Evaluation of pediatric patients with COVID-19 in a Turkish university hospital.

Background: Although COVID-19 has a milder course in pediatric patients than in adults, it can have a severe and fatal course in children with an underlying disease (UD). Aims: In this study, we aimed to evaluate the demographic, clinical, laboratory, and radiological characteristics, treatment methods, and prognosis of pediatric patients diagnosed with COVID-19. Patients and Methods: The files of patients aged 0-18 years diagnosed with COVID-19 were retrospectively evaluated. Clinically and radiologically suspicious cases were accepted as confirmed cases if SARS-CoV-2 PCR positivity was found in nasopharyngeal swab samples. The severity of the disease was defined as asymptomatic, mild, moderate, and severe according to clinical, laboratory, and radiological features. Results: A total of 322 pediatric patients, 51.2% male and 48.8% female, were included in the study. The median age of the patients was 12.08 years (1 month-18 years). Of the 322 patients, 81 (25.1%) were asymptomatic. Disease severity was as follows: 218 were (67.7%) mild, 14 were (4.3%) moderate, and 9 (2.7%) were severe. 35.7% of the patients were hospitalized. Six percent were admitted to the intensive care unit, and three (0.93%) patients died. The mortality rate in patients with the UD was 3.3%. Conclusion: In our study, we determined that the disease had a more severe course in patients with initial procalcitonin, D-dimer, troponin increase, and thrombocytopenia. Although COVID-19 has a mild course in children, this is unfortunately not true for children with an UD.

[Autophagy Does Not Contribute to TKI Response in a Imatinib-resistant Chronic Myeloid Leukemia Cell Line].

Autophagy is an evolutionarily conserved cellular process in which components of the cytoplasm are delivered to lysosomes for degradation and has been proposed to play a role in imatinib resistance in chronic myeloid leukemia cells. Chronic myeloid leukemia is a clonal myeloproliferative disorder arising from the neoplastic transformation of the hematopoietic stem cell. We used a Bcr-Abl-independent and imatinib-resistant K562 subpopulation (K562-IR) that we generated earlier in our laboratory for this study. We showed that in the presence of imatinib autophagy was triggered via LC3I/II transformation, p62 protein expression and acidic vacuoles accumulation in tyrosine kinase inhibitor-sensitive K562 cells; whereas in the cell line K562-IR which is imatinib-resistant and Bcr-Abl independent, autophagy is not triggered. With ongoing research and trails to combine tyrosine kinase inhibitors with autophagy inhibitors, our results suggest a model of resistance in which treatment with a TKI inhibitor does not increase autophagy, basically because its presence does not cause cellular stress due to Bcr-Abl signaling not being required for survival.

Apigenin alleviates methotrexate-induced liver and kidney injury in mice.

Methotrexate (MTX) is a drug used in the treatment of various types of cancer and inflammatory diseases, but its clinical use has been restricted due to its toxicity. Apigenin (API) is an effective flavonoid with antioxidant and anti-inflammatory properties. The aim of this study was to determine the protective effect of API against MTX-induced liver and kidney toxicity. Four groups with 12 male mice each were used. The control and API groups were received 0.9% saline (ip) and API (3 mg/kg ip) for 4 days, respectively. The MTX group were given a single dose of MTX (20 mg/kg ip) on the fourth day. The MTX + API group were administered API for 7 days and then MTX on fourth day. Blood, liver and kidney were collected to evaluate tissue injury markers, oxidative stress biomarkers, and histopathological and immunohistochemical assessments. In MTX-treated group, significant increases in aminotransferases activities, creatinine and malondialdehyde (MDA) levels and significant decreases in catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase1 (SOD1) activities and glutathione (GSH) levels were determined compared to the control group. Furthermore, histopathological changes and significant increases in caspase-3, C-reactive protein (CRP), granulocyte colony-stimulating factor (G-CSF), and inducible nitric oxide synthase (iNOS) expressions were detected in both liver and kidney tissues of MTX-treated mice. Pretreatment with API alleviates liver and kidney toxicity by attenuating oxidative stress and tissue injury markers, histopathological alterations, and apoptosis and inflammation. These results suggest that API has a protective effect against oxidative stress and liver-kidney toxicity induced by MTX.

Evaluation of the diagnostic validity of noninvasive tests for predicting liver fibrosis stage in chronic hepatitis B patients.

BACKGROUND AND STUDY AIM: The aim of this study was to evaluate the effectiveness of noninvasive tests in predicting liver fibrosis levels in chronic hepatitis B (CHB) patients. PATIENTS AND METHODS: A total of 539 treatment naive patients aged 18 years and older with CHB who underwent liver biopsy were included. Patients with coinfections and comorbidities were excluded. Data were obtained retrospectively from patient' follow- up files. Liver biopsy was evaluated according to the Ishak scoring system. SPSS 22.0 program was used for statistical analysis. Diagnostic sensitivity of APRI, FIB-4, NLR, GPR, AAR, RPR, API, King's score, Fibro Q and MPV was determined for predicting ≥F2, ≥F3, ≥F4, ≥F5 groups. RESULTS: The median age of the CHB patients was 41 ±11.57 / year and 49.2% of the patients were female. The distribution of fibrosis stages was : F0, 16.5% ; F1, 26.4% ; F2, 39.7% ; F3, 10.4% ; F4, 4.1% ; F5, 2.4% ; F6 0.4%. Age, AST, ALT, GGT, ALP, RDW, HBV DNA levels were significantly higher, platelet and albumin levels were significantly lower in the ≥F3 group. All noninvasive tests except NLR and AAR predicted ≥F3 adequately (AUROC >0.5). King's score for predicting ≥F2, ≥F5, and GPR for predicting ≥F3 had the highest diagnostic power. The tests predicted the fibrosis stage better, as the fibrosis stage progressed. CONCLUSION: As a result, most of the noninvasive tests we evaluated could predict significant fibrosis and cirrhosis with significant accuracy. The rate of unnecessary biopsies can be reduced with the help of these noninvasive tests.

The effect of knowledge levels of individuals receiving basic first aid training in Turkey on the applications of first aid.

OBJECTIVES: To evaluate the knowledge level of individuals who attended a first aid training update program, and to determine the factors affecting their approaches in such cases. METHODS: This is a descriptive cross-sectional study. The sample of the research consists of 747 individuals (laypersons) who applied to the first aid training update organized in an institution in Istanbul providing health education between 01.02.2018 and 01.08.2018, and who agreed to participate in the research. These first aid trainings are provided by healthcare professionals who have first aid certificate of authority within the scope of first aid regulation. Data were collected using the "Participant Information Form" and the "Basic First Aid Knowledge Level Evaluation Form". RESULTS: The participants administered first aid within the three years of time following their basic first aid training course (24.6%). They administered first aid primarily in emergency cases of fainting (29.6%) and the majority of them (95.7%) did not perform cardiopulmonary resuscitation during their basic first aid effort. Of the participants, 73.9% answered incorrectly the question: "The letter 'A' in the abbreviation ABC of basic life support administration stands for airway". In our study, it was also found that there was a significant relationship between the total knowledge score and the number of trainings update and first aid intervention in the last three years (P < 0.05, P < 0.001, respectively). CONCLUSIONS: It was determined that individuals had a high level of knowledge about basic first aid and one-quarter of the participants had administered first aid in the last three years. In order for individuals not to lose their knowledge and skills gained through first aid training; updating training and providing first aid training programs to individuals in society can be a guide for bystanders who provide faster and sufficient first aid in cases of emergency.

Atopy patch test in children with cow's milk and hen's egg allergy: Do clinical symptoms matter?

INTRODUCTION AND OBJECTIVES: Since early 2000s, atopy patch test (APT) has been used to determine non-IgE and mixed-type food allergies. Previous studies have reported conflicting results about the diagnostic value of APT in food allergies, due to non-standardized methods. We aimed to determine the diagnostic efficacy of APT compared to open oral food challenge (OFC) in patients diagnosed with cow's milk allergy (CMA) and hen's egg allergy (HEA) manifesting as atopic dermatitis (AD) and gastrointestinal system symptoms. MATERIALS AND METHODS: In patients with suspected AD and/or gastrointestinal manifestations due to CMA and HEA, the results of OFC, APT, skin prick test (SPT) and specific IgE (sIgE) were reviewed. Specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of sIgE, SPT, APT and SPT+APT were calculated. RESULTS: In total 133 patients with suspected CMA (80) and HEA (53) were included in the study. In patients with CMA presenting with gastrointestinal symptoms, APT had sensitivity of 9.1%, specificity of 100%, PPV of 100% and NPV of 48.7%. In atopic dermatitis patients, sensitivity of APT was 71.4%, specificity 90.6%, PPV 62.5% and NPV 93.6%. In patients diagnosed with HEA, the sensitivity, specificity, PPV and NPV values of APT were 72.0%, 78.6%, 47.2% and 75.0%, respectively. In patients diagnosed with HEA presenting with AD, sensitivity of APT was 87.5%, specificity 70.6%, PPV 73.7% and NPV 85.7%. Atopy patch test had lower sensitivity (44.4%) and higher specificity (90.9%) in patients diagnosed with HEA presenting with gastrointestinal symptoms than those presenting with AD. CONCLUSION: Our study showed that APT provided reliable diagnostic accuracy in atopic dermatitis patients. However, APT had low sensitivity in patients with gastrointestinal symptoms

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Atopy patch test in children with cow's milk and hen's egg allergy: Do clinical symptoms matter?

INTRODUCTION AND OBJECTIVES: Since early 2000s, atopy patch test (APT) has been used to determine non-IgE and mixed-type food allergies. Previous studies have reported conflicting results about the diagnostic value of APT in food allergies, due to non-standardized methods. We aimed to determine the diagnostic efficacy of APT compared to open oral food challenge (OFC) in patients diagnosed with cow's milk allergy (CMA) and hen's egg allergy (HEA) manifesting as atopic dermatitis (AD) and gastrointestinal system symptoms. MATERIALS AND METHODS: In patients with suspected AD and/or gastrointestinal manifestations due to CMA and HEA, the results of OFC, APT, skin prick test (SPT) and specific IgE (sIgE) were reviewed. Specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of sIgE, SPT, APT and SPT+APT were calculated. RESULTS: In total 133 patients with suspected CMA (80) and HEA (53) were included in the study. In patients with CMA presenting with gastrointestinal symptoms, APT had sensitivity of 9.1%, specificity of 100%, PPV of 100% and NPV of 48.7%. In atopic dermatitis patients, sensitivity of APT was 71.4%, specificity 90.6%, PPV 62.5% and NPV 93.6%. In patients diagnosed with HEA, the sensitivity, specificity, PPV and NPV values of APT were 72.0%, 78.6%, 47.2% and 75.0%, respectively. In patients diagnosed with HEA presenting with AD, sensitivity of APT was 87.5%, specificity 70.6%, PPV 73.7% and NPV 85.7%. Atopy patch test had lower sensitivity (44.4%) and higher specificity (90.9%) in patients diagnosed with HEA presenting with gastrointestinal symptoms than those presenting with AD. CONCLUSION: Our study showed that APT provided reliable diagnostic accuracy in atopic dermatitis patients. However, APT had low sensitivity in patients with gastrointestinal symptoms.

Temporal Trends in the Epidemiology of HIV in Turkey.

OBJECTIVE: The aim of this study was to analyze the temporal trends of HIV epidemiology in Turkey from 2011 to 2016. METHODS: Thirty-four teams from 28 centers at 17 different cities participated in this retrospective study. Participating centers were asked to complete a structured form containing questions about epidemiologic, demographic and clinical characteristics of patients presented with new HIV diagnosis between 2011 and 2016. Demographic data from all centers (complete or partial) were included in the analyses. For the cascade of care analysis, 15 centers that provided full data from 2011 to 2016 were included. Overall and annual distributions of the data were calculated as percentages and the Chi square test was used to determine temporal changes. RESULTS: A total of 2,953 patients between 2011 and 2016 were included. Overall male to female ratio was 5:1 with a significant increase in the number of male cases from 2011 to 2016 (p<0.001). The highest prevalence was among those aged 25-34 years followed by the 35-44 age bracket. The most common reason for HIV testing was illness (35%). While the frequency of sex among men who have sex with men increased from 16% to 30.6% (p<0.001) over the study period, heterosexual intercourse (53%) was found to be the most common transmission route. Overall, 29% of the cases presented with a CD4 count of >500 cells/mm3 while 46.7% presented with a CD4 T cell count of <350 cells/mm3. Among newly diagnosed cases, 79% were retained in care, and all such cases initiated ART with 73% achieving viral suppression after six months of antiretroviral therapy. CONCLUSION: The epidemiologic profile of HIV infected individuals is changing rapidly in Turkey with an increasing trend in the number of newly diagnosed people disclosing themselves as MSM. New diagnoses were mostly at a young age. The late diagnosis was found to be a challenging issue. Despite the unavailability of data for the first 90, Turkey is close to the last two steps of 90-90-90 targets.

Author Correction: Metagenomics of pigmented and cholesterol gallstones: the putative role of bacteria.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Seroprevalence of measles, mumps, rubella, and varicella zoster virus antibodies among healthcare students: analysis of vaccine efficacy and cost-effectiveness.

OBJECTIVE: The aims of this study are to determine the seroprevalence for measles, mumps, rubella, and varicella zoster virus (VZV) in a cohort of nursing students, to evaluate vaccination response rates of nonimmune students, and to calculate the cost of vaccinating students based on seroprevalence screening. METHODS: A cross-sectional study was conducted August 2015-November 2016 among 326 healthy nursing students aged 14.1-18.1 years. Serum IgG antibodies were measured by ELISA. Results were analyzed by the Chi-square test; a p-value of < 0.05 was considered statistically significant. RESULTS: The number of seropositive participants (%) was 308 (94.5%) for rubella, 295 (90.5%) for VZV, 244 (74.9%) for measles, and 219 (67.2%) for mumps. A significant correlation was found between measles IgG and age. A relationship was also observed between VZV IgG and kindergarten attendance. Response rates to measles, rubella, VZV, and mumps vaccination were 96%, 92.3%, 87.5%, 78.8%, respectively. The total cost of vaccination after IgG screening was less than vaccination without screening. CONCLUSIONS: In this study, participants' immunity to measles and VZV was low. Prevaccination serological screening was cost-effectiveness method for preventing measles, mumps, rubella, and varicella infections. We believe that administering booster measles, mumps, and rubella (MMR) vaccine doses or developing a special MMR vaccination strategy for at-risk groups may prevent MMR outbreaks.

Is Adenoidectomy and/or Tonsillectomy a Risk Factor for Allergic Diseases and Asthma in Adulthood?

OBJECTIVE: To determine the relationship between adenoidectomy and/or tonsillectomy in childhood and allergic diseases in adulthood. MATERIALS AND METHODS: A survey investigating the history of adenoidectomy and/or tonsillectomy was administered to patients that were followed-up by our department between January and June 2014 with the diagnosis of asthma, allergic rhinitis, urticaria-angioedema, drug allergy, food allergy, and venom allergy; patients willing to participate were included in the study. The relationship and risk ratios were analyzed. RESULTS: Totally, 510 (female/male: 379/131) patients were included in the study: 248 with asthma, 205 with rhinitis, 82 with drug allergy, 73 with urticaria, 24 with food allergy, and 14 with venom allergy. Of these, 65 (12.7%) had undergone adenoidectomy and/or tonsillectomy. Of these 65 patients, 41 had asthma, 33 had allergic rhinitis, and 28 had other allergic diseases. No relation between the history of atopy and adenoidectomy and/or tonsillectomy (p=0.129) was detected; however, there was a positive correlation between asthma and patients aged <15 years having a history of tonsillectomy and/or adenoidectomy (p=0.020). The risk of asthma was determined to be increased by 1.96 fold among the patients, provided the patient had undergone adenoidectomy and/or tonsillectomy (confidence interval [CI]:1.14-3.36). No connection was observed between atopic and non-atopic asthmatic patients in relation to adenoidectomy and/or tonsillectomy (p=0.46). No relationship was observed between allergic rhinitis and adenoidectomy and/or tonsillectomy. CONCLUSION: Adenoidectomy and/or tonsillectomy in childhood increase the risk of asthma in adulthood, whereas it does not increase the risk of atopy. This result signifies the criticality of adenoidectomy or tonsillectomy in the pathogenesis of asthma.

Metagenomics of pigmented and cholesterol gallstones: the putative role of bacteria.

There is growing evidence for bacteria playing a role in the pathogenesis and formation of pigmented gallstones from humans. These studies mainly involved cultivation of gallstone-associated bacteria and 16S rRNA profiling, providing an indirect link between processes involved in gallstone formation by the bacteria in-situ. Here, we provide functional metagenomic evidence of a range of genes involved in bile stress response, biofilm formation, and anaerobic energy metabolism by Gram-negative Klebsiella in pigmented gallstones from a 76-year-old male patient. Klebsiella was also present in one cholesterol-type stone in a 30-year-old female patient who had additional cholesterol gallstones characterised by Gram-positive bacteria. Pigmented stones further revealed a predominance of genes involved in carbohydrate metabolism, whilst cholesterol stones indicated a profile dominanted by protein metabolism possibly reflecting known chemical differences between Gram-negative and Gram-positive biofilm matrices. Archaeal genes were not detected. Complementary carbon and hydrogen isotopic analyses of cholesterol within the patients' stones revealed homogeneity, suggesting a common diet or cholesterol biosynthesis pathway that has little influence on microbial composition. This pilot study provides a framework to study microbial processes that play a potential role in gallstone formation across markedly different types of stones and patient backgrounds.

Three-dimensional shaping technique for coil placement using the steam-shaped microcatheter for ruptured blood blister-like aneurysm.

Treatment of blood blister-like aneurysm (BBA) is a challenge due to its unfavourable morphology, small size and the friable neck of BBA. In the management of ruptured BBA, coil placement can be achieved by stent-assisted coil embolisation. We propose to incorporate a new technique using a steam-shaped microcatheter to improve safety. A 59-year-old woman was transferred to our hospital and diagnosed with subarachnoid haemorrhage (SAH) due to a ruptured BBA of the left internal carotid artery (ICA) at the C2 portion. For coil embolisation, we selected the aneurysm sac using a three-dimensional shaping technique and the jailing method. Post-embolisation angiography revealed complete occlusion of the aneurysmal sac. For safe treatment and stability of BBA, the shape of the catheter tip and the distal portion of the microcatheter are two important factors to consider. The proposed technique could help resolve the problem of catheter shaping in the treatment of BBA.

Managing atypical and typical herpetic central nervous system infections: results of a multinational study.

There have been many studies pertaining to the management of herpetic meningoencephalitis (HME), but the majority of them have focussed on virologically unconfirmed cases or included only small sample sizes. We have conducted a multicentre study aimed at providing management strategies for HME. Overall, 501 adult patients with PCR-proven HME were included retrospectively from 35 referral centres in 10 countries; 496 patients were found to be eligible for the analysis. Cerebrospinal fluid (CSF) analysis using a PCR assay yielded herpes simplex virus (HSV)-1 DNA in 351 patients (70.8%), HSV-2 DNA in 83 patients (16.7%) and undefined HSV DNA type in 62 patients (12.5%). A total of 379 patients (76.4%) had at least one of the specified characteristics of encephalitis, and we placed these patients into the encephalitis presentation group. The remaining 117 patients (23.6%) had none of these findings, and these patients were placed in the nonencephalitis presentation group. Abnormalities suggestive of encephalitis were detected in magnetic resonance imaging (MRI) in 83.9% of the patients and in electroencephalography (EEG) in 91.0% of patients in the encephalitis presentation group. In the nonencephalitis presentation group, MRI and EEG data were suggestive of encephalitis in 33.3 and 61.9% of patients, respectively. However, the concomitant use of MRI and EEG indicated encephalitis in 96.3 and 87.5% of the cases with and without encephalitic clinical presentation, respectively. Considering the subtle nature of HME, CSF HSV PCR, EEG and MRI data should be collected for all patients with a central nervous system infection.

Mutation analysis of the NRXN1 gene in autism spectrum disorders.

The aim of this study was to identify the sequence mutations in the Neurexin 1 (NRXN1) gene that has been considered as one of the strong candidate genes. A total of 30 children and adolescents (aged 3-18) with non syndromic autism were enrolled this study. Sequencing of the coding exons and the exon-intron boundaries of the NRXN1 gene was performed. Two known mutations were described in two different cases. Heterozygous S14L was determined in one patient and heterozygous L748I was determined in another patient. The S14L and L748I mutations have been described in the patients with autism before. Both of these mutations were inherited from their father. In this study, two of 30 (6.7%) autism spectrum disorder (ASD) patients carrying NRXN1 gene mutations were detected. It indicates that variants in the NRXN1 gene might confer a risk of developing nonsyndromic ASD. However, due to the reduced penetrance in the gene, the causal role of the NRXN1 gene mutations must be evaluated carefully in all cases.

Role of inflammation in sensory neuropathy in prediabetes or diabetes.

OBJECTIVES: Prediabetes includes individuals with impaired glucose metabolism, and it has been associated with various complications of diabetes mellitus (DM), including peripheral neuropathy. We aimed to investigate the associations between pro-inflammatory (TNF-α) and anti-inflammatory (IL-10) cytokines and neuropathy of very distal sensory nerves in patients with prediabetes or type 2 DM. MATERIALS AND METHODS: We included 50 patients with prediabetes, 50 patients with type 2 DM, and 44 controls in the study. Plasma levels of HbA1c, TNF-α, and IL-10 were analyzed. Electrodiagnostic testing was performed on dorsal sural and medial plantar sensory nerves, which are the very distal sensory nerves of the feet. RESULTS: Abnormalities in nerve conduction studies (NCS) of the dorsal sural and medial plantar sensory nerves were substantially higher in patients with prediabetes or type 2 DM. In addition, plasma levels of TNF-α were significantly higher in patients with type 2 DM than in controls, whereas IL-10 levels were significantly lower in patients with both prediabetes and diabetes. However, we found no correlation between the levels of HbA1c, TNF-α, IL-10, and abnormalities in NCS of the dorsal sural or medial plantar sensory nerves in either patient group. CONCLUSIONS: To our knowledge, this is the first study to assess the relationships between TNF-α, IL-10, and NCS of the most distal sensory nerves in patients with prediabetes or type 2 DM. The mechanisms involved in the pathogenesis of DM and diabetic peripheral neuropathy are complex. The pro-inflammatory stage and the high incidence of neuropathy in patients with prediabetes may suggest a possible causative effect; however, the potential role of inflammation in the pathogenesis of peripheral neuropathy needs further clarification.

Molecular mechanism by which acyclic retinoid induces nuclear localization of transglutaminase 2 in human hepatocellular carcinoma cells.

Nuclear accumulation of transglutaminase 2 (TG2) is an important step in TG2-dependent cell death. However, the underlying molecular mechanisms for nuclear translocation of TG2 are still poorly understood. In this study, we demonstrated that acyclic retinoid (ACR) induced nuclear accumulation of TG2 in JHH-7 cells, a hepatocellular carcinoma (HCC) leading to their apoptosis. We further demonstrated molecular mechanism in nuclear-cytoplasmic trafficking of TG2 and an effect of ACR on it. We identified a novel 14-amino acid nuclear localization signal (NLS) (466)AEKEETGMAMRIRV(479) in the 'C' domain and a leucine-rich nuclear export signal (NES) (657)LHMGLHKL(664) in the 'D' domain that allowed TG2 to shuttle between the nuclear and cytosolic milieu. Increased nuclear import of GAPDH myc-HIS fused with the identified NLS was observed, confirming its nuclear import ability. Leptomycin B, an inhibitor of exportin-1 as well as point mutation of all leucine residues to glutamine residues in the NES of TG2 demolished its nuclear export. TG2 formed a trimeric complex with importin-α and importin-ß independently from transamidase activity which strongly suggested the involvement of a NLS-based translocation of TG2 to the nucleus. ACR accelerated the formation of the trimeric complex and that may be at least in part responsible for enhanced nuclear localization of TG2 in HCC cells treated with ACR.

N-acetyl cysteine reduces oxidative toxicity, apoptosis, and calcium entry through TRPV1 channels in the neutrophils of patients with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common inflammatory and oxidant disease with an uncertain pathogenesis. N-acetyl cysteine (NAC) decreases oxidative stress, intracellular free calcium ion [Ca(2+)]i, and apoptosis levels in human neutrophil. We aimed to investigate the effects of NAC on apoptosis, oxidative stress, and Ca(2+) entry through transient receptor potential vanilloid 1 (TRPV1) and TRP melastatin 2 (TRPM2) channels in neutrophils from patients with PCOS. Neutrophils isolated from PCOS group were investigated in three settings: (1) after incubation with TRPV1 channel blocker capsazepine or TRPM2 channel blocker 2-aminoethyl diphenylborinate (2-APB), (2) after supplementation with NAC (for 6 weeks), and (3) with combination (capsazepine + 2-APB + NAC) exposure. The neutrophils in TRPM2 and TRPV1 experiments were stimulated by N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP; 1 µM) and capsaicin (10 µM) as concentration agonists, respectively. Neutrophil lipid peroxidation and capsaicin-induced increase in [Ca(2+)]i concentrations were reduced by capsazepine and NAC treatments. However, the [Ca(2+)]i concentration did not change by fMLP stimulation. Neutrophil lipid peroxidation, apoptosis, caspase-3, caspase-9, cytosolic reactive oxygen species production, and mitochondrial membrane depolarization values were decreased by NAC treatment although neutrophil glutathione peroxidase and reduced glutathione levels were increased by the NAC treatment. Serum lipid peroxidation, luteinizing hormone, testosterone, insulin, interleukin-1 beta, and homocysteine levels were decreased by NAC treatment although serum vitamin A, beta-carotene, vitamin E, and total antioxidant status were increased by the NAC treatment. In conclusion, NAC reduced oxidative stress, apoptosis, cytokine levels, and Ca(2+) entry through TRPV1 channel, which provide supportive evidence that oxidative stress and TRPV1 channel plays a key role in etiology of PCOS.