<abstract>
<title style='display:none'>Abstract</title>
<sec><title style='display:none'>BACKGROUND AND AIM</title>
Dengue viral disease (DVD) is a tropical arboviral disease that is caused by dengue virus (DENV), which is transmitted mainly by the bite of female Aedes aegypti mosquitoes. No specific antiviral drug is approved yet to manage the patients with DENV infection, who are managed using symptomatic therapy and supportive care.
</sec>
<sec><title style='display:none'>AIM</title>
As a consequence, we intend to review the potential of Nilavembu kudineer in the management of DENV infection.
</sec>
<sec><title style='display:none'>MATERIALS AND METHODS</title>
To find articles pertinent to the clinical, <italic>in vitro</italic>, and <italic>in silico</italic> studies evaluating the effectiveness of <italic>Nilavembu Kudineer</italic> in the management of DENV infection, the literature was searched in databases such as Medline/PubMed Central/PubMed, Google Scholar, Science Direct, EBSCO, Scopus, Web of science, Embase, Directory of open access journals, and reference lists.
</sec>
<sec><title style='display:none'>RESULTS</title>
<italic>Nilavembu Kudineer</italic> may be able to alleviate signs and symptoms experienced by patients with DENV infection, according to few clinical, <italic>in vitro</italic>, and <italic>in silico</italic> studies.
</sec>
<sec><title style='display:none'>CONCLUSION</title>
The effectiveness of <italic>Nilavembu Kudineer</italic> in patients with DENV infection would further be demonstrated by additional randomized controlled clinical trials.
</sec>
</abstract>

Efficacy of Nilavembu Kudineer for Dengue Fever Management – An Overview of Clinical and Preclinical Evidences

<abstract>
<title style='display:none'>Abstract</title>
<sec><title style='display:none'>AIM</title>
The objective of the study is to evaluate the prevalence characteristics of allergic asthma in a sample of dairy farmers.
</sec>
<sec><title style='display:none'>METHODS</title>
We performed a cross-sectional study including 83 dairy farmers (mean age: 52.6 ± 8.7 years; mean exposure duration: 23.7 ± 7.6 years) compared to 80 office controls (mean age: 52.7 ± 8.2 years) matched for age, smoking habits, and socioeconomic status. Methods of evaluating examined subjects included a questionnaire on respiratory symptoms in the past 12 months, baseline spirometry and histamine challenge, and skin prick tests to standard inhalant and occupational allergens.
</sec>
<sec><title style='display:none'>RESULTS</title>
The frequency of asthma was non-significantly higher in dairy farmers than in controls (7.2% vs. 5%). The frequency of allergic asthma was non-significantly higher in dairy farmers than in controls (6% vs. 3.8%). The frequency of allergic asthma was significantly higher compared to non-allergic asthma in both groups, while the frequency of subjects with allergic asthma who are sensitized to occupational allergens (wheat, corn, rye, cow hairs, molds) was similar in dairy farmers and controls. The risk of sensitization to occupational allergens was non-significantly higher among dairy farmers with allergic asthma (OR = 1,39 [0,18–12,28] CI 95%), compared to office controls. The risk for asthma development was non-significantly higher in subjects sensitized to occupational allergens compared to those who are not sensitized to them both in dairy farmers (OR = 2.00 [0.11–40.60] CI 95%) and office controls (OR = 3.00 [0.00–197.11] CI 95%). The risk for asthma development was about 4 times higher in subjects with atopy compared to those without atopy among dairy farmers (OR = 4.00 [0.22–104.88] CI 95%), while in office controls was almost identical (OR = 1.00 [0.00–39.77] CI 95%). Having in mind sensitization to certain inhalant allergens, asthma was significantly associated with sensitization to <italic>Dermatophagoides pteronyssinus</italic> both in dairy farmers (p &lt; 0.01) and office controls (p &lt; 0.05).
</sec>
<sec><title style='display:none'>CONCLUSION</title>
The results suggest that occupational exposure among dairy farmers was associated with a higher prevalence respiratory symptoms, lung function impairment, and allergic asthma development. Study findings also can contribute in the detection of critical points for action, predict asthma development, and indicate the need for reduction of adverse occupational exposures by appropriate preventive measures, use of respiratory protective equipment, and implementation of engineering controls.
</sec>
</abstract>

Prevalence and Characteristics of Allergic Asthma in a Sample of Dairy Farmers

<abstract>
<title style='display:none'>Abstract</title>
<sec><title style='display:none'>BACKGROUND</title>
The preservation of post-extraction alveola, as part of guided bone regeneration, is recommended for the creation of a biological foundation for future implant-prosthetic or prosthetic production. Several graft materials are used, either independently or in a combination of each other. Advanced platelet-rich fibrin (A-PRF) as an autologous blood derivate in the recent years has been increasingly used because of its properties in angiogenesis, epithelialization, and hemostasis. Simple production, low cost, and non-use of anticoagulants are advantages for more mass use of it.
</sec>
<sec><title style='display:none'>CASE PRESENTATION</title>
Two clinical cases are described, one is using a combination of A-PRF with xenograft, and the second clinical case is using a solo A-PRF, for socket preservation.
</sec>
<sec><title style='display:none'>CONCLUSION</title>
The properties of A-PRF for preserving both bone volume and quality have been confirmed, highlighting its potential as a valuable therapeutic tool. Furthermore, the post-operative period following A-PRF treatment has been found to be free of significant discomfort and morbidity for patients, suggesting that this approach may represent a safe and effective means of promoting optimal clinical outcomes.
</sec>
</abstract>

Advanced Platelet-rich Fibrin versus Sticky Bone in Socket Preservation - Clinical and X-ray Assessment: Case Report

<abstract>
<title style='display:none'>Abstract</title>
<sec><title style='display:none'>BACKGROUND</title>
Immunologic occupational asthma (OA), a more prevalent OA type than non-immunologic OA, became an important public health problem in the last decades worldwide.
</sec>
<sec><title style='display:none'>AIM</title>
To present the distribution of new diagnosed cases of immunologic OA in the RN Macedonia in the period 2015–2022 by occupation.
</sec>
<sec><title style='display:none'>METHODS</title>
Immunologic OA was diagnosed by the serial measurement of peak expiratory flow rate (PEFR) at and away from work or by combination of serial PEFR measurement at and away from work and non-specific bronchial provocation at and away from work in workers with diagnosed asthma and work-relatedness of the symptoms. Sensitization to common inhalant and occupational allergens was evaluated by skin prick test.
</sec>
<sec><title style='display:none'>RESULTS</title>
The annual incidence rate of the diagnosed immunologic OA in this period varied from 1.9 / 100,000 working population in 2015–2.6 / 100,000 in 2022 with a drop in 2020 and 2021, i.e. in the period of COVID-19 pandemic (0.6 and 0.5, respectively). Cleaning, bakery, cleaning, textile manufacture, wood industry, agriculture, and metal-parts manufacture were the most important occupations for the development of immunologic OA. More than a half of the new diagnosed immunologic OA cases were atopics.
</sec>
<sec><title style='display:none'>CONCLUSION</title>
Our findings indicated the occupations with the highest incidence of immunologic OA that could enable targeting of preventive measures and activities to reduce the occurrence of immunologic OA as well as its adverse health outcomes.
</sec>
</abstract>

Incidence of Immunological Occupational Asthma in 2015–2022 by Occupation: Macedonian Experience

<abstract>
<title style='display:none'>Abstract</title>
<sec><title style='display:none'>BACKGOUND</title>
The prevalence of rheumatoid arthritis (RA) and its specific autoantibodies varies in different populations. This variability depends on the genetic polymorphism of the immune response genes among which the HLA system plays a major role.
</sec>
<sec><title style='display:none'>AIM</title>
We conducted a preliminary study of the distribution of HLA-DRB1 and HLA-DQB1 first field level alleles in a sample of 100 Albanian patients with RA.
</sec>
<sec><title style='display:none'>METHODS</title>
In this context, we studied the HLA-DRB1 and HLA-DQB1 first-level allele frequencies in 100 Albanian patients with RA and considering their rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) serologic subgroups. We compared them with the respective frequencies in a population of 191 Albanian individuals without known pathology.
</sec>
<sec><title style='display:none'>RESULTS</title>
No differences were found between the controls and the RA patient group, but three statistically significant differences were found: an increase in DRB1*04 among ACPA-positive, RF-positive and ACPA-positive/ RF-positive patients, a significant decrease in DRB1*11 among ACPA-positive/RF-positive, and also a decrease in DRB1*13 among RF-positive patient subgroups. The frequencies of DRB1 allotypes in ACPA+ and RF+ patients compared to their counterpart ACPA− and RF−patient subgroups showed the predisposing effect of HLA-DRB1*04 for ACPA and RF seropositivity (p, respectively, 0.0008 and 0.0017) and the protective role of HLA-DRB1*11 for ACPA and RF positivity (p, respectively, 0.007 and 0.02). The same protective role from the RF positivity is also found with the HLA-DRB1*13 alleles (p = 0.007). As far as the DQB1 locus is concerned, a protective association has been found between the HLA-DQB1*06 alleles with both RF+ and RF+ ACPA+ positivity (p, respectively, 0.05 and 0.04) when comparing the control group with the respective RA patient subgroups. In ACPA+ and RF+ patients compared to the ACPA− and RF− patient subgroups, the only detected difference was between RF (+) and RF (−) patients (p =0.04).
</sec>
<sec><title style='display:none'>CONCLUSION</title>
The relatively low frequencies of DRB1*04 and high (DRB1*11 and DRB1*13) in the Albanian population might explain the rather low positivity rate of ACPA and RF antibodies among the Albanian RA patients. Our study demonstrates that DRB1*11, DRB1*13 and DQB1*06 may be negatively associated with RA. Conversely, DRB1*04 may confer susceptibility to RA in Albanian population.
</sec>
</abstract>

The Protective Effect of HLA-DRB1 and HLA-DQB1 Alleles to ACPA-Positive and RF-Positive RA in Albanian Population

<abstract>
<title style='display:none'>Abstract</title>
<sec><title style='display:none'>AIM</title>
The link between the development of melanoma skin cancer and obesity is gaining recently an increased attention. A plethora of immune-related factors sustain a chronic inflammatory state modulated by the metabolic imbalance, the main examples being tumor necrosis factor alpha, interleukin 6, monocyte chemoattractant protein (MCP1), and several adipokines. Among the adipokines leptin (LEP) is steadily increasing interests as it involved in modulating different signaling pathways (e.g., JAK2/STAT3 and MAPK cascade/FOS) and immune cells fate by promoting the switch of memory cells to T helper-1 cell response, increases CD4+CD25- T-cell proliferation, and reduces autophagy during T-cell receptor stimulation. Our work investigates in a pilot study, using protein microarray technology, the LEP circulatory levels in melanoma patients in comparison to other cytokines and chemokines already reported as significantly involved in melanoma initiation and progression.
</sec>
<sec><title style='display:none'>METHODS</title>
Serum from melanoma cases and pool of serum from healthy volunteers were analyzed by an antibody array platform for a 42-cytokine profile.
</sec>
<sec><title style='display:none'>RESULTS</title>
The investigation of cytokines, chemokines, and growth factors has shown that all the proinflammatory circulating molecules are elevated in the melanoma patient’s serum. Inflammatory cytokines were found elevated and were correlated to the more advanced stage of the investigated patient (M2). The highest circulatory level was registered for LEP in both melanoma cases; moreover, in M1 patient, although the LEP level was completely comparable with the one found in M2, its IL-1 serum level was normal. In addition, there are ten analytes that show clear abnormal values and in patient M2 high LEP concentration is correlated with high IL-1, MCP-2, MCP-3, MCSF, and TARC serum concentrations.
</sec>
<sec><title style='display:none'>CONCLUSION</title>
Leptin is pleiotropic adipocytokine involved in various diseases, including skin cancer and melanoma. As it is involved in favoring inflammation and further tumorigenesis, the development of effective leptin-based therapeutic approaches opens new possibilities of adjuvant therapy in skin cancers.
</sec>
</abstract>

Systemic Circulating Leptin – Aiding New Dimension of Immune-Related Skin Carcinogenesis and Lipid Metabolism

<abstract>
<title style='display:none'>Abstract</title>
Chimaeric antigen receptor (CAR) T lymphocytes (CAR-T) discovered in 1992 have been in the recent years in the spotlight of both researchers and clinicians. Immune therapy with engineered CAR-T cells has been approved by the FDA since 2017 for pediatric and young adult acute lymphoblastic leukemia. Since then, around ten therapies were approved for hematological cancers. In contrast to the other immune therapies CAR-T cell therapy is considered a “living drug” with the capacity of self-replicating. Having this particular characteristic, the manufacturing process has in general several steps that should be followed in the process of obtaining specific CAR-T cells. There are mandatory steps for obtaining a CAR-T cell culture: Leukapheresis, activation, gene delivery, expansion, and cryopreservation. All these seminal stages have various sub-stages that can differ from one procedure to other as detailed in the paper. Leukapheresis harvests peripheral blood mononuclear cells, followed by an enrichment of a certain cellular population or a depletion phase to remove contaminants as red blood cells and platelets. T cell population that is obtained needs to be activated using activating antibodies (Abs), magnetic beads coated with activating Abs or artificial antigen-presenting cells. After activation, T cells are subjected to genetic engineering that can be done using electroporation of naked DNA, plasmids, or viral vectors to insert the specific CAR. The last phases of CAR-T cell manufacturing are the expansion of these specific cells and, if not freshly inoculated to the patients, the final step is cryopreservation. The main drawback of CAR-T cell therapy is its high cost; therefore, new automated platforms would decrease their cost. The described stages are still variable within CAR-T manufacturing. Therefore, the future of this immune therapy will have to tackle standardization and automated technology, directions that will increase healthcare system availability.
</abstract>

CAR-T Cells – Main Steps for Obtaining a Proper “Live Drug” Adoptive Therapy

<abstract>
<title style='display:none'>Abstract</title>
<sec><title style='display:none'>BACKGROUND</title>
At present, complete blood count (CBC) testing is one of the most common clinical tests. The XN-3000 used in our hospital utilizes the principles of impedance and semiconductor laser flow cytometry, which contains two types of leukocyte fractionation methods: White cell nucleated (WNR) and white cell differential (WDF) channels.
</sec>
<sec><title style='display:none'>CASE PRESENTATION</title>
Herein, we present the case of a 63-year-old male patient who was admitted to our hospital for the treatment of non-small cell lung cancer (T4N3M1 [LYM, HEP, and OSS]). Biochemical data showed abnormal liver function and anemia. WNR results showed poor leukocyte and debris fractions compared with WDF results, and leukocyte counts were different between the two channels. However, the poor fractionation of the leukocyte and debris fractions in the WNR was resolved at the twofold dilution stage. To investigate the cause of the problem, precipitates affecting the WNR measurement were visually checked. Consequently, insoluble precipitates were observed in the WNR mixture of the specimen of the patient. In our hospital, we measure 1200 CBCs/day and very rarely encounter abnormal specimens such as in the presented case. Normally, leukocyte counts are reported in priority to those measured by the WNR channel; however, in this case, the switching function was effective in giving priority to WDF count results because of the appearance of abnormal WNR plots. However, a system that can promptly confirm events when results are reported is necessary.
</sec>
<sec><title style='display:none'>CONCLUSION</title>
We very rarely encounter abnormal specimens such as in the presented case. Normally, leukocyte counts are reported in priority to those measured by the WNR channel; however, in this case, the switching function was effective in giving priority to WDF count results because of the appearance of abnormal WNR plots. However, a system that can promptly confirm events when results are reported is necessary. When no clinical request for WDF measurement was made, the WNR scattergram must be confirmed, dilution measurement, if necessary, must be performed, or the WDF must be measured and reported to the clinician as useful criteria for diagnosis.
</sec>
</abstract>

Deviation in White Blood Cell Count Measurement between WNR and WDF Channels on an Automated Hematology Analyzer XN-3000: A Case Report

<abstract>
<title style='display:none'>Abstract</title>
<sec><title style='display:none'>BACKGROUND</title>
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome is a rare, potentially life-threatening, drug-induced hypersensitivity reaction. This condition is characterized by a range of symptoms, including cutaneous reaction, hematologic abnormalities, lymphadenopathy, and potential involvement of internal organs. Most DRESS cases are associated with certain medications such as antiseizure drugs, allopurinol, antibacterial sulfonamides, minocycline, and vancomycin.
</sec>
<sec><title style='display:none'>CASE PRESENTATION</title>
We presented a case of 70-year-old women exhibiting maculopapular rash affecting the face, abdomen, and extremities. She experienced generalized pruritus, along with ulcerative crusty lesions on the mouth and mucopurulent conjunctivitis, all of which had persisted for 1 week. She was recently diagnosed with hyperuricemia and had been undergoing treatment with allopurinol for 4 weeks. During her hospital stay, the rash intensified, and there was a worsening involvement of the mucosa in the oral and ocular area. Allopurinol was promptly discontinued, and the patient was prescribed a daily dose of 100 mg prednisolone, gradually tapering off over a 2-month period. Additionally, the treatment included anticoagulants, antibiotics, local application of mild steroid emulsions, antiseptic, and antifungal therapy for the oral mucosa. Antibiotic solutions and natural tear eye drops were used. Over the 2-month period, the rash completely resolved, and the liver enzymes returned to normal levels.
</sec>
<sec><title style='display:none'>CONCLUSION</title>
DRESS syndrome is an unpredictable drug-induced reaction identified by symptoms such as rash, fever, lymphadenopathy, and potential internal organ involvement. Allopurinol is among the medications associated with this condition, particularly when there is a reduced renal clearance and simultaneous use of thiazide diuretics. Prompt withdrawal of the causative drug is the universally accepted approach to manage drug-induced hypersensitivity reactions. The use of systemic corticosteroids can reduce symptoms of delayed hypersensitivity reactions. However, the absence of randomized controlled trials leaves uncertainty about the necessity of administering steroids, sparking a controversial debate regarding their use in such cases.
</sec>
</abstract>

Drug Rash with Eosinophilia and Systemic Symptoms Syndrome: Case Report and Literature Review

<abstract>
<title style='display:none'>Abstract</title>
Asthma affects the respiratory system and causes airway inflammation. The indication of asthma includes a triad of airway inflammation, hyperresponsiveness, and obstruction. Nitric Oxide (NO) is a gas that is exhaled and is a sign of airway inflammation. NO levels in the exhaled breath of patients with type 2 asthma are elevated, and fractional exhaled nitric oxide (FeNO) is an objective biomarker of airway inflammation. Measurements of FeNO are noninvasive, require minimal patient effort, and are easy to collect in clinical settings. The current review is a systematic review performed using PubMed, Science Direct, and Google Scholar according to The Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol (PRISMA-P) guidelines. This review discusses the entanglement of understanding FeNO measurement and supplementing existing diagnostic and assessment tools for inflammatory lung diseases. Monitoring FeNO can also help identify different asthma phenotypes within the asthma syndrome and suggest the optimal administration of inhaled corticosteroids (ICS) as elevated FeNO levels indicate ICS response. Non-adherence to ICS is a significant contributor to the failure of asthma treatment. A FeNO suppression test can be done to determine non-adherence. FeNO levels should be used with a careful history, conventional spirometric testing with bronchodilator reversibility, measures of bronchial hyperreactivity using methacholine, and other measures of eosinophilic inflammation, such as a peripheral blood eosinophil cell count. FeNO is more sensitive and specific when paired with other lung function tests.
</abstract>

The Potential of Fractional Exhaled Nitric Oxide as a Biomarker in Predicting and Optimizing Use of Treatment in Asthma

<abstract>
<title style='display:none'>Abstract</title>
<sec><title style='display:none'>BACKGROUND</title>
Epidermolysis bullosa (EB) is a skin fragility disorder that results in the disruption of the dermoepidermal junction and painful blisters on the skin and mucous membranes. Currently, there is almost no definite treatment for EB patients.
</sec>
<sec><title style='display:none'>AIM</title>
This study aims to assess the effect of topical formulation based on <italic>Arnebia euchroma</italic> (AE) on lesions induced by EB.
</sec>
<sec><title style='display:none'>MATERIALS AND METHODS</title>
All patients with EB diseases treated with Hochobeh ointment (AE+Beewax+Olive oil) in 2022 at our dermatological clinic were included in the study. EB diseases were diagnosed based on the following criteria: (1) clinical features (2) histopathological findings (3) Linear depositions of IgG, IgA, IgM 4. salt-split skin (SSS) or other immune serological tests compatible with the diagnosis of EB disease. Hochobeh ointment and lotion treatment were initiated. Clinical evaluations were repeated 3 and 7 days after the treatment began, and photographs were taken to document the changes in clinical severity. EB Disease Activity and Scarring Index (EBDASI) and EB Quality of Life (EB-QoL) questionnaires were used to assess the severity of EB and the quality of life, respectively. All statistical analyses were performed using statistical package for the social sciences version 16.
</sec>
<sec><title style='display:none'>RESULTS</title>
Overall, fourteen patients were included. Improvement in clinical features, including reduction of infection and inflammation and improvement of wound healing, was observed. EBDASI and EB-QoL scores decreased significantly after treatment (91.5 ± 45.7 vs. 68.9 ± 43, p = 0.001; 24.6 ± 6.7 vs. 18 ± 5.2, p = 0.001, respectively).
</sec>
<sec><title style='display:none'>CONCLUSION</title>
Hochobeh ointment may be effective in treating EB skin and mucosal lesions.
</sec>
</abstract>

Topical Formulation Based on Arnebia euchroma as a Novel Possible Efficient Treatment on Epidermolysis Bullosa Lesions: A Case Series of Fourteen Patients

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South East European Journal of Immunology

 South East European Journal of Immunology (SEEJIM) is a top-tier, open-access medical science journal published by the Scientific Foundation SPIROSKI, Rajko Zhinzifov No 48, 1000...

 South East European Journal of Immunology (SEEJIM) is a top-tier, open-access medical science journal published by the Scientific...