Priority Treatment Research Articles

Real-world effectiveness and safety of Azvudine in hospitalized patients with SARS-CoV-2 infection: a multicenter, retrospective cohort study.

Azvudine has been designated as a priority treatment for patients infected with SARS-CoV-2, however, clinical evidence in hospitalized cases remains insufficient. We performed a multi-center, retrospective cohort study to evaluate effectiveness and safety of azvudine in hospitalized patients with SARS-CoV-2 in China (NCT06349655). Kaplan-Meier method, Cox regression model, subgroup analysis and seven sensitive analyses were employed. A total of 32864 hospitalized patients with SARS-CoV-2 were enrolled, in which 5735 azvudine recipients and 5735 controls were selected using 1:1 propensity score matching. Based on Kaplan-Meier analysis, azvudine significantly reduced rates of all-cause death (P < 0.0001) and composite disease progression (P = 0.00019). Cox regression analysis demonstrated that hazard ratios of all-cause death and composite disease progression were 0.68 (95%CI: 0.598-0.775, P < 0.001) and 0.88 (95% CI: 0.795-0.976, P = 0.016), respectively. Subgroup analysis showed preference of azvudine for patients receiving antibiotics in reducing all-cause death and composite disease progression. Seven sensitivity analyses verified the robustness of our results. Safety analysis on adverse events showed no significant difference between both groups. This study suggested that azvudine may reduce all-cause death and composite disease progression in hospitalized patients with SARS-CoV-2 infection without serious adverse events. However, the findings are susceptible to some potential biases, and further studies still need to identify the efficacy of azvudine.

Terazosin, a repurposed GPR119 agonist, ameliorates mitophagy and β-cell function in NAFPD by inhibiting MST1-Foxo3a signalling pathway.

GPR119 agonists are being developed to safeguard the function of pancreatic β-cells, especially in the context of non-alcoholic fatty pancreas disease (NAFPD) that is closely associated with β-cell dysfunction. This study aims to employ a drug repurposing strategy to screen GPR119 agonists and explore their potential molecular mechanisms for enhancing β-cell function in the context of NAFPD. MIN6 cells were stimulated with palmitic acid (PA), and a NAFPD model was established in GPR119-/- mice fed with a high-fat diet (HFD). Terazosin, identified through screening, was utilized to assess its impact on enhancing β-cell function via the MST1-Foxo3a pathway and mitophagy. Terazosin selectively activated GPR119, leading to increased cAMP and ATP synthesis, consequently enhancing insulin secretion. Terazosin administration improved high blood glucose, obesity, and impaired pancreatic β-cell function in NAFPD mice. It inhibited the upregulation of MST1-Foxo3a expression in pancreatic tissue and enhanced damaged mitophagy clearance, restoring autophagic flux, and improving mitochondrial quantity and structure in β-cells. Nevertheless, GPR119 deficiency negated the positive impact of terazosin on pancreatic β-cell function in NAFPD mice and abolished its inhibitory effect on the MST1-Foxo3a pathway. Terazosin activates GPR119 on the surface of pancreatic β-cells, enhancing mitophagy and alleviating β-cell dysfunction in the context of NAFPD by suppressing the MST1-Foxo3a signalling pathway. Terazosin could be considered a priority treatment for patients with concomitant NAFPD and hypertension.

A Probabilistic Statistical Risk Assessment Method for Soil Erosion Using Remote Sensing Data: A Case Study of the Dali River Basin

Soil erosion risk assessment enables the identification of areas requiring priority treatment and avoids wasting human and material resources. The factor scoring method used in existing studies has high subjectivity, and the method of expressing erosion risk according to the soil erosion intensity ignores the random nature of the occurrence of erosion; therefore, neither method accurately reflects the risk of soil erosion. In order to address this issue, this study proposes a soil erosion risk assessment method that integrates the outcome and the probability of occurrence of soil erosion by means of a probabilistic statistical model. Subsequently, experimental research is conducted in the Dali River Basin. On the basis of long time-series data, using mathematical statistics as a tool and drawing on the empirical frequency formula, the probabilistic statistical risk assessment model is combined with the Modified Universal Soil Loss Equation (RUSLE) model to account for the probability of regional soil erosion at different intensity levels in the long time-series, which is combined with the intensity of erosion to carry out soil erosion risk assessment. The results of our study show the following: (1) The central and southwestern regions of the Dali River Basin (DRB) present medium and high levels of soil erosion risk, with the proportion of low-risk areas increasing annually, accounting for 78.97% of the DRB in 2020, while extremely high-risk areas account for only 0.40% of the DRB. (2) The major components impacting soil erosion risk in the DRB, as revealed by the geodetector, are the normalized difference vegetation index (NDVI) and slope, where the interaction between the two dominated the spatial variation in soil erosion risk. (3) Comparing the soil erosion risk and its status in the coming years, the proposed assessment method based on the occurrence probability can reveal the future soil erosion risk better than the traditional assessment method.

New prognostic model for liver transplantation outcomes in hepatocellular carcinoma

Background. Liver transplantation remains a priority treatment option for hepatocellular carcinoma in the presence of liver cirrhosis; yet precise outcome prediction post-operation continues to be a complex challenge. Existing prognostic model often overlook patient age and donor type. Enhanced models that incorporate these parameters can improve prediction accuracy and treatment efficacy, which is critically important in the dynamically evolving field of transplantation.Objective. The aim of this study is to develop a prognostic model for liver transplantation outcomes in patients with hepatocellular carcinoma and liver cirrhosis.Material and methods. This retrospective study included 69 patients with hepatocellular carcinoma on the background of liver cirrhosis who underwent liver transplantation between May 2010 and December 2022. Of these, 42 patients (61%) received organs from living donors, and 27 (39%) from deceased donors. The study involved analysis of alpha-fetoprotein levels in blood, as well as assessment of radiological (maximum tumor nodule size, number of nodules) and histological parameters (maximum tumor nodule size, number of nodules, presence of vascular invasion). Cox regression model was used to predict recurrence-free survival, and the results for five-year recurrence-free survival, recipient age, and donor type were reused in the Cox model to predict overall survival.Results. Four models for predicting recurrence-free survival and overall survival based on histological and radiological data were developed, demonstrating high prognostic value with C-indexes on training/test data of 0.76/1; 0.73/1; 0.78/0.8; 0.6/0.8 respectively. All models showed recurrence-free survival prediction accuracy comparable to the Milan criteria. The model outcomes are available as a calculator on the website https://nadit.ru/calculate_HCC.Conclusion. The developed prognostic models are vital tools for personalized outcome prediction after liver transplantation for hepatocellular carcinoma. To enhance the accuracy of these models, further amalgamation and validation of data from various medical centers, as well as open scientific collaboration, are necessary.

379. SUCCESSFUL MANAGEMENT OF ANASTOMOTIC LEAKAGE FOLLOWING ESOPHAGECTOMY USING ENDO-VACUUM ASSISTED CLOSURE (EVAC) THERAPY: A CASE REPORT

Abstract Background Esophagectomy is a crucial curative treatment for potentially resectable esophageal cancer. However, anastomotic leakage poses a significant complication, with reported incidences ranging from 11.4% to 21.2% and mortality rates between 7.2% and 35%. Endoluminal or cavitary type of vacuum therapy (EVAC) represents a minimally invasive approach adapted from negative pressure wound closure techniques. Our case demonstrates the successful application of EVAC in managing a significant postoperative leak. Methods A 70-year-old male who underwent esophagectomy for early esophageal cancer. On postoperative day 23, a 20mm-sized large anastomotic leakage was detected, leading to the insertion of Endo-VAC for treatment. Endoscopically exchange was regularly. Results Endoscopically exchange was performed seven times, gradually reducing the size of the leakage hole. In the end, the anastomotic leakage was completely healed, and the patient was discharged on postoperative day 86. The patient id currently undergoing outpatient follow-up with no recurrence or metastasis of the disease confirmed. Conclusion Through our case, we highlight the potential suitability of EVAC therapy as a less invasive and effective treatment modality for anastomotic leakage following esophagectomy. This approach may be considered as a priority treatment for anastomotic leak.

Numerical modeling of a coal/ammonia Co-fired fluidized bed: Control and kinetics analysis of nitrogen oxides emissions

The potential increase in nitrogen oxide emissions in the coal/ammonia co-firing can hinder the large-scale utilization of ammonia to reduce carbon emissions. In this work, a fluidized bed simulation model was established to investigate the NOx and N2O behaviors in the process of coal/ammonia co-firing. The effects of several variables on nitrogen oxides emission characteristics were studied, including the ammonia ratio, temperature, excess air ratio, and air/ammonia distribution strategies. The findings indicate that NOx and N2O concentrations rise and then decline with the NH3 co-firing ratio (CR-NH3) increased, peaking at 10 % and 5 % CR-NH3. The formation of N2O is insensitive to the addition of ammonia, while NOx emissions vary dramatically with different ammonia ratios. Higher temperatures enhance the formation of NOx but inhibit the generation of N2O within 750 °C–950 °C. As the temperature rises, the primary decomposition path of N2O shifts from N2O→N2H2→NNH→N2 to N2O→NO2→NO→N2. The generations of NOx and N2O are both enhanced due to the weakness of the reduced atmosphere with the excess air ratio increased. When the primary air ratio is raised, N2O gradually takes over as the main source of nitrogen oxides instead of NOx. The specific primary air ratio in the fluidized bed should be considered in the priority treatment of NOx or N2O in the process of lowering nitrogen oxides emissions. Ammonia distribution strategies have opposite effects on NOx and N2O emissions. With more NH3 introduced as a secondary fuel, the dilute phase area can change from the main source of NO to the consumption area of NO. The present findings can help control the emissions of nitrogen oxides during coal/ammonia co-combustion in coal-fired circulating fluidized bed power plants.

Drug-resistant epilepsy: Current concepts, pathogenesis, risk factors, outcomes of surgical treatment

Despite the wide choice of antiepileptic drugs (AEDs), a third of patients remain resistant to the effects of modern AEDs. Drug-resistant epilepsy (DRE) is characterized by the inability to control seizures in a patient when using at least two adequate AED regimens at an effective daily dose as monotherapy or in combination. In this case, the mechanisms responsible for drug resistance are mainly either increased excretion of AEDs by transporters from epileptogenic tissue (the multidrug transporter hypothesis) or a decrease in the sensitivity of drug receptors in epileptogenic brain tissue. It is assumed that there are other mechanisms, but they remain understudied. A number of factors are associated with the risk of DRE developing in patients with diagnosed epilepsy, including genetic, iatrogenic, brain malformations, and others. Patients with DRE have a higher probability of developing psychopathological disorders (depression, anxiety, psychosis), the proportion of which is significantly higher than in the general population. They have a 10-fold increased risk of death due to injury, cognitive decline, and sudden unexpected death in epilepsy (SUDEP). The priority treatment method for DRE is surgery. Early identification of DRE is critical for identifying potential treatment alternatives and determining whether a patient is a surgical candidate. Analysis of data from clinical and instrumental research of operated patients with DRE in the early and late postoperative period will allow us to identify factors of unfavorable outcome and to increase the effectiveness of treatment for this category of patients.The aim was to study and to summarize literature data on the pathogenesis and risk factors of drug resistance to antiepileptic drugs in patients with epilepsy, justifying the need for timely identification of drug resistance and referral of patients with drugresistant epilepsy to specialized centers for possible surgical treatment.

POST-TRAUMATIC HEMORRHAGE IN A PREGNANT WOMAN IN THE PRACTICE OF PRIMARY EMERGENCY MEDICAL TEAMS

Pregnancy is a unique period in a woman's life. It involves physiological changes, as well as mental and emotional ones for the mother-to-be. Pregnant women are at a higher risk of death from trauma compared to the rest of the female population. Medical activities aimed at treating pregnant trauma patients are issues that pose serious challenges for members of emergency medical teams. They require interdisciplinary medical knowledge, that of anatomy, physiology, trauma, but also obstetric and possibly neonatal care. In the pre-hospital setting, diagnosis and assistance is severely limited, so it is crucial that the pregnant woman be brought as quickly as possible to a hospital with appropriate diagnostic and specialty facilities. The aim of this study was to discuss the problem of uncontrolled internal hemorrhage in a pregnant woman, its consequences and the pre-hospital management of primary emergency medical teams. The research method was a review of the literature and recommendations of specialists of international organizations established to develop guidelines for emergency medicine. Based on the analysis, the following conclusions were drawn: 1. A traumatized pregnant woman should be given priority and special treatment in prehospital care due to measures that affect at least two lives - that of the mother and that of the child/children. 2. Due to the changes taking place in the body of the mother-to-be, injuries in pregnant women occur more frequently than in women who are not pregnant. 3. In pregnant women, the forces acting during the trauma, lead to different injuries than in non-pregnant women. 4. The effects of injuries sustained during pregnancy depend on the mechanism of injury, the severity of the injury and the stage of pregnancy. 5. Hypovolemia associated with decompensation of traumatic shock in a pregnant woman indicates an inauspicious prognosis for the health and life of the mother and baby. 6. Medical emergency procedures in pregnant trauma patients are similar to those used for other patients, but require some modifications related to the anatomical and physiological changes that occur during pregnancy. 7. Examining a pregnant patient may be difficult due to the anatomical and physiological changes occurring during this period. Increased heart rate and decreased blood pressure should not be considered a consequence of pregnancy if other causes are not ruled out. 8. It seems reasonable to introduce TXA acid into the regimens of basic emergency teams for victims with symptoms of hemorrhagic shock.

Botulinum toxinA for idiopathic overactive bladder in women

Following adescription of the historic evolution of botulinum toxinA detrusor injections for neurogenic and nonneurogenic bladder overactivity, which was mainly driven by German-speaking countries, the terminological revolution of 2002 and the influence on design and outcomes of upcoming approval studies for the indication overactive bladder (OAB) are examined. OnabotulinumtoxinA (100 IU) for second-line treatment of OAB received European approval in 2013. PhaseIV observational studies concerning therapeutic persistence and adherence with onabotulinumtoxinA are analyzed and compared with therapeutic alternatives. Predictors of treatment success and complications are identified and compared to the required preinterventional diagnostic effort. Since onabotulinumtoxinA and sacral neuromodulation (SNM) are competing for second-line OAB treatment, both options are compared with regard to differential indications, effectivity, durability and patient adherence. Gender-specific causes of urgency and urge incontinence in women are differentiated from the diagnosis of OAB and require priority treatment. On the basis of diagnostic examination results, an algorithm for invasive second-line treatment of OAB is presented, since overly liberal utilization of onabotulinumtoxinA in therapy-naive OAB patients has not proven superiority over oral antimuscarinergic standard therapy, which can only be explained by improper patient selection.

THE IMPACT OF BILATERAL VISION STATUS ON VISION-RELATED QUALITY OF LIFE IN PEOPLE WITH DIABETES MELLITUS.

To assess the impact of bilateral vision status on vision-related quality of life (VR-QOL) in patients with Type 2 diabetes in a Chinese cohort. Patients with presenting visual acuity (PVA) and VR-QOL data from the Fushun Diabetic Retinopathy Cohort Study were included. Vision-related quality of life was assessed using the National Eye Institute Visual Function Questionnaire-25. Monocular PVA (Snellen) was categorized into three levels for both the better-seeing eye and worse-seeing eye: 1) high PVA (H, > 6/18); 2) moderate PVA (M, 6/18-6/60); and 3) low PVA (L, < 6/60). Based on the monocular PVAs, six categories of bilateral vision status were defined (H-H, H-M, H-L, M-M, M-L, and L-L). The parameters of VR-QOL were analyzed between the groups. A total of 1,717 patients were enrolled. For better-seeing eyes in the same PVA level, the Visual Function Questionnaire-25 composite score decreased significantly with declining PVA in the worse-seeing eye (H-M vs. H-L: 80.5 ± 17.9 vs. 73.6 ± 22.5, P = 0.01; M-M vs. M-L: 78.7 ± 19.6 vs. 69.1 ± 26.4, P = 0.01). Conversely, for worse-seeing eyes in the same PVA level, there was no significant difference in the Visual Function Questionnaire-25 composite score as PVA changed in the better-seeing eye (H-M vs. M-M, 80.5 ± 17.9 vs. 78.7 ± 19.6, P = 0.30; H-L vs. M-L: 73.6 ± 22.5 vs. 69.1 ± 26.4, P = 0.25). The PVA of the worse-seeing eye in bilateral vision has a greater impact on VR-QOL in diabetic patients. Priority treatment may be considered for the worse-seeing eye for diabetic patients with different bilateral vision statuses, to better improve VR-QOL.

The Comparative Effectiveness of Using Cold Water Oral Spray and Cold Saline Oral Spray for Thirst Relief in Patients With Endotracheal Intubation in the Intensive Care Unit

Thirst is a common symptom among patients with endotracheal intubation in the intensive care unit (ICU), with an estimated prevalence of 88%. This study was designed to compare the effectiveness of cold saline spray and cold water spray in alleviating thirst, and to explore the maintenance and sustained effects of both groups in relieving thirst among patients with endotracheal intubation in the ICU. Patients with indwelling tracheal tubes in the medical ICU were recruited from one medical center in northern Taiwan and randomly assigned to either the cold saline (n = 18) or cold water (n = 18) group. The cold saline group received three rounds of cold saline spray at a temperature of 2°C - 8°C. Each round consisted of 10 sprays directed toward each of the four surfaces of the oral cavity followed by a 5-minute wait period. This process was repeated three times, with 30-minute intervals between interventions. The cold water group received the same intervention steps using a cold water spray at 2°C - 8°C. Thirst intensity was measured using a numeric rating scale before and after each of the three interventions in both groups. Demographic and relevant physiological data were collected on the participants by reviewing their medical records. Both of the interventions were found to effectively alleviate thirst intensity, with no significant difference between the two groups in terms of thirst intensity reduction after each intervention detected. Only the cold water spray had a maintenance effect, while the two groups had a continuous sustained effect in alleviating thirst intensity. Both of the interventions effectively alleviated thirst, and the cold water spray had both maintenance and sustained effects in alleviating thirst intensity. Based on the results, the cold water spray method may be considered as the priority treatment for thirst alleviation by healthcare providers in the clinical management of patients with tracheal intubation.

Eating disorders: the increase in requests for help and the optimization of resources

IntroductionThis work aims to provide an updated overview of the eating disorders (EDs) which are a widespread pathology nowadays. Informations related to the clinical-nosographic characteristics, an in-depth analysis about systemic-relational theories and historical evolution are provided. In addition, current informations about epidemiological data, recovery, treatment related implications, new neuroscientific theories and risk factors are shown. Given the complexity of these disorders, the lack of resources and the the increasing demands for treatment, the main object is related to the construction of a questionnaire to manage the waiting lists.Objectives Building a waiting list management model for EDs, Study and compare advantages and disadvantages of the source allocation ethical models (utilitarianism, prioritarianism, egalitarianism), Analyze EDs leading experts (doctors, dietitians, psychologists, psychiatrists) and EDs patients positioning with respect to priority treatment factors. Promote constructive dialog between EDs experts from different backgrounds and EDs patients.MethodsIn order to know the various treatment alternatives available, the different levels and reference structures are illustrated. In addition, it is also suggested different reasoning based on the ethical models of egalitarianism, utilitarianism and prioritarianism in order to build a waiting list management model, which is the maximum goal of this work. This model needs to be supported by a series of validated tools such as the clinical interview and self-administered questionnaires to investigate psychopathological aspects and psychiatric symptoms. Going into more details, a questionnaire is proposed to the EDs leading experts, so that they can provide their own priority factors list and related thoughts in order to build “the most ethical” waiting list.ResultsIt is expected that both patients and clinicians tend to give priority to patients with greater psychophysical severity, not exclusively on the basis of physical parameters. Further hypothesis related to clinicians lead us believe that they tend to use utilitarian logics, in compliance with the demonstrated efficacy of early intervention. An evaluation that could lead to a disagreement between experts and patients is related to prioritize patients in the initial phase of the disease, which could be supported by clinicians, but not by patients, probably in connection with their personal experiences. In fact, this favoritism could have a negative impact on the care of the most serious cases who risk to be left to themselves.ConclusionsThis work aims to encourage a constructive dialogue between experts and patients with EDs in order to build a functional intervention model which should be “the most ethical as possible” in order to save the greatest number of lives in respect of mental suffering.Disclosure of InterestNone Declared

Resistance to dopamine agonists in the treatment of prolactinomas: diagnostic criteria, mechanisms and ways to overcome it

The priority treatment approach for prolactinomas is therapy with dopamine agonists, which allows for elimination of clinical symptoms, normalization of prolactin levels, reduction of the adenoma size and prevention of metabolic abnormalities in the majority of patients. Nevertheless, 10 to 20% of patients are resistant to dopamine agonists. The aim of this review is to analyze literature data on the source mechanisms and potential ways to overcome the resistance of prolactinomas to dopamine agonists. The criteria of a prolactinoma's resistance to dopamine agonists are as follows: 1) no normalization of serum prolactin levels and/or 2) no reduction of the adenoma volume by at least 50% after treatment of bromocriptine at a dose of ≤ 15 mg/day or cabergoline at a dose of ≤ 3 mg/week for at least 6 months. Full resistance is characterized by both no biochemical and no anti-tumor effects, whereas in partial resistance, prolactin levels can be decreased but not normalized, or the adenoma size can be reduced by less than 50% of the initial. The clinical and morphological predictors of prolactinoma resistance to dopamine agonists are male gender, young age, big size of the adenoma and its invasion into the sinus cavernosus, hypointensive and/or heterogeneous MRI signal on Т2 weighed images, and cystic components within the tumor. The main molecular genetic markers are: decreased expression of dopamine and estrogen receptors, higher proliferation index Ki-67 ≤ 3%, as well as the MENIN, AIP, SF3B1, PRDM2 gene mutations. In case of resistance to bromocriptine, it is recommended to switch the patient to cabergoline. In partial resistance to standard doses of cabergoline, it is possible to increase the dose up to a maximally tolerated. Neurosurgery and/or radiation surgery is recommended in cases of full resistance to dopamine agonists or an aggressive tumor. For very aggressive/malignant tumors, or in the event of their extended growth after surgery, temozolomide is recommended as adjuvant therapy.

Analysis Of The Priority Handling Of Enveromental Drainage Construction Project At Dinas Pekerjaan Umum Dan Penataan Ruang Banjarbaru City

Flood is one of the main problems of big cities in Indonesia, including Banjarbaru City. This is often caused by the not supportive existing drainage capacity when compared to the increasing of crowded urban conditions and reduced green open space. Handling of drainage including rehabilitation is necessary so that drainage can function properly as expected. On the other hand the Banjarbaru City Government has a limited budget each year that can be disbursed for drainage handling. The purpose of this thesis is to analyze criteria and subcriteria that are important in determining the priority of drainage handling. The ANP (Analytic Network Process) method is analyzed using the criteria in the Minister of Public Works regulation number 12/PRT/M/2014 tentang Penyelenggaraan Sistem Drainase Perkotaan to determine priorities for handling environmental drainage with important criteria, namely aspects of inundation, economic loss, social disruption and government facilities, loss of disturbance. transportation, loss to residential areas, and loss of personal property rights. Based on these 6 criteria, priorities for handling environmental drainage in Banjarbaru City are determined. Furthermore, an analysis is carried out to evaluate the priority of the choices that occur. This study suggests to decision makers that ANP can be used to analyze drainage management priorities in Banjarbaru City. This research focuses on variables consisting of criteria or considerations which form the background for priorities in handling the environmental drainage system in Banjarbaru City. The primary data results obtained from the field survey were followed by analysis using the ANP method with data tabulation calculations and assisted by Super Decisions software to determine the priority scale for handling environmental drainage in Banjarbaru City. The treatment priority scale in the Super Decisions software, the data of which is based on field survey results and data tabulation calculations, found that there are several locations that have a large priority scale but treatment has not been carried out due to several factors that are not contained in Minister of Public Works Regulation 12/PRT/M/2014 concerning Implementation of Urban Drainage Systems.

Enamel Hypoplasia among Tikrit City School Children Aged 6 Years to 13 Years Old

Enamel hypoplasia: its deficiency could be occurring when the enamel of the tooth does not form completely; this is may be due to many diseases or malnutrition. Enamel hypoplasia could be appear as horizontal lines or chain of grooves or pits over the outer surface of the tooth. The purpose of this current study was to find out the prevalence of enamel hypoplasia for the permanent and deciduous teeth in primary school children in Tikrit city, because children with enamel hypoplasia can suffer from cosmetic issues, tooth sensitivity and increased risk of dental caries. This current study is cross-sectional study was conducted through a clinical examination of teeth among 720 children of age rang (6 to 13) years enrolled in primary public schools of Tikrit city; they were accepted to participate in study after the aim of study was explained. The prevalence of enamel hypoplasia was studied in relation to age and gender. Diagnosis of enamel hypoplasia takes place by well trained dentist. The prevalence of enamel hypoplasia was founded to (6.2%); boys more affected than girls with odds ratio 1.03 and there was no statistically significant differences. The anterior teeth were the most affected teeth with enamel hypoplasia specially the upper permanent central incisor (2.9%). Developmental enamel hypoplasia has a high level of importance because of being predictors of dental caries. Children suffered from enamel hypoplasia require a preventive intervention as a priority and early treatment.

Allogeneic hematopoietic stem cell transplantation from matched related donors for acute myeloid leukemia.

In patients with acute myeloid leukemia (AML), allogeneic hematopoietic stem cell transplantation (HSCT) remains the priority treatment option as the most effective prevention of relapse. When an HLA-matched sibling is available, these transplants are preferred. We stratificated patients according to risk, disease state (an active disease, the 1st or 2nd complete remission ‒ CR1, CR2, which was achieved after the 1st or 2nd induction) and type of graft (from brother or sister). Finally, the overall survival (OS) of patients in individual groups was evaluated. The retrospective single-center study included 104 transplantations in 97 adult patients with AML who underwent HSCT from matched sibling donor in aperiod of 10 years between January 2011 and December 2020. 54 patients (55.7%) were alive as of the January 1, 2022. The median OS of the entire group, as well as the cohort with favorable (5y-OS 75.0%) and intermediate prognosis risk (5y‒OS 78.5%) was not reached. We found that patients, who required second induction therapy to achieve CR, had poorer OS after allogeneic HSCT, median 20.7 months (95% CI, 6.5-35.5) than those who achieved CR after first induction, median not reached (95% CI, 63.5‒63.5, p=0.0048). Statistically significant effect on OS shows transplantation in CR2 (HR 6.76, CI 95% 2.19‒20.80, p=0.0009), In addition, this parameter influenced OS more than achieving CR up to the 2nd induction course (HR 2.44, CI 95% 1.17‒5.11; p=0.0180) or entry to transplantation without CR (HR 2.81, CI 95% 1.09‒7.26; p=0.0326). The results presented in the work show the high efficiency of HSCT in each risk group. The number of induction therapies required to achieve CR is agood prognostic factor. The gender of asibling has no impact on OS (Tab. 11, Fig. 7, Ref. 18). Text in PDF www.elis.sk Keywords: acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation, overall survival, remission status, donor tender.

Russian development for drug independence in endocrinology: comparative analysis of bioequivalence, safety and tolerability of the first domestic liraglutide

Liraglutide is one of the analogues of the incretin hormone human glucagon-like peptide-1 (GLP-1) and is currently a priority treatment for diseases such as type 2 diabetes mellitus (mono- and combination therapy), obesity and overweight in the presence of at least one concomitant disease.The aim of the work was to assess the bioequivalence and comparability of the safety and tolerability profile of the drug Enligria® (liraglutide 6 mg/ml, Promomed RUS LLC, Russia) and the drug Saxenda® (liraglutide 6 mg/ml, Novo Nordisk AS, Denmark) after a single dose in healthy volunteers.Materials and methods. This study was an open-label, randomized, crossover comparative study to evaluate pharmacokinetic parameters, safety, tolerability and immunogenicity. The study comprised 26 healthy volunteers, 26 of whom were included in the bioequivalence assessment population. The study consisted of 2 periods, in each of which the volunteers received either the test drug (liraglutide at a single dose of 0.6 mg) or the reference drug (liraglutide at a single dose of 0.6 mg) once. The washout period between each dose was 7 days. Blood plasma samples were taken to determine the concentration of liraglutide in the range from 0 to 72 hours in each study period. Liraglutide concentrations were determined using a previously validated enzyme-linked immunosorbent assay (ELISA) method. A quantitative determination of antibodies to liraglutide in the blood serum samples was carried out using a microplate photometer and ready-made ELISA kits pre-validated by the manufacturer. The conclusion about the equivalence of the compared drugs was made based on the ratio of the parameters Cmax, AUC0→t and AUC0→t of the studied drug in relation to the reference one.Results. The pharmacokinetic parameters of the drugs were comparable to each other. The resulting 90% confidence intervals for the ratio of the values of Cmax, AUC0-t and AUC0-∞ of the Russian test and reference drug were 87.18–110.46, 84.40–104.11 and 86.69–103.22% respectively, which satisfied the criteria for assessing bioequivalence. The tolerability of the drugs in the volunteers was notified as good. The incidence of adverse events was comparable for the test and reference drugs. No serious adverse events were reported throughout the study. According to the results of the immunogenicity analysis, no antibodies to russian produced liraglutide were detected in the blood serum of the volunteers, which indicated the lack of the drug immunogenicity.Conclusion. During the study, the pharmacokinetic equivalence of the test and reference drugs was confirmed. The Russian drug Enligria® (liraglutide 6 mg/ml, Promomed RUS LLC, Russia) in comparison with a foreign drug Saxenda® (liraglutide 6 mg/ml, Novo Nordisk AS, Denmark).

Auto-dissemination of Cordyceps fumosorosea amongst adult females of the two-spotted spider mite.

Tetranychus urticae is an important pest worldwide. The auto-dissemination of spores of entomopathogenic fungi from an infected individual to conspecifics may be important for controlling pests that can build high populations. The current study was carried out to determine the auto-dissemination of the entomopathogenic fungus Cordyceps fumosorosea strain PFs-1 (Priority®) between T. urticae females. The study consisted of four experiments. First, the efficacy of entomopathogenic fungus bioassays was assessed in Petri dishes (experiment 1) and on potted bean plants (experiment 2). In the auto-dissemination trials (experiments 3 and 4, in Petri dishes and on potted plants, respectively), contaminated adult females (1-5) were released among uncontaminated females (10 individuals). All experiments were carried out separately, and observations were made on days 3, 5, and 7. In exp. 1, the control was different from Priority on all observation days. In exp. 2, the average number of surviving individuals in the control was significantly higher than in the Priority treatment. In the auto-dissemination experiments, as the number of contaminated individuals increased, the mortality rate of uncontaminated individuals also increased, in exp. 3 (Petri dishes) on all observation days, and in exp. 4 (potted plants) only on days 5 and 7. The median lethal time (LT50)decreased as the number of individuals contaminated with Priority increased in both Petri dish and pot trials. Consequently, the effectiveness of biological control may increase with the occurrence of indirect contamination from infected to uncontaminated individuals.

Use of High-Resolution Signal Controller Data to Measure Transit Signal Priority Performance: A Case Study in the Boston Region

Automated traffic signal performance measures (ATSPMs) have been developed to organize data within a traffic signal, which will then be used to evaluate and monitor signal timing strategies. Past research has summarized the use of ATSPMs for performance-based management of a traffic signal system. The National Cooperative Highway Research Program Research Report 954 focused on many measures useful for general traffic, but did not consider transit agencies as specific stakeholders. ATSPMs do provide insights into measuring the number of preemption events, and the percentage of transit vehicles arriving on green, but additional information is needed to determine the effectiveness of transit signal priority or other transit preferential treatment strategies. This paper proposes a method for evaluating transit performance at signalized intersections more fully using the high-resolution data available within modern traffic signal controllers. The addition of transit-specific inputs within the ATSPM enumerations is used to produce transit-specific signal performance measures designed to be useful to practitioners. The methodology can be followed by other agencies seeking to enhance the capabilities of existing automatic vehicle location systems to further describe the performance at each signalized intersection. By incorporating transit into the ATSPM system, an agency can better assess the delay of buses, which can contribute to schedule adherence, on-time performance, and overall bus service. The methodology is presented as a prototype for further development and adaptation to individual agency objectives and data sources.

Pregnancy-specific alcohol policies and admissions to substance use disorder treatment for pregnant people in the USA.

We examined relationships between pregnancy-specific alcohol policies and admissions to substance use disorder treatment for pregnant people in the USA. We merged state-level policy and treatment admissions data for 1992-2019. We aggregated data by state-year to examine effects of nine pregnancy-specific alcohol policies on the number of admissions of pregnant women where alcohol was reported as the primary, secondary, or tertiary substance related to the treatment episode (N = 1331). We fit Poisson models that included all policy variables, state-level controls, fixed effects for state and year, state-specific time trends, and an offset variable of the number of pregnancies in the state-year to account for differences in population size and fertility. When alcohol was reported as the primary substance, civil commitment [incidence rate ratio (IRR) 1.45, 95% CI: 1.10-1.89] and reporting requirements for assessment and treatment purposes [IRR 1.36, 95% CI: 1.04-1.77] were associated with greater treatment admissions. Findings for alcohol as primary, secondary, or tertiary substance were similar for civil commitment [IRR 1.31, 95% CI: 1.08-1.59] and reporting requirements for assessment and treatment purposes [IRR 1.21, 95% CI: 1.00-1.47], although mandatory warning signs [IRR 0.84, 95% CI: 0.72-0.98] and priority treatment for pregnant women [IRR 0.88, 95% CI: 0.78-0.99] were associated with fewer treatment admissions. Priority treatment findings were not robust in sensitivity analyses. No other policies were associated with treatment admissions. Pregnancy-specific alcohol policies related to greater treatment admissions tend to mandate treatment rather than make voluntary treatment more accessible, raising questions of ethics and effectiveness.