Multitask Weakly Supervised Generative Network for MR-US Registration.

Registering pre-operative modalities, such as magnetic resonance imaging or computed tomography, to ultrasound images is crucial for guiding clinicians during surgeries and biopsies. Recently, deep-learning approaches have been proposed to increase the speed and accuracy of this registration problem. However, all of these approaches need expensive supervision from the ultrasound domain. In this work, we propose a multitask generative framework that needs weak supervision only from the pre-operative imaging domain during training. To perform a deformable registration, the proposed framework translates a magnetic resonance image to the ultrasound domain while preserving the structural content. To demonstrate the efficacy of the proposed method, we tackle the registration problem of pre-operative 3D MR to transrectal ultrasonography images as necessary for targeted prostate biopsies. We use an in-house dataset of 600 patients, divided into 540 for training, 30 for validation, and the remaining for testing. An expert manually segmented the prostate in both modalities for validation and test sets to assess the performance of our framework. The proposed framework achieves a 3.58 mm target registration error on the expert-selected landmarks, 89.2% in the Dice score, and 1.81 mm 95th percentile Hausdorff distance on the prostate masks in the test set. Our experiments demonstrate that the proposed generative model successfully translates magnetic resonance images into the ultrasound domain. The translated image contains the structural content and fine details due to an ultrasound-specific two-path design of the generative model. The proposed framework enables training learning-based registration methods while only weak supervision from the pre-operative domain is available.

Shape completion in the dark: completing vertebrae morphology from 3D ultrasound.

PURPOSE: Ultrasound (US) imaging, while advantageous for its radiation-free nature, is challenging to interpret due to only partially visible organs and a lack of complete 3D information. While performing US-based diagnosis or investigation, medical professionals therefore create a mental map of the 3D anatomy. In this work, we aim to replicate this process and enhance the visual representation of anatomical structures. METHODS: We introduce a point cloud-based probabilistic deep learning (DL) method to complete occluded anatomical structures through 3D shape completion and choose US-based spine examinations as our application. To enable training, we generate synthetic 3D representations of partially occluded spinal views by mimicking US physics and accounting for inherent artifacts. RESULTS: The proposed model performs consistently on synthetic and patient data, with mean and median differences of 2.02 and 0.03 in Chamfer Distance (CD), respectively. Our ablation study demonstrates the importance of US physics-based data generation, reflected in the large mean and median difference of 11.8 CD and 9.55 CD, respectively. Additionally, we demonstrate that anatomical landmarks, such as the spinous process (with reconstruction CD of 4.73) and the facet joints (mean distance to ground truth (GT) of 4.96 mm), are preserved in the 3D completion. CONCLUSION: Our work establishes the feasibility of 3D shape completion for lumbar vertebrae, ensuring the preservation of level-wise characteristics and successful generalization from synthetic to real data. The incorporation of US physics contributes to more accurate patient data completions. Notably, our method preserves essential anatomical landmarks and reconstructs crucial injections sites at their correct locations.

CACTUSS: Common Anatomical CT-US Space for US examinations.

PURPOSE: The detection and treatment of abdominal aortic aneurysm (AAA), a vascular disorder with life-threatening consequences, is challenging due to its lack of symptoms until it reaches a critical size. Abdominal ultrasound (US) is utilized for diagnosis; however, its inherent low image quality and reliance on operator expertise make computed tomography (CT) the preferred choice for monitoring and treatment. Moreover, CT datasets have been effectively used for training deep neural networks for aorta segmentation. In this work, we demonstrate how leveraging CT labels can be used to improve segmentation in ultrasound and hence save manual annotations. METHODS: We introduce CACTUSS: a common anatomical CT-US space that inherits properties from both CT and ultrasound modalities to produce an image in intermediate representation (IR) space. CACTUSS acts as a virtual third modality between CT and US to address the scarcity of annotated ultrasound training data. The generation of IR images is facilitated by re-parametrizing a physics-based US simulator. In CACTUSS we use IR images as training data for ultrasound segmentation, eliminating the need for manual labeling. In addition, an image-to-image translation network is employed for the model's application on real B-modes. RESULTS: The model's performance is evaluated quantitatively for the task of aorta segmentation by comparison against a fully supervised method in terms of Dice Score and diagnostic metrics. CACTUSS outperforms the fully supervised network in segmentation and meets clinical requirements for AAA screening and diagnosis. CONCLUSION: CACTUSS provides a promising approach to improve US segmentation accuracy by leveraging CT labels, reducing the need for manual annotations. We generate IRs that inherit properties from both modalities while preserving the anatomical structure and are optimized for the task of aorta segmentation. Future work involves integrating CACTUSS into robotic ultrasound platforms for automated screening and conducting clinical feasibility studies.

Persistent basal ganglia involvement in aminoacylase-1 deficiency: expanding imaging findings and review of literature.

BACKGROUND: Aminoacylase-1 deficiency (ACY1D) is an autosomal recessive rare inborn error of metabolism, which is caused by disease-causing variants in the ACY1. This disorder is characterized by increased urinary excretion of specific N-acetyl amino acids. Affected individuals demonstrate heterogeneous clinical manifestations which are primarily neurologic problems. In neuroimaging, corpus callosum hypoplasia, cerebellar vermis atrophy, and delayed myelination of cerebral white matter have been reported. AIMS: Finding disease-causing variant and expanding imaging findings in a patient with persistent basal ganglia involvement. METHODS: Whole-exome sequencing was performed in order to identify disease-causing variants in an affected 5-year-old male patient who presented with neurologic regression superimposed on neurodevelopmental delay following a febrile illness. He had inability to walk, cognitive impairment, speech delay, febrile-induced seizures, truncal hypotonia, moderate to severe generalized dystonia, and recurrent metabolic decompensation. RESULTS: All metabolic tests were normal except for a moderate metabolic acidosis following febrile illnesses. The results of serial brain magnetic resonance imaging (MRI) at ages 1 and 4.5 years revealed persistent bilateral and symmetric abnormal signals in basal ganglia mainly caudate and globus pallidus nuclei with progression over time in addition to a mild supratentorial atrophy. A homozygous missense variant [NM_000666.3: c.1057C>T; p.(Arg353Cys)] was identified in the ACY1, consistent with aminoacylase-1 deficiency. Variant confirmation in patient and segregation analysis in his family were performed using Sanger sequencing. CONCLUSIONS: Our findings expanded the phenotype spectrum of ACY1-related neurodegeneration by demonstrating persistent basal ganglia involvement and moderate to severe generalized dystonia.

Anatomy-aware computed tomography-to-ultrasound spine registration.

BACKGROUND: Ultrasound (US) has demonstrated to be an effective guidance technique for lumbar spine injections, enabling precise needle placement without exposing the surgeon or the patient to ionizing radiation. However, noise and acoustic shadowing artifacts make US data interpretation challenging. To mitigate these problems, many authors suggested using computed tomography (CT)-to-US registration to align the spine in pre-operative CT to intra-operative US data, thus providing localization of spinal landmarks. PURPOSE: In this paper, we propose a deep learning (DL) pipeline for CT-to-US registration and address the problem of a need for annotated medical data for network training. Firstly, we design a data generation method to generate paired CT-US data where the spine is deformed in a physically consistent manner. Secondly, we train a point cloud (PC) registration network using anatomy-aware losses to enforce anatomically consistent predictions. METHODS: Our proposed pipeline relies on training the network on realistic generated data. In our data generation method, we model the properties of the joints and disks between vertebrae based on biomechanical measurements in previous studies. We simulate the supine and prone position deformation by applying forces on the spine models. We choose the spine models from 35 patients in VerSe dataset. Each spine is deformed 10 times to create a noise-free data with ground-truth segmentation at hand. In our experiments, we use one-leave-out cross-validation strategy to measure the performance and the stability of the proposed method. For each experiment, we choose generated PCs from three spines as the test set. From the remaining, data from 3 spines act as the validation set and we use the rest of the data for training the algorithm. To train our network, we introduce anatomy-aware losses and constraints on the movement to match the physics of the spine, namely, rigidity loss and bio-mechanical loss. We define rigidity loss based on the fact that each vertebra can only transform rigidly while the disks and the surrounding tissue are deformable. Second, by using bio-mechanical loss we stop the network from inferring extreme movements by penalizing the force needed to get to a certain pose. RESULTS: To validate the effectiveness of our fully automated data generation pipeline, we qualitatively assess the fidelity of the generated data. This assessment involves verifying the realism of the spinal deformation and subsequently confirming the plausibility of the simulated ultrasound images. Next, we demonstrate that the introduction of the anatomy-aware losses brings us closer to state-of-the-art (SOTA) and yields a reduction of 0.25 mm in terms of target registration error (TRE) compared to using only mean squared error (MSE) loss on the generated dataset. Furthermore, by using the proposed losses, the rigidity loss in inference decreases which shows that the inferred deformation respects the rigidity of the vertebrae and only introduces deformations in the soft tissue area to compensate the difference to the target PC. We also show that our results are close to the SOTA for the simulated US dataset with TRE of 3.89 mm and 3.63 mm for the proposed method and SOTA respectively. In addition, we show that our method is more robust against errors in the initialization in comparison to SOTA and significantly achieves better results (TRE of 4.88 mm compared to 5.66 mm) in this experiment. CONCLUSIONS: In conclusion, we present a pipeline for spine CT-to-US registration and explore the potential benefits of utilizing anatomy-aware losses to enhance registration results. Additionally, we propose a fully automatic method to synthesize paired CT-US data with physically consistent deformations, which offers the opportunity to generate extensive datasets for network training. The generated dataset and the source code for data generation and registration pipeline can be accessed via https://github.com/mfazampour/medphys_ct_us_registration.

The association between leisure-time physical activity and blood pressure changes from adolescence to young adulthood: Tehran Lipid and Glucose Study.

The effectiveness of long-term leisure time physical activity (LTPA) on blood pressure (BP) changes is still under debate. Since adolescence lifestyle behaviors shape the adulthood health profile, this study aimed to investigate the sex-specific impact of LTPA on BP changes from adolescence to young adulthood. This longitudinal study uses the data of 1412 adolescents (52% females) aged 12-18 years through a median follow-up of 12.2 years in the Tehran Lipid and Glucose Study (TLGS) framework. LTPA was calculated using the reliable and valid Iranian version of the modified activity scale (MAQ), and BP was measured at least twice by trained physicians. The linear mixed model was used to examine the study variables, considering individual and intrapersonal differences during the study. The majority of participants consistently demonstrated insufficient LTPA throughout the follow-up assessments, ranging from 54.7 to 67.1% for males and 77.7-83.4% for females. Despite a declining trend in LTPA (ß = - 2.77 for males and ß = - 1.43 for females), an increasing trend was noticeable in SBP, DBP, and BMI (ß = 1.38, ß = 1.81, ß = 0.97 for males, and ß = 0.10, ß = 0.20, ß = 0.97 for females, respectively). The unadjusted model revealed a significant trend in all variables for both sexes, except for female BP (P = 0.45 for SBP and P = 0.83 for DBP). Using the adjusted model, no significant association was observed between LTPA and changes in BP over time in both sexes. Our study indicates no association between LTPA and BP changes from adolescence to young adulthood. Insufficient LTPA levels, particularly among Iranian females, are likely the primary factor. Further research is crucial to identify appropriate LTPA levels to promote cardiovascular health and implement targeted interventions to achieve optimal LTPA levels in the Iranian population.

Expression assay of the COLQ in a family with congenital myasthenic syndrome and symptomatic carriers.

Congenital myasthenic syndromes-5 (CMS5) is a rare autosomal recessive heterogeneous disorder, caused by pathogenic variants in the COLQ that lead to skeletal muscle weakness and abnormal fatigability. The onset is usually from birth to childhood. Disease-causing variants in the collagen-like tail subunit are the most explained etiology in synaptic CMS, causing defected acetylcholinesterase. In this study whole-exome sequencing (WES) was performed in an affected boy with muscle weakness, ophthalmoplegia, and bilateral ptosis and gene expression assay by qRT-PCR was performed in entire family. A homozygous nonsense variant in the COLQ [NM_005677.4:c.679C>T], (p.Arg227Ter) was identified in the proband. Segregation analysis by Sanger sequencing confirmed the homozygous state in the proband and heterozygous state in his parents and four of the siblings. The mRNA expression level in the proband was 0.02 of a healthy person, and in the carriers were 0.42 of a healthy person. This study presents an Iranian family with two affected children and eight symptomatic carriers with attenuated mRNA expression. This study provides evidence that carriers of the COLQ disease-causing variants could become symptomatic with some yet unknown pathogenesis mechanism and underscore the importance of further investigations to elucidate this mechanism.

Expanding the neuroimaging findings of guanidinoacetate methyltransferase deficiency in an Iranian girl with a homozygous frameshift variant in the GAMT.

Guanidinoacetate methyltransferase deficiency (GAMTD) is a treatable neurodevelopmental disorder with normal or nonspecific imaging findings. Here, we reported a 14-month-old girl with GAMTD and novel findings on brain magnetic resonance imaging (MRI).A 14-||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||month-old female patient was referred to Myelin Disorders Clinic due to onset of seizures and developmental regression following routine vaccination at 4 months of age. Brain MRI, prior to initiation of treatment, showed high signal intensity in T2-weighted imaging in bilateral thalami, globus pallidus, subthalamic nuclei, substantia nigra, dentate nuclei, central tegmental tracts in the brainstem, and posterior periventricular white matter which was masquerading for mitochondrial leukodystrophy. Basic metabolic tests were normal except for low urine creatinine; however, exome sequencing identified a homozygous frameshift deletion variant [NM_000156: c.491del; (p.Gly164AlafsTer14)] in the GAMT. Biallelic pathogenic or likely pathogenic variants cause GAMTD. We confirmed the homozygous state for this variant in the proband, as well as the heterozygote state in the parents by Sanger sequencing.MRI features in GAMTD can mimic mitochondrial leukodystrophy. Pediatric neurologists should be aware of variable MRI findings in GAMTD since they would be misleading to other diagnoses.

A lightweight neural network with multiscale feature enhancement for liver CT segmentation.

Segmentation of abdominal Computed Tomography (CT) scan is essential for analyzing, diagnosing, and treating visceral organ diseases (e.g., hepatocellular carcinoma). This paper proposes a novel neural network (Res-PAC-UNet) that employs a fixed-width residual UNet backbone and Pyramid Atrous Convolutions, providing a low disk utilization method for precise liver CT segmentation. The proposed network is trained on medical segmentation decathlon dataset using a modified surface loss function. Additionally, we evaluate its quantitative and qualitative performance; the Res16-PAC-UNet achieves a Dice coefficient of 0.950 ± 0.019 with less than half a million parameters. Alternatively, the Res32-PAC-UNet obtains a Dice coefficient of 0.958 ± 0.015 with an acceptable parameter count of approximately 1.2 million.

Double-Expressor Appendiceal Burkitt's Lymphoma: A Case Report and Literature Review.

Background: Appendiceal lymphoma is a very rare entity accounting for 0.015% of all gastrointestinal lymphoma cases. Acute appendicitis is the most common presentation of primary appendix neoplasms. Burkitt's lymphoma presenting as an acute appendicitis is a rare entity with around 21% of the cases presenting as a lower iliac fossa mass. Case Presentation. A 23-year-old male was admitted to the surgical ward as a case of acute appendicitis with localized tenderness in the right iliac fossa, positive rebound tenderness, a positive Rovsing's sign, and ultrasound findings of suspected complicated appendicitis. Appendectomy was performed. Histopathological examination of the appendectomy specimen revealed a double-expressor non-Hodgkin diffuse large cell lymphoma with Burkitt's-like morphology. He was sent for chemotherapy treatment. Conclusion: Only 34 cases of Burkitt's lymphoma have been reported to present as acute appendicitis. Histological examination following appendectomy for an apparent appendicitis is essential. Furthermore, complete blood count and a computed tomography scan aid the diagnosis of lymphoma. Double-expressor lymphoma has been shown to have poor outcomes. Therefore, prompt and aggressive treatment is vital.

Genetic Analysis of Forty MLPA-Negative Duchenne Muscular Dystrophy Patients by Whole-Exome Sequencing.

This manuscript aimed to determine the underlying point mutations causing Duchenne muscular dystrophy (DMD) in a heterogeneous group of Iranian patients, who are clinically suspected. Whole-exome sequencing was utilized to detect disease-causing variants in 40 MLPA-negative DMD patients. Disease-causing variants were detected in the DMD gene in 36/40 of the patients (90%), and 4/40 of them (10%) remained undiagnosed. WES analysis revealed that nonsense variant was the most common type in our study (23/36 of the cases). Besides, 12/36 of the cases had frameshift variant, and one of the patients had a likely pathogenic splice variant in the DMD gene. Carrier testing revealed that 21/40 of the mothers had the identified variant. Therefore, most variants were inherited (58.3%), while 19/40 were de novo (41. 7%). The present study has demonstrated the importance of performing WES to detect disease-causing point mutations in MLPA-negative DMD patients and to identify carrier females. Due to regulatory challenges, the clinical development of therapeutic approaches is time-consuming and may not be available to all patients shortly. Therefore, it appears that the techniques used to accurately detect disease-causing variants in carrier mothers are a more efficient solution to prevent the increased prevalence of DMD.

Evaluation of Serum and Salivary Iron and Ferritin Levels in Children with Dental Caries: A Meta-Analysis and Trial Sequential Analysis.

BACKGROUND AND OBJECTIVE: Dental caries appears to be related to iron deficiency anemia and to low ferritin levels. In the present meta-analysis, we report salivary and serum iron and ferritin levels in children with dental caries, compared to healthy controls. MATERIALS AND METHODS: We searched in Web of Science, Cochrane Library, Scopus, and PubMed/Medline databases to extract studies published until 25 July 2021. We calculated mean differences (MD) and 95% confidence intervals (CI) of salivary and serum iron and ferritin levels in children with dental caries, always compared to healthy controls. In addition, we applied a trial sequential analysis (TSA). RESULTS: A total of twelve articles covering thirteen studies were included in the meta-analysis. The pooled MD for salivary iron level was -5.76 µg/dL (p = 0.57), and -27.70 µg/dL (p < 0.00001) for serum iron level: compared to healthy controls, children with dental caries did not show different salivary iron levels, while children with caries had significantly lower serum iron levels. The pooled MD of salivary ferritin level was 34.84 µg/dL (p = 0.28), and the pooled MD of serum ferritin level was -8.95 µg/L (p = 0.04): compared to healthy controls, children with dental caries did not have different salivary iron levels, but significantly lower serum ferritin levels. CONCLUSIONS: The findings of the present meta-analysis showed that salivary levels of iron and ferritin did not differ between children with and without caries, though compared to healthy controls, children with caries had significantly lower salivary and serum iron and ferritin levels. The results are of practical and clinical importance: Possibly, iron and ferritin supplementation might prevent or attenuate dental caries in children at risk. Further, children with caries might suffer from further iron- and ferritin-related health issues. Lastly, serum blood samples, but not saliva samples inform accurately about the current iron and ferritin concentrations in children with or without caries.

Whole-exome sequencing identified first homozygous frameshift variant in the COLEC10 gene in an Iranian patient causing 3MC syndrome type 3.

BACKGROUND: 3MC syndrome type 3 is an autosomal recessive disorder caused by mutations in the COLEC10 gene besides other genes like COLEC11 and MASP1. This disorder is characterized by facial dysmorphism, cleft lip and palate, postnatal growth deficiency, cognitive impairment, hearing loss, craniosynostosis, radioulnar synostosis, genital and vesicorenal anomalies, cardiac anomalies, caudal appendage, and umbilical hernia. METHODS: In the present study, whole-exome sequencing was performed in order to identify disease causing variant in an Iranian 7-year-old affected girl with craniosynostosis, dolichocephaly, blepharoptosis, clinodactyly of the 5th finger, high myopia, long face, micrognathia, patent ductus arteriosus, downslanted palpebral fissures, telecanthus, and epicanthus inversus. Identified variant confirmation in the patient and segregation analysis in her family were performed using Sanger sequencing method. RESULTS: A novel homozygous frameshift deletion variant [NM_006438.5: c.128_129delCA; p.(Thr43AsnfsTer9)] was identified within the COLEC10 gene. Up to now, only three 3MC syndrome patients with mutations in the COLEC10 gene have been reported, and here, we report the fourth patient and the first homozygous frameshift variant. CONCLUSION: Other genes and factors responsible for 3MC syndrome occurrence are remained to be discovered. We believe further investigation of the genes in the lectin complement pathway is needed to be done for the identification of other causes of this disease.

SWIR emissive RosIndolizine dyes with nanoencapsulation in water soluble dendrimers.

Shortwave infrared (SWIR) emission has great potential for deep-tissue in vivo biological imaging with high resolution. In this article, the synthesis and characterization of two new xanthene-based RosIndolizine dyes coded PhRosIndz and tolRosIndz is presented. The dyes are characterized via femtosecond transient absorption spectroscopy as well as steady-state absorption and emission spectroscopies. The emission of these dyes is shown in the SWIR region with peak emission at 1097 nm. TolRosIndz was encapsulated with an amphiphilic linear dendritic block co-polymer (LDBC) coded 10-PhPCL-G3 with high uptake yield. Further, cellular toxicity was examined in vitro using HEK (human embryonic kidney) cells where a >90% cell viability was observed at practical concentrations of the encapsulated dye which indicates low toxicity and reasonable biocompatibility.

Immunohistochemistry and Radiomic Features for Survival Prediction in Small Cell Lung Cancer.

Background: The aim of the study was to evaluate the role of different immunohistochemical and radiomics features in patients with small cell lung cancer (SCLC). Methods: Consecutive patients with histologically proven SCLC with limited (n = 47, 48%) or extensive disease (n = 51, 52%) treated with radiotherapy and chemotherapy at our department were included in the analysis. The expression of different immunohistochemical markers from the initial tissue biopsy, such as CD56, CD44, chromogranin A, synaptophysin, TTF-1, GLUT-1, Hif-1 a, PD-1, and PD-L1, and MIB-1/KI-67 as well as LDH und NSE from the initial blood sample were evaluated. H-scores were additionally generated for CD44, Hif-1a, and GLUT-1. A total of 72 computer tomography (CT) radiomics texture features from a homogenous subgroup (n = 31) of patients were correlated with the immunohistochemistry, the survival (OS), and the progression-free survival (PFS). Results: The median OS, calculated from diagnosis, was 21 months for patients with limited disease and 13 months for patients with extensive disease. The expression of synaptophysin correlated with a better OS (HR 0.546 95% CI 0.308-0.966, p = 0.03). The expression of TTF-1 (HR 0.286, 95% CI: 0.117-0.698, p = 0.006) and a lower GLUT-1 H-score (median = 50, HR: 0.511, 95% CI: 0.260-1.003, p = 0.05) correlated with a better PFS. Patients without chromogranin A expression had a higher risk for developing cerebral metastases (p = 0.02) and patients with PD 1 expression were at risk for developing metastases (p = 0.02). Our radiomics analysis did not reveal a single texture feature that correlated highly with OS or PFS. Correlation coefficients ranged between -0.48 and 0.39 for OS and between -0.46 and 0.38 for PFS. Conclusions: The role of synaptophysin should be further evaluated as synaptophysin-negative patients might profit from treatment intensification. We report an, at most, moderate correlation of radiomics features with overall and progression free survival and no correlation with the expression of different immunohistochemical markers.

Self-Assembling PCL-PAMAM Linear Dendritic Block Copolymers (LDBCs) for Bioimaging and Phototherapeutic Applications.

This study represents a successful approach toward employing polycaprolactone-polyamidoamine (PCL-PAMAM) linear dendritic block copolymer (LDBC) nanoparticles as small-molecule carriers in NIR imaging and photothermal therapy. A feasible and robust synthetic strategy was used to synthesize a library of amphiphilic LDBCs with well-controlled hydrophobic-to-hydrophilic weight ratios. Systems with a hydrophobic weight ratio higher than 70% formed nanoparticles in aqueous media, which show hydrodynamic diameters of 51.6 and 96.4 nm. These nanoparticles exhibited loading efficiencies up to 21% for a hydrophobic molecule and 64% for a hydrophilic molecule. Furthermore, successful cellular uptake was observed via trafficking into endosomal and lysosomal compartments with an encapsulated NIR theranostic agent (C3) without inducing cell death. A preliminary photothermal assessment resulted in cell death after treating the cells with encapsulated C3 and exposing them to NIR light. The results of this work confirm the potential of these polymeric materials as promising candidates in theranostic nanomedicine.

Understanding impact of pre-dissolved polymers on dissolution behavior of soluble carbamazepine cocrystal.

Cocrystallization is a novel approach for tackling the lower solubility concerns when they can yield solution concentration a lot better than their corresponding parent drug in crystalline form. To get the actual solubility and dissolution gains offered by the cocrystals, phase changes in solution (dissolution) has to be interrupted. In current study, we selected commonly used polymers in order to study their effects on the super saturation of carbamezepine-succinic acid (CBZ-SUC) cocrystal during dissolution studies. To observe solid phase changes during dissolution in situ Raman spectroscopy was used. At the completion of each test the solid phase was analyzed by Fourier-transform infrared spectroscopy (FTIR) and powder X-Ray diffractometry. In polymers absence, no dissolution improvement was achieved by the cocrystal owing to its quick transformation to the stable carbamazepine dihydrate (CBZDH). Pre-dissolved PVP at 2% w/v concentration did not inhibit CBZ crystallization as a dihydrate, whereas at 0.025% w/v pre-dissolved hydroxypropyl methyl cellulose acetate succinate (HPMCAS) did stabilize the cocrystal in buffer solution (pH 6.8) for the course of time studied. This cocrystal stabilization resulted in enhanced CBZ solubility ( Ì´ 4fold) caused by cocrystal super saturation state. Seeding of this stable supersaturated state with 1% w/v CBZDH resulted in CBZ crystallization as dihydrate with ultimate loss of solubility advantage.

Effect of fingolimod on white blood cell, lymphocyte and neutrophil counts in MS patients.

INTRODUCTION: Fingolimod is an immunomodulating oral treatment used for treating relapsing-remitting multiple sclerosis (RRMS). The exact mechanism for its action in preventing relapses is unknown. Also, its affect on immune cell populations remains unestablished. OBJECTIVES: This study will measure the changes in cell populations of WBCs, lymphocytes, and neutrophils in MS patients after one month of treatment. METHODS: 66 MS patients from Isfahan Province with RRMS were chosen based on certain exclusion criteria and eligibility for fingolimod oral treatment. Initial cell counts for WBC, lymphocyte, and neutrophil cell populations were achieved. Fingolimod .5 mg daily treatment was then initiated under the supervision of a physician. After one month of treatment, cell counts were repeated. Statistical analysis was performed using SPSS. RESULTS: Both lymphocyte and WBC mean cell counts were significantly decreased in this patient cohort. Neutrophil average cell counts were significantly increased in this 66 patient cohort. Only the decrease of WBC populations was significant for both male and female cohorts individually. Only female sub-cohorts were significantly changed for neutrophils and lymphocytes, increased and decreased respectively. Male sub-cohorts maintained the same directionality but failed to produce statistical significance. CONCLUSION: While fingolimod has been effectively proven as reducing lymphocyte cells in most patient populations, its effects on neutrophils have not been studied in abundance. Also, there may be sex-related differences in responses to fingolimod treatment with regards to lymphocytes and neutrophils, suggesting a possible difference in RRMS pathogenesis between males and females.

Effect of posterior fusion surgery on idiopathic scoliosis in Iran.

BACKGROUND: Scoliosis is a sideways curve in the spine. Considering that postoperative complications are common among these patients, the aim of this study is to examine the postoperative complications of posterior fusion surgery with instrumentation among adult patients with idiopathic scoliosis. METHODS: In this cross-sectional descriptive study, the postoperative complications were examined among 93 patients with idiopathic scoliosis who underwent posterior fusion surgery with instrumentation. The convenience sampling was used by referring to the files of these patients. The patients were classified into four groups according to the type of scoliosis deformity (long C-shaped, thoracic, thoracolumbar/lumbar, and double-curve) and the complications were compared together. RESULTS: Postoperative respiratory problems were significantly different between the four groups of scoliosis deformity (P = 0.009); 35 cases of postoperative complications occurred and 20 of them were related to postoperative pulmonary complications. CONCLUSION: Postoperative complications are common among patients with idiopathic scoliosis who underwent posterior fusion surgery with instrumentation; in addition, pulmonary complications are the most common postoperative complication among these patients.