Computed protein-protein enthalpy signatures as a tool for identifying conformation sampling problems

Understanding the thermodynamic signature of protein-peptide binding events is a major challenge in computational chemistry. The complexity generated by both components possessing many degrees of freedom poses a significant issue for methods that attempt to directly compute the enthalpic contribution to binding. Indeed, the prevailing assumption has been that the errors associated with such approaches would be too large for them to be meaningful. Nevertheless, we currently have no indication of how well the present methods would perform in terms of predicting the enthalpy of binding for protein-peptide complexes. To that end, we carefully assembled and curated a set of 11 protein-peptide complexes where there is structural and isothermal titration calorimetry data available and then computed the absolute enthalpy of binding. The initial "out of the box" calculations were, as expected, very modest in terms of agreement with the experiment. However, careful inspection of the outliers allows for the identification of key sampling problems such as distinct conformations of peptide termini not being sampled or suboptimal cofactor parameters. Additional simulations guided by these aspects can lead to a respectable correlation with isothermal titration calorimetry (ITC) experiments (R2 of 0.88 and an RMSE of 1.48 kcal/mol overall). Although one cannot know prospectively whether computed ITC values will be correct or not, this work shows that if experimental ITC data are available, then this in conjunction with computed ITC, can be used as a tool to know if the ensemble being simulated is representative of the true ensemble or not. That is important for allowing the correct interpretation of the detailed dynamics of the system with respect to the measured enthalpy. The results also suggest that computational calorimetry is becoming increasingly feasible. We provide the data set as a resource for the community, which could be used as a benchmark to help further progress in this area

Alkid resin metoduyla hazırlanan wistar ratlarının müze-sergi ve eğitim materyali olarak kullanımı

Alkyd Resin method, patented by the Turkish Patent Institute, is a cadaver preparation and preservation technique. This study examines whether exhibition-museum materials can be produced from rat cadavers processed with alkyd resin method in different postures and whether dissection and suturing can be performed on the samples. Besides, samples prepared with alkyd resin and samples prepared freshly were compared in terms of dissection and suturing. 14 Wistar Albino Rats were used in the study. Seven were prepared with alkyd resin method and the others were freshly prepared for comparison in terms of suturing and dissection. The alkyd resin method was applied to two cadavers as a pretrial and to five cadavers for them to be museum-exhibition and educational materials. Alopecia was detected in two cadavers. In some of the exhibition samples processed with the method mentioned, shrinkage and hardening of the skin was noticed. All the samples prepared with this method became products suitable for suturing and dissection. The exhibition-museum materials prepared with the alkyd resin method have maintained their first body postures. We believe that alkyd resin method can be applied to the entire body, and the products can be used for exhibition and educational purposes. Furthermore, the method should be further popularized, and it should be applied to cadavers of different species so that its applicability increases.Scientific and Technological Research Council of Turkey [TUBITAK] [215O580]This study was supported by Scientific and Technological Research Council of Turkey [TUBITAK] (Project No: 215O580

Geleneksel bir tekniğin gelişimi: Medial malleol kırıklarının tedavisinde 4 mm’lik kanüllü vida ve Kirschner teli tekniği ile 4 mm’lik kanüllü vida, Kirschner teli tekniği ve kayma önleyici mini plak tespitinin karşılaştırılması

BACKGROUND: In this study, we aimed to compare a 4-mm lag screw and Kirschner wire technique versus a 4-mm lag screw and Kirschner wire (K-wire) technique with additional miniplate fixation for the treatment of medial malleolar fractures. METHODS: A total of 23 patients who were diagnosed with isolated fractures of the medial malleolus and operated in our center were retrospectively analyzed. The patients were divided into two groups: Group A, medial malleolar fracture fixed with a 4-mm cannulated screw and a K-wire (n=11) and Group B, a 4-mm cannulated screw and K-wire used for fixation with miniplate fixation for extra stability (n=12). Clinical outcomes were assessed using the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hind foot Score at 2, 6, 12, and 24 months postoperatively. At 12-24 months, the presence of pain and tenderness in the medial malleolus with palpation was evaluated using the visual analog scale (VAS) pain scores. RESULTS: The mean time to union was 2.23 +/- 0.56 (range, 1.8-2.9) months in Group A and 2.46 +/- 0.45 (range, 1.9-3.1) months in Group B, indicating no statistically significant difference between the two groups (p 0.01). However, there was no statistically significant difference in the mean AOFAS scores at 6 and 12 months between the groups (p 0.05). The mean VAS pain scores at 12-24 months postoperatively did not significantly differ between the groups (p>0.05). CONCLUSION: Our study results suggest that the treatment of medial malleolar fractures with a cannulated screw and K-wire with additional stabilization using a miniplate ensures favorable early outcomes with early return to daily living activities. However, both techniques have similar outcomes in the mid-term

A new technique for preparing cadavers using PMMA: Rat and mouse example

Background: Polymethyl methacrylate is a member of the acrylic polymer family with superior optical properties. It is used in dentistry, hospital incubators, lenses, and various surgical fields, especially ortho-pedics. In this preliminary study, we aimed to prepare cadavers using the industrial form of polymethyl methacrylate.Methods: The new technique consists of fixation, washing, purification, impregnation, and polymerization. For the study, two whole rat bodies, two rat front legs and two rat hind legs, one half rat body, two whole mouse bodies, and all internal organs were used. Wistar albino rats and BALB/c mice were used. After the cadaver samples were fixed and washed, they were passed through an alcohol series starting from 50%, completing the purification process. In the next step, a solution was prepared by mixing 100 ml of Thinner into 1000 ml of a mixture containing styrene, methyl methacrylate, and Co(II)2-ethyl hexanoate. The samples were immersed in the solution under negative pressure (from 10 mmHg to 400 mmHg), allowing the samples to absorb the solution thoroughly. They were then treated with methyl ethyl ketone peroxide and the polymerization step was terminated.Results: The cadaver samples obtained using polymer were hard, they maintained the given shape, and showed a relatively transparent quality. The production of these materials took 35 days, excluding fixation. The tissue samples were odorless in the process after polymerization. Also, there was no decay in the samples after the production stage and they could be stored under room conditions.Conclusion: This study determined that cadavers could be prepared using polymethyl methacrylate and methyl ethyl ketone peroxide. The polymer used here cost about $5. The cadavers can be safely exhibited in room conditions for five years without requiring special conditions like pools or cold storage. Further re-search should compare this technique with the plastination technique in terms of texture, color, weight, application time, and cost.(c) 2022 Elsevier GmbH. All rights reserved

The contribution of scholars to the anatomy of the eye and adnexa in islamic geography

From the early period of Islam, Muslim scholars have translated the ancient Greek medical works, and they reached a much more advanced level. Blindness was a major cause of disability in all Islamic geography, so physicians from Islamic territory, particularly Yuhanna ibn Masawayh, Hunain Ibn Ishaq, Rhazes, Ali bin Isa, Ibn-i Sina, and Ibn Al-Haitam, were particularly focused on the anatomy of the eye and diagnosis and treatment of eye diseases. In this study, we aimed to report the contributions of the Muslim scholar on the anatomy of the eye and adnexa for the first time in the literature

Plasticity of the selectivity filter is essential for permeation in lysosomal TPC2 channels

Two-pore channels are pathophysiologically important Na⁺- and Ca²⁺-permeable channels expressed in lysosomes and other acidic organelles. Unlike most other ion channels, their permeability is malleable and ligand-tuned such that when gated by the signaling lipid PI(3,5)P2, they are more Na⁺-selective than when gated by the Ca²⁺ mobilizing messenger nicotinic acid adenine dinucleotide phosphate. However, the structural basis that underlies such plasticity and single-channel behavior more generally remains poorly understood. A recent Cryo-electron microscopy (cryo-EM) structure of TPC2 bound to PI(3,5)P₂ in a proposed open-channel conformation provided an opportunity to address this via molecular dynamics (MD) simulation. To our surprise, simulations designed to compute conductance through this structure revealed almost no Na⁺ permeation events even at very high transmembrane voltages. However further MD simulations identified a spontaneous transition to a dramatically different conformation of the selectivity filter that involved expansion and a flip in the orientation of two core asparagine residues. This alternative filter conformation was remarkably stable and allowed Na⁺ to flow through the channel leading to a conductance estimate that was in very good agreement with direct single-channel measurements. Furthermore, this conformation was more permeable for Na⁺ over Ca²⁺. Our results have important ramifications not just for understanding the control of ion selectivity in TPC2 channels but also more broadly in terms of how ion channels discriminate ions

Prognostic markers of mortality in patients with methanol poisoning

Aim: Methanol is a kind of alcohol, which is used in industry in numerous different products. Methanol intoxication entails high mortality and morbidity rates. In this study, we aimed to investigate the effectiveness of laboratory parameters in determining the severity of exposure in patients presenting with methanol intoxication. Material and Methods: The study was performed in the university hospital between January 1, 2015, and January 1, 2020. All data were obtained retrospectively from the hospital automation system. Receiver Operating Characteristic (ROC) curve was used to determine ideal cut-off values. A logistic regression model was used to perform univariate and multivariate analyses. Results: The study included 49 patients and 3 of them were women. Thirty (61%) received both hemodialysis and intravenous ethanol for treatment. Univariate analysis revealed increased mortality in patients with pH below 7.00, HCO3 below 8.40 (mmol/L), lactate 4.35 (mmol/L), glucose 183 (mg/dl) and above, PCO2 42.7 (mmHg), high osmolarity, and a high anion gap. The results of multivariate logistic regression analysis for model 1 is (pH, bicarbonate, lactate, glucose, PCO2, osmolarity, and anion gap); pH = 4.35 (OR:31.66, 95% CI 3.25-308.5, p=0.003) and PCO2 >= 42.7 (OR: 7.01, 95% CI 1.12-43.96, p=0.038). Discussion: Laboratory parameters would predict mortality. PH emerged as a predictive mortality marker, while blood lactate and high partial carbon dioxide pressure were capable of predicting mortality if pH was excluded. Starting on the treatment with clinical diagnoses decreases mortality in methanol intoxication

Comparison of the caregiver burden of the mothers of children with cerebral palsy and healthy children

The study aims to compare caregiver burden levels of mothers of children with cerebral palsy (CP) to mothers with healthy children. Methods: Participants comprised 40 mothers of children with CP (Group 1), and controls comprised 40 mothers with healthy children(Group 2). Caregiver burden inventory (CBI), hospital anxiety depression scale (HADS) were applied. The functional status of children with CP was evaluated by the Gross Motor Function Classification System (GMFCS). Secondary problems accompanying CP were also noted. Results: A secondary problem was seen in 75% of children with CP. The caregiver burden (CB) and the frequency of depression among Group 1 mothers were significantly higher than Group 2 mothers (p<0,001). CB was found to be higher in children with CP with poor functional status. The CB of caregivers in children with CP with secondary problems was significantly higher than the mothers of children without secondary problems (p<0.05). Conclusion: CP causes a higher burden on care for mothers than on healthy children, and at the same time, more frequent depression is observed in these mothers. Long-term prospective studies are needed to investigate the possible effects of the time shift in the functional status of patients with CP on the CB

Oksitlenmiş rejenere selülozdan Üretilen absorbe edilebilir bir hemostatın rat modelinde adezyon oluşumu Üzerine etkisi

Objective: This study aimed to analyze the effect of an absorbable hemostat produced from oxidized regenerated cellulose (ORC) on pelvic adhesion formation in a rat model using an adhesion scoring system and immunohistochemical staining. Methods: This randomized, controlled experimental study included 20 female Wistar-Albino rats that were equally divided into the following groups: control and absorbable hemostat groups. The uterine horns of all the rats were exposed by laparotomy and using 10 W bipolar cautery. Five standard lesions were applied to the antimesenteric areas of each uterine horn. The experimental group received an absorbable hemostat to the traumatized uterine surfaces, whereas the control group did not. After a 28-day follow-up period, a relaparotomy was performed, and adhesions were evaluated based on an adhesion scoring system, and histological sections from areas with adhesion were obtained for immunohistochemical staining. Immunohistochemical staining included analysis of Ki-67 (proliferation index), CD-31 (neovascularization index), and Masson Trichrome [(MTC) fibrosis and collagen formation index]. Additionally, acute and chronic inflammation indices were determined via polymorphonuclear leukocytes (PMNL) and mononuclear leukocytes (MNL), respectively. Results: The intensity and scope of adhesion and overall adhesion ratings were substantially higher in the absorbable hemostat group than the control group (2.8 +/- 0.85 vs. 2.2 +/- 0.53, 0.92 +/- 0.26 vs. 0.61 +/- 0.25, and 3.72 +/- 0.96 vs. 2.81 +/- 0.75, respectively). Staining results for Ki-67, CD-31, MTC, PMNL, and MNL were also significantly higher in the absorbable hemostat group than in the control group (p<0.05 for all). Conclusion: The obtained results suggest that the use of ORC-based absorbable hemostats in pelvic surgery may increase adhesion formation on peritoneal surfaces by increasing inflammation, vascularity, and collagen formation

Location of the Optic Foramen Relative to the Sphenoid Sinus and Orbital Apex Structures

Background: Orbital decompression is performed to reduce intraorbital pressure by removing the fat tissue and bone around the orbit. Access to proper equipment, experienced personnel, and adequate anatomical knowledge are essential to perform this procedure. To achieve maximum decompression, surgeons need to open the orbit up to the apex, including the optic foramen and the annulus of Zinn. Objectives: This study aimed to determine the location of the sphenoid sinus relative to the optic foramen using computed tomog-raphy (CT) scan, which is essential for orbital decompression surgery, in the Central Anatolia Region, Turkey. Patients and Methods: This cross-sectional study was conducted on 64 patients from the Turkish population between March 15 and April 15, 2021 in the Central Anatolia Region. The patients were selected using the purposive sampling method. Based on the cranial CT scans, a total of 128 orbits were evaluated using the hospital's picture archiving and communication system. Patients included in this study were admitted to the hospital with headache. However, their CT images, evaluated by an experienced radiologist, were reported to be normal. The relationship between the optic foramen and the anterior surface of the sphenoid sinus was examined, and the location of the optic foramen was determined as anterior, posterior, or equal to the sphenoid sinus. Descriptive statistics were measured for statistical analysis. Results: The participants of this study included 32 men and 32 women in the age range of 20 -67 years. Based on the analyses, the optic foramen was mainly opposite to the anterior aspect of the sphenoid sinus in both females and males; this finding was more prominent in females. In the right orbit, the mean distance of the optic foramen to the anterior surface of the sphenoid sinus was +6.97 mm if the optic foramen was anterior to the anterior surface of the sphenoid sinus, while it was-4.1 mm if the optic foramen was located posteriorly to the anterior surface of the sphenoid sinus. Similarly, in the left orbit, the mean distance of the optic foramen to the anterior surface of the sphenoid sinus was +6.97 mm if the optic foramen was located anteriorly, while it was-4.15 mm if the optic foramen was located posteriorly to the anterior surface of the sphenoid sinus. The position of the optic foramen was symmetrical in 60.9% of cases in the two orbits. Conclusion: Based on the results of CT scan, the optic foramen was mainly located opposite to the anterior aspect of the sphenoid sinus; this finding was more frequently observed in females (59.4%) than in males (40.6%). The present results can provide further information for surgeons to perform orbital decompression or surgeries posterior to the orbit