; collagen production, cytokeratin, VEGF and MMP-9 expression enhanced, especially in the RF + PMF applied group. eNOS, Hif-1α and VEGF expression levels were found to be significantly highest in both days of RF + PMF-applied group. CONCLUSIONS: This study revealed that both in vitro RF and PMF applications can cause notable changes in factors that are required for tissue repair on wound healing such as epithelization, connective tissue formation, collagen production and angiogenesis via vasodilatory Hif-1α/eNOS pathway and VEGF signaling. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A pulmonary mass extending into the left atrium through the pulmonary vein: a rare diagnosis with an unusual origin.

INTRODUCTION: Myxofibrosarcoma usually occurs in the extremities of middle-aged to older adults. Metastatic myxofibrosarcomas generally emerge in the lung. In this case report, we aim to present a case of primary pulmonary myxofibrosarcoma with tumor thrombus extending into the left atrium without pulmonary vein or atrial invasion. CASE PRESENTATION: A 55-year-old male who was being followed up due to a pulmonary nodule presented with a mass extending from the left lower lobe to the left atrium. No extrathoracic malignancy was detected in the pre-operative examination. The mass extending into the left atrium without invasion was excised with the lower lobe of the left lung. A post-operative histopathological examination revealed myxofibrosarcoma. CONCLUSION: Very few cases of cervical, thoracic wall, mediastinum and cardiac primary myxofibrosarcoma have been documented, and to the best of our knowledge, only one primary pulmonary myxofibrosarcoma case has previously been reported in the English literature. Here, we present a case of primary pulmonary myxofibrosarcoma that extended to the left atrium through the pulmonary vein. In such rare clinical presentations, intracardiac tumor resection should precede pulmonary resection due to the possibility of catastrophic tumor embolisms.

Comparison of craniotomy and limited membranectomy with conventional techniques in the treatment of chronic subdural hematoma.

Background/aim: Chronic subdural hematoma is the most frequently operated on intracranial hemorrhage worldwide. Although surgical results are satisfactory, recurrence remains an important problem. In this study, it was aimed to evaluate patients who underwent craniotomy with limited membranectomy (CwLM) in terms of recurrence rate and other complications. Materials and methods: Electronic records of 291 consecutive patients who were operated on at our clinic (Atatürk University Yakutiye Research Hospital) between 2015 and 2020 were retrospectively reviewed. Their radiological images at the time of admission, clinical status, any early postoperative complications, and clinical status at the 6-month follow-up were all evaluated. Results: According to the results of the study, postoperative mortality and morbidity of patients who underwent CwLM were similar to those with minimally invasive methods, and it reduced recurrence, especially in laminar and separated subtypes. Conclusion: It is our belief that CwLM will be an appropriate treatment approach in suitable patients (radiologically detected) in chronic subdural hematoma, where recurrence is an important problem.

Monoamine oxidase A and B inhibitory activities of 3,5-diphenyl-1,2,4-triazole substituted [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives.

Monoamine oxidase (EC 1.4.3.4, MAO) is a flavin adenine dinucleotide-containing flavoenzyme located on the outer mitochondrial membrane and catalyzes the oxidative deamination of monoaminergic neurotransmitters and dietary amines. MAO exists in humans as two isoenzymes, hMAO-A and hMAO-B, which are distinguished by their tertiary structures, preferred substrates and inhibitors, and selective inhibition of these isoenzymes are used in the treatment of different diseases such as Alzheimer's, Parkinson's and depression. In the present study, we report the design, synthesis and characterization of 3,5-diphenyl-1,2,4-triazole substituted [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives as novel and selective inhibitors of hMAO-B. Twenty one compounds (38, 39a-h, 41a-d, 42a-h) were screened for their inhibitory activity against hMAO-A and hMAO-B by using in vitro Amplex Red® reagent based fluorometric method and all compounds were found to be as selective h-MAO-B inhibitors to a different degree. The compound 42e and 42h displayed the highest inhibitory activity against hMAO-B with IC50 values of 2.51 and 2.81 µM, respectively, and more than 25-fold selectivity towards inhibition of hMAO-B. A further kinetic evaluation of the most potent derivative (42e) was also performed and a mixed mode of inhibition of hMAO-B by the compound 42e was determined (Ki = 0,26 µM). According to our findings the [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole emerged as a promising scaffold for the development of novel and selective hMAO-B inhibitors.