Unsatisfactory Treatment Research Articles

Metalloenzyme Inhibitors against Zoonotic Infections: Focus on Leishmania and Schistosoma.

The term "zoonosis" denotes diseases transmissible among vertebrate animals and humans. These diseases constitute a significant public health challenge, comprising 61% of human pathogens and causing an estimated 2.7 million deaths annually. Zoonoses not only affect human health but also impact animal welfare and economic stability, particularly in low- and middle-income nations. Leishmaniasis and schistosomiasis are two important neglected tropical diseases with a high prevalence in tropical and subtropical areas, imposing significant burdens on affected regions. Schistosomiasis, particularly rampant in sub-Saharan Africa, lacks alternative treatments to praziquantel, prompting concerns regarding parasite resistance. Similarly, leishmaniasis poses challenges with unsatisfactory treatments, urging the development of novel therapeutic strategies. Effective prevention demands a One Health approach, integrating diverse disciplines to enhance diagnostics and develop safer drugs. Metalloenzymes, involved in parasite biology and critical in different biological pathways, emerged in the last few years as useful drug targets for the treatment of human diseases. Herein we have reviewed recent reports on the discovery of inhibitors of metalloenzymes associated with zoonotic diseases like histone deacetylases (HDACs), carbonic anhydrase (CA), arginase, and heme-dependent enzymes.

A formative cross-sectional study to assess caregiver’s health-seeking behaviour and knowledge surrounding malaria, and understand the burden of malaria among children under-five in conflict-affected communities of Cameroon

BackgroundMalaria remains a major global health problem often worsened by political instability and armed conflict. The purpose of the study was to explore community knowledge, attitudes and practices on malaria prevention, and to understand the burden of malaria and health-seeking behaviours of caregivers of children under-five in conflict-affected communities of the South West and Littoral Regions of Cameroon.MethodsA cross-sectional survey involving internally displaced persons (IDPS), host population, and their children under-five was conducted across 80 communities. The survey was conducted from May to June 2021. Participants were interviewed using a structured questionnaire. Malaria prevalence for children under-five was determined using rapid diagnostic tests (RDT) on blood samples. Association between variables and displacement status was measured using chi square test and multivariate logistic regression model was fitted to identify factors associated with adequate knowledge on malaria prevention.ResultsA total of 2386 adults participated in the study and 1543 RDTs were conducted for children under-five. Adequate levels of knowledge and attitudes on malaria prevention was recorded among 1258 (52.9%) of the participants, with very strong evidence to suggest the level to be higher among the host (59.5%) compared to the IDPs (49.5%) and returnees (39.7%) (p < 0.001). Good practices towards malaria prevention was 43.3%, with very strong evidence indicating lower levels among IDPs (42.8%) and returnees (28.5%) compared to the host (49.4%) (p < 0.001). Malaria prevalence for children under-five was 54.0% and adequate health-seeking for suspected episodes of malaria was 53.0%, without any difference among IDPs (51.78%) and returnees (48.7%) compared to host populations (55.4%) (p = 0.154). Multivariate logistic regression model showed that there was quite strong evidence to suggest primary and secondary levels of education have higher odds of having correct knowledge of malaria prevention (adjusted odds ratio (AOR) 1.71, 95% confidence interval (CI): 1.11–2.64, p = 0.015 and AOR 1.80, 95% CI 1.15–2.82, p = 0.010 respectively). There was very strong evidence to suggest that owning a radio or a television was associated with greater odds of having a higher knowledge on malaria prevention (AOR 1.49, 95% CI 1.233–1.81, p = 0.000 and AOR 1.47, 95% CI 1.18–1.84, p = 0.001).ConclusionOver half of the population have correct knowledge and attitudes towards malaria prevention but gaps in complete knowledge remained. Some of the caregivers know the correct malaria preventive practices coupled with largely unsatisfactory treatment approaches and reflected by the high prevalence of malaria among their children. In order to effectively treat malaria, innovative strategies should target community participation.

The biological characteristic and therapeutic prospect of bladder cancer stem cells

Bladder cancer (BC), arising from bladder epithelial cells, is the most prevalent malignant tumor of the urinary system. Its main pathological variants include transitional cell carcinoma (TCC), squamous cell carcinoma, and adenocarcinoma, with TCC further divided into non-muscle-invasive BC (NMIBC) and muscle-invasive BC (MIBC). NMIBC accounts for 70% of all BC cases and is characterized by a favorable prognosis yet a high recurrence rate (31 &amp;ndash; 78%). Conversely, MIBC accounts for the remainder of BC cases, characterized by high heterogeneity and poor prognosis. Current treatment methods for BC predominantly encompass surgical resection, radiotherapy, chemotherapy, and immunotherapy. However, these methods lack specificity, exhibit limited clinical efficacy, and often yield unsatisfactory treatment outcomes, predisposing BC to recurrence. On the other hand, BC stem cells (BCSCs) are a subset of cells within heterogeneous BC, possessing robust abilities in self-renewal, differentiation, tumorigenicity, metastasis, and drug resistance. They play a pivotal role in the initiation, progression, metastasis, and relapse of BC, rendering them ideal targets for targeted therapy. Research efforts in this field are currently focused on investigating the evolutionary origins, biomarkers, mechanism governing stemness maintenance, drug resistance, metastasis, metabolic reprogramming, immune evasion, and targeted therapies related to BCSCs. This article provides a comprehensive review of the latest advancements in the biological characteristics and therapeutic prospects of BCSCs.

Abstract 5981: Treatment of cholangiocarcinoma using humanized monoclonal antibodies targeting claudin-1

Abstract Introduction: Cholangiocarcinoma (CCA) is a highly aggressive adenocarcinoma of the hepatobiliary system showing an alarming rise in incidence and mortality with unsatisfactory treatment options. Claudin-1 (CLDN1) is a transmembrane protein expressed in tight junctions, but exposed at the cell surface on cancer epithelial cells. Using highly specific monoclonal antibodies (mAbs) targeting the extracellular loop 1 of exposed CLDN1 with an excellent safety profile (Roehlen, Saviano et al. Science Transl Med 2022), we aimed to investigate the role of CLDN1 as therapeutic target for CCA. Methods: Integrative CCA patient CLDN1 expression analyses, spatial transcriptomics and mouse models were used to evaluate the role of CLDN1 as an oncogenic driver for CCA. Proof-of-concept studies were performed in cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse as well as patient CCA organoid models using humanized CLDN1 mAbs. Results: Integrative expression analyses of CLDN1 in CCA patient tissues revealed robust CLDN1 upregulation across several cohorts and patients with well-characterized driver mutations. scRNASeq and spatial transcriptomics of patient CCA showed that CLDN1 expression in cancer cells is associated with stemness, oncogenic signaling and EMT. Gain-of-function studies using an orthotopic HDTVi and syngeneic mouse model revealed a decrease in survival and an enhanced tumor growth, unraveling a functional role of CLDN1 as an oncogenic driver in CCA. Targeting exposed CLDN1 using highly CLDN1-specific mAb demonstrated a robust anti-tumoral effect across intra- and extra-hepatic CCA mouse models, with a significant inhibition of metastatic disease including models with medium or low CLDN1 expression. Functional studies in patient-derived CCA organoids demonstrated that CLDN1 mAb decreased cellular viability and altered cancer cell plasticity and fate. Mechanistically, CLDN1 mAb treatment suppressed gene expression of pathways mediating proliferation, stemness and EMT by inhibition of Notch1, SRC-FAK, and Hippo-YAP signaling. Conclusion: These results demonstrate that CLDN1 is a CCA driver and therapeutic target. The proof-of-concept studies in patient-derived models pave the way for the clinical development of CLDN1 mAbs to improve the outcomes of patients with advanced CCA. Citation Format: Zeina Nehme, Marion Muller, Emilie Crouchet, Frank Juehling, Julien Moehlin, Romain Désert, Jade Brochon, Fabio Del Zompo, Natascha Roehlen, Christine Thumann, Patrick Pessaux, Emanuele Felli, Aïna Venkatasamy, Patrice Marchand, Mihaela Alina Onea, Roberto Iacone, Markus Meyer, Alberto Toso, Nabeel Bardeesy, Lipika Goyal, Vikas Prakash Ranvir, Mirian Fernández-Vaquero, Mathias Heikenwälder, Tessa Ostyn, Tania Roskams, Patrice Laquerriere, Catherine Schuster, Laurent Mailly, Thomas F. Baumert. Treatment of cholangiocarcinoma using humanized monoclonal antibodies targeting claudin-1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5981.

Mesenchymal Stem Cells-Involved Strategies for Rheumatoid Arthritis Therapy.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the joints and bone destruction. Because of systemic administration and poor targeting, traditional anti-rheumatic drugs have unsatisfactory treatment efficacy and strong side effects, including myelosuppression, liver or kidney function damage, and malignant tumors. Consequently, mesenchymal stem cells (MSCs)-involved therapy is proposed for RA therapy as a benefit of their immunosuppressive and tissue-repairing effects. This review summarizes the progress of MSCs-involved RA therapy through suppressing inflammation and promoting tissue regeneration and predicts their potential clinical application.

Clinical and laboratory evaluation of the effectiveness of the nootropic drug Actitropil (fonturacetam) in the treatment of asthenic syndrome

Background. Asthenia is one of the most common symptoms in the clinical practice of a doctor of any specialty. This is due to the high incidence of this pathology: in patients with chronic somatic diseases from 45% to 90%, with an acute pathological process – about 55%. There are no uniform standards for the treatment of asthenic disorder; however, the basis for the medical correction of this pathology is nootropic drugs.&#x0D; Aim. To study the clinical efficacy and safety of the nootropic drug Actitropil (fonturacetam) in patients with various types of asthenic disorder.&#x0D; Materials and methods. The observational clinical program included 50 patients (average age 43.22±14.60) with asthenic symptoms. Patients received Actitropil (fonturacetam) at a dose of 200 mg per day, divided into two doses. The duration of therapy was 30 days, the total duration of follow-up was 60 days. The effectiveness of treatment was evaluated before and after the course of therapy, as well as in the delayed period according to the scales of asthenia MFI-20, well-being, activity, mood SAN, anxiety and depression HADS (part 1), sleep quality Spiegel, quality of life EQoL-5D-3L. Patients' satisfaction with the treatment and tolerability of therapy were also assessed on 5-point scales; adverse events were recorded and the number of patients with good, satisfactory and unsatisfactory treatment results was calculated based on the subjective assessment of the subjects. Blood parameters analysis was used as laboratory assessment methods: erythrocytes, leukocytes, reticulocytes, platelets, hemoglobin, hematocrit, blood sedimentation rate, total protein, glucose, alanine aminotransferase, aspartate aminotransferase, prothrombin and thrombin time, prothrombin, international normalised ratio, activated partial thromboplastin time, fibrinogen.&#x0D; Results and conclusion. The results of the study showed high efficacy (98%) and safety of the use of Actitropil (absence of adverse events, low adverse events level during the course of treatment, no negative effect on liver function, blood coagulation and carbohydrate metabolism) in the treatment of various types of asthenic syndrome, including those associated with comorbid diseases. There is a significant therapeutic effect of Actitropil on concomitant symptoms of asthenia: anxiety, sleep status and quality of life. The antiasthenic effect of the drug does not differ depending on age and increases in the delayed period.

Predicting the risk of dentin sensitivity development in dental patients

The main predisposing factors for DS occurrence and development in dental patients have been identified, and the DS prognosis program and the DS prognosis index have been developed.The program and the prognosis index were tested in 95 dental patients. The control group consisted of 30 patients. Clinical parameters were assessed before treatment, after 1 week, and 1, 6, 12 months. The treatment effectiveness was assessed using the number of good, satisfactory, and unsatisfactory treatment results in each group.The results of clinical observation of patients showed that the use of the DS prognosis program and the DS prognosis index makes it possible not only to clearly inform patients about the level of risk of developing DS, but also to constantly monitor prognostic signs, which increases the treatment effectiveness by 47 %.Good treatment results in 97 % of cases in a long-term period determine the feasibility of including the program we developed and the prognosis index in the complex treatment of DS in dental patients.

Coagulation as an effective method for cyanobacterial bloom control: A review.

Eutrophication, the over-enrichment with nutrients, for example, nitrogen and phosphorus, of ponds, reservoirs and lakes, is an urgent water quality issue. The most notorious symptom of eutrophication is a massive proliferation of cyanobacteria, which cause aquatic organism death, impair ecosystem and harm human health. The method considered to be most effective to counteract eutrophication is to reduce external nutrient inputs. However, merely controlling external nutrient load is insufficient to mitigate eutrophication. Consequently, a rapid diminishing of cyanobacterial blooms is relied on in-lake intervention, which may encompass a great variety of different approaches. Coagulation/flocculation is the most used and important water purification unit. Since cyanobacterial cells generally carry negative charges, coagulants are added to water to neutralize the negative charges on the surface of cyanobacteria, causing them to destabilize and precipitate. Most of cyanobacteria and their metabolites can be removed simultaneously. However, when cyanobacterial density is high, sticky secretions distribute outside cells because of the small size of cyanobacteria. The sticky secretions are easily to form complex colloids with coagulants, making it difficult for cyanobacteria to destabilize and resulting in unsatisfactory treatment effects of coagulation on cyanobacteria. Therefore, various coagulants and coagulation methods were developed. In this paper, the focus is on the coagulation of cyanobacteria as a promising tool to manage eutrophication. Basic principles, applications, pros and cons of chemical, physical and biological coagulation are reviewed. In addition, the application of coagulation in water treatment is discussed. It is the aim of this review article to provide a significant reference for large-scale governance of cyanobacterial blooms. PRACTITIONER POINTS: Flocculation was a promising tool for controlling cyanobacteria blooms. Basic principles of four kinds of flocculation methods were elucidated. Flocculant was important in the flocculation process.

CACA guidelines for holistic integrative management of urothelial carcinoma

Bladder urothelial carcinoma (UC) is the most common malignant tumor of the urinary system. It has the characteristics of high recurrence rate and poor prognosis. It is a malignant disease that threatens the safety of human life. The incidence rate has gradually increased in recent years. UC has the following characteristics: non-specific clinical symptoms, difficult preoperative qualitative diagnosis, unsatisfactory clinical treatment effect and poor prognosis. Therefore, a clear diagnosis plays a decisive role in the selection and formulation of surgical plans, and reasonable treatment is the key to improving the prognosis of patients and increasing their long-term survival rate. Based on the research evidence of diagnosis, evaluation, and treatment and the clinical experience of experts, the Cancer Nutrition Professional Committee of the Chinese Anti-Cancer Association formulated the "Guidelines for the Diagnosis and Treatment of Bladder Urothelial Carcinoma" for the reference of clinicians. It is hoped that this guideline can provide clinicians with the best and effective reference for clinical diagnosis and treatment, so as to achieve the best therapeutic effect for patients with UC in our country.

Weak Points of Double-Plate Stabilization Used in the Treatment of Distal Humerus Fracture through Finite Element Analysis.

Multi-comminuted, intra-articular fractures of the distal humerus still pose a challenge to modern orthopedics due to unsatisfactory treatment results and a high percentage (over 50%) of postoperative complications. When surgical treatment is chosen, such fractures are fixed using two plates with locking screws, which can be used in three spatial configurations: either parallel or one of two perpendicular variants (posterolateral and posteromedial). The evaluation of the fracture healing conditions for these plate configurations is unambiguous. The contradictions between the conclusions of biomechanical studies and clinical observations were the motivation to undertake a more in-depth biomechanical analysis aiming to indicate the weak points of two-plate fracture stabilization. Research was conducted using the finite element method based on an experimentally validated model. Three variants of distal humerus fracture (Y, λ, and H) were fixed using three different plate configurations (parallel, posterolateral, and posteromedial), and they were analyzed under six loading conditions, covering the whole range of flexion in the elbow joint (0-145°). A joint reaction force equal to 150 N was assumed, which corresponds with holding a weight of 1 kg in the hand. The biomechanical conditions of bone union were assessed based on the interfragmentary movement (IFM) and using criteria formulated by Steiner et al. Results: The IFMs were established for particular regions of all of the analyzed types of fracture, with distinction to the normal and tangential components. In general, the tangential component of IFM was greater than normal. A strong influence of the elbow joint's angular position on the IFM was observed, with excessive values occurring for flexion angles greater than 90°. In most cases, the smallest IFM values were obtained for the parallel plaiting, while the greatest values were obtained for the posteromedial plating. Based on IFM values, fracture healing conditions in particular cases (fracture type, plate configuration, loading condition, and fracture gap localization) were classified into one of four groups: optimal bone union (OPT), probable union (PU), probable non-union (PNU), and non-union (NU). No plating configuration is able to ensure distal humerus fracture union when the full elbow flexion is allowed while holding a weight of 1 kg in the hand. However, flexion in the range of 0-90° with such loadings is acceptable when using parallel plating, which is a positive finding in the context of the early rehabilitation process. In general, parallel plating ensures better conditions for fracture healing than perpendicular plate configurations, especially the posteromedial version.

Magnolin alleviated DSS-induced colitis by inhibiting ALOX5-mediated ferroptosis.

Inflammatory bowel disease (IBD) is a chronic and incurable disorder associated with higher cancer risk and currently faces unsatisfactory treatment outcomes. Ferroptotic cells secrete damage-associated molecular patterns (DAMPs) that recruit and activate immune cells, particularly macrophages. Magnolin has excellent antioxidant and anti-inflammatory properties, but its effect on IBD has not yet been clearly understood. This study aimed to investigate the therapeutic effects and mechanism of magnolin in IBD. For this purpose, in vivo and in vitro colitis models were established using dextran sulfate sodium (DSS), followed by optimization of magnolin concentration 2.5 μg/mL in vitro and 5 mg/kg in vivo. Bioinformatics analysis identified potential magnolin target sites and evaluated ferroptosis-associated gene expressions. Body weight, food intake, disease activity index (DAI), pathological changes, and inflammation levels were assessed. The effect of magnolin on ferroptosis and macrophages was evaluated using quantitative real time-polymerase chain reaction (qRT-PCR), immunofluorescent staining, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and western blotting. Results indicated that magnolin at a lower dose (5 mg/kg) alleviated DSS-induced colitis symptoms and reduced inflammation in mice. The bioinformatics analysis showed arachidonate 5-lipoxygenase (ALOX5) as a potential magnolin target. Furthermore, magnolin inhibited the expression of ALOX5 with no effect on GPX4. Moreover, magnolin regulated macrophage differentiation into the M2 phenotype and suppressed pro-inflammatory factors, that is, interleukin-6 and tumor necrosis factor-α (IL-6 and TNFα). These results suggested that magnolin possesses significant therapeutic potential in treating IBD by suppressing ALOX5-mediated ferroptosis, inhibiting M1 while promoting M2 macrophages, which is envisaged to provide novel strategies for treating IBD.

Mechanisms of oxidative stress in interstitial cystitis/bladder pain syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by bladder and/or pelvic pain, increased urinary urgency and frequency and nocturia. The pathophysiology of IC/BPS is poorly understood, and theories include chronic inflammation, autoimmune dysregulation, bacterial cystitis, urothelial dysfunction, deficiency of the glycosaminoglycan (GAG) barrier and urine cytotoxicity. Multiple treatment options exist, including behavioural interventions, oral medications, intravesical instillations and procedures such as hydrodistension; however, many clinical trials fail, and patients experience an unsatisfactory treatment response, likely owing to IC/BPS phenotype heterogeneity and the use of non-targeted interventions. Oxidative stress is implicated in the pathogenesis of IC/BPS as reactive oxygen species impair bladder function via their involvement in multiple molecular mechanisms. Kinase signalling pathways, nociceptive receptors, mast-cell activation, urothelial dysregulation and circadian rhythm disturbance have all been linked to reactive oxygen species and IC/BPS. However, further research is necessary to fully uncover the role of oxidative stress in the pathways driving IC/BPS pathogenesis. The development of new models in which these pathways can be manipulated will aid this research and enable further investigation of promising therapeutic targets.

IMMUNOLOGIC CHARACTERIZATION OF PECULIARITIES OF PROGNOSIS AND PROPHYLAXIS OF PURULENT-SEPTIC COMPLICATIONS OF LIVER ECHINOCOCCOSIS

The application of the developed therapeutic and diagnostic algorithms allowed, in the main group of patients in comparison with the control group, to increase the number of good treatment results from 30.9% to 35.1%, satisfactory - from 53.4% to 56.4% and to reduce unsatisfactory treatment results from 14.8% to 8.1%, and lethality - from 1.0% to 0.3%.

Individual deviations from normative electroencephalographic connectivity predict antidepressant response

BackgroundAntidepressant medications yield unsatisfactory treatment outcomes in patients with major depressive disorder (MDD) with modest advantages over the placebo, partly due to the elusive mechanisms of antidepressant responses and unexplained heterogeneity in patient's response to treatment. Here we develop a novel normative modeling framework to quantify individual deviations in psychopathological dimensions that offers a promising avenue for the personalized treatment for psychiatric disorders. MethodsWe built a normative model with resting-state electroencephalography (EEG) connectivity data from healthy controls of three independent cohorts. We characterized the individual deviation of MDD patients from the healthy norms, based on which we trained sparse predictive models for treatment responses of MDD patients (102 sertraline-medicated and 119 placebo-medicated). Hamilton depression rating scale (HAMD-17) was assessed at both baseline and after the eight-week antidepressant treatment. ResultsWe successfully predicted treatment outcomes for patients receiving sertraline (r = 0.43, p < 0.001) and placebo (r = 0.33, p < 0.001). We also showed that the normative modeling framework successfully distinguished subclinical and diagnostic variabilities among subjects. From the predictive models, we identified key connectivity signatures in resting-state EEG for antidepressant treatment, suggesting differences in neural circuit involvement between sertraline and placebo responses. ConclusionsOur findings and highly generalizable framework advance the neurobiological understanding in the potential pathways of antidepressant responses, enabling more targeted and effective personalized MDD treatment. Trial registrationEstablishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC), NCT#01407094.

DETERMINATION OF THE RISK OF OBTAINING UNSATISFACTORY RESULTS OF SURGICAL TREATMENT OF PATIENTS WITH STATIC DEFORMITIES OF THE FOREFOOT WHEN USING VARIOUS SURGICAL APPROACHES

The main method of treatment of static deformations of the forefoot (SDPVS) is surgical. The most static deformities of the foot in its front part most often include valgus deformity of the first toe — Hallux valgus (HV), hammer-like deformities of 2–4 toes, and Taylor's deformity. Objective. To assess the effectiveness of surgical treatment of SDPVS and to determine the risk of obtaining an unsatisfactory result with different surgical approaches. Methods. The treatment of 565 patients (1009 feet) was analyzed, the main group — 729 feet, control 280 feet. The groups of patients differed in the methods of surgical treatment of deformities of the forefoot. The choice of surgical intervention in the main group was carried out according to the algorithmized system of surgical treatment of patients with SDPVS. Results. The results of treatment of patients with static deformities of the front part of the foot in the main group were significantly (p &lt; 0.001) better than the results in the control group of patients. In the main group, good results accounted for 55.0 % of cases, satisfied — 39.2 %, unsatisfactory — 5.8 %, compared to the control group — 26.1 %, 43.2 and 30.7 %, respectively. The reduction of the relative risk of obtaining an unsatisfied result (RRR) in the main group when using the proposed algorithmized system of treatment of SDPVS is 68 %. In the treatment of combined VDPPS with deformities of 2–5 toes, the risk of an unsatisfactory result is higher compared to isolated VDPPS in both groups. The risk of an unsatisfactory treatment result in patients with combined HV deformity and deformities of 2–5 toes in the control group is 15.9 % higher (RR = 0.159 ± 0.174) than in the main group. The use of the proposed approach to the selection of surgical treatment tactics based on the developed algorithmized system of surgical treatment of SDPVS can reduce the relative risk of obtaining unsatisfactory treatment results by 84 % (RRR = 0.841).

Retreatment of endodontics using hybrid instrumentation in a tooth with periapical pathology

Aim: Report a clinical case of endodontic retreatment using a hybrid instrumentation technique, L&amp;C paste associated with glycerin as intracanal medication and bioceramic cement. Methods: A 42-year-old male, melanoderma patient, attended the Nilton Lins University Dentistry clinic complaining of tooth fracture and sensitivity in the upper frontal region and pain on chewing. The image exams, showed a bone radiolucense on the root tip, suggestive of a periapical lesion. Clinicaly, pain on vertical percussion was observed. The findings indicated an unsatisfactory primary endodontic treatment. Given the characteristics presented, endodontic reintervention in two sessions was chosen. Results: After the endodontic obturation, the patient was followed through a year. During the months of follow-up, it was observed decrease of the radiolucense on the root tip, as well as the appearance of radiopaque areas, suggestive of bone formation, indicating the effectiveness of the proposed treatment. Conclusion: Therefore, the endodontic reintervention using hybrid instrumentation technique, L&amp;C paste associated with glycerin as intracanal medication and bioceramic cement, showed a satisfactory result in the controlling of the infection. After 1 year, signs of bone remodeling can be seen, meeting the heal expectations predicted in the case planning, leaving the tooth suitable for prosthetic rehabilitation and return to its function.

Programmable Electro-Assembly of Collagen: Constructing Porous Janus Films with Customized Dual Signals for Immunomodulation and Tissue Regeneration in Periodontitis Treatment.

Currently available guided bone regeneration (GBR) films lack active immunomodulation and sufficient osteogenic ability- in the treatment of periodontitis, leading to unsatisfactory treatment outcomes. Challenges remain in developing simple, rapid, and programmable manufacturing methods for constructing bioactive GBR films with tailored biofunctional compositions and microstructures. Herein, the controlled electroassembly of collagen under the salt effect is reported, which enables the construction of porous films with precisely tunable porous structures (i.e., porosity and pore size). In particular, bioactive salt species such as the anti-inflammatory drug diclofenac sodium (DS) can induce and customize porous structures while enabling the loading of bioactive salts and their gradual release. Sequential electro-assembly under pre-programmed salt conditions enables the manufacture of a Janus composite film with a dense and DS-containing porous layer capable of multiple functions in periodontitis treatment, which provides mechanical support, guides fibrous tissue growth, and acts as a barrier preventing its penetration into bone defects. The DS-containing porous layer delivers dual bio-signals through its morphology and the released DS, inhibiting inflammation and promoting osteogenesis. Overall, this study demonstrates the potential of electrofabrication as a customized manufacturing platform for the programmable assembly of collagen for tailored functions to adapt to specific needs in regenerative medicine.

Aesthetically acceptable cephalometric treatment goal differences for straight, concave, and convex facial profiles between genders

ABSTRACT Purpose Modern orthodontics focus on achieving functional and aesthetically pleasing results. However, traditional cephalometric norms do not necessarily correspond to facial aesthetics, leading to unsatisfactory treatment outcomes. This study aimed to establish cephalometric treatment goals for each facial profile (concave, straight, and convex) by comparing the cephalometric variables of each type. Materials and methods The post-treatment lateral cephalograms of 180 orthodontic subjects (18–37 years old) were assessed. Profile silhouettes were scored for attractiveness by 15 Thai laypersons using a 5-point Likert scale. Cephalograms scoring above 3 were divided into the three facial profile groups (n = 60). Fifty-five cephalometric variables were measured, and the statistical analysis was performed using SPSS software. Results One-hundred and eighty aesthetically acceptable silhouettes comprised concave, straight, and convex facial profiles with a 1:1 male-to-female ratio. All types shared similarities in the cranial base and maxilla. The convex profiles more frequently displayed skeletal and dental base Class II, skeletal open bite, retruded and retroclined upper incisors, protruded and proclined lower incisors, obtuse nasolabial angles, protruded upper and lower lips, and retruded chins. The opposite findings were observed in the concave profiles. However, all profile types had similar upper and lower teeth relative to A point to pogonion line; and upper and lower lip positions relative to subnasale to soft tissue pogonion line and the true vertical line passing through soft tissue nasion. Conclusion Universal treatment goals for all profile types combined with customized values for each profile type to achieve an aesthetically acceptable facial profile are recommended.

ПРИЧИНЫ НЕУДОВЛЕТВОРИТЕЛЬНЫХ РЕЗУЛЬТАТОВ ЛЕЧЕНИЯ ОСТРЫХ ГНОЙНО-ДЕСТРУКТИВНЫХ ЗАБОЛЕВАНИЙ ЛЁГКИХ У БОЛЬНЫХ С SARS-COV-2

Objective: To identify the reasons for unsatisfactory treatment results for acute purulent destructive lung diseases (APDLD) in patients with SARS-CoV-2. Methods: Sixty-five patients with APDLD on the background of SARS-CoV-2 infection were included in the study; 37 (57%) patients (Group 1) with APDLD were treated in a Tashkent Specialized Clinic for Infectious Diseases, and 28 (43%) patients with APDLD (Group 2) were hospitalized in the clinic of the General and Children’s Surgery Department of the Tashkent Medical Academy with a history of a recent SARS-CoV-2 infection. The patients were investigated using clinical, laboratory, and instrumental methods; the results were processed using statistical methods. Results: Complete recovery of patients was achieved in 16% of patients of Group 1 and 32% of Group 2 (p&gt;0.05); clinical recovery was shown in 30% and 43% of patients in Groups 1 and 2 respectively (p&gt;0.05). In Group 1 the results of treatment were more frequently disappointing than in Group 2 (54% vs. 25%, p=0.036), of which 19% were fatal in Group 1 and 11% in Group 2 (p&gt;0.05). For the fatal outcome, the most dangerous was the early period after hospitalization. Morphological changes in the lungs of deceased patients included homogeneous fibrin deposits, which were combined with pronounced interstitial edema and capillary microthrombi around purulent foci. Conclusion: Traditional clinical and laboratory methods for assessing the severity of the condition of patients of both groups during and after SARSCoV-2 infection do not reflect the complete objective picture of the disease, as an accurate picture can only be obtained by applying the criteria for septic complications. Traditional treatment for APDLD is acceptable for patients of Group II. In patients of Group I with a severe, complicated, and progressive course, many methods of conventional therapy proved to be ineffective. Keywords: Acute purulent destructive diseases of the lungs, SARS-CoV-2, endothelial dysfunction of the lungs, treatment results, complications.

Neuroinflammation mechanism underlying neuropathic pain: the role of mesenchymal stem cell in neuroglia.

Pain is an essential aspect of the body's physiological response to unpleasant noxious stimuli from either external sustained injuries or an internal disease condition that occurs within the body. Generally, pain is temporary. However, in patients with neuropathic pain, the experienced pain is persistent and uncontrollable, with an unsatisfactory treatment effectiveness. The activation of the immune system is a crucial factor in both central and peripheral neuropathic pain. The immune response plays an important role in the progression of the stages of neuropathic pain, and acts not only as pain mediators, but also produce analgesic molecules. Neuropathic pain has long been described as a result of dysfunctional nerve activities. However, there is substantial evidence indicating that the regulation of hyperalgesia is mediated by astrocytes and microglia activation. Mesenchymal stem cells currently hold an optimal potential in managing pain, as they can migrate to damaged tissues and have a robust immunosuppressive role for autologous or heterologous transplantation. Moreover, mesenchymal stem cells revealed their immunomodulatory capabilities by secreting growth factors and cytokines through direct cell interactions. The main idea underlying the use of mesenchymal stem cells in pain management is that these cells can replace damaged nerve cells by releasing neurotrophic factors. This property makes them the perfect option to modulate and treat neuropathic pain, which is notoriously difficult to treat.