Intravenous Immunoglobulins Alone for the Desensitization of Lung Transplant Recipients with Preformed Donor Specific Antibodies and Negative Flow Cytometry Crossmatch.

BACKGROUND: The lack of evidence regarding optimal desensitization strategies for lung transplant candidates with preformed donor specific anti-human leukocyte antigen antibodies (DSAs) has led to varying approaches among centers towards this patient group. Our institution's desensitization protocol for recipients with preformed DSAs and negative flow cytometry crossmatch (FCXM) consists of intravenous immunoglobulin (IVIG) as the sole therapy. The study aimed to determine outcomes using this approach. METHODS: This retrospective study included adults who underwent lung-only transplantation for the first time between January 2015 and March 2022 at a single center. We excluded patients with positive or missing FCXM results. Transplant recipients with any DSA ≥ 1000 MFI on latest testing within three months of transplant were considered DSA-positive, while recipients with DSAs <1000 MFI and those without DSAs were assigned to the low-level/negative group. Graft survival (time to death/retransplantation) and chronic lung allograft dysfunction (CLAD)-free times were compared between groups using Cox proportional hazards models. RESULTS: Thirty-six out of 167 eligible patients (22%) were DSA-positive. At least 50% of preformed DSAs had documented clearance (decrease to <1000 MFI) within the first 6 months of transplant. Multivariable Cox regression analyses did not detect a significantly increased risk of graft failure (aHR 1.04 95%CI 0.55-1.97) or chronic lung allograft dysfunction (aHR 0.71 95%CI 0.34-1.52) in DSA-positive patients compared to patients with low-level/negative DSAs. Incidences of antibody-mediated rejection (p = 1.00) and serious thromboembolic events (p = 0.63) did not differ between study groups. CONCLUSION: We describe a single-center experience of administering IVIG alone to lung transplant recipients with preformed DSAs and negative FCXM. Further studies are required to confirm the efficacy of this strategy against other protocols.

Design anticancer potential of Zn(II)isoleucinedithiocarbamate complex on MCF-7 cell lines: synthesis, characterization, molecular docking, molecular dynamic, ADMET, and in-vitro studies.

Cisplatin is a cancer medication widely used today, but it still poses some problems due to its toxic properties in the body. To overcome this issue, a new complex has been developed as a potential anticancer drug prospect by minimizing its toxic consequences. A novel Zn(II)IleDTC complex containing isoleucine dithiocarbamate ligands has been produced and analyzed using a range of analytical and spectroscopic methods. The Zn(II) IleDTC complex were characterized using various methods, including UV-Vis spectroscopy, FT-IR, determination of melting point, conductivity, and HOMO-LUMO analysis. Furthermore, computational NMR spectrum analysis was conducted in this study. Molecular docking studies was conducted to evaluate the potential of Zn(II) isoleucine dithiocarbamate as an HIF1 inhibitor. The results showed that the Zn complex exhibited a good docking score of -6.6 and formed hydrogen bonds with ARG 17, VAL264, and GLU15, alkyl bonds with TRP27 and LEU32, and Pi-Alkyl bonds with PRO41 and ARG44. This suggests that the Zn(II) isoleucine dithiocarbamate complex could be a promising candidate for cancer treatment with potential HIF1 inhibition properties. To assess the dynamic stability and efficacy of protein-ligand interactions over time, molecular dynamics simulations was conducted for both individual proteins and protein complexes. The cytotoxicity evaluation of Zn(II) isoleucine dithiocarbamate against MCF-7 cells obtained an IC50 value of 362.70 µg/mL indicating moderate cytotoxicity and morphological changes of cancer cells causing cancer cells to undergo apoptosis. The Zn(II) isoleucine dithiocarbamate complex may have promising potential as an anticancer compound due to its significant inhibitory effect on the breast cancer cell line (MCF7). According to the ADMET study, the complex exhibits drug-like characteristics with low toxicity, further supporting its potential as a viable drug candidate.

Effects of dietary boron supplementation on the testicular function and thyroid activity in male goats: Involvement of CYP17A1 gene.

The physiological effects of dietary boron (B) supplementation for farm animals specifically goat on male fertility are still scarce and need deep investigation. Thus, the current study was designed to investigate how adding B to the diet of male goats affected their testicular and thyroid activity. For that purpose, twelve male goats were divided randomly into two groups (six animals each); control group that was fed the basal diet and B group that was fed the basal diet containing 70 mg B/kg diet for 6 months. Serum samples were collected at different intervals, while testicular biopsies were obtained at the end of the experiment. The results showed that 6 months of dietary B supplementation resulted in a significant increment in serum B concentration. The results of repeated measure analysis showed that there were significant GROUP and TIME × GROUP interactions effects on blood testosterone levels (F = 119.408, p = .000 and F = 6.794, p = .013, respectively), demonstrating that compared with control, B supplementation caused a significant rise in serum testosterone levels over time. However, the mean animal body weights and the serum levels of triiodothyronine (T3) and thyroxine (T4) were kept comparable with the control ones at the different time points. The most striking finding is that B supplementation increased significantly the mRNA expression of the CYP17A1 which is essential for steroidogenesis (p < .001). In addition, a histological examination of testicular tissue corroborated our findings and demonstrated that B supplementation had a positive effect. As a result, B might be considered an excellent food supplement that could be safely added to the male goats' diet at the current dose to improve their reproductive capacity.

Novel therapeutic strategies for spinal osteosarcomas.

At the dawn of the third millennium, cancer has become the bane of twenty-first century man, and remains a predominant public health burden, affecting welfare and life expectancy globally. Spinal osteogenic sarcoma, a primary spinal malignant tumor, is a rare and challenging neoplastic disease to treat. After the conventional therapeutic modalities of chemotherapy, radiation and surgery have been exhausted, there is currently no available alternative therapy in managing cases of spinal osteosarcoma. The defining signatures of tumor survival are characterised by cancer cell ability to stonewall immunogenic attrition and apoptosis by various means. Some of these biomarkers, namely immune-checkpoints, have recently been exploited as druggable targets in osteosarcoma and many other different cancers. These promising strides made by the use of reinvigorated immunotherapeutic approaches may lead to significant reduction in spinal osteosarcoma disease burden and corresponding reciprocity in increase of survival rates. In this review, we provide the background to spinal osteosarcoma, and proceed to elaborate on contribution of the complex ecology within tumor microenvironment giving arise to cancerous immune escape, which is currently receiving considerable attention. We follow this section on the tumor microenvironment by a brief history of cancer immunity. Also, we draw on the current knowledge of treatment gained from incidences of osteosarcoma at other locations of the skeleton (long bones of the extremities in close proximity to the metaphyseal growth plates) to make a case for application of immunity-based tools, such as immune-checkpoint inhibitors and vaccines, and draw attention to adverse upshots of immune-checkpoint blockers as well. Finally, we describe the novel biotechnique of CRISPR/Cas9 that will assist in treatment approaches for personalized medication.

Daily energy expenditure in rats following structured exercise training is affected by dietary phosphorus content.

P ingestion has been found to alter energy balance, while regular physical exercise (E) was reported to be associated with energy compensation. However, it is not clear whether dietary P would affect energy compensation following structured E. Two experiments were performed, low P (LP) (0·1, 0·2 and 0·3 %P) and high P (HP) (0·3 , 0·6 and 1·2 %P) diets. In each experiment, male rats were randomly divided into three groups (n 8), in which a sedentary or a moderate-intensity exercise routine (30 min 5 d a week) was implemented. Energy intake (EI); efficiency and stores; body measures and total energy expenditure (TEEx) were monitored for 6 weeks. In the LP experiment, EI and weight gain were the lowest in the 0·1 and 0·2 %P as compared with the 0·3 %P. In the HP experiment, EI was highest in the high P (0·6 and 1·2 %P) groups, while weight gain was reduced. In both experiments, exercise was able to reduce body fat accumulation and to maintain a higher % lean body mass. In the LP diets experiment, the similarity in TEEx between the sedentary and exercising groups suggests the probability of a reduction in normal daily activities, which indicates the presence of compensation for the energy expended during exercise by a subsequent reduction in EE. In contrast, the elevated TEEx in the HP exercising groups (0·6 and 1·2 %P) argue against the presence of energy compensation. In conclusion, high dietary P decreases the body's capability to compensate for the energy deficit induced by E, consequently maintaining an elevated TEEx.

Effect of temperature and/or sweetness of beverages on body composition in rats.

Sweetened beverages are mainly consumed cold and various processes are activated in response to external temperature variations. However, the effect of internal temperature variations through the ingestion of cold beverages is far from clear. Two experiments were conducted to investigate the effect of beverage temperature on body composition. Sprague-Dawley rats (5-6-week-old males) had free access to food and beverage for 8 weeks. Energy intake, body weight and body composition were monitored. In Expt 1, two groups of rats (n 9) consumed water at room temperature (NW about 22°C) or cold (CW about 4°C). In Expt 2, rats were offered room-temperature (N) or cold (C) sweetened water (10 % sucrose CSu (n 7) and NSu (n 8); or 0·05 % acesulfame K CAk (n 6) and NAk (n 8)) for 12 h, followed by plain water. Our results show that in Expt 1, CW had higher lean body mass (P < 0·001) and lower body fat gain (P = 0·004) as compared with NW. In Expt 2, body weight (P = 0·013) and fat (P ≤ 0·001) gains were higher in the non-energetic sweetened groups, while lean body mass was not affected by the type of sweeteners or temperature. In conclusion, cold water ingestion improved lean body mass gain and decreased fat gain because of increased energy expenditure, while non-energetic sweetener (acesulfame K) increased body fat gain due to improved energy efficiency. Internal cold exposure failed to increase energy intake in contrast to that of external cold exposure.

Red blood cell transfusion in surgery: an observational study of the trends in the USA from 2011 to 2016.

Guidelines recommend restrictive red blood cell transfusion strategies. We conducted an observational study to examine whether the rate of peri-operative red blood cell transfusion in the USA had declined during the period from 01 January 2011 to 31 December 2016. We included 4,273,168 patients from all surgical subspecialties. We examined parallel trends in rates of the following: pre-operative transfusion; prevalence of bleeding disorders and coagulopathy; and minimally invasive procedures. To account for changes in population and procedure characteristics, we performed multivariable logistic regression to assess whether the risk of receiving a transfusion had declined over the study period. Clinical outcomes included peri-operative myocardial infarction, stroke and all-cause mortality at 30 days. Peri-operative red blood cell transfusion rates declined from 37,040/441,255 (8.4%) in 2011 to 46,845/1,000,195 (4.6%) in 2016 (p < 0.001) across all subspecialties. Compared with 2011, the corresponding adjusted OR (95%CI) for red blood cell transfusion decreased gradually from 0.88 (0.86-0.90) in 2012 to 0.51 (0.50-0.51) in 2016 (p < 0.001). Pre-operative red blood cell transfusion rates and the prevalence of bleeding disorders decreased, whereas haematocrit levels and the proportion of minimally invasive procedures increased. Compared with 2011, the adjusted hazard ratios (95%CI) in 2012 and 2016 were 0.96 (0.90-1.02) and 1.05 (0.99-1.11) for myocardial infarction, 0.91 (0.83-0.99) and 0.99 (0.92-1.07) for stroke and 0.98 (0.94-1.02) and 0.99 (0.96-1.03) for all-cause mortality. Use of peri-operative red blood cell transfusion declined from 2011 to 2016. This was not associated with an increase in adverse clinical outcomes.

An atypical pulmonary fibrosis is associated with co-inheritance of mutations in the calcium binding protein genes S100A3 and S100A13.

BACKGROUND: Pulmonary fibrosis is one of the leading indications for lung transplantation. The disease, which is of unknown aetiology, can be progressive, resulting in distortion of the extracellular matrix (ECM), inflammation, fibrosis and eventual death. METHODS: 13 patients born to consanguineous parents from two unrelated families presenting with interstitial lung disease were clinically investigated. Nine patients developed respiratory failure and subsequently died. Molecular genetic investigations were performed on patients' whole blood or archived tissues, and cell biological investigations were performed on patient-derived fibroblasts. RESULTS: The combination of a unique pattern of early-onset lung fibrosis (at 12-15 years old) with distinctive radiological findings, including 1) traction bronchiectasis, 2) intralobular septal thickening, 3) shrinkage of the secondary pulmonary lobules mainly around the bronchovascular bundles and 4) early type 2 respiratory failure (elevated blood carbon dioxide levels), represents a novel clinical subtype of familial pulmonary fibrosis. Molecular genetic investigation of families revealed a hypomorphic variant in S100A3 and a novel truncating mutation in S100A13, both segregating with the disease in an autosomal recessive manner. Family members that were either heterozygous carriers or wild-type normal for both variants were unaffected. Analysis of patient-derived fibroblasts demonstrated significantly reduced S100A3 and S100A13 expression. Further analysis demonstrated aberrant intracellular calcium homeostasis, mitochondrial dysregulation and differential expression of ECM components. CONCLUSION: Our data demonstrate that digenic inheritance of mutations in S100A3 and S100A13 underlie the pathophysiology of pulmonary fibrosis associated with a significant reduction of both proteins, which suggests a calcium-dependent therapeutic approach for management of the disease.

New insight into the diagnostic cut-off value of serum anti-Toxocara IgG for ocular toxocariasis in uveitis patients.

Uveitis is one of the commonest causes of vision loss worldwide and its exact etiology is still not clarified in most patients. The current study is a trial to assess the efficacy of serum anti-Toxocara immunoglobulin G (IgG) by enzyme-linked immunosorbent assay (ELISA) as a diagnostic tool for ocular toxocariasis (OT) and to detect OT prevalence and the associated ocular manifestations in sera of patients with uveitis. One hundred and twelve patients (62 females and 50 males) with uveitis were diagnosed by ophthalmologists, radiologists and rheumatologists according to ocular manifestations, laboratory and radiological investigations. Serum anti-Toxocara IgG titers were determined by ELISA in sera of all patients. Our results revealed that OT is highly associated with intermediate and posterior uveitis. Children and young adult females, especially those residing in rural areas, complained mainly of diminution of vision in the left eye, with strabismus and leukocoria. At a cut-off value of 0.258, the sensitivity and specificity of IgG ELISA were 93.3% and 100%, respectively. In conclusion, at a novel cut-off value of 0.258 the serum anti-Toxocara IgG ELISA is predicted to be a diagnostic tool for OT regarding sensitivity and specificity. Also, it has potential importance in the interpretation and differential diagnosis of OT. Thus, serum anti-Toxocara IgG ELISA should be a routine test for screening of suspected cases.

Tea catechins induce crosstalk between signaling pathways and stabilize mast cells in ulcerative colitis.

It is well documented that nutraceuticals, in general, and Green tea catechins, in particular, possess a potential therapeutic value in inflammatory bowel diseases (IBD) due to their anti-oxidative and anti-inflammatory effects. This study aimed to investigate the possible mechanism of action of catechins in a rat model of colitis induced by 2.4.6 trinitrobenzene sulfonic acid (TNBS). Thirty-five young adult Sprague-Dawley rats were divided into four groups: normal control (n=5), catechins (n=9), TNBS (n=9) and TNBS plus catechins (n=12) treated. Catechin in the form of Epigallocatechin-3-gallate (EGCG) was administered daily by intraperitoneal injection, 1 week before the induction date of UC. Biopsies of the descending colon were collected on days 3, 10 and 17, and partly frozen for molecular studies or fixed for light microscopy. The status of intestinal tissue alterations and mast cells number were also assessed, as well as the mRNA expressions of IL-6, TNF-a and NF-kB, and determination of ROS expression. Histological data depicted a significant amelioration in the TNBS- and EGCG-treated rats compared to the non-treated animals. Catechin expressed strong anti-inflammatory and anti-oxidant effects, ameliorated ulcerative colitis and stabilized mast cells. The mechanism of action occurred basically through the NF-kB pathway and possibly through a crosstalk with other pathways.

Early outcomes of spinal growth tethering for idiopathic scoliosis with a novel device: a prospective study with 2 years of follow-up.

QUESTIONS/PURPOSES: Adolescent idiopathic scoliosis is a 3D spine deformity that worsens during the whole growth. New methods for spinal growth modulation with flexible spinal implants have been described to avoid progression of the deformity during growth spurt. The main limitations are that no specific ancillaries and devices are available, which makes the surgery technically demanding. METHODS: We have developed a new method of spinal growth tethering using minimal invasive videothoracoscopic approach. Fixation is performed with staples and synthetic ligament on the lateral aspect of vertebral bodies on main curvature convexity. Patients with progressive thoracic idiopathic scoliosis despite the brace treatment were included. The clinical and radiological examinations were compared before and 2 years after surgery. RESULTS: Six patients with flexible thoracic curves with a mean age 11.2 ± 1.2 years and a mean Cobb angle 45° ± 10° (35-60) were operated. All were skeletally immature. At last follow-up, the Cobb angle was stable. None of the patient underwent fusion. CONCLUSIONS: The procedure allowed a stabilization of the deformity during growth spurt. Validated devices and further studies with longer term follow-up are needed to confirm the efficiency of this technique. This small cohort of patients is a source of reflection for further medical devices developments. LEVEL OF EVIDENCE: Level 4 case series comparing to not randomized studies.

Assessment of antisperm antibodies in a sample of Egyptian patients with hepatitis C virus infection.

Association of hepatitis C virus (HCV) with autoimmune phenomena and impaired semen parameters has been previously reported. The aim of this study was to investigate the influence of HCV infection on the development of antisperm antibodies (ASAs) in HCV-positive males. The study was conducted on 30 HCV-infected individuals and 30 healthy control subjects. In both patients and control groups, liver enzymes and reproductive hormones were measured; computer-assisted semen analysis (CASA) was performed; HCV-RNA in serum was measured and IgG and IgA ASAs in semen were determined. Free testosterone, sperm concentration, progressive and total motility were significantly lower in HCV patients than in the control group, whereas ASAs of the IgG and IgA classes were significantly higher in HCV patients. However, correlations between viral load and the examined semen parameters and ASAs were nonsignificant. In conclusion, HCV may be responsible for the increased ASAs detected in HCV patients in the present study, possibly providing another plausible explanation for the decreased sperm motility reported in HCV patients. These findings could be of value in fertility management of HCV patients.

The role of NADPH-derived reactive oxygen species production in the pathogenesis of endometriosis: a novel mechanistic approach.

Endometriosis is defined as endometriotic tissue growing outside the uterine cavity. It is a common gynecological disorder in women of reproductive age and is associated with chronic pelvic pain and infertility. Despite several studies and theories to explain its cause, the exact pathogenesis of endometriosis remains unclear. Retrograde menstruation is the most plausible theory, however, it is not exclusive. The disparity between the actual prevalence of retrograde menstruation and the prevalence of endometriosis suggests that other factors may determine the susceptibility to endometriosis development. Oxidative stress has been associated with endometriosis. This study aimed to explore the role of NADPH oxidase family in the production of reactive oxygen species (ROS) and to determine whether ROS induce the proliferation of endometriotic implants via mammalian target of rapamycin (mTOR) signaling. Anonymous endometriotic tissue samples were collected from women undergoing laparoscopy for endometriosis. The samples were stained with dihydroethidium and fluorescent images of the slides were taken to detect ROS production. After extraction of RNA from the samples and c-DNA generation, quantitative real-time PCR, protein extraction and Western blot were performed to study gene and protein expression of NADPH oxidase 1 (NOX 1), mTOR and fibronectin. The results showed an increase in ROS levels and NOX 1 gene and protein expression in the endometriotic tissues compared to the normal surrounding tissue control. Also, mTOR and fibronectin, gene expression was found to be increased. Up regulation of NOX at gene and protein level leads to increased production of ROS in the endometriotic tissue, which in turn causes proliferation of the ectopic tissue via alteration of the mTOR signaling pathway. Increased fibronectin gene expression points towards tissue injury in endometriosis as compared to the normal surrounding tissue. This manuscript adds a new insight into the pathogenesis of endometriosis and serves as a background for development of new treatments for the disease-associated pain and infertility.

Tracheobronchial anomalies in a patient with Schimke immuno-osseous dysplasia (SIOD).

Schimke Immuno-osseous Dysplasia (SIOD) is a rare genetic disorder with multiple systemic manifestations. Pulmonary manifestations have been described but not well characterized. They are believed to be secondary to decreased elasticity, and include emphysema, pulmonary hypertension and bronchiectasis. We describe a 24-year-old female patient with SIOD with tracheobronchial anomalies not reported before, including tracheomalacia and a tracheal bronchus with Epstein-Barr virus (EBV) related leiomyoma causing endobronchial obstruction. Such anomalies, in addition to the difficult upper airway associated with SIOD present specific challenges during management. This case reports documents tracheobronchial abnormalities that have not been described before in SIOD.

Seminal Tumour necrosis factor-related apoptosis-inducing ligand and its relationship to infertility in Egyptian patients with varicocele.

Germ cell apoptosis has been proposed as one of the mechanisms by which varicocele can influence fertility. The aim of this study was to investigate the relationship between seminal tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) levels and male infertility in patients with varicocele. This study included 112 males: 30 fertile males with varicocele, 44 infertile males with varicocele and 38 healthy fertile control subjects without varicocele. Semen analysis was performed, and serum levels of reproductive hormones were measured. Seminal TRAIL levels in the infertile varicocele group were significantly higher than in the fertile varicocele and the control groups (P = 0.014). A significant negative correlation was found between seminal TRAIL and progressive (P < 0.001) and total motility scores (P < 0.001) in the infertile varicocele group. A significant negative correlation was also detected between seminal TRAIL levels and normal sperm morphology in the fertile varicocele (P = 0.007) and infertile varicocele patients (P = 0.047). Seminal TRAIL was significantly correlated with varicocele grade whether the patients were fertile (P = 0.001) or infertile (P = 0.035). Seminal TRAIL may thus have a potential role in varicocele-associated male infertility through its negative effect on sperm motility and morphology.

Microwave ablation of a large renal aspergilloma.

Increasing numbers of immunocompromised patients have led to a corresponding rise in the incidence of invasive Aspergillus infections. Despite advances in antifungal therapy coupled with reduction in immunosuppression, invasive aspergillosis is associated with significant morbidity and mortality. Although surgical debulking has proven effective in difficult-to-treat cases, patient comorbidities may prevent such intervention. Non-invasive alternatives to surgery are needed. Microwave ablation has many advantages over other ablative techniques, including convection profile, faster heating time, and higher intra-lesion temperatures, which may be associated with greater therapeutic efficacy. We report a case of microwave ablation as an adjunct to medical therapy in angioinvasive renal aspergilloma.

Estrogens control inflammation in experimental colitis.

There is now a wealth of experimental evidence indicating that the deficit in endogenous estrogen facilitates the onset of inflammation that can be antagonized by estrogen replacement therapy. This work investigated the role of estrogen in the control of intestinal inflammation in a panel of colitis models, focusing on the morphological changes, the activity of mast cells, the expression of cytokines (IL-1beta, IL-6, and TNF-alpha), fibronectin and reactive oxygen species. Two hundred adult male rats were divided into 4 groups: colitis was induced in Group I and Group II but only the latter was treated with estrogen; Group III received estrogen only, and Group IV saline. Colitis was induced in 4 models using: iodoacetamide; iodoacetamide + enteropathogenic E. coli; 2, 4, 6-Trinitrobenzene sulfonic acid; and dextran sulfate sodium salt. Macroscopic and microscopic evaluations of abdominal structures as well as molecular analysis were made on days 7, 14, 28 and 56. There was a significant improvement in the health condition of the estrogen-treated rats: the inflammation scores were reduced by at least 10-15%, the number of mast cells in the colon decreased by 30%, fibronectin expression was only 50% and reactive oxygen species decreased by 30%. In addition, there was a significant decrease in TNF-alpha, IL-6 and IL-1beta expression by about 25%. In conclusion, there was an improvement in the inflammatory status in all estrogen-treated groups through the duration of the experiment at all-time points. In addition, there was less tissue necrosis as depicted by less fibronectin and a marked antioxidant effect.

Spica cast as an alternative to general anesthesia for lower limb MRI in young children.

BACKGROUND: The conventional approach for MRI procedures in very young children is to use general anesthesia which comes with inherent risks. Non-pharmacological strategies to reduce anxiety in children have also been described, but they all require patient cooperation. The purpose of the study was to evaluate the ability to complete diagnosis using temporary spica cast immobilization (TSCI) in children less than 3 years old undergoing MRI procedures for lower limb disorders. MATERIALS AND METHODS: A retrospective review identified 14 children under 3 years old that had required an MRI for a lower limb disorder, using TSCI. The MRI procedure was performed for evaluation of hip dysplasia, bone infections, limping, evaluation of soft tissue tumor and femoral head osteonecrosis. A spica cast was fitted by the pediatric orthopedic team. The MRI procedure was subsequently performed. RESULTS: Diagnosis was achieved in all cases. The radiologist identified movement artifacts (14 %) that did not impair the image quality enough to prevent interpretation. CONCLUSION: TSCI is a safe, effective and costless procedure avoiding general anesthesia for young patients under 3 years old who require MRI for pelvis or lower limb disorders. LEVEL OF EVIDENCE: IV.

Subtractive proteomics-guided vaccine targets identification and designing of multi-epitopes vaccine for immune response instigation against Burkholderia pseudomallei.

In this study, a methodical workflow using subtractive proteomics, vaccine designing, molecular simulation, and agent-based modeling approaches were used to annotate the whole proteome of Burkholderia pseudomallei (strain K96243) for vaccine designing. Among the total 5717 proteins in the whole proteome, 505 were observed to be essential for the pathogen's survival and pathogenesis predicted by the Database of Essential Genes. Among these, 23 vaccine targets were identified, of which fimbrial assembly chaperone (Q63UH5), Outer membrane protein (Q63UH1), and Hemolysin-like protein (Q63UE4) were selected for the subsequent analysis based on the systematic approaches. Using immunoinformatic approaches CTL (cytotoxic T lymphocytes), HTL (helper T lymphocytes), IFN-positive, and B cell epitopes were predicted for these targets. A total of 9 CTL epitopes were added using the GSS linker, 6 HTL epitopes using the GPGPG linker, and 6 B cell epitopes using the KK linker. An adjuvant was added for enhanced antigenicity, an HIV-TAT peptide for improved delivery, and a PADRE sequence was added to form a 466 amino acids long vaccine construct. The construct was classified as non-allergenic, highly antigenic, and experimentally feasible. Molecular docking results validated the robust interaction of MEVC with immune receptors such as TLR2/4. Furthermore, molecular simulation revealed stable dynamics and compact nature of the complexes. The binding free energy results further validated the robust binding. In silico cloning, results revealed GC contents of 50.73 % and a CIA value of 0.978 which shows proper downstream processing. Immune simulation results reported that after the three injections of the vaccine a robust secondary immune response, improved antigen clearance, and effective immune memory generation were observed highlighting its potential for effective and sustained immunity. Future directions should encompass experimental validations, animal model studies, and clinical trials to substantiate the vaccine's efficacy, safety, and immunogenicity.

Stability of asymmetric Schwarzschild-Rindler-de Sitter thin shell wormhole.

The paper examines the dynamics of asymmetric thin shell wormholes that connect two distinct spacetimes using the cut and paste technique. The focus is on analyzing the linear stability of these wormholes by considering radial perturbations and utilizing the modified generalized Chaplygin gas equation of state. The specific case of an asymmetric wormhole connecting Schwarzschild-Rindler spacetime to Schwarzschild-Rindler-de Sitter space-time is analyzed using this formalism. Our investigation uncovers the existence of both stable and unstable regions, which are contingent upon the appropriate selection of various parameters within the metric spacetime and equation of state. Additionally, we determine that stability regions exist as a consequence of the square speed of sound. By increasing the value of the cosmological constant, the stability region is expanded. Furthermore, the stability regions are augmented by the influence of Rindler parameters, while the stability regions are also affected by adjustments in the equation of state parameters, leading to their enlargement.