Search

Abstract Background Transcranial direct current stimulation (tDCS) is capable of eliciting changes in cortical neuroplasticity. Increasing duration or repetition of tDCS during the after-effects of a first stimulation has been hypothesized to enhance efficacy. Computational models suggest sequential stimulation patterns with changing polarities to further enhance effects. Lasting tDCS effects on neural plasticity are of great importance for clinical applications. Objective The study systematically examined the influence of different tDCS paradigms on long term potentiation (LTP)-like plasticity in humans, focusing on stimulation duration, repetition frequency and sequential combinations of changing polarities as the underlying characteristics. Methods Amplitude changes of motor evoked potentials (MEP) were measured in response to paired associative stimulation (PAS) 6 h after application of different tDCS protocols. In total, 36 healthy participants completed the study, randomised into three groups with different stimulation protocols (N = 12 each). Results tDCS was able to display lasting modulatory effects on the inducibility of LTP-like plasticity in the human motor cortex 6 h after stimulation. TDCS with the anode on primary motor cortex significantly increased MEP amplitudes following PAS induction. Further analyses highlighted single stimulation block duration to be of higher importance than repetitive protocols for efficacy of effects. Conclusions tDCS is capable of inducing lasting changes in the brain’s capability to interact with future stimuli. Especially, effects on the inducibility of LTP-like plasticity might only be detectable with specific tests such as PAS and might otherwise be overlooked. Refined tDCS protocols should focus on higher current and duration of single stimulations instead of implementing complex repetitive schedules.

Background: Transcranial direct current stimulation (tDCS) is capable of eliciting changes in cortical neuroplasticity. Increasing duration or repetition of tDCS during the after-effects of a first stimulation has been hypothesized to enhance efficacy. Computational models suggest sequential stimulation patterns with changing polarities to further enhance effects. Lasting tDCS effects on neural plasticity are of great importance for clinical applications. Objective: The study systematically examined the influence of different tDCS paradigms on long term potentiation (LTP)-like plasticity in humans, focusing on stimulation duration, repetition frequency and sequential combinations of changing polarities as the underlying characteristics. Methods: Amplitude changes of motor evoked potentials (MEP) were measured in response to paired associative stimulation (PAS) 6 h after application of different tDCS protocols. In total, 36 healthy participants completed the study, randomised into three groups with different stimulation protocols (N = 12 each). Results: tDCS was able to display lasting modulatory effects on the inducibility of LTP-like plasticity in the human motor cortex 6 h after stimulation. TDCS with the anode on primary motor cortex significantly increased MEP amplitudes following PAS induction. Further analyses highlighted single stimulation block duration to be of higher importance than repetitive protocols for efficacy of effects. Conclusions: tDCS is capable of inducing lasting changes in the brain's capability to interact with future stimuli. Especially, effects on the inducibility of LTP-like plasticity might only be detectable with specific tests such as PAS and might otherwise be overlooked. Refined tDCS protocols should focus on higher current and duration of single stimulations instead of implementing complex repetitive schedules. [ABSTRACT FROM AUTHOR]

Introduction: The experience of grief is one of the most painful challenges an individual may face, often leading to symptoms of depression and potentially resulting in self-harming behavior. This study was conducted to compare the effectiveness of schema therapy and acceptance and commitment therapy on the suicidal behaviors of depressed patients experiencing grief.Method: The present study employed a quasi-experimental design featuring a pre-test and post-test, along with a follow-up involving a control group. The statistical population comprised depressed patients experiencing grief who were referred to the Toos Rehabilitation and Treatment Center in Mashhad in 2023. After screening and conducting an initial diagnosis, 45 individuals were selected through purposive sampling and randomly assigned to three groups of 15 participants each: two experimental groups and one control group. Data were collected using depression questionnaires (BDI-II) and assessments of suicidal behaviors (R-SBQ). Initially, all three groups were pre-tested. One experimental group then underwent schema therapy, while the other experimental group received acceptance and commitment therapy for eight 90-minute sessions, held once a week. The control group did not receive any treatment. After the sessions, all three groups underwent post-testing, and follow-up assessments were conducted on all three groups three months later. The data were analyzed using repeated measures analysis of variance (ANOVA) and the Bonferroni post-hoc test.Results: The results indicated that suicidal behaviors decreased from pre-test to post-test and follow-up in both the schema therapy and acceptance and commitment therapy groups (P

ABSTRACT Background Glioblastoma multiforme (GBM) poses a significant health challenge as the most common primary malignancy of the adult central nervous system. Gender‐ and age‐related differences in GBM influence prognosis and treatment complexities. This multicenter retrospective study explores gender and age disparities in GBM patients, investigating their impact on occurrence and survival outcomes. Methods This multicenter retrospective study involved GBM patients treated in Guilan Province, Iran. Patients' data, including age, gender, tumor location, and histopathological diagnosis date, was collected from medical records. Results In a cohort of 164 GBM patients, the average age was 54.34 ± 14.16 years, with a higher prevalence among men (59.8%) and patients aged ≤ 60 years (64.6%). The tumor sites exhibited overlapping features in 68% of cases, with the frontal and temporal lobes being the most common specific locations. The mean survival was 12.88 ± 14.14 months, one‐year survival of 45%, with women showing significantly higher one‐year survival (60% vs. 40%) and longer mean survival (16.14 ± 17.35 vs. 10.75 ± 11.15 months). Furthermore, Patients ≤ 60 years had significantly higher one‐year survival (75% vs. 35%). In subgroup analysis, women had significantly higher survival rates in patients ≤ 60 years. However, among patients over 60, women exhibited a more pronounced decline in survival rates, with no statistically significant difference between men and women in this age group. Conclusion This study highlights that both age and gender significantly affect GBM survival outcomes. Younger patients, particularly women, exhibited better survival rates, while older patients, especially women, showed poorer outcomes. These findings suggest the need to stratify treatment approaches by both age and gender to optimize care and improve survival in GBM patients. Further research is recommended to explore these associations.

Abstract Background Cherubism is known as a very rare autosomal dominant familial disorder of childhood caused by a mutation in the SH3BP2 gene on 4p16.3. It has not yet been observed at birth and is usually diagnosed in children aged 2–7. Here, we present a non-hereditary case of cherubism at a very early age. Case presentation A 6-month-old girl presented with bilateral progressive jaw enlargement. On physical examination, bilateral asymmetrical jaw enlargement, predominantly on the left side, and some enlarged, non-tender, mobile submandibular lymph nodes were detected. No other abnormality was observed. Further investigations with radiology suggested cherubism and Burkitt’s lymphoma as differential diagnoses. Later on, histopathologic evaluations were suggestive of cherubism. No surgical interventions were indicated, and the child is on regular follow-ups. Conclusion Non-hereditary Cherubism, despite scarcity, can present in children below two years of age, even as early as the beginning of primary dentition. Accurate and swift diagnosis is essential to avert physical and psychological complications. Our case report shows the importance of keeping cherubism in mind as a differential diagnosis of bone disease, even in children under a year old, and the value of interdisciplinary collaboration in dealing with rare genetic disorders.

A zoonotic disease called brucellosis can cause flu-like symptoms and heart inflammation. The bacteria responsible for this disease can also enter the brain, causing a condition called neurobrucellosis that can result in long-term neurological problems. In this study, researchers aimed to determine the changes in the hippocampal cells of rats infected with Brucella. For the study, 24 adult male albino rats were inoculated with 1 × 106 CFU Brucella abortus 544. The rats were then deeply anesthetized, and their hippocampus samples were taken for stereological, histological, and molecular studies. The results showed that the infected rats had increased microgliosis and astrogliosis. Furthermore, a high level of caspase-3 in their hippocampal tissue indicated their susceptibility to apoptosis. Additionally, there was a decrease in expression of Ki67, which further supported this. Sholl's analysis confirmed a significant failure in glial morphology. The study demonstrated that the pathogen has the ability to destroy the hippocampus and potentially affect its normal physiology. However, more research is needed to clarify various aspects of neurobrucellosis.

Background: The aggregation of clonal plasma cells causes plasma cell neoplasms, which vary in severity and clinical outcomes. The present research focused on the epidemiological, clinical, immunologic, and cytogenetic characteristics of plasma cell neoplasms. Methods: In this five-year retrospective cross-sectional study, demographic information such as age and sex, calcium elevation, renal insufficiency, anemia, and bone lesion (CRAB) characteristics, as well as laboratory data including bone marrow and peripheral blood film results, immunohistochemistry, flow cytometry, and cytogenetic study outcomes were collected at Shiraz University of Medical Sciences, Shiraz, Iran. The collected data were analyzed using SPSS Statistics software (version 20.0). Descriptive statistics were reported as numbers, percentages, and mean±SD.Results: 417 newly diagnosed plasma cell neoplasm patients were confirmed by bone marrow or other tissue biopsy tests. 279 patients were men (66.9%). The most prevalent age group was 60-64 years old (18.46%). Plasma cell myeloma (PCM) affected 355 (85.13%) patients, while monoclonal gammopathy of undetermined significance (MGUS) affected 6 (1.43%) patients. Solitary plasmacytoma was seen in 56 (13.42%) patients. At the time of diagnosis, 119 (33.52%) of 355 PCM patients were asymptomatic, whereas 236 (66.47%) patients had at least one CRAB symptom, 55 (15.49%) had two or more, and 14 (3.94%) had three or more. There were 7 (1.97%) cases of amyloidosis. Cytogenetic abnormalities were found in 51.28% (40/78) of the patients. Twenty-one individuals (52.5%) were hyperdiploid with multiple trisomy, while 19 (47.50%) were not. Conclusion: When diagnosed, Iranian PCM patients might have more advanced disease. PCM was more prevalent in young adults, and hyperdiploid was the most common cytogenetic finding in this investigation.

Abstract Background Metabolic and bariatric surgery (MBS) is safe and efficacious in treating adolescents with severe obesity. Behavioral/lifestyle programs can support successful preparation for surgery and post-MBS weight loss, but no standardized lifestyle intervention exists for adolescents. Here we describe the process of developing and adapting the Diabetes Prevention Program Group Lifestyle Balance (DPP/GLB) curriculum to support adolescents pre- and post-MBS. Methods We collected both qualitative and quantitative data from a diverse group of adolescents (N = 19, mean age 15.2 years, range 13–17, 76% female, 42% non-Hispanic Black, 41% Hispanic, 17% other). Additionally, we included data from 13 parents, all of whom were mothers. These participants were recruited from an adolescent MBS program at Children’s Health System of Texas. In an online survey, we asked participants to rank their preferences and interests in DPP/GLB content topics. We complemented these results with in-depth interviews from a subset of 10 participants. This qualitative data triangulation informed the development of the TeenLYFT lifestyle intervention program, designed to support adolescents who were completing MBS and described here. This program was adapted from adolescent and parent DPP/GLB content preferences, incorporating the social cognitive model (SCM) and the socioecological model (SEM) constructs to better cater to the needs of adolescent MBS patients. Results Adolescents’ top 3 ranked areas of content were: (1) steps to adopt better eating habits and healthier foods; (2) healthy ways to cope with stress; and (3) steps to stay motivated and manage self-defeating thoughts. Nearly all adolescent participants preferred online delivery of content (versus in-person). Mothers chose similar topics with the addition of information on eating healthy outside the home. Key themes from the adolescent qualitative interviews included familial support, body image and self-confidence, and comorbidities as key motivating factors in moving forward with MBS. Conclusions The feedback provided by both adolescents and parents informed the development of TeenLYFT, an online support intervention for adolescent MBS candidates. The adapted program may reinforce healthy behaviors and by involving parents, help create a supportive environment, increasing the likelihood of sustained behavior change. Understanding adolescent/parent needs to support weight management may also help healthcare providers improve long-term health outcomes for this patient population.

Background: Case presentation: In this study, we presented an Iranian female with triple-negative breast cancer that developed acro-metastasis to the hand Conclusions: However, bone metastasis is the most common kind of neoplasm extension that we can witness in the breast cancer, acro-metastasis to the hand is an extremely rare kind of bone metastasis that we can expect.

Key Clinical Message Intracranial RDD is rare medical event mimicking different diagnoses. Although the surgical resection is the best treatment option, but radiation therapy can also achieves long‐term suboptimal outcomes. Abstract An 83‐year‐old male with a history of tension‐type headaches was evaluated. He was conscious with no focal neurological deficits. His brain MRI revealed an enhancable bifrontal tumor originating from falx cerebri and superior sagittal sinus dura. Due to the patient's preference and decline for gross total resection, she underwent a stereotactic biopsy. The pathology was positive for Rosai–Dorfman diseases. He received definitive targeted radiation with a total dose of 4500 cGy administered in 200 cGy daily fractions. His 4‐year follow‐up showed regional tumor control with excellent neurological outcome.

Abstract Background Alcoholic liver disease (ALD) is a globally critical condition with no available efficient treatments. Methods Herein, we generated chitosan (CS) nanoparticles cross-linked with two different agents, hydroxypropyl methylcellulose phthalate (HPMCP; termed as CS/HPMCP) and tripolyphosphate (TPP; termed as CS/TPP), and loaded them with berberine (BBr; referred to as CS/HPMCP/BBr and CS/TPP/BBr, respectively). Alongside the encapsulation efficiency (EE) and loading capacity (LC), the releasing activity of the nanoparticles was also measured in stimulated gastric fluid (SGF) and stimulated intestinal fluid (SIF) conditions. The effects of the prepared nanoparticles on the viability of mesenchymal stem cells (MSCs) were also evaluated. Ultimately, the protective effects of the nanoparticles were investigated in ALD mouse models. Results SEM images demonstrated that CS/HPMCP and CS/TPP nanoparticles had an average size of 235.5 ± 42 and 172 ± 21 nm, respectively. The LC and EE for CS/HPMCP/BBr were calculated as 79.78% and 75.79%, respectively; while the LC and EE for CS/TPP/BBr were 84.26% and 80.05%, respectively. pH was a determining factor for releasing BBr from CS/HPMCP nanoparticles as a higher cargo-releasing rate was observed in a less acidic environment. Both the BBr-loaded nanoparticles increased the viability of MSCs in comparison with their BBr-free counterparts. In vivo results demonstrated CS/HPMCP/BBr and CS/TPP/BBr nanoparticles protected enzymatic liver functionality against ethanol-induced damage. They also prevented histopathological ethanol-induced damage. Conclusions Crosslinking CS nanoparticles with HPMCP can mediate controlled drug release in the intestine improving the bioavailability of BBr.

Abstract Background Chronic itch (chronic pruritus) is a major therapeutic challenge that remains poorly understood despite the extensive recent analysis of human pruriceptors. It is unclear how the peripheral nervous system differentiates the signaling of non-histaminergic itch and pain. Methods Here we used psychophysical analysis and microneurography (single nerve fiber recordings) in healthy human volunteers to explore the distinct signaling mechanisms of itch, using the pruritogens β-alanine, BAM 8-22 and cowhage extract. Results The mode of application (injection or focal application using inactivated cowhage spicules) influenced the itch/pain ratio in sensations induced by BAM 8-22 and cowhage but not β-alanine. We found that sensitizing pre-injections of prostaglandin E2 increased the pain component of BAM 8-22 but not the other pruritogens. A-fibers contributed only to itch induced by β-alanine. TRPV1 and TRPA1 were necessary for itch signaling induced by all three pruritogens. In single-fiber recordings, we found that BAM 8-22 and β-alanine injection activated nearly all CM-fibers (to different extents) but not CMi-fibers, whereas cowhage extract injection activated only 56% of CM-fibers but also 25% of CMi-fibers. A “slow bursting discharge pattern” was evoked in 25% of CM-fibers by β-alanine, in 35% by BAM 8-22, but in only 10% by cowhage extract. Conclusion Our results indicate that no labeled line exists for these pruritogens in humans. A combination of different mechanisms, specific for each pruritogen, leads to itching sensations rather than pain. Notably, non-receptor-based mechanisms such as spatial contrast or discharge pattern coding seem to be important processes. These findings will facilitate the discovery of therapeutic targets for chronic pruritus, which are unlikely to be treated effectively by single receptor blockade.

Pulmonary Lymphangioleiomyomatosis (LAM) is a rare disease of the lung and lymphatic system that primarily affects women of childbearing age. LAM is a progressive disease with a terrible prognosis, which worsens over time and is extremely difficult to treat. In this study, we discuss the case of a 31-year-old woman with LAM who was initially misdiagnosed with leiomyoma and the way that led to a true diagnosis and effective treatment. Following a precise diagnosis based on comprehensive clinical data and particular immunohistochemical tests, sirolimus treatment was initiated, and the patient entirely responded to the treatment. This case report demonstrated that LAM is an uncommon condition that is challenging to diagnose, which causes its treatment to be delayed.

Abstract Carbon nanomaterials are widely used in biomedical applications due to their versatile properties. These are the attractive candidates for the carrying of anticancer drugs, genes, and proteins for chemotherapy. Imatinib is an effective chemotherapy drug whose toxicity has created a significant limitation in treatment. In this research, a new biocompatible nanocarrier based on albumin-magnetite graphene oxide conjugates was reported for the loading and release of imatinib. The magnetite graphene oxide nanocomposite was investigated by ultra violet-visible spectroscopy (UV-Vis), field emission scanning electron microscope (FE-SEM), X-ray diffraction spectroscopy (XRD) and energy diepersive X-ray spectroscopy (EDX) methods. The crystallite size of Fe3O4 nanoparticles on graphene oxide obtained from XRD is about 14 nm which is in agreement well with the SEM results. We show that magnetite graphene oxide conjugated with albumin is an extremely efficient carrier. An efficient loading of IM, 81% at pH 7.0, time 2 h and initial concentration of 1 mg/mL was seen onto magnetite graphene oxide-albumin in comparison to graphene oxide and magnetite graphene oxide due to the presence of oxygen and nitrogen functional groups of albumin. Upon the pH 9.0 and 7.0, 7% and 16% imatinib could be released from the magnetite graphene oxide-albumin in a time span of 5 h but when exposed pH 4.0 the corresponding 31% was released in 5 h. After 20 h, 21, 42 and 68% of imatinib was released at pH 9.0, 7.0 and 4.0, respectively. This illustrates the major benefits of the developed approach for biomedical applications. Graphical Abstract

Abstract Introduction: Metabolic and bariatric surgery (MBS) is safe and efficacious for adolescents with severe obesity. Pairing MBS with behavioral lifestyle interventions may be effective for optimizing treatment outcomes. However, no standardized program exists. Adolescent perspectives are critical to understanding how to design interventions to enhance engagement, sustain motivation, and meet informational needs for pre- and post-MBS self-management behaviors. The aim of this study was to develop an MBS lifestyle support intervention built on evidence-based content with input from adolescents and their families. Methods: A mixed-methods design identified adolescent preferences for MBS lifestyle support. Data were collected from a racially and ethnically diverse sample of adolescents (N = 17, 76% females, 24% males 41.2% non-Hispanic Black, 41.2% Hispanic/Latino, 11.8% non-Hispanic White, 5.8% Other) and their mothers (N = 13, 38.4% Hispanic) recruited from an MBS clinic. Quantitative surveys and qualitative interviews assessed preferred types of pre-post MBS content, modality, frequency, and delivery platforms to inform the design of the intervention. Mixed methods data were triangulated to provide a comprehensive understanding of adolescent/parent preferences. Results: Adolescents prioritized eating well, managing stress, and maintaining motivation as desired support strategies. Parents identified parental support groups and nutrition guidance as priorities. Peer support and social media platforms were identified as key approaches for boosting motivation and engagement. Conclusions: The patient voice is an important first step in understanding how, and whether behavioral lifestyle programs combined with MBS for weight management can be optimized. Adolescent preferences may enhance program fit and identify health behavior supports needed to sustain behavior change.

As the most lethal gynecologic oncological indication, carcinoma of the ovary has been ranked as the 5th cause of cancer-related mortality in women, with a high percentage of the patients being diagnosed at late stages of the disease and a five-year survival of ~ 30%. Ovarian cancer patients conventionally undergo surgery for tumor removal followed by platinum- or taxane-based chemotherapy; however, a high percentage of patients experience tumor relapse. Cancer immunotherapy has been regarded as a silver lining in the treatment of patients with various immunological or oncological indications; however, mirvetuximab soravtansine (a folate receptor α-specific mAb) and bevacizumab (a VEGF-A-specific mAb) are the only immunotherapeutics approved for the treatment of ovarian cancer patients. Chimeric antigen receptor T-cell (CAR-T) therapy has achieved tremendous clinical success in the treatment of patients with certain B-cell lymphomas and leukemias, as well as multiple myeloma. In the context of solid tumors, CAR-T therapies face serious obstacles that limit their therapeutic benefit. Such hindrances include the immunosuppressive nature of solid tumors, impaired tumor infiltration, lack of qualified tumor-associated antigens, and compromised stimulation and persistence of CAR-Ts following administration. Over the past years, researchers have made arduous attempts to apply CAR-T therapy to ovarian cancer. In this review, we outline the principles of CAR-T therapy and then highlight its limitations in the context of solid tumors. Ultimately, we focus on preclinical and clinical findings achieved in CAR-T-mediated targeting of different ovarian cancer-associated target antigens.

Abstract Background The concept of critical value is not evident in surgical pathology, and there is no established protocol for determining, reporting, and documenting these results. Materials and methods A questionnaire was designed regarding critical value in surgical pathology, and all pathologists and some clinicians from five laboratories were asked to participate through an invitation link. The most important items were selected, and all pathologists were instructed to follow a standard operating procedure to deal with critical results for a year. Results A total of 43 pathologists and 44 non-pathologists participated in the study. Some critical or unexpected items were selected. Most participants agreed that the optimal time to announce critical reports is within 24 h of establishing the final diagnosis, and a phone call was the most dependable communication option. In addition, the most qualified recipients were the attending physicians. Therefore, a written policy was implemented for a year. One hundred seventy-seven critical or unexpected cases (0.5%) were detected. Mucormycosis and cytomegalovirus (CMV) were the most frequent critical cases. Conclusion There are no set criteria for critical items or the reporting process in surgical pathology. It is possible to establish more uniform norms for reporting these cases by boosting pertinent research efforts and recruiting more pathologists and physicians. Additionally, it is advised that each medical facility compile its own unique critical or unexpected diagnosis list.

Background: In the present paper, the main diagnostic tool for re-evaluation of axillary lymph node involvement and planning of surgery after neoadjuvant chemotherapy (NAC) is ultrasound whose accuracy we aimed to determine herein. The high precision of ultrasound in diagnosis of metastatic axillary lymph nodes in untreated patients is well known; however, its worth in patients who received NAC is highly controversial.Method: We enrolled 165 breast cancer patients receiving NAC in this retrospective cohort study. They all had undergone post-NAC ultrasound done before surgery. The ultrasound reports were reassessed and validated by a breast radiologist. Finally, the histopathology reports were compared to those of the ultrasound.Results: Among 165 surveyed post-NAC ultrasounds, 53 women had positive results and 112 had negative results. Pathology and ultrasound reports were accordant in 93 women and adverse in 112 others. The false negative rate of post-NAC axillary ultrasound was calculated as 60.6%. The sensitivity and specificity of post-NAC AxUS were 39.4% and 79%, respectively. After NAC, there were certain changes in ultrasound reports from positive to negative in 50% and pathologic complete clearance was observed in just 28% of the women who were initially clinically lymph node positive.Conclusion: Ultrasound was not found to be an accurate and appropriate tool for evaluation of axillary lymph node involvement in breast cancer patients who receive NAC. By changing the primarily established surgical plan from ALND to SLNB, based on the ultrasound findings, patients may remain undertreated. Furthermore, the axillary nodes pathologic clearance after NAC was observed in less than one third of the women who were initially clinically node positive; accordingly, surgeons should be cautious about the optimum response of axillary metastatic lymph nodes to NAC.

Introduction: Neoplastic cell infiltration into the central nervous system (CNS) is a serious complication of hematologic neoplasms. Successful management of CNS involvement requires early detection and treatment, as well as reliable criteria to evaluate the patient's treatment response. This study aimed to evaluate the agreement between flow cytometry (FCM) and conventional cytology (CC) findings for the detection of CNS involvement in hematologic malignancies. Methods: A total of 120 patients were examined in this study, including 111 patients with a previous diagnosis of hematologic malignancies and nine patients with abnormal CNS manifestations. Demographic information, including age and sex, and data on diagnosis and previous bone marrow immunophenotyping were collected for analysis. The cerebrospinal fluid (CSF) was divided into two halves; one was sent to the cytology laboratory, and the other was sent for the FCM analysis. Results: Out of 120 CSF samples evaluated in this study, the results of FCM and CC were concordant in 111 cases (79.4% agreement), including 96 FCM-/CC- and 15 FCM+/CC + cases (P

Abstract Introduction Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and T cell/histiocyte-rich large B-cell lymphoma (THRLBCL) have overlapping histological features that make their diagnosis challenging. Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is a recently proposed diagnostic marker for Hodgkin’s lymphoma. The aim of this study was to determine the ability of IMP3 in differentiating NLPHL from THRLBCL. Methods In this retrospective study, the formalin-fixed paraffin-embedded blocks from 56 patients (28 NLPHL and 28 large B cell lymphoma (LBCL, including 16 THRLBCL and 12 DLBCL, NOS) cases based on immunohistochemistry (IHC) were included. Sample sections were stained for IMP3 using IHC method. Moderate to strong staining in at least 10% of tumor cells was considered positive IMP3 expression. Results The mean age of the patients was 41.25 ± 16.08 years old. The majority of the patients were male. There was a significant age difference between NLPHL (34.61 ± 16.44 years old) and LBCL (47.89 ± 12.85 years) groups (p = 0.001). No significant difference was seen in gender and site between NLPHL and LBCL groups. The expression of IMP3 was mainly strong in LBCL group, while it was heterogeneously distributed among NLPHL samples ranging from weak to strong (p

Introduction:Palpable thyroid nodules are stated in 4 to 7% of individuals. This study was designed to evaluate the relation of Thyroid Imaging Reporting and Data System (TIRADS) and fine-needle aspiration (FNA) based cytology reports in patients with thyroid nodules.Materials and Methods:In this retrospective cross-sectional study, individuals with thyroid nodules who were selected for ultrasonographic-guided FNA enrolled in this study. Demographic data, radiologic assessment, and cytology report were gathered based on hospital medical records. TIRADS grading of the nodules was assessed for each nodule. Cytology was performed on all samples. Sensitivity and specificity were calculated by comparing cytology with ACR-TIRADS and also cytology with TIRADS 4-5 cut-off point as a radiologic malignant lesion.Results:172 patients were studied, 151 of whom were female and 21 were male. The mean age of the patients was 49.46 years. Most of the patients had TIRADS 4 (53.5%) followed by 3 (31.4%), and 5 (11.6%). 151 patients (87.8%) had a benign lesion in cytology. Of them, 118 had colloid nodules. There was a statistically significant relation between TIRADS and cytology (p-value

Abstract Background Schizophrenia, a chronic mental disorder, has been recognized as one of the heritable diseases with an increased level of dopamine neurotransmitter. Monoamine oxidase A (MAOA) plays a vital role in the catabolism of dopamine. It is a mitochondrial enzyme which is encoded by the MAOA gene located on the X chromosome. The aim of this study was to detect potential biomarker in order to diagnose schizophrenia. Hence, the association of uVNTR repetitions of the MAOA gene and Schizophrenia was investigated. Method Blood samples were collected from 102 schizophrenic patients (67 males and 35 females), and 103 volunteers with mental health (65 males and 38 females). Genomic DNA was extracted and the uVNTR polymorphisms were examined using specific primed PCR. Results The analysis indicated that genotype 3/3repetition (rep) showed the highest frequency in females. While genotype 4 and 3.5 reps revealed the highest frequencies among schizophrenic patients and healthy controls in men, respectively. There were no significant statistical differences in the number of uVNTR repeats of the MAOA gene between control and case individuals neither in women (OR = 0.35, 95% CI = 0.60–1.43 P = 0.845) nor in men (OR = 0.36, 95% CI = 0.80–1.64, P = 0.365). Conclusion In the current study, the number of uVNTR sequence repetitions located in the promoter of the MAOA gene was not associated with the risk of schizophrenia in Iranian patients.

Abstract Background Mantle cell lymphoma (MCL) has remained incurable in most patients. The expression of PD-L1 as a prognostic and predictive marker has not been fully evaluated in MCL. The current study aimed to determine PD-1/PD-L1 expression in MCL specimens and its significance as an immune check point inhibitor. Methods This retrospective study was conducted on the formalin-fixed paraffin-embedded blocks of 79 confirmed MCL patients based on immunohistochemistry (IHC). The IHC method was used to stain patient samples for PD1 and PDL1. Positive PD-1/PD-L1 expression was defined as moderate to strong or memberanous or memberanous/cytoplasmic staining in at least 5% of tumor and/or 20% of associated immune cells. Tumor aggressiveness was determined based on Ki67 and variant. Results The mean age of the patients was 60.08 ± 10.78 years old. Majority of the patients were male. The prevalence of aggressive tumor was 25%. Positive PD1 and PDL1 expression were identified in 12 (15.0%) and 3 (3.8%) of tumor cells, respectively. PD1 and PDL1 were positive in zero (0%) and 7 (8.9%) of background cells, respectively. There was no significant difference in terms of study parameters between positive and negative groups for both PD1 and PDL1 proteins. PD1 tumor cell percentage was negatively correlated with age (r = -0.254, p = 0.046). Conclusion Our results suggest that neither PD-1 nor its ligands represent relevant targets for MCL treatment. Age may impact the efficiency of immune checkpoint inhibitors and could be related to the increased incidence of MCL with age.

Early-stage detection is a vital factor in the later treatment and prognosis of cancer. Enhancing the sensitivity and specificity of the cancer detection pathological and experimental approaches can affect the morbidity and mortality of this disease. A folic acid (FA)-functionalized silica quantum dots (SiQDs)/KCC-NH2@SiO2 nanomaterials were synthesized and characterized as a bioimaging agent of the MCF 7 cancer cells. These nanoparticles showed biocompatible nature with specificity towards folate receptor (FR)-overexpressed MCF 7 cancer cells. Viability findings suggested that the SiQDs/KCC-NH2@SiO2/FA nanomaterials have nontoxic nature towards the cells in the concentration of 200 μg/mL. Fluorescence microscopy images were utilized to estimate the cell internalization of the nanoparticles and further verified by the flow cytometry technique. The differentiation ability of the nanoparticles was also approved by incubation with FR-negative HEK 293 normal cells. The SiQDs/KCC-NH2@SiO2/FA nanoparticle exhibited high stability, bright and high quantum yield fluorescence emission, proposing as a high-quality material for in vivo bioimaging of FR-overexpressed circulating tumoral cancer cells (CTCs).

Mutations in tumor suppressor p53 protein can occur at different phases of malignant transformation and affect the patient's prognosis. This study aimed to evaluate the expression of mutant p53 protein in Iranian patients with the primary and recurrence oral squamous cell carcinoma (OSCC). This retrospective cross-sectional study conducted on a group of patients with the primary OSCC (n=122) and the control subjects with oral noncancerous reactive lesions (n=80). Immunohistochemistry was performed with the DO-7 monoclonal antibody against p53 protein, and samples with ≥10% immunostaining were considered positive. Statistical analyses were carried out using SPSS. Positive staining for p53 was observed in none of the control subjects and 57.4% (70 of 122) of the primary OSCC patients (p

Triple-negative breast cancer (TNBC) is known as the most intricate and hard-to-treat subtype of breast cancer. TNBC cells do not express the well-known estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) expressed by other breast cancer subtypes. This phenomenon leaves no room for novel treatment approaches including endocrine and HER2-specific antibody therapies. To date, surgery, radiotherapy, and systemic chemotherapy remain the principal therapy options for TNBC treatment. However, in numerous cases, these approaches either result in minimal clinical benefit or are nonfunctional, resulting in disease recurrence and poor prognosis. Nowadays, chimeric antigen receptor T cell (CAR-T) therapy is becoming more established as an option for the treatment of various types of hematologic malignancies. CAR-Ts are genetically engineered T lymphocytes that employ the body’s immune system mechanisms to selectively recognize cancer cells expressing tumor-associated antigens (TAAs) of interest and efficiently eliminate them. However, despite the clinical triumph of CAR-T therapy in hematologic neoplasms, CAR-T therapy of solid tumors, including TNBC, has been much more challenging. In this review, we will discuss the success of CAR-T therapy in hematological neoplasms and its caveats in solid tumors, and then we summarize the potential CAR-T targetable TAAs in TNBC studied in different investigational stages.

Background: The use of biomarkers has become increasingly important in the diagnosis and treatment of several malignancies, including breast cancer. Among the established biomarkers, receptor tyrosine-protein kinase erbB-2 (HER-2/ neu) has been found to be of a predictive and prognostic role in breast cancer patients. Method: 94 patients with primary breast cancer were enrolled in our prospective study between 2016 and 2017. 5 cc clot blood samples were taken for serum HER- 2/neu testing at the time of diagnosis of breast cancer. The patients’ demographic data, tumor characteristics, including tumor size, tumor grade, presence of lymph node involvement, and stage, hormone receptor, and tissue HER-2/neu status of the subjects were recorded following tumor removal. Results: All of the patients were female with the age range of 27 to 80 years (the mean of age was 49.66. 36 patients (38.3%) had positive tissue HER-2 results and 58 (61.7%) had negative results. In those with high level serum HER-2 ECD, 28(77.7%) had positive tissue HER-2 and 8(22.2%) had negative results. Moreover, in the patients with low level serum HER-2 ECD, 8(13.7%) had positive tissue HER-2 and 50(86.2%) had negative results with the sensitivity of 77.7% and specificity of 86.2%. HER2 ECD levels were highly concordant with tissue HER2 status, with a P value of less than 0.001, which was considered to be statistically significant. Among different clinicopathologic variables, serum and tissue HER-2/nu were significantly correlated with only tumor grade. Conclusion: A significantly increased release of HER2 ECD levels may accurately predict tumor HER2 status as detected with immunohistochemistry and/or in situ hybridizations studies.

Having systematic simulation and optimization models with high computational accuracy is one of the most important problems in developing decision support systems. In the present research, a specific methodology was proposed for decentralized calibration of complex water resources system models by using the structural capabilities of the melody search algorithm. This methodology was implemented in the framework of a self-adaptive simulation–optimization model that helps fine-tune complex water resources models by introducing a new definition of the way sub-memories are related to each. The introduced structure aims to achieve the highest possible level of consistency, which is estimated by using different criteria, between model results and observed data at several control points of surface flows. The introduced strategy was put to the test in developing a water resources model for the Great Karun Watershed, Iran, and was found to produce accurate results compared to some other well-known optimization algorithms such as GA, HS, PSO, SGHS, EMPSO, and SaMeS. In an attempt to determine the effect of calibration on water resources system modeling, 16 calibration models of different dimensions are developed and their computational costs are compared in terms of their computation time and effects on the accuracy of the results. HIGHLIGHTS A modified version of melody search algorithm is proposed to calibrate distributed water resources simulation models.; The efficiency of the proposed algorithm in solving calibration problems is evaluated compared to some other well-known metaheuristic algorithms.; The effect of calibration dimension on the result accuracy and the computational cost of the calibration process are considered using 16 different models.;

Glomus jugulare is known as a benign tumor that could involve in different parts of the body. The most prevalent site of involvement is head and neck area. This disease is rare and few of the cases are bilateral. However, in familial cases bilateral or multicenter lesions are even rarer, in which there is an autosomal dominant pattern of inheritance. The most efficient treatment is believed to be surgery or radiotherapy depending on the location and certain other factors, such as age and performance status. Sporadic bilateral lesion is rarely seen and most bilateral cases are familial. Herein, we reported a case of bilateral glomus jugulare of carotid with no history of this tumor in family or any other familial diseases. Our subject was a 67-year-old man. The diagnosis was made via Tru-cut biopsy. He was treated successfully by 3- dimensional conformal radiotherapy up to a dose of 60 Gy. The follow-up computed tomography scan revealed partial tumor responses. He had no family history of any systemic disease related to functional glomus jugulare, such as uncontrolled hypertention or mass in the neck. He also had no history of catecholeamine exceretion-related symptoms.

Abstract Background Although life-threatening hemorrhage is a usual manifestation of acute promyelocytic leukemia (APL), thrombotic events seem to be more common in APL compared to other subtypes of acute leukemia. The treatment and prophylaxis of thrombosis are controversial due to the high risk of bleeding caused by disseminated intravascular coagulation (DIC) and thrombocytopenia. To the best of our knowledge we report the first case of APL in a patient with prosthetic heart valves successfully treated with a combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO). We hope this case report helps clinicians to manage different spectra of coagulopathy in APL successfully. Case presentation A 38-year-old Asian man presented with diagnosis of APL confirmed by bone marrow biopsy. He was on warfarin due to prosthetic mitral and aortic valves. He was at risk of both hemorrhagic events due to DIC and life-threatening valve thrombosis. Our management regimen included unfractionated heparin adjusted according to the platelet count to prevent both valve thrombosis and bleeding events. The patient tolerated treatment well without any hemorrhagic or thrombotic events, and complete molecular remission was achieved by ATRA and ATO without the need for chemotherapeutic agents. Conclusion Although this case is exceptional, a precise evaluation may be needed to select the appropriate dose and type of anticoagulant to treat a patient with APL.

Background & Objective: Thiopurine drugs are considered as a treatment modality in various autoimmune disorders including pemphigus vulgaris (PV). These drugs are metabolized by an enzyme “Thiopurine S-methyl transferase” (TPMT). Various variants of this enzyme may have decreased activity leading to serious drug side effects. To investigate the phenotype and genotype of TPMT in PV patients receiving thiopurine drugs. Methods: 50 patients (29 women and 21 men) with pemphigus vulgaris treating with standard dose of Thiopurine drugs were selected. Sex, age, result of liver function test and complete blood count were recorded. Genotyping of two common non-functional allele (TPMT*2 and TPMT*3C) by Allele-specific and RFLP-PCR was performed. TPMT enzymatic level was determined by an ELISA based method. Results: Of patients, 36 (72%) were found to have normal TPMT level; and 12, (24%) had higher level of enzyme and 2, 4% had low TPMT enzyme, but none of the patients showed mutant TPMT*2 and TPMT*3C alleles. None of the patients showed hepatotoxicity and bone marrow suppression. Conclusion: The phenotypic assay based on ELISA method may have false positive and misleading results but genotyping using PCR-RFLP and allele specific PCR is accurate, simple and cost-effective and can be used in patients decided to undergo thiopurine treatment.

Background: Synovial sarcoma is an aggressive soft tissue sarcoma. It has a wide spectrum of histopathologic patterns and uncertain immunohistochemistry, rendering it a diagnostic challenge. The objective of this study was to investigate the diagnostic utility and impact of SS18-SSX rearrangement evaluation in an Iranian population previously diagnosed with synovial sarcoma without such molecular tests. Method: We conducted this cross-sectional study on 44 formalin-fixed paraffin-embedded tissue blocks obtained from 23 synovial sarcoma patients (males, 69%; mean age, 36.4 years) and 11 cases with other neoplasms as negative controls. We assessed these specimens for SSX-SS18 gene rearrangement by break-apart fluorescent in situ hybridization (FISH) probes. Results: FISH study showed SS18-SSX fusion gene in 17 (73.91%) cases while six (26.09%) cases and negative controls did not show SS18-SSX fusion. Histopathologic type of tumor was significantly related to the presence of rearrangement (P=0.002) (rearranged: 11 biphasic and six monophasic tumors; non-rearranged: three monophasic and three poorly-differentiated tumors). Conclusion: This study supports the idea that molecular studies contribute to the confirmation of synovial sarcoma diagnosis, particularly in monophasic and poorly-differentiated subtypes, which show vague immunohistochemical results.

Background: The use of amide-based local anesthetics is generally considered to be safe. However, the literature on their safety in patients with hepatic injury is scarce. For the first time, the present study aimed to evaluate the effect and safety of five commonly used amide-based local anesthetics in the setting of hepatic failure.Methods: A total of 96 Sprague-Dawley rats were studied from September 2015 to September 2016 in the Animal Laboratory Center, Shiraz University of Medical Sciences, Shiraz, Iran. They divided into three groups, namely a control, induced liver failure (LF), and non-LF groups. The rats were administered local anesthetic agents (lidocaine, prilocaine with felypressin, lidocaine with epinephrine, mepivacaine, articaine, and prilocaine). The effect of these drugs was evaluated by comparing the liver enzyme levels of the rats. The data were analyzed using SPSS software. The independent t test, one-way ANOVA, and the post hoc tests were used to compare groups. A PResults: In non-LF rats, mepivacaine, lidocaine, and lidocaine with epinephrine caused a significant increase in aspartate aminotransferase (AST) level compared with the effect of prilocaine with felypressin and articaine. In non-LF rats, only mepivacaine resulted in a significant increase in AST level compared with lidocaine (P=0.007) and prilocaine with felypressin (P=0.044). In this group, only mepivacaine caused a significant increase in alanine transaminase (ALT) level compared with lidocaine (P=0.016). Whereas in the LF group, mepivacaine caused an increase in ALT level compared with the effect of both prilocaine with felypressin (P=0.009) and articaine (PConclusion: Articaine and prilocaine with felypressin local anesthetics induced the least change in hepatic enzyme levels in rats with abnormal hepatic function.

Background: Resveratrol and Berberis integerrima (B. integerrima) are known to be natural antioxidants and regulators of human metabolism. However, the effects of resveratrol and B. integerrima on the ovarian morphology in polycystic ovary syndrome (PCOS) are not obvious. Objective: This study aimed to determine the effect of the hydroalcoholic extract of B. integerrima in combination with resveratrol on some biochemical parameters and ovarian morphology in the letrozole-induced PCOS rat. Materials and Methods: Seventy adult female Sprague-Dawley rats aged 10-12 weeks weighing 200 ± 20 gr were randomly divided into seven groups (n = 10/each). Group I): normal; Group II): vehicle; Group III): letrozole-induced PCOS 1 mg/kg letrozole orally, rats receiving 1 cc normal saline orally; Group IV): PCOS + receiving 150 mg/kg metformin orally; Group V): PCOS + receiving 20 mg/kg resveratrol orally; Group VI): PCOS + 3 gr/kg barberry orally; and Group VII): PCOS + receiving 3 gr/kg barberry and 20 mg/kg resveratrol orally. All animals were followed-up for 63 days. The biochemical parameters and histological assessments of ovaries were performed. Results: Resveratrol alone and/or in combination with B. integerrima treatment in rats led to a significant decrease in low-density lipoprotein, triglyceride, malondialdehyde, and tumor necrosis factor-alpha concentrations (p = 0.02). The groups IV, V, VI, and VII showed a decrease in insulin resistance and an increase in the superoxide dismutase, total antioxidant capacity, and high-density lipoprotein (p = 0.01). No significant difference was observed between the level of serum glucose in the treatment groups. Number of cystic follicles had a significant decrease in barberry, resveratrol, and their combination groups (p < 0.001). Conclusion: Resveratrol, B. integerrima, and their combination as natural products with fewer side effects might be effective as an alternative medicine in treatment of PCOS.

In this article, we explore and interpret organizational identity transformation associated with open innovation strategy of the largest telecommunication company in Italy, Telecom Italia (TIM). When TIM established eight joint laboratories within five major Italian universities to benefit from opening its business model, it transferred some of the R&D employees to the new laboratories to work with the university scientists. This organizational transformation created underexplored conditions for R&D employees engaged in the open innovation activities of the firm. Our interpretive phenomenological analysis (IPA) answers the question of “How do R&D employees experience organizational identity change in the process of open innovation?”. We based our analysis on interpreting lived experiences of 14 employees. Studying the phenomena of organizational identity change during the process of open innovation implementation suggests the following: (1) The process of open innovation through mobility of skilled R&D employees triggers organizational identity ambiguity and change, (2) Organizational identity ambiguity phase in the process of open innovation can be shortened by the support of parent company and managerial skills highlighting sensemaking mechanisms, (3) Constructing a shared organizational identity with university members involved in this process is an undeniable element of OI success for this strategy. We contribute to the literature by establishing linkages among organizational identity and open innovation and by building on recent works on the role of individuals within open innovation ecosystem. Our qualitative analysis draws on a conceptual framework for open innovation and organizational identity transformation.

Background: Lung cancer is one of the most frequently diagnosed malignant neoplasms in the world. The pulmonary carcinomas are divided into two major categories, namely small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC).Traditionally, the treatment for NSCLC was based on tumor stage, irrespective of histologic subtypes; over the recent years, however, with the development of targeted therapies with different adverse or therapeutic effects on each subtype, it is crucial to correctly subcategorize NSCLC. Utilizing Immunohistochemical (IHC) markers may be conducive to obtain this objective, yet no single marker is sensitive or specific enough to differentiate SCC and adenocarcinoma. Therefore, in the present research, we want to use a panel consisting of P63, CK 5/6, TTF-1, and Napsin A. Methods: 83 cases of NSCLC (36 adenocarcinoma, 37 squamous cell carcinoma and 10 poorly differentiated carcinoma) were selected. IHC examination for P63, TTF-1, Napsin A, and CK 5/6 were performed on tissue sections obtained from formalin-fixed, paraffin embedded blocks. Results: TTF1 had 94% sensitivity and 69% specificity with PPV 73% and NPV 92%, and NaspsinA had 91% sensitivity and 97% specificity with PPV 97% and NPV 92% as regards the diagnosis of adenocarcinoma. P63 had 100% sensitivity and 84% specificity with PPV 87% and NPV 100%, and CK5/6 had 100% sensitivity and 69% specificity with PPV 78% and NPV 100% in the diagnosis of squamous cell carcinoma. Conclusion: Using an IHC panel of TTF-1, Napsin A, P63, and CK5/6 it is possible to reliably diagnose poorly differentiated NSCLC with no evident glandular or squamous differentiation.

Introduction: Primary Diffuse Large B Cell Lymphoma of CNS (PCNSL) is a rare variant of Diffuse Large B Cell Lymphoma (DLBCL) and presents with an aggressive clinical course and usually resistant to commonly used therapy regimens. Recently, role of immune checkpoint molecules including PD-1 and PD-L1 confirmed in some solid tumors and lymphoma resulting tumor cells escape the immune system and help to survive and to spread. Inhibitors of PD-1 and PD-L1 have shown lasting responses in several solid and some hematological tumors, while limited studies evaluate checkpoint molecules on PCNSL. Method: In this study, we investigated PD-1 and PD-L1 expression by immunostaining on 71 patients with PCNSL and correlation with demographic data, location of the tumor, proliferation rate, cell of origin, and CD8 positive T cell infiltration in tumor microenvironment. Results: 16 from71 showed PD-1 expression, while PD-L1 expression were 42/71. No association was determined between PD-1/PD-L1 expression and gender, cell of origin, and proliferation rate, but a highly significant difference was determined between the infiltration of CD8 positive T cells in two groups of PD-1/PD-L1 positive and negative. Conclusion: This study revealed expression of check point molecules in remarkable number of PCNSL which may open new therapeutic recommendations in this aggressive lymphoma type.

Background: Type 2 diabetes is a progressive disease. This study Compared effects of combination of turmeric, ginger and cinnamon hydroalcoholic extracts with metformin on body weight, glycemic control, inflammation, oxidative stress and pancreatic histopatalogical changes in diabetic rat. Methods: Rats were randomly assigned to four groups of 13 animals. Diabetes was induced by a single injection of streptozotocin (STZ, 65 mg/kg) and nicotinamide (110 mg/kg, 15 min before STZ injection). Normal control (NC) and diabetic control (DC) rats received 1 mL of distilled water and two other diabetic groups received either 300 mg/kg (HETGCC) or 100 mg/kg metformin for 6 weeks. Results: HETGCC and metformin significantly decreased serum glucose, glycated hemoglobin (HbA1c), Homeostatic Model Assessment for Insulin Resistance (HOMA index), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and malondialdehyde (MDA) levels and significantly increased high-density lipoprotein cholesterol (HDL-C) concentrations compared to DC group. A significant increase in the number and diameter of the islets of Langerhans (IL) and body weight was seen in HETGCC group compared to DC rats and a significant increase in quantitative insulin sensitivity check index (QUICKI) was observed in metformin treated group. HETGCC and metformin did not have significant effects on hsCRP, insulin and triglyceride (TG) concentrations in diabetic rats. Conclusion: HETGCC was shown to reduce the risk of diabetes and improve complications associated with diabetes such as hyperglycemia,dyslipidemia, oxidative stress, inflammation, histopathological statue of islets of Langerhans and weight loss in T2D patients.