Thermodynamic and Structural Study of Budesonide-Exogenous Lung Surfactant System.

The clinical benefits of using exogenous pulmonary surfactant (EPS) as a carrier of budesonide (BUD), a non-halogenated corticosteroid with a broad anti-inflammatory effect, have been established. Using various experimental techniques (differential scanning calorimetry DSC, small- and wide- angle X-ray scattering SAXS/WAXS, small- angle neutron scattering SANS, fluorescence spectroscopy, dynamic light scattering DLS, and zeta potential), we investigated the effect of BUD on the thermodynamics and structure of the clinically used EPS, Curosurf®. We show that BUD facilitates the Curosurf® phase transition from the gel to the fluid state, resulting in a decrease in the temperature of the main phase transition (Tm) and enthalpy (ΔH). The morphology of the Curosurf® dispersion is maintained for BUD < 10 wt% of the Curosurf® mass; BUD slightly increases the repeat distance d of the fluid lamellar phase in multilamellar vesicles (MLVs) resulting from the thickening of the lipid bilayer. The bilayer thickening (~0.23 nm) was derived from SANS data. The presence of ~2 mmol/L of Ca2+ maintains the effect and structure of the MLVs. The changes in the lateral pressure of the Curosurf® bilayer revealed that the intercalated BUD between the acyl chains of the surfactant's lipid molecules resides deeper in the hydrophobic region when its content exceeds ~6 wt%. Our studies support the concept of a combined therapy utilising budesonide-enriched Curosurf®.

Prediction of the burden of road traffic injuries in Iran by 2030: Prevalence, death, and disability-adjusted life years.

PURPOSE: Road traffic accidents pose a global challenge with substantial human and economic costs. Iran experiences a high incidence of road traffic injuries, leading to a significant burden on society. This study aims to predict the future burden of road traffic injuries in Iran until 2030, providing valuable insights for policy-making and interventions to improve road safety and reduce the associated human and economic costs. METHODS: This analytical study utilized time series models, specifically autoregressive integrated moving average (ARIMA) and artificial neural networks (ANNs), to predict the burden of road traffic accidents by analyzing past data to identify patterns and trends in Iran until 2030. The required data related to prevalence, death, and disability-adjusted life years (DALYs) rates were collected from the Institute for Health Metrics and Evaluation database and analyzed using R software and relevant modeling and statistical analysis packages. RESULTS: Both prediction models, ARIMA and ANNs indicate that the prevalence rates (per 100,000) of all road traffic injuries, except for motorcyclist road injuries which have an almost flat trend, remaining at around 430, increase by 2030. Based on estimations of both models, the rates of death and DALYs due to motor vehicle and pedestrian road traffic injuries decrease. For motor vehicle road injuries, estimated trends decrease to approximately 520 DALYs and 10 deaths. Also, for pedestrian road injuries these rates reached approximately 300 DALYs and 6 deaths, according to the models. For cyclists and other road traffic injuries, the predicted DALY rates by the ANN model increase to almost 50 and 8, while predictions conducted by the ARIMA model show a static trend, remaining at 40 and approximately 6.5. Moreover, these rates for the prediction of death rate by the ANN model increased to 0.6 and 0.1, while predictions conducted by the ARIMA model show a static trend, remaining at 0.43 and 0.07. According to the ANN model, the predicted rates of DALY and death for motorcyclists decrease to 100 and approximately 2.7, respectively. On the other hand, predictions made by the ARIMA model show a static trend, with rates remaining at 200 and approximately 3.2, respectively. CONCLUSION: The prevalence of road traffic injuries is predicted to increase, while the death and DALY rates of road traffic injuries show different patterns. Effective intervention programs and safety measures are necessary to prevent and reduce road traffic accidents. Different interventions should be designed and implemented specifically for different groups of pedestrians, cyclists, motorcyclists, and motor vehicle drivers.

Polymyxin B-Enriched Exogenous Lung Surfactant: Thermodynamics and Structure.

The use of an exogenous pulmonary surfactant (EPS) to deliver other relevant drugs to the lungs is a promising strategy for combined therapy. We evaluated the interaction of polymyxin B (PxB) with a clinically used EPS, the poractant alfa Curosurf (PSUR). The effect of PxB on the protein-free model system (MS) composed of four phospholipids (diC16:0PC/16:0-18:1PC/16:0-18:2PC/16:0-18:1PG) was examined in parallel to distinguish the specificity of the composition of PSUR. We used several experimental techniques (differential scanning calorimetry, small- and wide-angle X-ray scattering, small-angle neutron scattering, fluorescence spectroscopy, and electrophoretic light scattering) to characterize the binding of PxB to both EPS. Electrostatic interactions PxB-EPS are dominant. The results obtained support the concept of cationic PxB molecules lying on the surface of the PSUR bilayer, strengthening the multilamellar structure of PSUR as derived from SAXS and SANS. A protein-free MS mimics a natural EPS well but was found to be less resistant to penetration of PxB into the lipid bilayer. PxB does not affect the gel-to-fluid phase transition temperature, Tm, of PSUR, while Tm increased by ∼+ 2 °C in MS. The decrease of the thickness of the lipid bilayer (dL) of PSUR upon PxB binding is negligible. The hydrophobic tail of the PxB molecule does not penetrate the bilayer as derived from SANS data analysis and changes in lateral pressure monitored by excimer fluorescence at two depths of the hydrophobic region of the bilayer. Changes in dL of protein-free MS show a biphasic dependence on the adsorbed amount of PxB with a minimum close to the point of electroneutrality of the mixture. Our results do not discourage the concept of a combined treatment with PxB-enriched Curosurf. However, the amount of PxB must be carefully assessed (less than 5 wt % relative to the mass of the surfactant) to avoid inversion of the surface charge of the membrane.

Vaccination and its impact on healthcare utilization in two groups of vaccinated and unvaccinated patients with COVID-19: A cross-sectional study in Iran between 2021 and 2022.

Background and Aims: One of the main responsibilities of health systems impacted by the global Coronavirus disease 2019 (COVID-19) pandemic, where the first case was discovered in Wuhan, China, in December 2019, is the provision of medical services. The current study looked into the impact of vaccination on the utilization of services provided to COVID-19 patients. Methods: This study was conducted in Iran between 2021 and 2022, utilizing a cross-sectional research design. The research team collected data on the utilization of provided services and the number of COVID-19 vaccines administered to 1000 patients in Iran through a random sampling approach. The data were analyzed with statistical methods, including the mean difference test, and multiple linear regression. Results: Regression estimates show that after controlling for confounding variables like age, type of admission, and comorbidities, vaccination reduces the utilization of healthcare services in the general majority of services. The study's results reveal a fall in COVID-19 patients' utilization of services, specifically in patients administered two or three doses of the vaccine. However, the reduction is not statistically significant. Regression models are in contrast to univariate analysis findings that vaccination increases the mean utilization of healthcare services for COVID-19 patients in general. Comorbidities are a crucial factor in determining the utilization of diagnostic and treatment services for COVID-19 patients. Conclusion: Full COVID-19 vaccination and other implementations, including investing in public health, cooperating globally, and vaccinating high-risk groups for future pandemics, are essential as a critical response to this pandemic as they reduce healthcare service utilization to alleviate the burden on healthcare systems and allocate resources more efficiently.

Engagement of private health sector in communicable disease and immunization programmes in Pakistan.

Background: In Pakistan, where the burden of communicable diseases remains high, the private sector accounts for 62% of health care provision. Aim: To describe the role of the private sector in communicable disease management in Pakistan and inform a more effective engagement towards achieving Universal Health Coverage. Methods: We searched the literature and available documents on policies, regulations and experiences in private health sector engagement in Pakistan. We interviewed policy level experts regarding the formulation of national health policies and plans and a sample of private providers using a structured questionnaire to assess their awareness of and engagement in communicable disease programmes. Results: Published reports described initiatives to engage the private sector in improving coverage for a package of care and programme-specific initiatives. Pakistan did not have a national policy for structural engagement, and regulations were limited. Policy level experts interviewed perceived the private sector as market-driven and poorly regulated. Thirty-nine percent of private sector providers interviewed were aware or had been trained in procedures or guidelines, and 23% of them had had their performance monitored by government. Conclusion: We recommend that the Ministry of Health provide overall vision for the operations of the public and private health sectors so that both sectors can complement each other towards the achievement of Universal Health Coverage, including for communicable diseases.

Coordinating external assistance for UHC: Pakistan's early experience of the SDG3 GAP.

Pakistan is a lower middle-income setting. External assistance for health and development partners play an important role in health sector development. The federal system and health care delivery as a devolved provincial subject warrant regular and effective coordination among federating units and partners. Pakistan was selected as a priority country in 2019 for the implementation of the Global Action Plan for Healthy Lives and Well-being for All (SDG3 GAP). Given the ongoing universal health coverage (UHC) reforms, the country prioritized two SDG3 GAP accelerators, related to primary health care (PHC) and sustainable financing for health (SFH). Eight partner agencies representing PHC and SFH accelerators jointly planned and conducted a 'PHC for UHC mission' to Pakistan in 2021. This mission paved the way for setting up an SDG3 GAP Coordination Committee and a 'PHC Service Delivery and Financing working group', which have been regularly coming together through in-person and virtual meetings; the latter was relatively uncommon previously and this new way of working provided a chance to build rapport, share workplans, identify duplications in technical assistance and jointly gauge governments' priorities. This has shifted the focus of reforms deliberations from 'what' to 'how', enabling joint strategic planning and implementation. The joint work by SDG3 GAP partners with the Ministry of National Health Services Regulation & Coordination linked discussions on health financing and service delivery reforms for the first time, and has contributed to advocacy, analysis, strategic policy dialogue, institutional strengthening and implementation of UHC reforms, with a focus on PHC. Even though joint work by SDG3 GAP partners undoubtedly shows the potential for better alignment and collaboration, translation of the commitment to better collaboration into concrete impact has been the result of committed and engaged staff members, rather than institutionalized change, which will require strong incentives for collaboration.

SN38 loaded nanostructured lipid carriers (NLCs); preparation and in vitro evaluations against glioblastoma.

SN38 is the active metabolite of irinotecan with 1000-fold greater cytotoxicity compared to the parent drug. Despite the potential, its application as a drug is still seriously limited due to its stability concerns and low solubility in acceptable pharmaceutical solvents. To address these drawbacks here nanostructured lipid carrier (NLC) containing SN38 was prepared and its cytotoxicity against U87MG glioblastoma cell line was investigated. The formulations were prepared using hot ultrasonication and solvent evaporation/emulsification methods. NLCs with a mean size of 140 nm and particle size distribution (PDI) of 0.25 were obtained. The average loading efficiency was 9.5% and its entrapment efficiency was 81%. In order to obtain an accurate determination of released amount of SN38 a novel medium and extraction method was designed, which lead to an appropriate in vitro release profile of the drug from the prepared NLCs. The MTT test results revealed the significant higher cytotoxicity of NLCs on U87MG human glioblastoma cell line compared with the free drug. The confocal microscopy images confirmed the proper penetration of the nanostructures into the cells within the first 4 h. Consequently, the results indicated promising potentials of the prepared NLCs as a novel treatment for glioblastoma.

Comparison of thermoluminescent dosimeter calibration irradiated in gamma knife and 60Co instruments.

AIM: By necessity of dosimeters calibration for evaluating delivered dose accuracy to organs out of the radiation field in patients undergoing gamma knife radiosurgery, we calibrated thermoluminescence dosimeters in gamma knife and 60Co instruments, and then, compared both results to investigate when one of these devices was out of reach, can we use one of this instruments instead of the ther. MATERIALS AND METHODS: To individual calibration by 60Co, thermoluminescent dosimeters (TLDs) were placed in a Perspex sheet with conditions of source-skin distance = 80 cm, field size = 10 cm × 10 cm, and dose = 100 cGy. For individual calibration by Gamma knife, TLDs placed in flat Perspex were located in a special sphere and were exposed with conditions of source to axis distance = 40 cm, field size = 18 mm, and dose = 100 cGy, and for group calibration, TLDs were divided into six groups and were exposed with doses of 0-1000 cGy in both devices. RESULTS: According to Fisher's exact test, calculated P = 0.27, so the difference is not significant. CONCLUSIONS: The result showed despite differences in calibration conditions, 60Co unit can be used to calibrate TLD dosimeter for estimating the accuracy of measurement of delivered dose to organs of patients undergoing Gamma Knife 4C radiosurgery treatment.

Radio-Protective Effects of Melatonin on Subventricular Zone in Irradiated Rat: Decrease in Apoptosis and Upregulation of Nestin.

Neural stem cells are self-renewing, multipotent cells that can be found in subventricular (SVZ) and subgranular (SGZ) zones of the brain. These zones are susceptible to irradiation-induced apoptosis and oxidative stress. Melatonin (MLT) is a natural protector of neural cells against toxicity. The aim of this study was to evaluate the effects of MLT as a radio-protective material effective in reducing tissue lesions in the SVZ of the brain and changing local apoptotic potential in rats. Twenty-five Gray irradiation was applied on adult rat brain for this study. One hour before irradiation, 100 mg/kg/IP MLT was injected, and 6 h later, the animals were sacrificed. The antioxidant enzymes and MDA activity levels were measured post-sacrifice. Also, the expression level of Nestin and caspase 3 were studied by immunohistochemistry. Spectrophotometric analysis showed significant increases in the amount of malondialdehyde (MDA) levels in the irradiation-exposed (RAD) group compared to that of the control (Co) group (P < 0.05). Pre-treatment with MLT (100 mg/kg) ameliorates the harmful effects of the aforementioned 25 Gy irradiation by increasing antioxidant enzyme activity and decreasing MDA levels. A significant reduction in apoptotic cells was observed in rats treated with MLT 1 h before exposure (P < 0.001). Nestin-positive cells were also reduced in the RAD group (P < 0.001). Our results confirm the anti-apoptotic and antioxidant role of MLT. The MLT concentration used may serve as a threshold for significant protection against 25 Gy gamma irradiations on neural stem cells in SVZ.

A Novel Strategy for Softening Gelatin-Bioactive-Glass Hybrids.

The brittle structure of polymer-bioactive-glass hybrids is a hurdle for their biomedical applications. To address this issue here, we developed a novel method to cease the overcondensation of bioactive-glass by polymer cross-linking. Here, an organosilane-functionalized gelatin methacrylate (GelMA) is covalently bonded to a bioactive-glass during the sol-gel process, and the condensation of silica networks is controlled by photo-cross-linking of GelMA. The physicochemical properties and mechanical strength of these hybrids are tunable by the incorporation of secondary cross-linking agents. These hydrogels display elastic properties with ultimate compression strain above 0.2 mm·mm(-1) and tunable compressive modulus in the range of 42-530 kPa. In addition, these hydrogels are bioactive because they promoted the alkaline phosphatase activity of bone progenitor cells. They are also well-tolerated in the mice subcutaneous model. Therefore, our method is efficient for the prevention of overcondensation and allows preparation of soft bioactive hydrogels from organic-inorganic matrices, suitable for soft and hard tissue regeneration.

Repeated sessions of transcranial direct current stimulation for treatment of chronic subjective tinnitus: a pilot randomized controlled trial.

Subjective tinnitus is an auditory phantom sensation characterized by the perception of sound in the absence of an identifiable external source. This distressing audiological symptom can severely affect the quality of life. Transcranial direct current stimulation (tDCS) is a noninvasive technique that can induce short-term relief in tinnitus in some patients. The purpose of this pilot double-blind randomized controlled trial was to investigate whether repeated application of anodal tDCS over left temporoparietal area could induce long-lasting relief in patients with chronic tinnitus. Twenty-two patients with chronic tinnitus for at least 6 months were randomly allocated into two groups and received five sessions of anodal (N = 11) or sham (N = 11) stimulation in five consecutive days. A current intensity of 2 mA for 20 min was used for anodal stimulation. Outcomes were assessed using Persian version of tinnitus handicap inventory (THI), loudness and distress visual analog scale (VAS) scores and clinical global impression (CGI) scale. The trial is registered at the Iranian Registry of Clinical Trials (IRCT) with the reference ID of IRCT2014082018871N1. No statistically significant difference was found between anodal and sham stimulation regarding either immediate or long-lasting effects over the 2 weeks follow-up period. Deterioration of symptoms and alteration in tinnitus characteristics were reported by a few patients. There were no significant long-term beneficial effects following tDCS of the left temporoparietal area.

Biomedical Applications of Biodegradable Polyesters.

The focus in the field of biomedical engineering has shifted in recent years to biodegradable polymers and, in particular, polyesters. Dozens of polyester-based medical devices are commercially available, and every year more are introduced to the market. The mechanical performance and wide range of biodegradation properties of this class of polymers allow for high degrees of selectivity for targeted clinical applications. Recent research endeavors to expand the application of polymers have been driven by a need to target the general hydrophobic nature of polyesters and their limited cell motif sites. This review provides a comprehensive investigation into advanced strategies to modify polyesters and their clinical potential for future biomedical applications.

Anterior Cruciate Ligament: Structure, Injuries and Regenerative Treatments.

Anterior cruciate ligament (ACL) is one of the most vulnerable ligaments of the knee. ACL impairment results in episodic instability, chondral and meniscal injury and early osteoarthritis. The poor self-healing capacity of ACL makes surgical treatment inevitable. Current ACL reconstructions include a substitution of torn ACL via biological grafts such as autograft, allograft. This review provides an insight of ACL structure, orientation and properties followed by comparing the performance of various constructs that have been used for ACL replacement. New approaches, undertaken to induce ACL regeneration and fabricate biomimetic scaffolds, are also discussed.

Dental treatment needs of permanent first molars in mashhad schoolchildren.

BACKGROUND AND AIMS: In spite of their enormous importance, permanent first molars might be affected by caries in children in developing countries. The aim of this study was to evaluate the treatment needs of first permanent molars in a group of schoolchildren in Mashhad. MATERIALS AND METHODS: This cross-sectional descriptive study was carried out on 700, 7-9 year-old students in primary schools in Mashhad. The schools were randomly selected from each district. Treatment needs and DMFT of first perma-nent molars were calculated. Data was analyzed using ANOVA, Chi-Square and t-test. RESULTS: A total of 95.3% of the children required dental treatment. Fissure sealant application and filling were the treat-ments most required in all age groups. The mean DMFT of first permanent molars was 1.31±1.4. It was significantly higher in girls than boys (P=0.040). CONCLUSION: Great treatment needs and caries prevalence in permanent first molars in Mashhad schoolchildren show that dental caries is still a serious problem in the children of our society; therefore, education of parents and teachers is necessary for promoting children's oral health.

Study on Theileria lestoquardi antigens as potential vaccine candidates.

Theileria lestoquardi is the causative agent of malignant theileriosis of sheep and goats, causing morbidity and mortality in these animals worldwide. Western blot analysis based on T. lestoquardi schizont antigens was carried out using sera collected from Iranian sheep, which had been immunized with T. lestoquardi schizont-infected cells. The results of Western blot analysis demonstrated that schizont-immunized animals produced antibodies reacting with protein bands at 73, 42, 20, 14, and 12 kDa. Comparison of the results of the current Western blotting test with earlier studies of Theileria spp. revealed two immunogenic schizont proteins with molecular weights of 73 and 42 kDa shared between T. annulata and T. lestoquardi. Two other proteins with molecular weights of 14 and 12 kDa have not been previously found in other Theileria species. Our results suggest that the 73-kDa protein could be a potential vaccine candidate and that the 14- and 12-kDa proteins could be considered as diagnostic antigens.