Quantum Mechanics-Based Fast and Reliable Prediction of Binding Pose Structures.

Predicting the binding poses of docking with an accurate estimation of binding energies is highly important but very challenging in computational drug design. A quantum mechanics (QM) calculation-based docking approach considering multiple conformations and orientations of the ligand is introduced here to tackle the problem. This QM docking consists of three steps: generating an ensemble of binding poses with a conventional docking simulation, computing the binding energies with self-consistent charge density functional theory tightly binding with dispersion correction (DFTB-D) to selecting the 10 top binding modes, and optimizing the selected binding mode structures using the ONIOM(DFTB:PM7) technique to determine the binding poses. The ONIOM(DFTB-D:PM6) docking approach is tested on 121 ligand-receptor biocomplexes with the crystal structures obtained from the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB). The result shows that the new method is highly satisfactory for the accurate prediction of the binding poses. The new docking method should be beneficial to structure-based drug design.

Outcomes of Ventral Onlay Buccal Mucosal Graft Urethroplasty in Bulbomembranous Urethral Strictures Post-transurethral Resection of the Prostate.

OBJECTIVE: To evaluate the outcomes of ventral onlay buccal mucosal graft urethroplasty (VOBMGU) in bulbomembranous urethral strictures after transurethral resection of the prostate. METHODS: After approval of the institutional ethical committee, we retrospectively examined the database of patients diagnosed with post-TURP urethral stricture (PTS) and treated by VOBMGU from January 2020 to January 2022. The patients were evaluated by retrograde urethrogram and voiding cystourethrogram. Follow-up evaluation included assessment of lower urinary tract symptoms, physical examination, uroflowmetry (Q-max and International Prostate Symptom Score) 3, 6, and 12months of follow-up. RESULTS: A total of 30 patients underwent VOBMGU for bulbomembranous PTS were included. The median age of the patients was 63.5 (11.25). The median stricture length was 3.5 (1.5) cm. During follow-up, the mean Q-max significantly increased to 21.1 ± 5.5 mL/s (P < .0001), 20.1 ± 5.4 mL/s (P < .001), and 19.1 ± 5.3 mL/s (P < .003) at 3, 6, and 12months, respectively. IPSS significantly decreased to 8.93 ± 6.37 at the 12-month follow-up mark (P < .0001). Three patients developed stricture recurrence and two patients developed postoperative urinary incontinence. CONCLUSION: VOBMGU in cases of bulbomembranous urethral PTS offered excellent functional outcomes with low stricture recurrence and minimal risk of incontinence. Further prospective studies are warranted to confirm the results.

A Dynamic Framework for Internet-Based Network Time Protocol.

Time synchronization is vital for accurate data collection and processing in sensor networks. Sensors in these networks often operate under fluctuating conditions. However, an accurate timekeeping mechanism is critical even in varying network conditions. Consequently, a synchronization method is required in sensor networks to ensure reliable timekeeping for correlating data accurately across the network. In this research, we present a novel dynamic NTP (Network Time Protocol) algorithm that significantly enhances the precision and reliability of the generalized NTP protocol. It incorporates a dynamic mechanism to determine the Round-Trip Time (RTT), which allows accurate timekeeping even in varying network conditions. The proposed approach has been implemented on an FPGA and a comprehensive performance analysis has been made, comparing three distinct NTP methods: dynamic NTP (DNTP), static NTP (SNTP), and GPS-based NTP (GNTP). As a result, key performance metrics such as variance, standard deviation, mean, and median accuracy have been evaluated. Our findings demonstrate that DNTP is markedly superior in dynamic network scenarios, a common characteristic in sensor networks. This adaptability is important for sensors installed in time-critical networks, such as real-time industrial IoTs, where precise and reliable time synchronization is necessary.

Dietary supplementation of Nile tilapia (Oreochromis niloticus) with ß-glucan and/or Bacillus coagulans: Synergistic impacts on performance, immune responses, redox status and expression of some related genes.

A 14-week feeding study was conducted to assess the effects of feed supplementation with prebiotics ß-glucan (BG group) and/or probiotics Bacillus coagulans (BC group) on O. niloticus growth performance, body analysis, intestinal structure, immunological response, and antioxidant status. The fish were equally divided into six groups, as follows: the fish group fed an un-supplemented diet served as a control group; the other fish groups were fed supplemented diets with 0.1 g ß-glucan kg-1; 1 g Bacillus coagulans kg-1; 2 g B. coagulans kg-1; 0.1 g ß-glucan combined with 1 g B. coagulans kg-1; 0.1 g ß-glucan combined with 2 g B. coagulans kg-1. The findings revealed that supplementing B. coagulans and the ß-glucan mixture improved growth performance and feed efficiency parameters (RGR and SGR) more than the other groups. The fish flesh analysis revealed increased crude protein and dry matter content and lower lipid and ash levels in the BG and BC supplemented groups than in the Control group. On the other hand, ß-glucan and B. coagulans supplementation significantly boosted antioxidant activity and immunological responses in serum as determined by CAT, MDA, lysozyme, and phagocytic activity. Dietary ß-glucan and B. coagulans supplementation remarkedly enhanced anterior intestine villus histomorphometry characteristics. Furthermore, B. coagulans, alone or in combination with ß-glucan, could reduce HSP70 and IL-1ß gene expression while increasing IL-8 and GH gene expression. According to the findings, B. coagulans and/or BG increased growth performance by increasing gut health and morphology. Furthermore, ß-glucan and B. coagulans supplementation enhanced Tilapia's body composition, immunological responses, and antioxidant status.

MDO: A Computational Protocol for Prediction of Flexible Enzyme-Ligand Binding Mode.

AIM: Developing a method for use in computer aided drug design Background: Predicting the structure of enzyme-ligand binding mode is essential for understanding the properties, functions, and mechanisms of the bio-complex, but is rather difficult due to the enormous sampling space involved. OBJECTIVE: Accurate prediction of enzyme-ligand binding mode conformation. METHOD: A new computational protocol, MDO, is proposed for finding the structure of ligand binding pose. MDO consists of sampling enzyme sidechain conformations via molecular dynamics simulation of enzyme-ligand system and clustering of the enzyme configurations, sampling ligand binding poses via molecular docking and clustering of the ligand conformations, and the optimal ligand binding pose prediction via geometry optimization and ranking by the ONIOM method. MDO is tested on 15 enzyme-ligand complexes with known accurate structures. RESULTS: The success rate of MDO predictions, with RMSD < 2 Å, is 67%, substantially higher than the 40% success rate of conventional methods. The MDO success rate can be increased to 83% if the ONIOM calculations are applied only for the starting poses with ligands inside the binding cavities. CONCLUSION: The MDO protocol provides high quality enzyme-ligand binding mode prediction with reasonable computational cost. The MDO protocol is recommended for use in the structure-based drug design.

Microbial dysbiosis in a mouse model of atopic dermatitis mimics shifts in human microbiome and correlates with the key pro-inflammatory cytokines IL-4, IL-33 and TSLP.

BACKGROUND: Cutaneous bacterial dysbiosis is a characteristic hallmark of atopic dermatitis (AD), and it decisively influences the severity of the disease. Despite this, frequently used murine models of AD have not been characterized regarding the changes in skin microbiome communities. OBJECTIVE: To analyse the skin microbiome of two frequently used murine models for AD for assessing their applicability in translational research. METHODS: AD was induced in mice by topical application of calcipotriol or oxazolone. Following comparable elicitation of AD-like dermatitis, including IgE induction, the skin microbial communities were analysed and compared with human AD. RESULTS: We detected critical differences in the microbiota composition of diseased skin. In contrast to calcipotriol treatment, application of oxazolone induced significant changes in the cutaneous microbiota and a drastic drop of bacterial richness. Furthermore, an expansion of Staphylococci, particularly S. xylosus, was observed in the oxazolone group, also displaying positive correlations with AD key markers including pH, TEWL, IL-4, TSLP and IL-33. CONCLUSIONS: In this article, we show that (a) the model of choice to investigate AD needs to be characterized for the cutaneous microbiota if applicable and (b) the oxazolone-mediated mixed Th1-Th2 immune response triggers microbiota-induced alterations which share similarities to dysbiosis in human AD and represents therefore a suitable model for translational research on AD if alterations of the microbiome are in the focus of the investigation.

Concepts and Updates in the Evaluation and Diagnosis of Common Disorders of Sexual Development.

Our understanding of disorders of sexual differentiation (DSD) has evolved from aberrations of human genital development to a broad group of complex disorders of etiological and functional significance. The unique challenge of DSD conditions is that they create a cause for significant angst and concern for both parents and physician, as they frequently lead to questions with regards to gender assignment, surgically corrective options, long-term outlook regarding gender identity, and reproductive potential. To further add to the burden, many patients who present with genital abnormalities do not have a clear explanation as to the underlying basis of their disorder. This review looks at DSD from a pediatric urology point of view with emphasis on evaluation, diagnosis, and algorithm for work-up. We also discuss novel genetic analysis techniques and their value in diagnosis. Overall, this is an all-encompassing review on a diagnostic approach to DSD, with inclusion of recent developments and controversies, which will benefit urologists and other physicians alike.

[Nephroprotection in young type 1 diabetic patients treated with converting enzyme inhibitor]. / Néphroprotection chez le jeune diabétique de type 1 traité par inhibiteur d'enzyme de conversion. Résultats préliminaires d'une étude prospective.

CONTEXT: Diabetic nephritis is a renal microangiopathy that represents a major cause of morbidity and mortality in diabetic patients. It is expressed either by microalbunuria, proteinuria or renal failure, depending on the stage of the diabetes. In this context, angiotensin converting enzyme inhibitors (ACEI) slow down the progression of renal damage. OBJECTIVE: To assess the nephroprotector effects of ACEI in young type 1 Moroccan diabetics with varying stages of renal damage. Methods Prospective study including 29 patients exhibiting a diabetic nephropathy and/or hypertension having been followed-up for 1 year and treated with ACEI. The following parameters were analysed on inclusion, at six months and after 1 year of treatment: systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), urinary excretion of albumin, 24-hour proteinuria, creatininemia, creatinine clearance, glycosylated haemoglobin, kalemia, total cholesterol and triglycerides. RESULTS: The mean age of our patients was of 23.6 +/- 5.5 years, the age at onset of diabetes was of 9.3 +/- 2.6 years. According to the renal damage, we determined 4 groups of patients: Group I: microalbuminuria (10 patients), Group II: proteinuria (7 patients), Group III: renal failure (6 patients), Group IV: isolated hypertension (6 patients). Study of the progression of the clinical and biological parameters, during treatment with converting enzyme inhibitors (combined with diuretics in Groups II and III) revealed: In Group I: a decrease in urinary excretion of albumin, which returned to normal in 3 cases, in Group II: a decrease in the proteinuria, which became a microalbuminuria in 4 cases, in Group III: a stabilisation of renal function concomitant to a reduction in proteinuria, in Group IV: a significant reduction in mean arterial pressure. CONCLUSION: One year of treatment with ACEI appears effective on reducing proteinuria levels and stabilising the renal function in young type 1 diabetic patients.

Outcome analysis of endoscopic sinus surgery for chronic sinusitis in patients having Samter's triad.

A study was conducted to assess outcome analysis in acetylsalicylic acid (ASA) triad patients after endoscopic sinus surgery (ESS). The control group consisted of patients with chronic sinusitis, with or without asthma, who had also undergone ESS. The study group contained 18 patients with the classic triad who were compared with 22 controls. The study was conducted in retrospective fashion highlighting clinical presentation, radiologic evaluation, surgical findings, and recurrence rate of nasal polyps. Although both groups had a relatively similar age of onset of symptoms, the symptomatic picture was different in the two groups. Radiologic evaluation of the nose and paranasal sinuses revealed more extensive involvement of the sinuses in ASA triad patients. Furthermore, ASA triad patients underwent a greater number of repeat operations. This review suggests that ASA triad patients respond less well to surgical intervention and that other treatment modalities should perhaps be explored.

[Pneumocephalus: a prognostic factor in head injuries. Results of a retrospective study of 167 patients]. / La pneumocéphalie: un indice pronostique chez le traumatisé crânien.Résultats d'une étude rétrospective chez 167 patients.

Presence of air within the cranial cavity has been described by several authors. Little attention has been paid to its significance. The goal of this study was to analyse the clinical characteristics and the evolution of patients with pneumocephalus. We reviewed the brain computed tomography scans of 167 consecutive head injury patients who were hospitalized between January 1992 and December 1993. This retrospective study revealed intracranial air in 33 cases (19%). The analysis of clinical characteristics showed that in the initial period the neurologic status was better in patients with pneumocephalus. However, 48 hours later, the proportion of patients presenting a deep coma increased We conclude that pneumocephalus is a significant risk factor in head injury patients.