Search results for: systemic inflammatory response syndrome

Authors: Alireza Monzavi Chaleshtari, Mahnaz Aliakbari Dehkordi, Mina Gholampour, Majid Saffarinia, Tayebeh Mohtashami, Amin Asadi Hieh

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The study aimed to assess the impact of positive psychology education on the social well-being of high school girls experiencing premenstrual syndrome (PMS). The statistical population comprised high school girls with PMS, with 30 randomly selected participants divided into two groups: 15 in the experimental group and 15 in the control group. The research employed a pre-test and post-test design using a standard questionnaire to evaluate premenstrual syndrome symptoms over a 7-day period before menstruation to a maximum of 2 days after menstruation, along with the Social Keys welfare questionnaire. During the study, the experimental group underwent an 8-session positive psychology group program. Data analysis was conducted using analysis of covariance. The results indicated a significant positive effect of positive psychology training on enhancing the social well-being of girls (p < 0.05). In conclusion, the findings suggest that positive psychology interventions can effectively increase social well-being among high school girls experiencing premenstrual syndrome.

Keywords: positive psychology, premenstrual syndrome, social welfare, girls

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Authors: Hakim Chayeb

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Macrophages (Mo) play an essential role in host defense against pathogens. These inflammatory cells contain a large group of inducible enzymes such as NO synthase (NOS). This study was conducted to characterize experimentally induced inflammation in vivo by lipopolysaccharides (LPS). LPS is an essential component of the outer membrane of Gram-negative bacteria and a potent inducer of macrophage. Except control rats, all rats received different doses of LPS intra-peritoneally. The involvement of inducible NO synthase (iNOS) and constitutive (cNOS ) in the modulation of the inflammatory response was studied by treating the rats with L-NAME (non-selective NOS inhibitor) or aminoguanidine (AG inhibitor of iNOS). Inhibitors were injected 24 hours before LPS administration. The results showed that esterase activity (a marker of macrophage infiltration) which is induced by LPS is reduced by AG, was potentiated by treatment with L-NAME in tissue homogenates of the liver, kidney and spleen. Meanwhile, the concentrations of nitric oxide (NO) induced by LPS were reduced with AG and are completely inhibited with L-NAME in the tissues studied. NO concentrations and plasma transaminase levels have undergone remarkable increases in rats treated with LPS alone. However, the AG significantly reduced these rates. Our results highlighted the role of NO synthase inhibitors in reducing of inflammatory responses that characterize many infectious diseases.

Keywords: aminoguanidine, esterase, LPS, L-NAME, macrophage, nitric oxide

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Authors: Uzma Saqib, Mirza S. Baig

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Myeloid differentiation primary response protein 88 (MYD88) has long been considered a central player in the inflammatory pathway. Recent studies clearly suggest that it is an important therapeutic target in inflammation. On the other hand, a recent study on the interaction between the orphan nuclear receptor (Nur77) and p38α, leading to increased lipopolysaccharide-induced hyperinflammatory response, suggests this binary complex as a therapeutic target. In this study, we have designed inhibitors that can inhibit both MYD88 and Nur77 at the same time. Since both MYD88 and Nur77 are an integral part of the pathways involving lipopolysaccharide-induced activation of NF-κB-mediated inflammation, we tried to target both proteins with the same library in order to retrieve compounds having dual inhibitory properties. To perform this, we developed a homodimeric model of MYD88 and, along with the crystal structure of Nur77, screened a virtual library of compounds from the traditional Chinese medicine database containing ~61,000 compounds. We analyzed the resulting hits for their efficacy for dual binding and probed them for developing a common pharmacophore model that could be used as a prototype to screen compound libraries as well as to guide combinatorial library design to search for ideal dual-target inhibitors. Thus, our study explores the identification of novel leads having dual inhibiting effects due to binding to both MYD88 and Nur77 targets.

Keywords: drug design, Nur77, MYD88, inflammation

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Authors: Sani Ismaila, Shafiu Yau, Abubakar Salisu, Buhari Salisu, Sharifat Balogun, Mustapha Abubakar, Biobaku Khalid, Agaie Bello

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Over the years, Japanese quail egg has been in use in the management of diseases. The objective of this study was to evaluate the analgesic, anti-inflammatory and gastroprotective effects of raw Quail egg (yolk + albumin) in rats. Pain was assessed in rats by recording the latent period and writing reflex, anti-inflammatory effect was determined using both motility and compression test, while the gastro-protective effects were assessed by observing the histology of the stomach after diclofenac-induced gastric ulcers and subsequent treatment with the quail egg, Rats were randomly assigned into 4 groups; Groups I: were the control non-treated (NT), Group II were treated with Tramadol 50 mg/kg/Os (TMD) or Indomethacin (IND) 5mg/kg/Os (positive control for the writhing reflex determination), while group III and IV were treated with 3 and 6g/kg of raw quail egg respectively). Groups treated with quail egg in both doses showed a significant increase in the latent period (p <0 .05) when compared to the control NT, but lower than the group treated with tramadol at 20mins interval (p<0.05). Writing reflexes decrease in groups II, III, and IV compared to the NT group (p < 0.05). While motility increases significantly (p < 0.05) in groups II, compared to I (p<0.05). Control non-treated rats showed a quicker and extensive response to compression using the Vanier calliper on the inflamed paw compared to groups II-IV (p < 0.05). Histological studies of the stomach revealed sloughing of the epithelia, cellular infiltration with micro abscesses in the non-treated, while groups treated concurrently with quail egg showed proliferation of the glandular epithelia and goblet cells, and those treated 30 minutes before diclofenac administration showed proliferation of glands and thickening of the squamous epithelia. This study showed that quail egg has analgesic, anti-inflammatory and gastro-protective potentials and can be used as adjuvant treatment whenever COX-2 enzymes inhibitors are indicated.

Keywords: analgesia, anti-inflammatory, gastroprotective effect, japanese quail egg

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Authors: Adineh Tajmousavilangerudi, Ali Zein Alabiden Tlais, Raffaella Di Cagno

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The SARS-Cov-2 pandemic has exposed our vulnerability to new illnesses and novel viruses that attack our immune systems, particularly in the elderly. The vaccine is being gradually introduced over the world, but new strains of the virus and COVID-19 will emerge and continue to cause illness. Aging is associated with significant changes in intestinal physiology, which increases the production of inflammatory products, alters the gut microbiota, and consequently establish inadequate immune response to minimize symptoms and disease development. In this context, older people who followed a Mediterranean-style diet, rich in polyphenols and dietary fiber, performed better physically and mentally (1,2). This demonstrates the importance of the human gut microbiome in transforming complex dietary macromolecules into the most biologically available and active nutrients, which in turn help to regulate metabolism and both intestinal and systemic immune function (3,4). The role of lactic acid fermentation is prominent also as a powerful tool for improving the nutritional quality of the human diet by releasing nutrients and boosting the complex bioactive compounds and vitamin content. the PhD project aims to design fermented and functional foods/beverages capable of modulating human immune function via the gut microbiome.

Keywords: functional bevarage, fermented beverage, gut microbiota functionality, immun system

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Authors: Chandralekha Ashangari, Amer Suleman

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Background and Purpose: The Postural Orthostatic Tachycardia Syndrome (POTS) affects primarily young women. POTS is a form of dysautonomia that is estimated to impact between 1,000,000 and 3,000,000 Americans, and millions more around the world. POTS is a form of orthostatic intolerance that is associated with many Gastrointestinal disturbances. The aim of this study is to determine the Gastrointestinal disturbances in Postural Orthostatic Tachycardia Syndrome (POTS) patients.2. Methods: 249 patients referred to our clinic from January to November with POTS. Reviewed the medical records of 249 POTS patients and gastrointestinal symptoms. Results: however out of 249 patients, 226 patients are female (90.76%; average age 32.69), 23 patients are male (9.24%; average age 27.91) Data analysis: Out of 249 patients 189 patients (76%) had vomiting or nausea, 150 patients (60%) had irritable bowel syndrome, 128 patients (51%) had bloating, 125 patients (50%) had constipation , 80 patients (32%) had abdominal pain, 56 patients (22%) had delayed gastric emptying, 24 patients (10%) had lactose intolerance, 8 patients (3%) had Gastroesophageal reflux disease, 5 patients (2%) had Iron deficiency anemia, 6 patients (2%) had Peptic ulcer disease, 4 patients (2%) had Celiac Disease. Conclusion: Patients with POTS have a very high prevalence of gastrointestinal symptoms however the majority of abnormalities appear to be motility related. Motility testing should be performed be performed in POTS patients. The diagnostic yield of endoscopic procedures appears to be low.

Keywords: gastrointestinal disturbances, Postural Orthostatic Tachycardia Syndrome (POTS), celiac disease, POTS patients

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Authors: Sina Mahdavi

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Background and Objective: Multiple sclerosis (MS) is the most common inflammatory autoimmune disease of the central nervous system (CNS) that affects the myelination process in the CNS. Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially Epstein-Barr virus (EBV) and MS, is one potential cause that is not well understood. In this study, we aim to summarize the available data on EBV infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis," "Epstein-Barr virus," and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched, and 14 articles were chosen, studied, and analyzed. Results: Demyelinated lesions isolated from MS patients contain EBNAs from EBV proteins. The EBNA1 domain contains a pentapeptide fragment identical to B-crystallin, a heat shock peptide, that is increased in peripheral B cells in response to B-crystallin infection, resulting in myelin-directed autoimmunity mediated by proinflammatory T cells. EBNA2, which is involved in the regulation of viral transcription, may enhance transcription from MS risk loci. A 7-fold increase in the risk of MS has been observed in EBV infection with HLA-DR15 synergy. Conclusion: EBV infection along with a variety of specific genetic risk alleles, cause inflammatory cascades in the CNS by infected B cells. There is a high expression of EBV during the course of MS, which indicates the relationship between EBV and MS, that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of EBV may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, Epstein-Barr virus, central nervous system, EBNAs

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Authors: Neena Kanojia, R. K. Kanojia

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Background: Osteoarthritis OA of the knee is one of the leading causes of disability characterized by degeneration of hyaline cartilage combined with reparative processes. Its strong association with metabolic syndrome is postulated to be due to both mechanical and biochemical factors. Our study aims to study differential effect of metabolic risk factors on cartilage degeneration and regeneration at biomarker level. Design: After screening 281 patients presenting with knee pain, 41 patients who met the selection criteria were included and were divided into metabolic MetS OA and non-metabolic Non-MetS OA phenotypes using National Cholesterol Education Programme-Adult Treatment Panel-III NCEP ATP III criteria for metabolic syndrome. Serum Cartilage Oligomeric Matrix Protein COMP and Procollagen type IIA N terminal Propeptide PIIANP levels were used as tools to assess cartilage degeneration and regeneration, respectively. Results: 22 among 41 patients 53.66% had metabolic syndrome. Covariates like age, gender, Kellgren Lawrence KL grades were comparable in both groups. MetS OA group showed significant increase in serum COMP levels (p 0.03 with no significant effect on serum PIIANP levels (p 0.46. Hypertriglyceridemia showed independent association with both cartilage anabolism (p 0.03 and catabolism (p 0.03. Conclusion: Metabolic syndrome, though has no effect on cartilage regeneration tends to shift cartilage homeostasis towards degeneration with hypertriglyceridemia showing significant independent effect on cartilage metabolism.

Keywords: metabolic, syndrome, cartilage, degernation

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Authors: Anna Amato

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Every child needs communication. If spoken language is not or not fully available due to congenital or acquired limitations, those affected need appropriate ways. These can be found in many possibilities of Augmentative and Alternative Communications (AAC). In the communication promotion of severely impaired children, who can use their own body communication forms only to a limited extent for the differentiated understanding, computers with eye control play an essential role. It takes some time to understand the individual forms of communication of the child. Children who depend on the AAC need competent support to learn to communicate in a motivated way in their everyday life. The aim of the present parents' survey (n = 4), which was evaluated descriptively, is to demonstrate the development of communicative abilities as well as the motivation to use complex communication aids with eye control by patients with atypical Rett Syndrome. An increase in communication skills, well-being, self-reliance, and self-esteem, an improvement in social participation, as well as a reduction in anger and screaming events, were noted. The complex visual communication tools were available daily for 3 out of 4 patients with atypical Rett Syndrome. It raises research questions regarding speech understanding and the ability to drive eye control technology in a larger group of atypical Rett Syndrome patients.

Keywords: augmentative and alternative communications, AAC, atypical Rett-syndrome, children, development

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Authors: Alireza Hassanshahi, Xanthe Strudwick, Zlatko Kopecki, Allison J Cowin

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Studies have shown that Flightless (Flii) is elevated in human wounds, including burns, and reducing the level of Flii is a promising approach for improving wound repair and reducing scar formation. The most effective approach has been to neutralise Flii activity using localized, intradermal application of function blocking monoclonal antibodies. However, large surface area burns are difficult to treat by intradermal injection of therapeutics, so the aim of this study was to investigate if a systemic injection of a monoclonal antibody against Flii could improve healing in mice following burn injury. Flii neutralizing antibodies (FnAbs) were labelled with Alxa-Fluor-680 for biodistribution studies and the healing effects of systemically administered FnAbs to mice with burn injuries. A partial thickness, 7% (70mm2) total body surface area scald burn injury was created on the dorsal surface of mice (n=10/group), and 100µL of Alexa-Flour-680-labeled FnAbs were injected into the intraperitoneal cavity (IP) at time of injury. The burns were imaged on days 0, 1, 2, 3, 4, and 7 using IVIS Lumina S5 Imaging System, and healing was assessed macroscopically, histologically, and using immunohistochemistry. Fluorescent radiance efficiency measurements showed that IP injected Alexa-Fluor-680-FnAbs localized at the site of burn injury from day 1, remaining there for the whole 7-day study. The burns treated with FnAbs showed a reduction in macroscopic wound area and an increased rate of epithelialization compared to controls. Immunohistochemistry for NIMP-R14 showed a reduction in the inflammatory infiltrate, while CD31/VEGF staining showed improved angiogenesis post-systemic FnAb treatment. These results suggest that systemically administered FnAbs are active within the burn site and can improve healing outcomes. The clinical application of systemically injected Flii monoclonal antibodies could therefore be a potential approach for promoting the healing of large surface area burns immediately after injury.

Keywords: biodistribution, burn, flightless, systemic, fnAbs

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Authors: Akhmadjon Sultanov, Eun-Ho Lee, Hye-Jin Park, Young-Je Cho

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This study tested the anti-inflammatory effect of wild indigo (Baptisia tinctoria) root in Raw 264.7 cells. We prepared two extracts of B. tinctoria; one in water and the other in 50% ethanol. Then we evaluated the toxicities of the B. tinctoria root extracts at 10 to 100 mg mL-1 concentrations in raw 264.7 cells and observed 80% cell viability. The anti-inflammatory effect of B. tinctoria root extract in lipopolysaccharide (LPS)-stimulated Raw 264.7 cells were observed with concentrations at 10, 30, and 50 μg mL-1. The results showed that 77.27-66.82% of nitric oxide (NO) production was inhibited by 50 μg mL-1 B. tinctoria root extract. The protein expression of Inducible NO synthase (iNOS) expression dramatically decreased by 93.14% and 52.65% in raw 264.7 cells treated with water and ethanol extracts of B. tinctoria root, respectively. Moreover, cyclooxygenase-2 (COX-2) protein expression decreased by 42.85% and 69.70% in raw 264.7 cells treated with water and ethanol extracts of B. tinctoria root, respectively. Furthermore, the mRNA expression of pro-inflammatory markers, such as tumor necrosis factor-alpha, interleukin-1β, interleukin-6, monocyte chemoattractant protein-1, and prostaglandin E synthase 2, was significantly suppressed in a concentration-dependent manner. Additionally, the B. tinctoria root extracts effectively inhibited enzymes involved in physiological activities. The B. tinctoria root extracts showed excellent anti-inflammatory effects and can be used as a functional material for biological activities.

Keywords: cytokine, macrophage, pro-inflammatory, protein expression, real-time PCR

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Authors: Taurino S. R. Neto, Epitácio D. S. Neto, Flávio Signorelli, Gustavo G. M. Balbi, Alex H. Higashi, Mário Luiz R. Monteiro, Eloisa Bonfá, Danieli C. O. Andrade, Leandro C. Zacharias

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Purpose: To perform a multimodal evaluation, including the use of Optical Coherence Angiotomography (OCTA), in patients with primary antiphospholipid syndrome (PAPS) without ocular complaints and to compare them with healthy individuals. Methods: A complete structural and functional ophthalmological evaluation using OCTA and microperimetry (MP) exam in patients with PAPS, followed at a tertiary rheumatology outpatient clinic, was performed. All ophthalmologic manifestations were recorded and then statistical analysis was performed for comparative purposes; p <0.05 was considered statistically significant. Results: 104 eyes of 52 subjects (26 patients with PAPS without ocular complaints and 26 healthy individuals) were included. Among PAPS patients, 21 were female (80.8%) and 21 (80.8%) were Caucasians. Thrombotic PAPS was the main clinical criteria manifestation (100%); 65.4% had venous and 34.6% had arterial thrombosis. Obstetrical criteria were present in 34.6% of all thrombotic PAPS patients. Lupus anticoagulant was present in all patients. 19.2% of PAPS patients presented ophthalmologic findings against none of the healthy individuals. The most common retinal change was paracentral acute middle maculopathy (PAMM) (3 patients, 5 eyes), followed by drusen-like deposits (1 patient, 2 eyes) and pachychoroid pigment epitheliopathy (1 patient, 1 eye). Systemic hypertension and hyperlipidaemia were present in 100% of the PAPS patients with PAMM, while only six patients (26.1%) with PAPS without PAMM presented these two risk factors together. In the quantitative OCTA evaluation, we found significant differences between PAPS patients and controls in both the superficial vascular complex (SVC) and deep vascular complex (DVC) in the high-speed protocol, as well as in the SVC in the high-resolution protocol. In the analysis of the foveal avascular zone (FAZ) parameters, the PAPS group had a larger area of FAZ in the DVC using the high-speed method compared to the control group (p=0.047). In the quantitative analysis of the MP, the PAPS group had lower central (p=0.041) and global (p<0.001) retinal sensitivity compared to the control group, as well as in the sector analysis, with the exception of the inferior sector. In the quantitative evaluation of fixation stability, there was a trend towards worse stability in the PAPS subgroup with PAMM in both studied methods. Conclusions: PAMM was observed in 11.5% of PAPS patients with no previous ocular complaints. Systemic hypertension concomitant with hyperlipidemia was the most commonly associated risk factor for PAMM in patients with PAPS. PAPS patients present lower vascular density and retinal sensitivity compared to the control group, even in patients without PAMM.

Keywords: antiphospholipid syndrome, optical coherence angio tomography, optical coherence tomography, retina

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Authors: Vladyslav Povoroznyuk, Larysa Martynyuk, Iryna Syzonenko, Liliya Martynyuk

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Osteoporosis is one of the important problems in postmenopausal women due to an increased risk of sudden and unexpected fractures. This study is aimed to determine the connection between bone mineral density (BMD) and trabecular bone score (TBS) in Ukrainian women suffering from metabolic syndrome. Participating in the study, 566 menopausal women aged 50-79 year-old were examined and divided into two groups: Group A included 336 women with no obesity (BMI ≤ 29.9 kg/m²), and Group B – 230 women with metabolic syndrome (diagnosis according to IDF criteria, 2005). Dual-energy X-ray absorptiometry was used for measuring of lumbar spine (L1-L4), femoral neck, total body and forearm BMD and bone quality indexes (last according to Med-Imaps installation). Data were analyzed using Statistical Package 6.0. A significant increase of lumbar spine (L1-L4), femoral neck, total body and ultradistal radius BMD was found in women with metabolic syndrome compared to those without obesity (p < 0.001) both in their totality and in groups of 50-59 years, 60-69 years, and 70-79 years. TBS was significantly higher in non-obese women compared to metabolic syndrome patients of 50-59 years and in the general sample (p < 0.05). Analysis showed significant positive correlation between body mass index (BMI) and BMD at all levels. Significant negative correlation between BMI and TBS (L1-L4) was established. Despite the fact that BMD indexes were significantly higher in women with metabolic syndrome, the frequency of vertebral and non-vertebral fractures did not differ significantly in the groups of patients.

Keywords: bone mineral density, trabecular bone score, metabolic syndrome, fracture

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Authors: Darma Putra Sitepu, Dewi Larasati, Yohanes Wolter Hendrik George

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Sepsis is a life-threatening medical emergency frequently observed in intensive care unit (ICU). Surviving Sepsis Campaign in 2018 has recommended the administration of early vasopressor in the first hour of sepsis or septic shock but has not yet included de-resuscitation protocol. De-resuscitation in acute management of septic shock is where patient received active removal of accumulated fluid. It has been proposed by some studies and ongoing clinical trials. Here we present a case with early vasopressor and de-resuscitation. Male, 27 years old presenting to the emergency room with shortness of breath, altered mental status, and widespread blisters on his body and lips started a few hours prior, after receiving non-steroidal anti-inflammatory drug through intravenous injection. Patient was hypotensive, tachycardic, and tachypneic at admission, diagnosed with Steven Johnson Syndrome with Septic Shock. Patient received fluid resuscitation, early vasopressor, and diuresis agent aimed to actively remove fluid after the initial phase of resuscitation. Patient was admitted to ICU and progressively recovering. At day-10, patient was stabilized and was transferred to general ward. Early vasopressor and de-resuscitation are beneficial for the patient.

Keywords: sepsis, shock, de-resuscitation, vasopressor, fluid, case report

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Authors: Mengnan Sun

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It is unclear about the association between air pollution and Tourette Syndrome (TS), although people have suspected that air pollution might trigger TS. TS is a type of neural system disease usually found among children. The number of TS patients has significantly increased in recent decades, suggesting an importance and urgency to examine the possible triggers or conditions that are associated with TS. In this study, the correlation between air pollution and three allergic diseases---asthma, allergic conjunctivitis (AC), and allergic rhinitis (AR)---is examined. Then, a correlation between these allergic diseases and TS is proved. In this way, this study establishes a positive correlation between air pollution and TS. Measures the public can take to help TS patients are also analyzed at the end of this article. The article hopes to raise people’s awareness to reduce air pollution for the good of TS patients or people with other disorders that are associated with air pollution.

Keywords: air pollution, allergic diseases, climate change, Tourette Syndrome

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Authors: Janneth Gonzalez, Andres Pinzon Velasco, Maria Angarita, Nicolas Mendoza

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Astrocytes play an important role in various processes in the brain, including pathological conditions such as neurodegenerative diseases. Recent studies have shown that the increase in saturated fatty acids such as palmitic acid (PA) triggers pro-inflammatory pathways in the brain. The use of synthetic neurosteroids such as tibolone has demonstrated neuro-protective mechanisms. However, there are few studies on the neuro-protective mechanisms of tibolone, especially at the systemic (omic) level. In this study, we performed the integration of multi-omic data (transcriptome and proteome) into a human astrocyte genomic scale metabolic model to study the astrocytic response during palmitate treatment. We evaluated metabolic fluxes in three scenarios (healthy, induced inflammation by PA, and tibolone treatment under PA inflammation). We also use control theory to identify those reactions that control the astrocytic system. Our results suggest that PA generates a modulation of central and secondary metabolism, showing a change in energy source use through inhibition of folate cycle and fatty acid β-oxidation and upregulation of ketone bodies formation.We found 25 metabolic switches under PA-mediated cellular regulation, 9 of which were critical only in the inflammatory scenario but not in the protective tibolone one. Within these reactions, inhibitory, total, and directional coupling profiles were key findings, playing a fundamental role in the (de)regulation in metabolic pathways that increase neurotoxicity and represent potential treatment targets. Finally, this study framework facilitates the understanding of metabolic regulation strategies, andit can be used for in silico exploring the mechanisms of astrocytic cell regulation, directing a more complex future experimental work in neurodegenerative diseases.

Keywords: astrocytes, data integration, palmitic acid, computational model, multi-omics, control theory

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Authors: Parinaz Tavakoli Zaniani, Dimitrios Balomenos

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Mitochondrial reactive oxygen species (mROS) play a crucial role in macrophage pro-inflammatory activation, although a detailed understanding of the mechanism and kinetics by which mROS drive signaling molecules is still lacking. In general, it is thought that NF-κB activation drives mROS and general ROS production. Here, We performed a detailed kinetic analysis of mROS production during macrophage activation. We found early mROS generation after LPS (lipopolysaccharide) stimulation. Remarkably as early as 5 minutes, mROS signaling promoted initial NF-κB, MAPK activation and pro-inflammatory cytokine production, as established through inhibition or quenching of mROS. On the contrary, NF-κB inhibition had no effect on mROS production. Our findings point to a mechanism by which mROS increase TRAF-6 ubiquitination and, thus NF-κB activity. mROS inhibition reduced LPS-induced lethality in an in vivo septic shock model by controlling pro-inflammatory cytokine production. Overall, our research provides novel insights into the role of mROS as a primary messenger in the pathway of macrophage and as a regulator of inflammatory responses. We found that early mROS production promotes initial NF-κB, and MAPK activation by regulating TRAF-6 ubiquitination and that mROS inhibition can reduce LPS-induced inflammatory cytokines and lethality in a septic shock model. These findings might lead to novel immunotherapeutic strategies targeting early mROS production and control of extreme inflammation in the context of sepsis and other inflammatory diseases.

Keywords: mitochondria, reactive oxygen species, nuclear factor κB, lipopolysaccharide, macrophages

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Authors: Mariam G. Eshak, Ahmed Abbas, M. I. El-Sabry, M. M. Mashaly

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This investigation was conducted to determine the physiological response and evaluate the expression of inflammatory and cell death genes and DNA damage induced by endotoxic shock in laying hens. Endotoxic shock was induced by a single intravenous injection of 107 Escherichia coli (E. coli,) colony/hen. In the present study, 240 forty-week-old laying hens (H&N) were randomly assigned into 2 groups with 3 replicates of 40 birds each. Hens were reared in battery cages with wire floors in an open-sided housing system under natural conditions. Housing and general management practices were similar for all groups. At 42-wk of age, 45 hens from the first group (15 replicate) were infected with E. coli, while the same number of hens from the second group was injected with saline and served as a control. Heat shock protein-70 (HSP-70) expression, plasma corticosterone concentration, body temperature, and the gene expression of bax, caspase-3 activity, P38, Interlukin-1β (Il-1β), and tumor necrosis factor alpha (TNF-α) genes and DNA damage in the brain and liver were measured. Hens treated with E. coli showed significant (P≤0.05) increase of body temperature by 1.2 ᴼC and plasma corticosterone by 3 folds compared to the controls. Further, hens injected with E.Coli showed markedly over-expression of HSP-70 and increase DNA damage in brain and liver. These results were synchronized with activating cell death program since our data showed significant (P≤0.05) high expression of bax and caspase-3 activity genes in the brain and liver. These results were related to remarkable over-inflammation gene expression of P38, IL-1β, and TNF-α in brain and liver. In conclusion, our results indicate that endotoxic shock induces inflammatory physiological response and triggers cell death program by promoting P38, IL-1β, and TNF-α gene expression in the brain and liver.

Keywords: chicken, DNA damage, Escherichia coli, gene expression, inflammation

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Authors: Anca Dinischiotu, Sorina Nicoleta Voicu

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Silica nanoparticles (SiO2-NPs) are widely used in consumer products such as paints, plastics, insulation materials, tires, concrete production, as well as in gene delivery systems and imaging procedures. Environmental human exposure to them occurs during utilization of these products, in a time-dependent manner, the uptake being by topic and inhalation route especially. SiO2-NPs enter cells and induce membrane damage, oxidative stress and inflammatory reactions in a concentration-dependent manner. In this study, MRC-5 cells (human fetal lung fibroblasts) were exposed to amorphous SiO2-NPs at a dose of 62.5 μg/ml for 24, 48 and 72 hours. The size distribution of NPs was a lognormal function, in the range 3-14 nm. A time-dependent decrease of total reduced glutathione concentration by 36%, 50%, and 78% and an increase of NO level by 62%, 32%, respectively 24% compared to control were noticed. An up-regulation of NF-kB expression by 20%, 50% respectively 10% and of Nrf-2 by 139%, 58%, and 16% compared to control after 24, 48 and 72 hours was noticed also. The expression of IL-1β, IL-6, IL-8, and COX-2 was up-regulated in a time-dependent manner. Also, the expression of MMP-2 and MMP-9 were down-regulated after 48 and 72 hours, whereas their activities raised in a time-dependent manner. Exposure of cells to NPs up-regulated the expression of inducible NO synthase, as previously was shown, and probably this is the reason for the increased level of NO, that can react with the thiol groups of reduced glutathione molecules, diminishing its concentration Nrf2 is a transcription factor translocated in nucleus, under oxidative stress, where downstream gene expression activates in order to modulate the adaptive intracellular response against oxidative stress. The cross-talk between Nrf2 and NF-kB activities regulates the inflammatory processes. The activation of NF-kB could activate up-regulation of IL-1β, IL-6, and IL-8. The increase of COX-2 expression could be correlated with IL-1β one. Also, probably in response to the pro-inflammatory cytokines, MMP-2 and MMP-9 were induced and activated. In conclusion, the exposure of MRC-5 cells to SiO2-NPs generated inflammation in a time-dependent manner.

Keywords: inflammation, MRC-5 cells, oxidative stress, silica nanoparticles

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Authors: Nashi Khan, Amina Khalid

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Aim: The purpose of this research was to find the psychiatric morbidity and level of sexual satisfaction among women with polycystic ovarian syndrome and their comparison with women with general medical conditions and to examine the correlation between psychiatric morbidity and sexual satisfaction among these women. Design: Cross sectional research design was used. Method: A total of 176 (M age = 30, SD = 5.83) women were recruited from both private and public sector hospitals in Pakistan. About 88 (50%) of the participants were diagnosed with polycystic ovarian syndrome (cases), whereas other 50% belonged to control group. Data were collected using semi structured interview. Sexual satisfaction scale for women (SSS-W) was administered to measure sexual satisfaction level and psychiatric morbidity was assessed by Symptom Checklist-Revised. Results: Results showed that participant’s depression and anxiety level had significant negative correlation with their sexual satisfaction level, whereas, anxiety and depression shared a significant positive correlation. There was a significant difference in the scores for sexual satisfaction, depression and anxiety for both cases and controls. These results suggested that women suffering from polycystic ovarian syndrome tend to be less sexually satisfied and experienced relatively more symptoms of depression and anxiety as compared to controls.

Keywords: level of sexual satisfaction, psychiatric morbidity, polycystic ovarian syndrome

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Authors: C. V. Pietreanu, S. E. Zaharia, C. Dinu

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The present research is built on three major pillars, commencing by making some considerations on accident investigation methods and pointing out both defining aspects and differences between linear and non-linear analysis. The traditional linear focus on accident analysis describes accidents as a sequence of events, while the latest systemic models outline interdependencies between different factors and define the processes evolution related to a specific (normal) situation. Linear and non-linear accident analysis methods have specific limitations, so the second point of interest is mirrored by the aim to discover the drawbacks of systemic models which becomes a starting point for developing new directions to identify risks or data closer to the cause of incidents/accidents. Since communication represents a critical issue in the interaction of human factor and has been proved to be the answer of the problems made by possible breakdowns in different communication procedures, from this focus point, on the third pylon a new error-modeling instrument suitable for risk assessment/accident analysis will be elaborated.

Keywords: accident analysis, multi-factorial error modeling, risk, systemic methods

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Authors: Nurvita Wijayanti

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The movie titled The King’s Speech is based on a true story telling an English king suffers from stuttering and how he gets the treatment from the therapist, so that he can reduce the high frequency on stuttering. The treatment uses the unique approach implying the linguistic principles. This study shows how the language works significantly in order to treat the stuttering sufferer using psychological approach. Therefore, the linguistic study is done to analyze the treatment activity. Halliday’s Systemic Functional Grammar is used as the main approach in this study along with qualitative descriptive method. The study finds that the therapist though using the orthodox approach applies the psycholinguistic method to overcome the king’s stuttering.

Keywords: psycholinguistics, stuttering, systemic functional grammar, treatment

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Authors: Seyedahmad Hosseini, Mohammadjavad Sotoudeheian

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Introduction: Allergic asthma is a heterogeneous immuno-inflammatory disease based on Th-2-mediated inflammation. Histopathologic abnormalities of the airways characteristic of asthma include epithelial damage and subepithelial collagen deposition. Objectives: Human bronchial epithelial cell genome expression of TNF‑α, IL‑6, ICAM‑1, VCAM‑1, nuclear factor (NF)‑κB signaling pathways up-regulate during inflammatory cascades. Moreover, immunofluorescence assays confirmed the nuclear translocation of NF‑κB p65 during inflammatory responses. An absolute LDH leakage assays suggestedLPS-inducedcells injury, and the associated mechanisms are co-incident events. LPS-induced phosphorylation of ERKand JNK causes inflammation in epithelial cells through inhibition of ERK and JNK activation and NF-κB signaling pathway. Furthermore, the inhibition of NF-κB mRNA expression and the nuclear translocation of NF-κB lead to anti-inflammatory events. Likewise, activation of SUMF2 which inhibits IL-13 and reduces Th2-cytokines, NF-κB, and IgE levels to ameliorate asthma. On the other hand, TNFα-induced mucus production reduced NF-κB activation through inhibition of the activation status of Rac1 and IκBα phosphorylation. In addition, bradykinin B2 receptor (B2R), which mediates airway remodeling, regulates through NF-κB. Bronchial B2R expression is constitutively elevated in allergic asthma. In addition, certain NF-κB -dependent chemokines function to recruit eosinophils in the airway. Besides, bromodomain containing 4 (BRD4) plays a significant role in mediating innate immune response in human small airway epithelial cells as well as transglutaminase 2 (TG2), which is detectable in saliva. So, the guanine nucleotide-binding regulatory protein α-subunit, Gα16, expresses a κB-driven luciferase reporter. This response was accompanied by phosphorylation of IκBα. Furthermore, expression of Gα16 in saliva markedly enhanced TNF-α-induced κB reporter activity. Methods: The applied method to form NF-κB activation is the electromobility shift assay (EMSA). Also, B2R-BRD4-TG2 complex detection by immunoassay method within saliva with EMSA of NF-κB activation may be a novel biomarker for asthma diagnosis and follow up. Conclusion: This concept introduces NF-κB signaling pathway as potential asthma biomarkers and promising targets for the development of new therapeutic strategies against asthma.

Keywords: NF-κB, asthma, saliva, T-helper

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Authors: Gina Cecilia Pistol, Loredana Calin, Mariana Stancu, Veronica Chedea, Ionelia Taranu

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Inflammatory-associated diseases have an increased trend in the past decades. The pharmacological strategies aimed to treat these inflammatory diseases are very expensive and with non-beneficial results. The current trend is to find alternative strategies to counteract or to control inflammatory component of diseases. The grape by-products either seeds or pomace are rich in bioactive compounds (e.g. polyphenols) which may be beneficial in prevention of inflammation associated with cancer progression and other pathologies with inflammatory component. The in vivo models are very useful for studying the immune and inflammatory status. The domestic pig (Sus scrofa domesticus) is related to human from anatomic and physiologic point of view, representing a feasible model for studying the human inflammatory pathologies. Starting from these data, we evaluated the effect of a diet containing 5% grape seed cakes (GS) on piglets blood biochemical parameters and immune pro- and anti-inflammatory biomarkers (IL-1 beta, IL-8, TNF-alpha, IL-6, IFN-gamma, IL-10, IL-4) in spleen and lymph nodes. 12 weaned piglets were fed for 30 days with a control diet or an experimental diet containing 5% GS. At the end of trial, plasma and tissue samples (spleen and lymph nodes) were collected and the biochemical and inflammatory markers were analysed by using biochemistry analyser and ELISA techniques. Our results showed that diet included 5% GS did not influence the health status determined by plasma biochemical parameters. Only a tendency for a slight increase of the biochemical parameters associated with energetic profile (glucose, cholesterol, triglycerides) was observed. Also, GS diet had no effect on pro- and anti-inflammatory cytokines content in spleen and lymph nodes tissue. Further experiments are needed in order to investigate other rate of dietary inclusion which could provide more evidence about the effect of grape bioactive compounds on pigs used as animal model.

Keywords: animal model, inflammation, grape seed by-product, immune organs

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Authors: Rofida Gamal, Mostafa Mohammed, Mariam Adel, Marwa Gamal, Marwa kamal, Ayat Saber, Maha Mamdouh, Amira Emad, Mai Ramadan

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Lynch Syndrome is an inherited genetic condition associated with an increased risk of colorectal and other cancers. Detecting Lynch Syndrome in individuals is crucial for early intervention and preventive measures. This study proposes a computational pipeline for Lynch Syndrome detection by integrating alignment, variant calling, and annotation. The pipeline leverages popular tools such as FastQC, Trimmomatic, BWA, bcftools, and ANNOVAR to process the input FASTQ file, perform quality trimming, align reads to the reference genome, call variants, and annotate them. It is believed that the computational pipeline was applied to a dataset of Lynch Syndrome cases, and its performance was evaluated. It is believed that the quality check step ensured the integrity of the sequencing data, while the trimming process is thought to have removed low-quality bases and adaptors. In the alignment step, it is believed that the reads were accurately mapped to the reference genome, and the subsequent variant calling step is believed to have identified potential genetic variants. The annotation step is believed to have provided functional insights into the detected variants, including their effects on known Lynch Syndrome-associated genes. The results obtained from the pipeline revealed Lynch Syndrome-related positions in the genome, providing valuable information for further investigation and clinical decision-making. The pipeline's effectiveness was demonstrated through its ability to streamline the analysis workflow and identify potential genetic markers associated with Lynch Syndrome. It is believed that the computational pipeline presents a comprehensive and efficient approach to Lynch Syndrome detection, contributing to early diagnosis and intervention. The modularity and flexibility of the pipeline are believed to enable customization and adaptation to various datasets and research settings. Further optimization and validation are believed to be necessary to enhance performance and applicability across diverse populations.

Keywords: Lynch Syndrome, computational pipeline, alignment, variant calling, annotation, genetic markers

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Authors: Faezah Shekh Abdullah, Mohd. Azizuddin Mohd. Yussof, Komathy Thiagarajan, Hasnoorina Husin, Noor Azreena Abd Aziz

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Polycystic ovary syndrome has been associated with multiple disorders such as endocrine disorder, metabolic syndrome, infertility, and endometrial cancer. Women with polycystic ovary syndrome (PCOS) are anticipated to develop three times more chances for endometrial cancer than women without PCOS. This study, therefore, was conducted to determine the association between polycystic ovary syndrome and endometrial cancer and to determine the cervical cytology features of PCOS. Patients attending the Subfertility Clinic of the National Population and Family Development Board were recruited and examined physically by medical practitioners. They were categorized into two groups; i) the PCOS group if they met Rotterdam Criteria 2004 and ii) the control group if they did not meet Rotterdam Criteria 2004. Cervical sampling was done on all patients via the Liquid-Based Cytology (LBC) method in the pre-and post-subfertility treatment. A total of 167 patients participated in the study, of which 79 belonged to the PCOS group and 88 to the control group. The findings showed no cervical and endometrial cancer cases in both groups. The Liquid-Based Cytology results in the PCOS group displayed more cases with cellular changes, i.e., benign inflammation, atrophic smear and Candida sp. infection. To conclude, no association was found between polycystic ovary syndrome and endometrial cancer. A more holistic study with a higher number of participants can further determine the association between endometrial cancer and PCOS. Furthermore, a longer duration between LBC pre- and post-subfertility treatment should be implied to observe changes in the cervical cells.

Keywords: endometrial cancer, liquid-based cytology, PCOS, polycystic ovary syndrome

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Authors: T. E. Tshikalange, B. C. Mophuting

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Traditional medicine often consists of complex ingredients prepared from a mixture of plant species. These herbal mixtures are used in the treatment of various ailments such as sexually transmitted diseases including HIV. The present study was carried out to determine the biological activities of the herbal mixture used traditionally in the treatment of sexually transmitted diseases. This herbal mixture consists of four plant species from families Asteraceae, Bignoniaceae, Fabaceae, and Myrtaceae. Five crude extracts (hexane, dichloromethane, methanol, water and boiled) of the herbal mixture were investigated for anti-gonococcal, anti-inflammatory, and reverse transcriptase activities. The anti-inflammatory activity of the plant extracts was determined by measuring the extract inhibitory effect on the pro-inflammatory enzyme lipoxygenase. The extracts were also tested for anti-HIV activity against recombinant HIV-1 enzyme using non-radioactive HIV-RT colorimetric assay. The boiled extract exhibited good anti-inflammatory activity with an IC₅₀ of 87 µg/ml compared to that of the positive control quercetin (IC₅₀= 92 µg/ml). All the other extracts showed little or no activity. Hexane extract was the only extract that showed reverse transcriptase extract inhibitory effect with an IC₅₀ of 74 µg/ml. Anti-gonococcal and cytotoxicity investigations are underway. The preliminary results support the use of herbal mixture by traditional healers.

Keywords: sexually transmitted diseases, lipoxygenase, anti-inflammatory, herbal mixture

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Authors: Ritu Karwasra, Surender Singh

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Inflammation is an important physiological response of the body’s self-defense system that helps in eliminating and protecting organism from harmful stimuli and in tissue repair. It is a highly regulated protective response which helps in eliminating the initial cause of cell injury, and initiates the process of repair. The present study was designed to evaluate the ameliorative effect of pomegranate rind extract on pain and inflammation. Hydroalcoholic standardized rind extract of pomegranate at doses 50, 100 and 200 mg/kg and indomethacin (3 mg/kg) was tested against eddy’s hot plate induced thermal algesia, carrageenan (acute inflammation) and Complete Freund’s Adjuvant (chronic inflammation) induced models in Wistar rats. Parameters analyzed were inhibition of paw edema, measurement of joint diameter, levels of GSH, TBARS, SOD, TNF-α, radiographic imaging, tissue histology and synovial expression of pro-inflammatory cytokine receptor (TNF-R1). Radiological and light microscopical analysis were carried out to find out the bone damage in CFA-induced chronic inflammatory model. Findings of the present study revealed that pomegranate rind extract at a dose of 200 mg/kg caused a significant (p<0.05) reduction in paw swelling in both the inflammatory models. Nociceptive threshold was also significantly (p<0.05) improved. Immunohistochemical analysis of TNF-R1 in CFA-induced group showed elevated level, whereas reduction in level of TNF-R1 was observed in pomegranate (200 mg/kg). Henceforth, we might say that pomegranate produced a dose-dependent reduction in inflammation and pain along with the reduction in levels of oxidative stress markers and tissue histology, and the effect was found to be comparable to that of indomethacin. Thus, it can be concluded that pomegranate is a potential therapeutic target in the pathogenesis of inflammation and pain, and punicalagin is the major constituents found in rind extract might be responsible for the activity.

Keywords: carrageenan, inflammation, nociceptive-threshold, pomegranate, histopathology

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Authors: Taleb L., Benarbia M., Brahmi M., Belmiloud H., Boukerche A.

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Introduction and purpose of the study: Cavum cancer in children and adolescents is rare and represents 8% of all nasopharyngeal cancers treated in our department. Our objective is to study its epidemiological, clinical, therapeutic, and evolutionary particularities. Material and methods: Retrospective study of 39 patients under 20 years old, treated for undifferentiated non-metastatic carcinoma of the nasopharynx at the Emir Abdelkader Cancer Center between 2014 and 2020. Results and statistical analysis: Median age was 14 years [7-19 years], with a sex ratio of 2.9. The median time to diagnosis was 5.6 months [1 to 14 months], the circumstances of the discovery of which were dominated by lymph node syndrome in 43.6% of cases (n=17) followed by a rhinological syndrome in 30.8% of cases (n=13). The tumor stage was T1 for two patients (5.1%), T2 for 8 (20.5%), T3 for 9 (23.1%), T4 for 20 (51.3%), N0 for 2 (5 .1%) N1 for 4 (10.3%), N2 for 28 (71.8%) and N3 for 5 (12.8%). All patients received induction chemotherapy followed by concomitant radiotherapy with cisplatin. The dose of irradiation delivered to the cavum and adenopathies was 66 Gy with fractionation of 2 Gy per session in 69.2% of cases (n=27) and 1.8 Gy in 30.8% of cases (n=12). With a median follow-up of 51 months (15 to 97 months), the locoregional, metastatic, specific, and overall relapse-free survival rates at five years were 91.1%, 73.5%, 66.1%, and 68.4, respectively. Conclusion: Chemotherapy and radiotherapy treatment of cavum cancer in children and adolescents has allowed excellent locoregional control despite the advanced stage of the disease. However, the frequency of metastatic relapses could justify the possible use of systemic maintenance treatment.

Keywords: cancer, nasopharynx, radiotherapy, chemotherapy, survival

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Authors: D. R. Apoorva

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Ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome is a rare oculocutaneous disorder of genetic origin. This disorder results from mutations in the membrane-bound transcription factor protease site, two genes that impair cholesterol homeostasis, and the ability to cope with endoplasmic reticulum stress. We report a rare case of IFAP syndrome with an atypical presentation, and it was interesting to note that the child had patchy non-scarring alopecia over the scalp along with unilateral madarosis. To our best knowledge, this unique presentation has not been described earlier. The child presented with photophobia and unilateral ptosis. The child also had short stature and intellectual disability. Skin histopathology was nonspecific and consisted of dilated hair follicles with keratin plugs extending above the skin surface. This rare oculocutaneous disorder requires proper documentation so that identification of its variants may be possible in the future. Early recognition of atypical presentations can help in preventing cardiovascular complications, which remain the major cause of death.

Keywords: alopecia, photophobia, ichthyosis follicularis, IFAP syndrome

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