Benchmarking ANI potentials as a rescoring function and screening FDA drugs for SARS-CoV-2 Mpro.

Here, we introduce the use of ANI-ML potentials as a rescoring function in the host-guest interaction in molecular docking. Our results show that the "docking power" of ANI potentials can compete with the current scoring functions at the same level of computational cost. Benchmarking studies on CASF-2016 dataset showed that ANI is ranked in the top 5 scoring functions among the other 34 tested. In particular, the ANI predicted interaction energies when used in conjunction with GOLD-PLP scoring function can boost the top ranked solution to be the closest to the x-ray structure. Rapid and accurate calculation of interaction energies between ligand and protein also enables screening of millions of drug candidates/docking poses. Using a unique protocol in which docking by GOLD-PLP, rescoring by ANI-ML potentials and extensive MD simulations along with end state free energy methods are combined, we have screened FDA approved drugs against the SARS-CoV-2 main protease (Mpro). The top six drug molecules suggested by the consensus of these free energy methods have already been in clinical trials or proposed as potential drug molecules in previous theoretical and experimental studies, approving the validity and the power of accuracy in our screening method.

The effects of using phase-contrast microscopy on oral hygiene training of patients receiving orthodontic treatment: A randomized controlled study.

OBJECTIVE: To investigate of effects of using phase-contrast video technique on education in oral hygiene training. This one blind, parallel randomized controlled trial was conducted in a tertiary clinic. Fifty-three patients who presented to the orthodontics department aged 12-20 years were divided into two groups randomly by computer-generated assigned codes to receive oral hygiene education. The participants were blinded to type of education method. Before orthodontic therapy, the control group was trained only by the conventional method, while the test group was trained by phase-contrast video microscopy method in addition to conventional method. Some images and videos of moving microorganisms in dental plaque were shown to the patients in test group on a computer monitor. SUBJECTS AND METHODS: The bacterial count, plaque index, and gingival index scores were compared. Measurements were obtained in baseline and follow-ups which were repeated with 1-month intervals after the training. RESULTS: The plaque index scores (1.05 ± 0.1 vs. 1.43 ± 0.2; P < 0.001) and gingival index scores (0.90 ± 0.1 vs. 1.14 ± 0.2; P < 0.001) in test group was statistically lower than those in control group at the end of the study. The gingival index scores reduced by 39% in test group vs. 14% in control group. The number of bacteria significantly decreased in the group trained with phase-contrast video microscope technique (8,059,133 ± 3016 vs. 10,830,600 ± 4919; 0.018). CONCLUSIONS: The training with phase-contrast microscopy has a more positive effect than the traditional method in oral hygiene education.

Effect of Potassium Nitrate and Boric Acid on the Bond Strength of Veneering Ceramics to Zirconia.

In this study, the effects of boric acid addition to the veneer ceramics and treatment of the ceramic cores immersed in potassium nitrate solution were evaluated to reduce the micro cracks that may occur in the internal structure of the ceramic, increase the mechanical properties and improve the chemical bonding strength of core ceramics. In the data obtained after the experiment, the average MPa values showed statistically significant differences according to the groups (p⟨0.001). The average value in the control group (C) was lower than the others. There was no statistically significant between the mean values of the boric acid application in the veneer ceramic (IB) group and zirconia core immersed in the potassium nitrate solution (IN) group. The highest mean values were observed between the veneer ceramic and the zirconia core by application of boric acid and potassium nitrate (IBN) group. As a result potassium nitrate and boric acid application affects the bond strength between zirconia core and veneer ceramic and increases mechanical properties of ceramics.

Quantum chemical calculations and interpretation of electronic transitions and spectroscopic characteristics belonging to 1-(3-Mesityl-3-methylcyclobutyl)-2-(naphthalene-1-yloxy)ethanone.

This comprehensive study reports the synthesis of the title compound, 1-(3-Mesityl-3-methylcyclobutyl)-2-(naphthalene-1-yloxy)ethanone (C26H28O2), and identification of the molecule by means of the standard experimental methods such as single-crystal X-ray diffraction, ultra violet-visible (UV-vis) spectra, Fourier transform infrared (FTIR) spectra, (13)C and (1)H NMR chemical shifts and quantum chemical calculations using density functional theory (B3LYP) method for the first time. The experimental results observed display that the synthesis of the C26H28O2 compound is perfectly conducted without any impurities. Additionally, the little deviations are noticed on the bond lengths and bond angles, confirming that the strong intra-molecular charge transfers appear in the due to the presence of the electron engagements and conjugative effects (bond weakening). Besides, the intermolecular C-H⋯O distance presents the interaction between the methylcyclobutyl C-H group and oxygen atom in the ethanone group. At the same time, the absorption wavelength (λmax) appears at 292 nm and interval 297-269 nm in the solvent of chloroform and THF as a consequence of the presence of effective π-π(∗) conjugated segments in the molecule studied. Besides, optical band gap energy of 3.22/3.25 eV (chloroform/THF), verifies the existence of the strong electronic donating groups in the structure. As for the quantum chemical computations, the determination of the optimized molecular structures, vibrational frequencies including infrared intensities, vibrational wavenumbers, thermodynamic properties, atomic charges, electronic transitions, dipole moment (charge distribution), optical band gap energy, (1)H and (13)C NMR chemical shifts are conducted using density functional theory/Becke-3-Lee-Yang-Parr (DFT/B3LYP) method with the standard 6-311++G(2d,2p) level of theory. The results obtained show that the strong intra-molecular charge transfer (ICT) appears between the donor and acceptor in the title compound due to the existence of the strong electronic donating groups and effective π-π(∗) conjugated segments with high electronic donor ability for the electrophilic attack (intermolecular interactions). Additionally, the presence of the non-uniform charge distributions (polar behavior) on the various atoms makes the title compound be useful to bond metallically.

A characterization study on 2,6-dimethyl-4-nitropyridine N-oxide by density functional theory calculations.

This study deals with the identification of a title compound, 2,6-dimethyl-4-nitropyridine N-oxide by means of theoretical calculations. The optimized molecular structures, vibrational frequencies, corresponding vibrational assignments, thermodynamic properties and atomic charges of the title compound in the ground state were evaluated using density functional theory (DFT) with the standard B3LYP/6-311G(d,p) method and basis set combination for the first time. Theoretical vibrational spectra were interpreted with the aid of normal coordinate analysis based on scaled density functional force field. The results show that the optimized geometric parameters (bond lengths and bond angles) and vibrational frequencies were observed to be in good agreement with the available experimental results. Based on the results of comparison between experimental results and theoretical data, the chosen calculation level is powerful approach for understanding the molecular structures and vibrational spectra of the 2,6-dimethyl-4-nitropyridine N-oxide. Moreover, we not only simulated frontier molecular orbitals (FMO) and molecular electrostatic potential (MEP) but also determined the transition state and energy band gap. Based on the investigations, the title compound is found to be useful to bond metallically and interact intermolecularly. Infrared intensities and Raman activities were also reported.

Investigation of antioxidant vitamins (A, E, C) and lipid peroxidation levels in rats injected N-(1,3-benzothiazol-2-yl)-N-(4,5-dihydro-1H-imidazol-2-yl) amine.

The present study examined the influence of synthetic N-(1,3-benzothiazol-2-yl)-N-(4,5-dihydro-1H-imidazol-2-yl) amine (2-Amdz) on levels of vitamins A, E and C and malondialdehyde (MDA) in rats. A total of 30 rats, divided into two groups, were used in the study. The control group was given only a subcutaneous injection of 250 microL 75% ethanol, every other day. The other group of rats was administered a subcutaneous injection of 2-Amdz (25 mg kg-1, dissolved in 250 microL of 75% ethanol). Injections were continued for 16 days. After the application of 2-Amdz for 16 days, the serum levels of vitamins A, E and C and malondialdehyde (MDA) were determined by HPLC. The serum vitamin A, E, and C levels decreased significantly compared to controls (p<0.05) whereas serum MDA levels were higher than control levels (p<0.005). As a result, it can be suggested that 2-Amdz induced a severe stress and more importantly, increased the amount of free radicals and significantly decreased the levels of serum antioxidant vitamins.

Prevalence of congenital abnormalities in Turkish school children.

19750 school children, ages 6 to 15 years, were examined by the authors of this study, 1,220 (6.18%) had congenital abnormalities. In this group, 4.23% were boys and 1.88% were girls. Case histories revealed inbreeding amongst the parents (families) of children with congenital malformation to be 8.9% and 8.2% for the rest of the families in this study. There were 27 different congenital abnormalities identified, with prevalence rates of 0.05/1,000 to 15.85/1,000. The most prevalent abnormalities were umbilical hernia (15.85/1000), inguinal hernia (14.50/1,000), pectus carinatum and excavatum (7.68/1,000), undescended testes (9.00/1,000 boys), congenital nevus (3.54/1,000), retractile testis (4.45/1,000 boys), pilonidal sinus (2.63/1,000), pes planus (2.28/1,000), and hemangioma (1.16/1,000). Of the 19,750 children, 70 had multiple anomalies (3.75/1,000).

Clinical electrophysiology relevant for early glaucoma diagnosis.

This review reports findings of the recent literature about electrophysiologic techniques that are used in glaucoma diagnosis and research. Included in this review are results obtained by recording electrical responses from the eye (electroretinograms) and from the brain (visual evoked potentials). Studies concerned the electroretinogram evoked by patterned stimuli that originates in the proximal retina and with flash-evoked responses that originate from the proximal retina, such as oscillatory potentials and scotopic threshold responses, from middle layers of the retina (B wave), and from the outer retina (A waves and C waves). Regarding the pattern electroretinogram, the authors agree on its usefulness in the diagnosis of glaucoma. However, the optimal stimulus conditions (temporal and spatial frequency, retinal location, contrast, and color), which component of the response to evaluate, and the value of the pattern electroretinogram in follow-up treatment are debatable. Flash-evoked components of the electroretinogram that have been considered in the past to be of low value in diagnosis of glaucoma now seem to be more important. New developments in visual evoked potentials techniques, such as photostress methods, contrast sensitivity measurements, ramp stimulation, and selective adaptation for isolating blue-cone activity seem to be promising in further increasing the diagnostic value of visual evoked potential measurements.

Pseudoexfoliation syndrome. Ocular manifestation of a systemic disorder?

The pseudoexfoliation syndrome has recently been suggested to represent the local manifestation of a more widespread disorder. In this study, a case of classic bilateral pseudoexfoliation syndrome with systemic distribution of pseudoexfoliation material involving a variety of organ systems is described. Using transmission electron microscopy, typical pseudoexfoliation fibers were identified in autopsy tissue specimens of skin, heart, lungs, liver, kidney, and cerebral meninges in addition to the classic intraocular locations. The pseudoexfoliation material was mainly localized to connective-tissue portions or septa traversing the various organs. The pseudoexfoliation fibers were consistently associated with connective-tissue components, particularly fibroblasts and collagen and elastic fibers; myocardial tissue specimens; and heart-muscle cells. These findings provide evidence for the systemic nature of the pseudoexfoliation syndrome, which apparently involves an aberrant connective-tissue metabolism throughout the body.

Neonatal peritonitis.

A retrospective study was undertaken over an eight-year period to assess the mortality rate of 66 newborns who had undergone surgery in our clinic because of peritonitis. The mortality rate for the patients admitted in poor condition was 95.2 percent, whereas it was 45.5 percent for those in good condition. There was a 100 percent mortality associated with newborns that had hypothermia and with those that had severe respiratory difficulties, whereas it was 92.3 percent for low-birth-weight infants and 86.5 percent for dehydrated infants. All babies with sclerema neonatorum died. The newborns with white blood cell counts under 5,000/mm3 also did not survive (83.3%). Etiologically, congenital megacolon, meconium ileus and spontaneous gastrointestinal perforations were the most frequent anomalies leading to death (100%). In the newborns with gastrointestinal perforations, most deaths occurred in patients with perforations of the cecum, duodenum and stomach (100%). Mortality seemed to be greater in patients with complications (77.3%), and it rose to 83.3 percent for patients who had to undergo a repeat operation due to complications. The overall mortality rate was found to be 71.2 percent.

[Orbital, osseous, meningeal and cerebral findings in oculodermal melanocytosis (nevus of Ota). Clinico-histopathologic correlation in 2 patients]. / Orbitale, osseale, meningeale und zerebrale Befunde bei okulodermaler Melanozytose (Nävus von Ota). Klinisch-histopathologische Korrelation an zwei Patienten.

In two patients suffering from congenital oculodermal melanocytosis (nevus of Ota) orbital, osseous, meningeal, and cerebral manifestations are documented. In a 38-year-old European with a nevus of Ota on the right side an ipsilateral orbital tumor was diagnosed and surgically removed. The histological examination revealed a primary spindle shaped malignant melanoma of the orbit. In addition, many benign melanocytes were found in the optic nerve, in the extraocular muscles, in the orbital fat tissue, and in the dura of the sphenoid. In a 17-year-old Ethiopian with a nevus of Ota of the right side an increase in size of the pigmented process was observed during puberty in the orbital fat tissue, in the extraocular muscles, in the optic nerve, in the periorbital bones, in the temporal muscle, and in the cortex of the frontal brain lobe. A deep excision from the lower eye lid revealed a histologically benign oculo-orbito-dermal melanocytosis. An irradiation was performed because of growth again after segmental excision, however without success. In the ipsilateral eye a secondary open-angle glaucoma was diagnosed. In the nevus of Ota an involvement of the orbit and of the meningo-cerebral tissue must be considered.

Alterations of saccadic eye movements in myotonic dystrophy.

Saccadic eye movements were examined by means of infrared reflection oculography in 8 patients having myotonic dystrophy and in 65 control subjects. In 7 patients typical alterations of the saccades could be observed. In comparison with the normal controls the saccades were significantly hypometric, of longer duration, of lower peak velocity, and showed a typical pattern of velocity and acceleration.

Modifications of thermoregulation in patients with suprasellar pituitary adenomas.

Thermoregulation was investigated pre and postoperatively in 5 and only preoperatively in 7 patients with suprasellar pituitary adenomas by exposing them to external cold and heat in a climatic chamber. Five healthy subjects served as controls. Body core and skin temperatures, oxygen consumption, electromyographic activity, skin blood flow and local sweating rates were continuously measured. Threshold temperatures for activation of heat production and heat loss were calculated from these data. Hormone analysis was performed before and after stimulation with releasing factors. In the patients, core temperatures as well as threshold temperatures for heat production and heat loss were elevated by about 0.5 degrees C as compared with controls. This elevation of core and threshold temperatures was achieved, despite a reduced resting metabolic rate, by a reduction of skin blood flow indicated by a low mean skin temperature. After successful operation the thermoregulatory alterations normalized. Serum levels of growth hormone were reduced preoperatively and stimulation by GHRF did not cause an appropriate increase. Prolactin was elevated in 6 patients with prolactinomas, but there was no correlation with changes in thermoregulatory threshold temperatures. Stimulation of the other hypophyseal hormones by the combined anterior pituitary function test revealed a normal hormonal response. Apart from prolactin there were no significant hormonal changes postoperatively. It is concluded that disturbances of temperature regulation are present in patients with suprasellar adenomas, but that they are not detectable by routine clinical methods. These alterations probably depend on a disturbance of hypothalamic function and are reversible by surgery.

Physical growth measurements of 18,719 primary school children living in Adana, Turkey.

Height and weight measurements of 18,719 healthy children were obtained and the results were compared with those obtained from children living in several regions of Turkey and the USA. The results of these measurements differed significantly. This study demonstrates that local growth standards should be established and used in the evaluation of children.

Dissociation between activation of the hypothalamo-hypophyseal antidiuretic system and the type of diuresis during acute intracranial hypertension. Experimental observation.

Acute cerebral compression by a supra- and infratentorial balloon produced a triphasic pattern of diuresis. The 1st phase was characterized by polyuria associated with five fold increase of plasma (p) antidiuretic hormone (ADH) concentration, decreased urine osmolality in spite of natriuresis and blood pressure elevation. The 2nd phase was characterized by oliguria, a decrease of pADH and reduced urine Na+ concentration, whereas urine osmolality transiently increased. At this stage there was respiratory arrest and fall of blood pressure. The final stage was diabetes insipidus (DI), when EEG activity had disappeared. An increase of serum osmolality mainly occurred during the last DI phase. Serum Na+ concentration fluctuated slightly during the whole period of diuresis. These results present evidence, that the diuresis pattern reflects the hypothalamo-hypophyseal antidiuretic system (HHAS) reaction to acute intracranial pressure (ICP) increase with the vegetative symptoms of cerebral shock.