Co-occurrence of Idiopathic Hypereosinophilic Syndrome in End-Stage Renal Disease Patients Undergoing Maintenance Hemodialysis.

Hypereosinophilic syndrome (HES) is defined as the presence of (1) peripheral blood eosinophilia >1.5 x 109/L for at least one month, (2) evidence of eosinophil-mediated organ damage and/or dysfunction, and (3) exclusion of other potential causes of eosinophilia. In hemodialysis patients, HES has been associated with manifestations because of low blood pressure or gastrointestinal symptoms that result in dialysis intolerance. Very few cases of HES co-occurrence in dialysis patients have been reported in the literature, and their clinical characteristics are not fully understood. Here, we report two end-stage renal disease patients diagnosed with idiopathic HES while undergoing maintenance hemodialysis. The first patient presented with unexplained persistent pruritus and intradialytic hypotension, which started 10 minutes after the dialysis session initiation. Hematologic studies revealed hypereosinophilia which remarkably improved on steroid therapy. The second patient was accidentally discovered with asymptomatic persistent hypereosinophilia. His blood counts improved initially on interferon treatment before achieving full remission on steroid therapy. Neither of the two patients reported any history of allergy or atopic manifestations. Our case report sheds light on the possible occurrence of HES in hemodialysis patients which may be confused with other dialysis-related complications. Although steroids remain the mainstay of treatment, the optimal dose and duration of treatment remain unknown.

Complementary and alternative medicine on cognitive defects and neuroinflammation after sepsis.

Sepsis-associated encephalopathy (SAE) is a common manifestation of sepsis, ranging from mild confusion and delirium to severe cognitive impairment and deep coma. SAE is associated with higher mortality and long-term outcomes, particularly substantial declines in cognitive function. The mechanisms of SAE probably include neuroinflammation that is mediated by systemic inflammation and ischemic lesions in the brain, a disrupted blood-brain barrier, oxidative stress, neurotransmitter dysfunction, and severe microglial activation. Increasing evidence suggests that complementary and alternative medicine, especially Traditional Chinese Medicine (TCM), is favorable in alleviating cognitive decline after sepsis. Here, we summarized the studies of traditional herbal remedies, TCM formulas and acupuncture therapy in animal models of neurological dysfunctions after sepsis in recent decades and reviewed their potential mechanisms.

Ethical and Legal Debates on Vaccine Infodemics.

Over the course of three and a half years, the global toll of coronavirus disease 2019 (COVID-19) has claimed the lives of millions of individuals. Scientific breakthroughs, exemplified by mRNA vaccines, have emerged as crucial tools in saving numerous lives and fortifying our defenses against future pandemics. However, the battle against the virus has been complicated by the dissemination of misleading political and ethical information, resulting in avoidable fatalities. Recognizing this phenomenon, the term 'infodemics' has been coined to denote the proliferation of false or misleading information that hinders effective social responses. Given the historical prevalence of infodemics surrounding vaccinations, this discussion delves into the ongoing ethical and legal deliberations concerning vaccination mandates, an indispensable health intervention in the face of pandemics. Governments bear the responsibility of safeguarding their citizens, acknowledging the social requirements imposed by the collective well-being. The protection of both citizens and healthcare workers becomes paramount, considering the potential risks of infection and mortality associated with individuals refusing vaccination. Historically, governments have played a pivotal role in eradicating pandemics through the implementation of vaccine mandates. However, the contemporary landscape is marked by the infusion of political and misleading misinformation, presenting new challenges. Governments are now confronted with an ethical duty to ensure that citizens possess the necessary information to make informed decisions and safeguard their well-being. While grappling with the realization that extraordinary circumstances demand extraordinary responses, the lessons from past pandemics underscore the imperative of prioritizing public health, especially in the context of the high numbers of casualties worldwide. This discourse explores the ethical and legal dimensions surrounding vaccine mandates, with particular emphasis on their relevance to healthcare workers.

DR-NASNet: Automated System to Detect and Classify Diabetic Retinopathy Severity Using Improved Pretrained NASNet Model.

Diabetes is a widely spread disease that significantly affects people's lives. The leading cause is uncontrolled levels of blood glucose, which develop eye defects over time, including Diabetic Retinopathy (DR), which results in severe visual loss. The primary factor causing blindness is considered to be DR in diabetic patients. DR treatment tries to control the disease's severity, as it is irreversible. The primary goal of this effort is to create a reliable method for automatically detecting the severity of DR. This paper proposes a new automated system (DR-NASNet) to detect and classify DR severity using an improved pretrained NASNet Model. To develop the DR-NASNet system, we first utilized a preprocessing technique that takes advantage of Ben Graham and CLAHE to lessen noise, emphasize lesions, and ultimately improve DR classification performance. Taking into account the imbalance between classes in the dataset, data augmentation procedures were conducted to control overfitting. Next, we have integrated dense blocks into the NASNet architecture to improve the effectiveness of classification results for five severity levels of DR. In practice, the DR-NASNet model achieves state-of-the-art results with a smaller model size and lower complexity. To test the performance of the DR-NASNet system, a combination of various datasets is used in this paper. To learn effective features from DR images, we used a pretrained model on the dataset. The last step is to put the image into one of five categories: No DR, Mild, Moderate, Proliferate, or Severe. To carry this out, the classifier layer of a linear SVM with a linear activation function must be added. The DR-NASNet system was tested using six different experiments. The system achieves 96.05% accuracy with the challenging DR dataset. The results and comparisons demonstrate that the DR-NASNet system improves a model's performance and learning ability. As a result, the DR-NASNet system provides assistance to ophthalmologists by describing an effective system for classifying early-stage levels of DR.

Splenic SUMO1 controls systemic inflammation in experimental sepsis.

Introduction: The recent discovery of TAK981(Subasumstat), the first-in-class selective inhibitor of SUMOylation, enables new immune treatments. TAK981 is already in clinical trials to potentiate immunotherapy in metastatic tumors and hematologic malignancies. Cancer patients have more than ten times higher risk of infections, but the effects of TAK981 in sepsis are unknown and previous studies on SUMO in infections are conflicting. Methods: We used TAK981 in two sepsis models; polymicrobial peritonitis (CLP) and LPS endotoxemia. Splenectomy was done in both models to study the role of spleen. Western blotting of SUMO-conjugated proteins in spleen lysates was done. Global SUMO1 and SUMO3 knockout mice were used to study the specific SUMO regulation of inflammation in LPS endotoxemia. Splenocytes adoptive transfer was done from SUMO knockouts to wild type mice to study the role of spleen SUMOylation in experimental sepsis. Results and discussion: Here, we report that inhibition of SUMOylation with TAK981 improved survival in mild polymicrobial peritonitis by enhancing innate immune responses and peritoneal bacterial clearance. Thus, we focused on the effects of TAK981 on the immune responses to bacterial endotoxin, showing that TAK981 enhanced early TNFα production but did not affect the resolution of inflammation. Splenectomy decreased serum TNFα levels by nearly 60% and TAK981-induced TNFα responses. In the spleen, endotoxemia induced a distinct temporal and substrate specificity for SUMO1 and SUMO2/3, and both were inhibited by TAK981. Global genetic depletion of SUMO1, but not SUMO3, enhanced TNFα production and metabolic acidosis. The transfer of SUMO1-null, but not wild-type, splenocytes into splenectomized wild-type mice exacerbated TNFα production and metabolic acidosis in endotoxemia. Conclusion: These results suggest that specific regulation of splenic SUMO1 can modulate immune and metabolic responses to bacterial infection.

Mobile-HR: An Ophthalmologic-Based Classification System for Diagnosis of Hypertensive Retinopathy Using Optimized MobileNet Architecture.

Hypertensive retinopathy (HR) is a serious eye disease that causes the retinal arteries to change. This change is mainly due to the fact of high blood pressure. Cotton wool patches, bleeding in the retina, and retinal artery constriction are affected lesions of HR symptoms. An ophthalmologist often makes the diagnosis of eye-related diseases by analyzing fundus images to identify the stages and symptoms of HR. The likelihood of vision loss can significantly decrease the initial detection of HR. In the past, a few computer-aided diagnostics (CADx) systems were developed to automatically detect HR eye-related diseases using machine learning (ML) and deep learning (DL) techniques. Compared to ML methods, the CADx systems use DL techniques that require the setting of hyperparameters, domain expert knowledge, a huge training dataset, and a high learning rate. Those CADx systems have shown to be good for automating the extraction of complex features, but they cause problems with class imbalance and overfitting. By ignoring the issues of a small dataset of HR, a high level of computational complexity, and the lack of lightweight feature descriptors, state-of-the-art efforts depend on performance enhancement. In this study, a pretrained transfer learning (TL)-based MobileNet architecture is developed by integrating dense blocks to optimize the network for the diagnosis of HR eye-related disease. We developed a lightweight HR-related eye disease diagnosis system, known as Mobile-HR, by integrating a pretrained model and dense blocks. To increase the size of the training and test datasets, we applied a data augmentation technique. The outcomes of the experiments show that the suggested approach was outperformed in many cases. This Mobile-HR system achieved an accuracy of 99% and an F1 score of 0.99 on different datasets. The results were verified by an expert ophthalmologist. These results indicate that the Mobile-HR CADx model produces positive outcomes and outperforms state-of-the-art HR systems in terms of accuracy.

Pathological fracture due to primary bone lymphoma in a patient with a history of prostate cancer: A case report and review of literature.

Primary bone lymphoma (PBL) is a rare extranodal presentation within lymphomas and primary bone malignancies. Pathologic fracture (PF) is a common complication of metastatic bone disease but is, rarely, the presentation of a primary bone tumor. We report a case of an 83-year-old man with a history of untreated prostate cancer, presenting with atraumatic fracture of his left femur after months of intermittent pains and weight loss. Radiographic workup revealed a lytic lesion suspicious for PF secondary to metastatic prostate cancer; however, initial core biopsy results were inconclusive for malignancy. A complete blood count with differential and complete metabolic panel was within normal limits. During surgical fixation and nailing of the femur, a reaming biopsy was performed as a repeat measure and revealed diffuse large B-cell lymphoma. Staging with positron emission tomography and computed tomography found no evidence of lymphatic or visceral involvement and chemotherapy was promptly initiated. This case highlights the diagnostic workup challenges for PF secondary to PBL, especially in the setting of concurrent malignancy. Because of the non-specific presentation of a lytic lesion on imaging associated with atraumatic fracture, we highlight PBL as an important diagnostic consideration.

Dermoscopic approach for differential diagnosing of autoimmune bullous disease: pemphigus vulgaris, pemphigus foliaceus, and IgA pemphigus.

INTRODUCTION: Dermoscopy is a noninvasive technique for the evaluation of different pigments and microstructures of the epidermis, dermoepidermal junction, and papillary dermis that are not apparent to the naked eye, which therefore improves diagnostic accuracy. AIM OF THE STUDY: This study aims to describe the characteristic dermoscopic features of bullous diseases and analyze the characteristic dermoscopic features of bullous diseases of the skin and hair. PATIENTS AND METHODS: A descriptive study was conducted to describe and analyze the characteristic dermoscopic features of bullous diseases in the Zagazig University Hospitals. RESULTS: This study enrolled 22 patients. Dermoscopy revealed yellow hemorrhagic crusts in all patients and white yellow structure with red halo in 90.9% of patients. Pemphigus vulgaris patients were identified by the presence of dermoscopic clues such as bluish deep discoloration, tubular scaling, black dots, hair casts, hair tufts, yellow dots with whitish halos (fried egg sign) and yellow follicular pustules that are not seen in pemphigus foliaceus and IgA pemphigus. DISCUSSION: Dermoscopy is an important tool that serves as a link between clinical and histopathological diagnoses, and it can easily be used in daily practice. Several suggestive dermoscopic features can help in the differential diagnosis of autoimmune bullous disease but only after making a provisional clinical diagnosis. Dermoscopy is a very useful tool in the differentiation of pemphigus subtypes.

Proposal of Diagnostic Approach of Periodontal Primary Non Hodgkin Lymphoma of Bone with Flow Cytometry as an Essential Diagnostic Component.

BACKGROUND: Primary bone lymphoma is a rare type of lymphoid neoplasm with favorable prognosis, where Primary Non Hodgkin Lymphoma of bone (PB-NHL) is most common with the subtype. Amongst PB-NHL, diffuse large Bcell lymphoma represents the majority of cases. The mandible is a very uncommon site of involvement, presenting as a painful bone mass with high suspicion of osteomyelitis. METHODS: We report the case of a 45-year-old male with no significant past medical history who was admitted to the hospital with a large right jaw mass and pain after recent tooth removal. The original tissue biopsy was not diagnostic, and cultures were found to be negative for microorganisms. Due to enlargement of the mass, a fine needle aspiration (FNA) was done. At the time of rapid onsite evaluation of the FNA, atypical lymphoid cells were seen, and material was obtained for flow cytometry (FC) evaluation. This revealed an aberrant clonal B-cell population. The consequent immunohistochemical evaluation of original material supported the diagnosis of PB-NHL. After chemotherapy patient improved. RESULTS: After an extensive English language literature review, we identified and summarized the clinical presentations, diagnostic procedures, histopathologic features, treatment methods, and outcomes of forty-two cases of periodontal PB-NHL. Based on our findings, we propose a set of clinical features at initial presentation to increase the clinical suspicion of periodontal PB-NHL for practitioners. CONCLUSION: Based on our institution's experience and the literature review conclusions, we propose the University of Texas Medical Branch diagnostic approach for PB-NHL and suggest that FNA and FC should be utilized as the essential diagnostic component. The fast and efficient diagnosis of PB-NHL can facilitate the correct treatment and sufficiently improve patient care.

Serum angiopoietin-2 level as a novel potential biomarker in oral lichen planus.

BACKGROUND: Lichen planus is a common chronic cutaneous inflammatory disease. Recent advances evidenced that angiogenesis is tightly connected to it. More recently, the endothelial specific growth factor angiopoietin-2 has been clarified to interact with vascular endothelial growth factor. Angiopoietin-2 level has not been investigated in lichen planus. AIM: To evaluate serum level of angiopoietin-2 in cutaneous and oral lichen planus. METHODS: Ninety patients were investigated, 45 patients with lichen planus. In addition to forty-five healthy control, the activity of the disease was estimated at the time of examination. The serum level of angiopoietin-2 had been estimated by enzyme-linked immunosorbent assay. The relationships between angiopoietin-2 serum level and disease severity, type of lichen, and visual analogue scale score (VAS) were determined. RESULTS: The serum levels of angiopoietin-2 were substantially higher in patients with both cutaneous and oral lesions than patients with cutaneous lichen planus only (P < .001). CONCLUSIONS: Serum angiopoietin-2 is elevated in patients compared with normal subjects and is correlated with the presence of oral lesions and disease severity, that reflects its role in angiogenesis and inflammation, and angiopoietin-2 serum level could be a potential marker for monitoring the oral lichen to identify possible malignant transformation.

Low-cost multiple FBG interrogation technique for static applications.

In this Letter, a low-cost interrogation technique for multiple fiber Bragg gratings (FBGs) is demonstrated. The design utilizes the major advantage of the distributed feedback lasers, which is tuning their emitted wavelength by current modulation and temperature variation. The sensitivity of this method and the influence of optical losses on the measurement have been carefully studied, and an accuracy of 5 pm is achieved.

Intra-abdominal infection (IAI) following cesarean section: a retrospective study in a tertiary referral hospital in Egypt.

BACKGROUND: The incidence of post cesarean intra-abdominal infection (IAI) and the independent risk factors associated with it were retrospectively studied at a tertiary referral hospital in Egypt. METHODS: The study targeted the period between January 2014 and December 2017 (4 years) at Minia University Hospital for Obstetrics and Gynecology (a tertiary referral hospital), Minia Governorate, Egypt. All cases that developed IAI following cesarean section (CS) during the study period were included (408 cases, which served as the case group); in addition, 1300 cases that underwent CS during the study period and were not complicated by IAI or surgical site Infection (SSI) were randomly chosen from the records (control group). The records of cases and controls were compared and bivariate analysis and multivariate logistic regression were used to identify risk factors for IAI. RESULTS: During the studied period, there were 35,500 deliveries in the hospital, and 14200 cases (40%) of these were by cesarean section, producing a rate of 40%. The incidence of IAI post CS was 2.87%, and the mortality rate was 1.2% (due to septicemia). The most identifiable risk factors for IAI were chorioamnionitis (AOR 9.54; 95% CI =6.15-16.2; p ≤ 0.001) and premature rupture of membranes (PROM) (AOR 7.54; 95% CI =5.69-10.24; p ≤ 0.001). Risk factors also included: prolonged duration of CS >  1 h (AOR 3.42; 95% CI =2.45-5.23; p = 0.005), no antenatal care (ANC) visits (AOR 3.14; 95% CI =2.14-4.26; p = 0.003), blood loss > 1000 ml (AOR 2.86; 95% CI =2.04-3.92; p = 0.011), emergency CS (AOR 2.24; 95% CI =1.78-3.29; p = 0.016), prolonged labor ≥24 h. (AOR 1.76; 95% CI =1.26-2.27; p = 0.034) and diabetes mellitus (AOR 1.68; 95% CI =1.11-2.39; p = 0.021). CONCLUSIONS: The incidence of IAI post CS in our hospital was 2.87%. Identification of predictors and risk factors for IAI is an important preventive measure.

B cells in chronic graft-versus-host disease.

Allogeneic hematopoietic stem cell transplantation (alloHCT) is the definitive therapy for numerous otherwise incurable hematologic malignancies and non-malignant diseases. The genetic disparity between donor and recipient both underpins therapeutic effects and confers donor immune system-mediated damage in the recipient, called graft-versus-host disease (GVHD). Chronic GVHD (cGVHD) is a major cause of late post-transplant morbidity and mortality. B cells have a substantiated role in cGVHD pathogenesis, as first demonstrated by clinical response to the anti-CD20 monoclonal antibody, rituximab. Initiation of CD20 blockade is met at times with limited therapeutic success that has been associated with altered peripheral B cell homeostasis and excess B Cell Activating Factor of the TNF family (BAFF). Increased BAFF to B cell ratios are associated with the presence of circulating, constitutively activated B cells in patients with cGVHD. These cGVHD patient B cells have increased survival capacity and signal through both BAFF-associated and B Cell Receptor (BCR) signaling pathways. Proximal BCR signaling molecules, Syk and BTK, appear to be hyper-activated in cGVHD B cells and can be targeted with small molecule inhibitors. Murine studies have confirmed roles for Syk and BTK in development of cGVHD. Emerging evidence has prompted investigation of several small molecule inhibitors in an attempt to restore B cell homeostasis and potentially target rare, pathologic B cell populations.

Acute Hepatitis Caused by Genotype 4 HCV Presenting with Microangiopathic Hemolytic Anemia.

Many cases have been reported about the role of chronic hepatitis C and interferon therapy in the development and recurrence of thrombotic thrombocytopenic purpura (TTP), but to our knowledge there is no previous report about the association between acute hepatitis C and any microangiopathic hemolytic anemia (MAHA) including TTP. We report a case of acute hepatitis C that presented with MAHA resembling TTP, which resolved with spontaneous clearance of viral infection.

Microwave assisted synthesis of some new thiazolopyrimidine and pyrimidothiazolopyrimidopyrimidine derivatives with potential antimicrobial activity.

BACKGROUND AND OBJECTIVE: A series of thiazolopyrimidine derivatives have been synthesized via multicomponent reaction and tested for biological activities. This research aims to develop a new synthetic method of poly fused pyrimidines under microwave irradiation. 6-Amino-4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitriles reacted with bromomalono-nitrile to give 3,7-diamino-5-aryl-5H-thiazolo[3,2-a]pyrimidine-2,6-dicarbonitrile more willingly than the isomeric 7H-thiazolo[3,2-a]pyrimidines. Thiazolopyrimidine derivatives reacted with carbon disulphide to produce 11-aryl-11H-1,2,3,4,7,8,9,10-octahydropyrimido[4″,5″:4',5']thiazolo[3',2'-a]pyrimido[4,5-d]pyrimidine-2,4,8,10-tetrathione. The above mentioned reactions were established by using both conventional methods and microwave-assisted irradiation. CONCLUSION: This work provides a new method for preparing poly fused pyrimidines. The microwave-assisted technique is preferable due to the yield enhancements attained, time saving, and environmental safety reactions. The newly prepared compounds were verified for their antimicrobial activities. Also, the absorption and emission of some of the prepared compounds were studied.

Bromination and diazo-coupling of pyridinethiones; microwave assisted synthesis of isothiazolopyridine, pyridothiazine and pyridothiazepines.

Isothiazolopyridines, pyridothiazines and pyridothiazepines are important compounds that possess valuable biological activities. This paper reports on the synthesis of these compounds using both conventional chemical methods and modern microwave techniques. 3-Bromo-6-hydroxy-4-methyl-2-thioxo-2,3-dihydropyridine-3-carboxamide, 5-arylazo-6-hydroxy-4-methyl-2-thioxo-1,2-dihydropyridine-3-carboxamides, 3,5-bis-arylazo-6-hydroxy-4-methyl-2-thioxo-2,3-dihydropyridine-3-caboxamide, 4-methyl-2,3,6,7-tetra-hydroisothiazolo[5,4-b]-pyridine-3,6-dione, 2,2'-(methylene-bis-(sulfanediyl))bis(4-methyl-6-oxo-1,6-dihydropyridine-3-carboxamide), 2-hydroxy-5-methyl-4H-pyrido[3,2-e][1,3]-thiazine-4,7(8H)-dione and 2-arylmethylene-8-hydroxy-6-methyl-2,3,4,5-tetrahydropyrido-[3,2-f][1,4]thiazepine-3,5-diones have been prepared from 6-hydroxy-4-methyl-2-thioxo-2,3-dihydropyridine-3-carboxamide. Some of these compounds were prepared using microwave-assisted reaction conditions, that provided higher yields in shorter times than the conventional methods.

Microwave assisted synthesis and unusual coupling of some novel pyrido[3,2-f][1,4]thiazepines.

3-Amino-3-thioxopropanamide (1) reacted with ethyl acetoacetate to form 6-hydroxy-4-methyl-2-thioxo-2,3-dihydropyridine-3-carboxamide (2), which reacted with α-haloketones 3 to produce 2,3-disubstituted-8-hydroxy-6-methyl-2H,5H-pyrido[3,2-f]-[1,4]thiazepin-5-ones 4a-c. Benzoylation of 4c led to the formation of the dibenzoate derivative 9. Compounds 4a-c could be prepared stepwise through the formation of S-alkylated derivatives 10a-c. Compounds 2, 4a-c, 9 and 10a-c were prepared using microwave as a source of heat, and gave better yields in shorter times than those achieved by traditional methods. Coupling of 4a-c with arenediazonium chlorides proceeded unusually to give the 6-hydroxy-4-methyl-2-(arylazo)thieno[2,3-b]pyridin-3(2H)-one ring contraction products 14. Structures of the newly synthesized compounds were proven by spectral and chemical methods.