Association of vitamin D deficiency and disease activity in systemic lupus erythematosus patients: Two-year follow-up study

Objectives: This study aims to determine the prevalence of vitamin D deficiency in Pakistani systemic lupus erythematosus (SLE) patients and the effect of vitamin D deficiency on the severity and outcomes of SLE.Patients and methods: This retrospective study evaluated SLE patients presenting to our hospital between January 2009 and December 2018. A total of 98 patients (13 males, 85 females; mean age 39.8±14.9 years; range, 16 to 73 years) with vitamin D levels available at the time of diagnosis were included in the study. Disease activity was measured using SLE disease activity score at the time of diagnosis and at the two-year mark.Results: Sixty-five patients were deficient in Vitamin D and out of those 46 were severely deficient. The severe disease group had more patients with vitamin D deficiency at both visits (43/78 and 33/46) while patients in remission all had normal vitamin D (12/12 and 14/14) (p≤0.001).Conclusion: Vitamin D deficiency is common in SLE patients and also significantly associated with increased disease activity at the time of diagnosis and at the two-year mark. We hope this study becomes a platform for the global medical community to come together and implement early screening and monitoring of vitamin D levels and to determine the optimal level of supplementation for prevention of poor outcomes in SLE

Leiomyoma of maxillary sinus

Leiomyoma is a benign smooth muscle tumor that most commonly occurs in the uterus; however, it can also manifest in various extragenital locations, including the maxillary sinus.1,2 While leiomyomas of the maxillary sinus are occasional, they present unique diagnostic and management challenges. The maxillary sinus, one of the paranasal sinuses in the facial bones, is typically associated with sinusitis or odontogenic infections.1 Therefore, clinicians primarily consider inflammatory or neoplastic etiologies when encountering a mass within the maxillary sinus. Among the possible neoplastic causes, leiomyoma is a less frequently encountered entity, but it should be considered in the differential diagnosis.1,2 Understanding the clinical presentation, radiological features, and appropriate management strategies for leiomyoma of the maxillary sinus is crucial for accurate diagnosis and effective treatment. This case report aims to contribute to the existing medical knowledge by presenting a unique case of leiomyoma arising in the maxillary sinus, discussing the diagnostic approach treatment options, and highlighting any noteworthy findings.2,3 Leiomyoma of the maxillary sinus can present with various symptoms, including nasal obstruction, facial pain or pressure, recurrent sinusitis, epistaxis (nosebleeds), or a palpable mass in the maxillary region.1,3 However, these symptoms are non-specific and can be mistaken for other sinus entities. Therefore, it is essential to consider leiomyoma as a differential diagnosis in patients with such clinical presentations. Diagnosing leiomyoma of the maxillary sinus can be challenging due to its rarity and overlapping symptoms with other sinus entities. Imaging studies, such as compute tomography (CT) or magnetic resonance imaging (MRI), play a crucial role in identifying the presence, location, and extent of the tumor.3,4 However, a definitive diagnosis requires a histopathological examination of the excised tissue. When encountering a maxillary sinus mass, the differential diagnosis includes various benign and malignant conditions. Potential differentials include inverted papilloma, angiofibroma, Schneiderian papilloma, mucocele, and even malignancies like sinonasal carcinoma or sarcoma. Proper evaluation, including clinical, radiological, and histopathological assessment, is necessary to differentiate leiomyoma from other lesions.4,5 Khanna et al.1 reported the case of a leiomyoma originating in the maxillary sinus in a 55-year-old female. The patient presented with facial pain and nasal obstruction. The CT revealed a well-defined mass in the maxillary sinus. Surgical excision was performed, and the histopathological examination confirmed the diagnosis of leiomyoma. Rana et al.2 presented a case of a 37-year-old male with a leiomyoma in the maxillary sinus. The patient complained of nasal obstruction and recurrent sinusitis. The CT imaging showed a polypoidal mass in the maxillary sinus, and endoscopic sinus surgery was performed to remove the tumor. Histopathological examination confirmed the diagnosis of leiomyoma. In a retrospective study by Li et al.3 seven cases of leiomyoma arising from the maxillary sinus were analyzed. The study highlighted these patients' clinical features, radiological findings, and treatment outcomes. The authors emphasized the importance of considering leiomyoma as a potential diagnosis when evaluating maxillary sinus masses. Khan et al.4 reported a case of leiomyoma originating from the maxillary sinus in a 50-year-old male. The patient presented with nasal obstruction, facial pain, and recurrent epistaxis. Imaging studies revealed a soft tissue mass in the maxillary sinus, and endoscopic sinus surgery was performed for complete excision. Histopathological examination confirmed the diagnosis of leiomyoma. Another case report by Nandedkar et al.5 described a rare presentation of leiomyoma in the maxillary sinus in a 24-year-old male. The patient presented with nasal obstruction and was found to have a mass in the maxillary sinus on imaging. Endoscopic sinus surgery was performed, and the tumor was completely excised. Histopathological examination confirmed the diagnosis of leiomyoma. These case reports and studies collectively highlight the variable clinical presentations, radiological features, and successful management strategies for the leiomyoma of the maxillary sinus. Due to the rarity of this condition, a high index of suspicion is required for accurate diagnosis, and surgical excision is the mainstay of treatment. Further research and case studies are needed to expand our knowledge and improve patient outcomes in this rare entity.3,5 The mainstay of treatment for leiomyoma of the maxillary sinus is surgical excision. The approach can vary depending on the size and location of the tumor. Endoscopic sinus surgery (ESS) is often employed as a minimally invasive technique for complete resection.2,3 In certain cases, an open surgical approach may be required for more extensive tumors. Surgery aims to achieve complete excision while preserving the surrounding structures and achieving symptomatic relief. Leiomyoma of the maxillary sinus has a favorable prognosis due to its benign nature. Complete surgical excision usually leads to the resolution of symptoms and low recurrence rates. Long-term follow-up is important to monitor for any recurrence or complications.1,2 It is important to note that the literature on leiomyoma of the maxillary sinus is limited to case reports and small studies due to its rarity. Further research and larger studies are needed to gather more data on this condition's clinical characteristics, optimal treatment approaches, and long-term outcomes. Postoperative care typically involves nasal irrigation, pain management, and antibiotics. Regular follow-up visits are essential to monitor the patient's recovery, assess for any signs of recurrence, and manage any postoperative complications.2,4 The prognosis of leiomyoma of the maxillary sinus is generally favorable. Since leiomyomas are benign tumors, they do not have the potential to metastasize or invade adjacent structures. With complete surgical excision, most patients experience symptom resolution and have low recurrence rates.4,5 In conclusion, leiomyoma of the maxillary sinus is a rare entity that requires consideration in the differential diagnosis of maxillary sinus masses. Despite the diagnostic challenges, accurate evaluation through clinical assessment, imaging studies, and histopathological examination is crucial for appropriate management. Surgical excision remains the primary treatment modality, with a favorable prognosis and low recurrence rates. Figure 1 refers to a 45-year-old female patient who presented to the otolaryngology clinic complaining of progressive nasal obstruction and intermittent dull facial pain on the right side. She reported that her symptoms had been gradually worsening over the past six months. There were no associated symptoms such as epistaxis, nasal discharge, or changes in smell. The patient had no significant medical history and did not report any history of previous sinus infections or allergies. She had no history of smoking or exposure to environmental toxins. On physical examination, tenderness was on palpation over the right maxillary sinus area. The nasal passages appeared patent, with no visible polyps or signs of inflammation. The rest of the head and neck examination, including the oral cavity, was unremarkable. A flexible nasal endoscopy revealed a bulging mass in the right middle meatus obstructing the ostium of the maxillary sinus. The rest of the nasal cavity and other sinus ostia appeared normal. A computed tomography (CT) scan of the paranasal sinuses was obtained, which demonstrated a well-defined, non-enhancing soft tissue mass filling the right maxillary sinus. There were no signs of erosion into surrounding structures or evidence of distant metastasis. Figure 1A – Gross photomicrograph shows a greyish white to tan-white well circumscribed but nonencapsulated tumor. The cut surface shows firm, whorled surface areas with hemorrhage (scale bar= 5 cm); B – shows a tumor composed of interlacing fascicles of smooth muscle bundles (H&E, 40X); C – Immunohistochemical reaction for smooth muscle actin (SMA) demonstrating smooth muscle bundles and vessel walls (100X); D – Immunohistochemical reaction for Desmin shows diffuse cytoplasmic positivity (100X).: Based on the clinical presentation and imaging findings, a provisional diagnosis of leiomyoma of the maxillary sinus was made. The patient was counseled about the benign nature of the tumor and the recommended treatment options. The patient underwent endoscopic sinus surgery (ESS) for complete excision of the leiomyoma. During the procedure, the tumor was identified and carefully dissected from the surrounding sinus mucosa. Hemostasis was achieved, and the surgical site was thoroughly irrigated. Histopathological examination of the excised specimen confirmed the diagnosis of leiomyoma, showing spindle-shaped cells with cigar-shaped nuclei arranged in fascicles. No malignant features or atypical mitotic figures were observed. The patient had an uneventful postoperative recovery with the resolution of her symptoms. She was followed up regularly to monitor for any signs of recurrence or complications. During the follow-up visits, the patient remained asymptomatic, with no signs of tumor recurrence or associated complications

DNA or Protein Methylation-Dependent Regulation of Activator Protein-1 Function

Epigenetic regulation and modification govern the transcriptional mechanisms that promote disease initiation and progression, but can also control the oncogenic processes, cell signaling networks, immunogenicity, and immune cells involved in anti-inflammatory and anti-tumor responses. The study of epigenetic mechanisms could have important implications for the development of potential anti-inflammatory treatments and anti-cancer immunotherapies. In this review, we have described the key role of epigenetic progression: DNA methylation, histone methylation or modification, and protein methylation, with an emphasis on the activator protein-1 (AP-1) signaling pathway. Transcription factor AP-1 regulates multiple genes and is involved in diverse cellular processes, including survival, differentiation, apoptosis, and development. Here, the AP-1 regulatory mechanism by DNA, histone, or protein methylation was also reviewed. Various methyltransferases activate or suppress AP-1 activities in diverse ways. We summarize the current studies on epigenetic alterations, which regulate AP-1 signaling during inflammation, cancer, and autoimmune diseases, and discuss the epigenetic mechanisms involved in the regulation of AP-1 signaling

STAT3 Differentially Regulates TLR4-Mediated Inflammatory Responses in Early or Late Phases

Toll-like receptor 4 (TLR4) signaling is an important therapeutic target to manage lipopolysaccharide (LPS)-induced inflammation. The transcription factor signal transducer and activator of transcription 3 (STAT3) has been identified as an important regulator of various immune-related diseases and has generated interest as a therapeutic target. Here, we investigated the time-dependent roles of STAT3 in LPS-stimulated RAW264.7 macrophages. STAT3 inhibition induced expression of the pro-inflammatory genes iNOS and COX-2 at early time points. STAT3 depletion resulted in regulation of nuclear translocation of nuclear factor (NF)-κB subunits p50 and p65 and IκBα/Akt/PI3K signaling. Moreover, we found that one Src family kinase, Lyn kinase, was phosphorylated in STAT3 knockout macrophages. In addition to using pharmacological inhibition of NF-κB, we found out that STAT3KO activation of NF-κB subunit p50 and p65 and expression of iNOS was significantly inhibited; furthermore, Akt tyrosine kinase inhibitors also inhibited iNOS and COX-2 gene expression during early time points of LPS stimulation, demonstrating an NF-κB- Akt-dependent mechanism. On the other hand, iNOS expression was downregulated after prolonged treatment with LPS. Activation of NF-κB signaling was also suppressed, and consequently, nitric oxide (NO) production and cell invasion were repressed. Overall, our data indicate that STAT3 differentially regulates early- and late-phase TLR4-mediated inflammatory responses

Parallel FPGA Routers With Lagrange Relaxation

Routing of the nets in Field Programmable Gate Array (FPGA) design flow is one of the most time consuming steps. Although Versatile Place and Route (VPR), which is a commonly used algorithm for this purpose, routes effectively, it is slow in execution. One way to accelerate this design flow is to use parallelization. Since VPR is intrinsically sequential, a set of parallel algorithms have been recently proposed for this purpose (ParaLaR and ParaLarPD). These algorithms formulate the routing process as a Linear Program (LP) and solve it using the Lagrange relaxation, an adapted sub-gradient method, and a Steiner tree algorithm. When tested on the MCNC benchmark circuits, using underlying VPR 7.0 for packing and placement, ParaLaR and ParaLarPD both outperformed VPR 7.0 for routing, with ParaLarPD being better. We have three main contributions here. Recently, in 2020, a new variant of VPR, i.e. VPR 8.0, has been proposed. Hence, first, we make ParaLarPD compatible for testing on MCNC benchmark circuits using VPR 8.0. Second, we adapt ParaLarPD for the larger benchmark circuits than MCNC, i.e., VTR, using both VPR 7.0 and VPR 8.0, and perform thorough evaluation. Finally, and third, we improve ParaLarPD further. We design a family of Lagrange heuristics that better the Lagrange relaxation process of ParaLarPD. We term our new algorithm ParaLarH and test it on both the benchmark circuits (MCNC and VTR) and using both the VPRs (VPR 7.0 and VPR 8.0). When tested on MCNC and VTR benchmark circuits, VPR (VPR 7.0 and VPR 8.0) is outperformed by both ParaLarH and ParaLarPD, with average gains given below. The minimum channel width improvements are 22% and 12%, respectively. The total wire length improvements for both are 45%. Finally, the average critical path delay improvements for both are almost the same (37% and 35%, respectively)

ParaLarPD: Parallel FPGA Router Using Primal-Dual Sub-Gradient Method

In the field programmable gate array (FPGA) design flow, one of the most time-consuming steps is the routing of nets. Therefore, there is a need to accelerate it. In a recent work by Hoo et al., the authors have developed a linear programming (LP)-based framework that parallelizes this routing process to achieve significant speed-ups (the resulting algorithm is termed as ParaLaR). However, this approach has certain weaknesses. Namely, the constraints violation by the solution and a standard routing metric could be improved. We address these two issues here. In this paper, we use the LP framework of ParaLaR and solve it using the primal–dual sub-gradient method that better exploits the problem properties. We also propose a better way to update the size of the step taken by this iterative algorithm. We call our algorithm as ParaLarPD. We perform experiments on a set of standard benchmarks, where we show that our algorithm outperforms not just ParaLaR but the standard existing algorithm VPR as well. We perform experiments with two different configurations. We achieve 20 % average improvement in the constraints violation and the standard metric of the minimum channel width (both of which are related) when compared with ParaLaR. When compared to VPR, we get average improvements of 28 % in the minimum channel width (there is no constraints violation in VPR). We obtain the same value for the total wire length as by ParaLaR, which is 49 % better on an average than that obtained by VPR. This is the original metric to be minimized, for which ParaLaR was proposed. Next, we look at the third and easily measurable metric of critical path delay. On an average, ParaLarPD gives 2 % larger critical path delay than ParaLaR and 3 % better than VPR. We achieve maximum relative speed-ups of up to seven times when running a parallel version of our algorithm using eight threads as compared to the sequential implementation. These speed-ups are similar to those as obtained by ParaLaR

Radiation-induced in vitro mutagenesis system for salt tolerance and other agronomic characters in sugarcane (Saccharum officinarum L.)

Gamma ray-induced in vitro mutagenesis and selection for salt (NaCl) tolerance were investigated in sugarcane (Saccharum officinarum L.). Embryogenic callus cultures were irradiated (10 to 80 Gy) and subjected to in vitro selection by exposure of irradiated callus to NaCl (0, 50, 100, 150, 200, and 250 mmol L− 1). Increasing NaCl concentrations resulted in growth reduction and increased membrane damage. Salt-selected callus lines were characterized by the accumulation of proline, glycine betaine, and Na+ and K+ concentration. Higher accumulation of proline and glycine betaine was observed in NaCl stressed callus irradiated at 20 Gy. Na+ concentration increased and K+ concentration decreased with increasing salt level. Irradiated callus showed 50–60% regeneration under NaCl stress, and in vitro-regenerated plants were acclimatized in the greenhouse, with 80–85% survival. A total of 138 irradiated and salt-selected selections were grown to maturity and their agronomic performance was evaluated under normal and saline conditions. Of these, 18 mutant clones were characterized for different agro-morphological characters and some of the mutant clones exhibited improved sugar yield with increased Brix%, number of millable canes, and yield. The result suggest that radiation-induced mutagenesis offers an effective way to enhance genetic variation in sugarcane