Natural history of ENPP1 deficiency: Nationwide Turkish Cohort Study of autosomal-recessive hypophosphataemic rickets type 2.

OBJECTIVE: Autosomal-recessive hypophosphataemic rickets type 2 (ARHR2) is a rare disease that is reported in survivors of generalized arterial calcification of infancy (GACI). DESIGN, PATIENTS AND MEASUREMENT: The objective of this study was to characterize a multicenter paediatric cohort with ARHR2 due to ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (ENPP1) deficiency and with a diagnosis of GACI or GACI-related findings. The clinical, biochemical and genetic characteristics of the patients were retrospectively retrieved. RESULTS: We identified 18 patients from 13 families diagnosed with ARHR2. Fifteen of the patients had an ENPP1 variation confirmed with genetic analyses, and three were siblings of one of these patients, who had clinically diagnosed hypophosphataemic rickets (HRs) with the same presentation. From nine centres, 18 patients, of whom 12 (66.7%) were females, were included in the study. The mean age at diagnosis was 4.2 ± 2.2 (1.6-9) years. The most frequently reported clinical findings on admission were limb deformities (66.6%) and short stature (44.4%). At diagnosis, the mean height SD was -2.2 ± 1.3. Five of the patients were diagnosed with GACI in the neonatal period and treated with bisphosphonates. Other patients were initially diagnosed with ARHR2, but after the detection of a biallelic variant in the ENPP1 gene, it was understood that they previously had clinical findings associated with GACI. Three patients had hearing loss, and two had cervical fusion. After the treatment of HRs, one patient developed calcification, and one developed intimal proliferation. CONCLUSION: ARHR2 represents one manifestation of ENPP1 deficiency that usually manifests later in life than GACI. The history of calcifications or comorbidities that might be associated with GACI will facilitate the diagnosis in patients with ARHR2, and patients receiving calcitriol and phosphate medication should be carefully monitored for signs of calcification or intimal proliferation.

Investigation of SARS-CoV-2 using RT-PCR in vaginal swab samples of female patients with a diagnosis of severe COVID-19.

OBJECTIVE: It is important to determine the presence of SARS-CoV-2 in the vaginal fluid samples of reproductive-aged women with severe disease during the acute stage of the disease and to determine the risks of transmission by sexual or vertical transmission. MATERIAL AND METHODS: Adult women with confirmed severe COVID-19 who were admitted to Ankara City Hospital intensive care unit (ICU) between December 1st, 2020, and January 1st, 2021, were enrolled in the study. Vaginal swab samples were collected within 48 h in the ICU using Dacron or rayon swabs and tested for SARS-CoV-2 using reverse transcription real-time polymerase chain reaction (RT PCR). RESULTS: Thirty women of reproductive age were included in the study, five (16.7%) of whom were pregnant. The mean age was 44.9 (±10.5) years. The most common symptoms were headache (100%), muscle soreness (86.7%), cough (76.7%), fever (60%), and nausea and vomiting (20%). Nineteen (63.3%) patients had underlying medical conditions. The time interval from obtaining vaginal swab samples to admission to the ICU was 48 h. The time between vaginal sampling and PCR positivity ranged from 2 to 18 days. SARS-CoV-2 was not detected in any vaginal samples. CONCLUSION: Our study showed that women with severe COVID-19 did not have SARS-CoV-2 in their vaginal fluids. Investigation of the presence of SARS-CoV-2 in vaginal secretions may help in determining the risks of sexual transmission and vertical transmission from mother to baby. Information on this subject is still limited. Larger studies on comprehensive biological samples are needed.

The clinical and demographical characteristics of Turkish pediatric lymphedema patients: a multicenter study.

BACKGROUND: Reducing lymphedema-associated burden and disability in the pediatric setting requires improved awareness and understanding clinical properties of the lymphedema. The aim of this study was to evaluate the clinical and demographic characteristics of patients with pediatric lymphedema presented to different lymphedema centers in Turkey. METHODS: The socio-demographic and clinical characteristics of the children including age, gender, presence of genetic syndromes, duration of edema, site and stage of lymphedema and the received therapies were determined. Parental and children education on self-management techniques were recorded. RESULTS: A total of 122 children (female: 66, male: 56) with a mean age of 120.7 ± 71.2 months were included from 7 centers. Of them; 92% had primary, 8% had secondary lymphedema mostly due to infection and trauma. Lymphedema was part of a syndrome in 18% of the children. The most common site of involvement was the lower extremity, followed by upper extremity and genital involvement. Lymphedema was complicated in 17 % of children, mainly with a clinical picture of cellulitis, infection, and pain. The median duration of lymphedema was 41 (5-216) months. Although most of the children had stage 2 lymphedema, only 40% of them received treatment. The most commonly received treatment was compression therapy. No family or child was educated for self- care management before. DISCUSSION: In conclusion, pediatric lymphedema has a comparable gender distribution and usually involves the lower extremities. Although most of the children had advanced disease, more than half of the patients did not receive any treatment indicating the unmet need for management of lymphedema. The education of patients and/or children about self-management methods were lacking. We suggest educational activities for both families of children with lymphedema and health care providers, in order to facilitate early reference to lymphedema units and to receive prompt preventive and therapeutic approaches for this suffering condition.

Secondary bacterial infections of the respiratory tract in COVID-19 patients.

INTRODUCTION: Secondary Bacterial Infections (SBIs) of the respiratory system are one of the biggest medical concerns in patients undergoing hospitalization with a diagnosis of COVID-19. This study aims to provide relevant data for the initiation of appropriate empirical treatment after examining the etiology and antimicrobial resistance of SBIs in COVID-19 patients under care in the Intensive Care Units (ICUs) in the largest pandemic hospital of our country. METHODOLOGY: Between March 16, 2020 and December 31, 2021, 56,993 COVID patients were hospitalized, of which 7684 were admitted to ICUs. A total of 1513 patients diagnosed with SBIs have been included in this study. During the course of the study, demographic data, clinical course, etiology and antimicrobial resistance data of all patients were collected. RESULTS: The most common causative agents of SBIs were inferred as Acinetobacter baumanii (35.1%), Staphylococcus aureus (15.2%), Klebsiella pneumoniae (12.3%) and Pseudomonas aeruginosa (10.4%). The isolation rates of carbapenem-resistant and colistin-resistant A. baumannii, K. pneumoniae and P. aeruginosa were 83.7%; 42.7%, 79.2%, and 5.6%, 42.7%, 1.7%, respectively. Acinetobacter pittii clustering was seen in one of the ICUs in the hospital. Multidrug resistant 92 (5.4%) Corynebacterium striatum isolates were also found as a causative agent with increasing frequency during the study period. CONCLUSIONS: SBI of the respiratory system is one of the major complications in patients hospitalized with COVID-19. The antimicrobial resistance rates of the isolated bacteria are generally high, which indicates that more accurate use of antibacterial agents is necessary for SBIs in patients hospitalized with COVID-19 diagnosis.

NUTRIC Score Is Not Superior to mNUTRIC Score in Prediction of Mortality of COVID-19 Patients.

Objectives: The NUTRIC (nutrition risk in the critically ill) score and the modified NUTRIC score are two scoring systems that show the nutritional risk status and severity of acute disease of patients. The only difference between them is the examination of interleukin-6 (IL-6) level. The aim of this study was to investigate whether or not the NUTRIC score is superior to the mNUTRIC score in the prediction of mortality of patients with COVID-19 followed up in the Intensive Care Unit (ICU). Material and Method. This retrospective study included 322 patients followed up in ICU with a diagnosis of COVID-19. A record was made of demographic data, laboratory values, clinical results, and mortality status. All the data of the patients were compared between high and low variations of the NUTRIC score and the mNUTRIC score. Results: A high NUTRIC score was determined in 62 patients and a high mNUTRIC score in 86 patients. The need for invasive mechanical ventilation, the use of vasopressors in ICU, the development of acute kidney injury, and mortality rates were statistically significantly higher in the patients with high NUTRIC and high mNUTRIC scores than in those with low scores (p = 0.0001 for all). The AUC values were 0.791 for high NUTRIC score and 0.786 for high mNUTRIC score (p = 0.0001 for both). No statistically significant difference was determined between the two scoring systems. Conclusion: Although the NUTRIC score was seen to be superior to the mNUTRIC score, no statistically significant difference was determined. Therefore, when IL-6 cannot be examined, the mNUTRIC score can be considered safe and effective for the prediction of mortality in COVID-19 patients.

Evaluation of peripapillary and subfoveal choroidal vascularity index in patients with multiple sclerosis.

PURPOSE: To evaluate the changes in the peripapillary choroidal vascularity index (PCVI) and subfoveal choroidal vascularity index (SFCVI) in multiple sclerosis (MS) patients and healthy subjects. METHODS: A total of 145 eyes of 73 patients were investigated in this cross-sectional study. 78 eyes of 39 MS patients (Group 1) and 67 eyes of 34 healthy subjects (Group 2) were evaluated. MS patients with a history of optic neuritis (ON) constituted Group 1a, those without a history of ON constituted Group 1b. RESULTS: The mean PCVI was significantly lower in Group 1 than Group 2 (61,39 ± 3,00% vs 64,49 ± 2,29%, respectively, p < 0.001). The mean SFCVI scores of Group 1 was significantly lower than Group 2 (64,01 ± 2,66% vs. 66,87 ± 2,14%, respectively, p < 0.001). The mean PCVI of Group 1a (59,26 ± 2,85%) was significantly lower compared to Group 1b (62,87 ± 2,08%) and Group 2 (64,49 ± 2,29%, p1 < 0.001, p2 < 0.001). The mean SFCVI of Group 1a was significantly lower than Group 2 (64.26 ± 2.75% vs. 66.87 ± 2.14%, respectively, p < 0.001). CONCLUSION: PCVI and SFCVI scores were significantly lower in MS patients compared to healthy controls. PCVI scores of MS patients who had a history of ON were significantly lower than those of patients without a previous ON attack, as were SFCVI scores. We consider that evaluation of PCVI and SFCVI might be useful for monitoring ocular involvement in patients with MS.

Evaluation of the impact of childhood obesity on retrobulbar hemodynamics and retinal microvasculature.

OBJECTIVE: To evaluate changes in retrobulbar ocular blood flow parameters by using Colour Doppler Imaging (CDI) and changes in foveal microvasculature by using Optical Coherence Tomography Angiography (OCTA) in pediatric obese patients and to compare them with a group of healthy children. METHODS: Children diagnosed with obesity without hypertension and diabetes (39 subjects, obese group) and age-matched healthy controls (26 subjects, control group) underwent CDI and OCTA imaging. Peak systolic velocity, end-diastolic velocity and resistivity index from ophthalmic, central retinal and posterior ciliary arteries on CDI; superficial and deep capillary plexus vascular density and foveal avascular zone area on OCTA imaging were obtained in each group. Central foveal and subfoveal choroidal thicknesses were also measured. CDI and OCTA parameters were compared between two groups. RESULTS: Peak systolic and end-diastolic velocities were found to be significantly lower in obese children than in controls in all three examined arteries (p < 0.05). Resistivity index values were similar between the groups. OCTA imaging did not reveal significant changes in superficial and deep capillary plexus vascular densities and foveal avascular zone area across analysed retinal regions between the groups. Subfoveal choroid was thicker in obese group than in control group (325.89 ± 52.77 µm vs. 304.52 ± 21.76 µm, p = 0.04). CONCLUSION: An apparent decrease was present in retrobulbar hemodynamics in obese children. This arises the possibility of early ocular macrovascular compromise rather than retinal microvascular impairment in childhood obesity.

Are angiotensin converting enzyme (ACE1/ACE2) gene variants associated with the clinical severity of COVID-19 pneumonia? A single-center cohort study.

OBJECTIVE: The impact of the coronavirus disease 2019 (COVID-19) pandemic has been unceasingly ongoing worldwide. Recent bioinformatics analysis and epidemiologic studies have highlighted that the functional polymorphisms on the angiotensin converting enzyme (ACE) gene may have an impact on the clinical progress of COVID-19. In this study, we aimed to determine the impact of the ACE1 gene I/D polymorphism and ACE2 peptidase-2 domain variants on disease severity. METHODS: Hundred patients with confirmed COVID-19 related pneumonia [50 patients with severe disease in intensive care unit (ICU) and 50 patients not in ICU] were compared on the basis of genetic and clinical characteristics. Genomic DNA was purified from peripheral blood lymphocytes with an automated QIA symphony DSP DNA Mini-Kit. The Sanger sequencing analysis was performed. The frequencies of ACE1 gene polymorphism and ACE2 PD variants were compared in patients hospitalized in ICU and those not in ICU. The Statistical Package for Social Sciences version 22.0 was used for statistical analysis. RESULTS: The sequencing analysis of the ACE2 gene exon 1 and 2 revealed none of the polymorphisms investigated or any other variants in the present cohort. The frequencies of the ACE1 ID, DD, and II genotypes were 51%, 31%, and 18%, respectively. The frequency of the D allele was similar between the ICU and non-ICU groups (50.4% versus 49.6%). Older age and the presence of advanced stage radiologic abnormalities on admission were detected as independent predictors of ICU requirement. CONCLUSION: No effect of any ACE1 gene polymorphism on predicting ICU requirement was detected. To the best of our knowledge, this is the first study investigating the impact of ACE gene polymorphisms on clinical severity of COVID-19 in a Turkish cohort.

Glucocorticoids in a Neonatal Hyperoxic Lung Injury Model: Pulmonary and Neurotoxic effects.

BACKGROUND: We aimed to compare the effect of dexamethasone (Dex), hydrocortisone (Hc), and methylprednisolone (Mpz) at equivalent doses on somatic growth, lung healing, and neurotoxicity in a hyperoxic rat model. We hypothesized that Mpz and Hc would be superior to Dex with less neurotoxicity by exerting similar therapeutic efficacy on the injured lung. METHODS: Neonatal rats were randomized to control, bronchopulmonary dysplasia (BPD), Dex, Hc, and Mpz groups. All drugs were administered daily following day 15 over 7 days. Histopathological and immunohistochemical analyses of the lung and brain were performed on day 22. RESULTS: All types had much the same impact on lung repair. Oxidative markers in the lung were similar in the steroid groups. While nuclear factor erythroid 2-related factor and heat-shock protein 70 dropped following steroid treatment, no difference was noted in other biochemical markers in the brain between the study groups. Apoptotic activity and neuron loss in the parietal cortex and hippocampus were noted utmost in Dex, but alike in other BPD groups. CONCLUSIONS: Mpz does not appear to be superior to Dex or Hc in terms of pulmonary outcomes and oxidative damage in the brain, but safer than Dex regarding apoptotic neuron loss. IMPACT: This is the first study that compared the pulmonary efficacy and neurotoxic effects of Dex, Hc, and Mpz simultaneously in an established BPD model. This study adds to the literature on the importance of possible antioxidant and protective effects of glucocorticoid therapy in an oxidative stress-exposed brain. Mpz ended up with no more additional neuron loss or apoptosis risk by having interchangeable effects with others for the treatment of established BPD. Mpz and Hc seem safe as a rescue therapy in terms of adverse outcomes for established BPD in which lung and brain tissue is already impaired.

Wild emmer wheat, the progenitor of modern bread wheat, exhibits great diversity in the VERNALIZATION1 gene.

Wild emmer wheat is an excellent reservoir of genetic variability that can be utilized to improve cultivated wheat to address the challenges of the expanding world population and climate change. Bearing this in mind, we have collected a panel of 263 wild emmer wheat (WEW) genotypes across the Fertile Crescent. The genotypes were grown in different locations and phenotyped for heading date. Genome-wide association mapping (GWAS) was carried out, and 16 SNPs were associated with the heading date. As the flowering time is controlled by photoperiod and vernalization, we sequenced the VRN1 gene, the most important of the vernalization response genes, to discover new alleles. Unlike most earlier attempts, which characterized known VRN1 alleles according to a partial promoter or intron sequences, we obtained full-length sequences of VRN-A1 and VRN-B1 genes in a panel of 95 wild emmer wheat from the Fertile Crescent and uncovered a significant sequence variation. Phylogenetic analysis of VRN-A1 and VRN-B1 haplotypes revealed their evolutionary relationships and geographic distribution in the Fertile Crescent region. The newly described alleles represent an attractive resource for durum and bread wheat improvement programs.

Does hospitalisation of a patient in the intensive care unit cause anxiety and does restriction of visiting cause depression for the relatives of these patients during COVID-19 pandemic?

OBJECTIVES: During the pandemic, anxiety and depression may occur increasingly in the whole society. The aim of this study was to evaluate the possible cause, incidence and levels of anxiety and depression in the relatives of the patients in the intensive care unit (ICU) in accordance with the patients' SARS-CoV-2 polymerase chain reaction (PCR) result. MATERIALS AND METHOD: The study was prospectively conducted on relatives of patients admitted to tertiary intensive care units during COVID-19 pandemic. Sociodemographic characteristics of the patients and their relatives were recorded. "The Turkish version of the Hospital Anxiety and Depression Scale" was applied twice to the relatives of 120 patients to determine the symptoms of anxiety and depression in accordance with the PCR results of the patients (PCR positive n = 60, PCR negative n = 60). RESULTS: The ratios above cut-off values for anxiety and depression among relatives of the patients were 45.8% and 67.5% for the first questionnaire and 46.7% and 62.5% for the second questionnaire, respectively. The anxiety and depression in the relatives of PCR-positive patients was more frequent than the PCR negative (P < .001 for HADS-A and P = .034 for HADS-D). The prevalence of anxiety and depression was significantly higher in female relatives (P = .046 for HADS-A and P = .009 for HADS-A). There was no significant correlation between HADS and age of the patient or education of the participants. The fact that the patients were hospitalised in the ICU during the pandemic was an independent risk factor for anxiety (AUC = 0.746) while restricted visitation in the ICU was an independent risk factor for depression (AUC = 0.703). CONCLUSION: Positive PCR and female gender were associated with both anxiety and depression while hospitalisation in the ICU due to COVID-19 was an independent risk factor for anxiety and restricted visitation in the ICU is an independent risk factor for depression.

Lactate/albumin ratio is more effective than lactate or albumin alone in predicting clinical outcomes in intensive care patients with sepsis.

This study aimed to compare the value of lactate, albumin, and lactate/albumin ratio for the prediction of mortality in sepsis patients. Patients admitted to the intensive care unit (ICU) due to sepsis between January 2016 and January 2019 were evaluated retrospectively. Lactate, albumin, and lactate/albumin ratio values were compared between surviving and non-surviving patients and their predictive value for mortality was evaluated. A total of 1136 sepsis patients admitted to the ICU were included in the study. The mortality rate was 42.7% (485/1136 patients). In ROC analysis for mortality prediction, the area under the curve and optimal cut-off values were 0.816 and >2.2 mmol/L for lactate, 0.812 and ≤26 g/L for albumin, and 0.869 and >0.71 for lactate/albumin ratio, respectively. Our analysis of lactate, albumin, and lactate/albumin ratio in the largest patient sample to date showed that lactate/albumin ratio was a stronger parameter than lactate or albumin alone in predicting mortality among sepsis patients in the ICU. Lactate/albumin ratio is an easily obtained parameter with potential value for critically ill patients.

A comparison of glycemic parameters and their relationship with C-peptide and Proinsulin levels during partial remission and non-remission periods in children with type 1 diabetes mellitus - a cross-sectional study.

BACKGROUND: Currently, there is a lack of data relating to glycemic parameters and their relationship with C-peptide (CP) and proinsulin (PI) during the partial remission period (PRP) in type 1 diabetes mellitus (T1D). The aim of this study was to evaluate glycemic parameters in children with T1D who are in the PRP using intermittently scanned continuous glucose monitoring systems (isCGMS) and to investigate any relationships between CP and PI levels. METHODS: The study included 21 children who were in the PRP and 31 children who were not. A cross-sectional, non-randomized study was performed. Demographic, clinical data were collected and 2 week- isCGMS data were retrieved. RESULTS: The Serum CP showed a positive correlation with time-in-range in the PRP (p:0.03), however PI showed no correlations with glycemic parameters in both periods. The Serum CP and PI levels and the PI:CP ratio were significantly higher in the PRP group than in the non-PRP group. In the non-PRP group, the PI level was below 0.1 pmol/L (which is the detectable limit) in only 2 of the 17 cases as compared with none in the PRP group. Similarly, only 2 of the 17 children in the non-PRP group had CP levels of less than 0.2 nmol / L, although both had detectable PI levels. Overall time-in-range (3. 9-1.0 mmol/L) was significantly high in the PRP group. In contrast, the mean sensor glucose levels, time spent in hyperglycemia, and coefficient of variation levels (32.2vs 40.5%) were significantly lower in the PRP group. CONCLUSIONS: Although the mean glucose and time in range during the PRP was better than that in the non-PRP group, the glycemic variability during this period was not as low as expected. While the CP levels showed an association with TIR during the PRP, there was no correlation between PI levels and glycemic parameters. Further studies are needed to determine if PI might prove to be a useful parameter in clinical follow-up.

Loss-of-function variants in SEMA3F and PLXNA3 encoding semaphorin-3F and its receptor plexin-A3 respectively cause idiopathic hypogonadotropic hypogonadism.

PURPOSE: Idiopathic hypogonadotropic hypogonadism (IHH) is characterized by absent puberty and subsequent infertility due to gonadotropin-releasing hormone (GnRH) deficiency. IHH can be accompanied by normal or compromised olfaction (Kallmann syndrome). Several semaphorins are known potent modulators of GnRH, olfactory, and vomeronasal system development. In this study, we investigated the role of Semaphorin-3F signaling in the etiology of IHH. METHODS: We screened 216 IHH patients by exome sequencing. We transiently transfected HEK293T cells with plasmids encoding wild type (WT) or corresponding variants to investigate the functional consequences. We performed fluorescent IHC to assess SEMA3F and PLXNA3 expression both in the nasal region and at the nasal/forebrain junction during the early human fetal development. RESULTS: We identified ten rare missense variants in SEMA3F and PLXNA3 in 15 patients from 11 independent families. Most of these variants were predicted to be deleterious by functional assays. SEMA3F and PLXNA3 are both expressed along the olfactory nerve and intracranial projection of the vomeronasal nerve/terminal nerve. PLXNA1-A3 are expressed in the early migratory GnRH neurons. CONCLUSION: SEMA3F signaling through PLXNA1-A3 is involved in the guidance of GnRH neurons and of olfactory and vomeronasal nerve fibers in humans. Overall, our findings suggest that Semaphorin-3F signaling insufficiency contributes to the pathogenesis of IHH.

Astaxanthin Prevents Lung Injury Due to Hyperoxia and Inflammation.

BACKGROUND/AIM: This study aimed to ascertain the effects of astaxanthin on the lungs of rat pups with bronchopulmonary dysplasia (BPD) induced by hyperoxia and lipopolysaccharide (LPS). MATERIALS AND METHODS: Forty-two newborn Wistar rats, born to spontaneous pregnant rats, were divided into three groups: Hyperoxia (95% O2) + lipopolysaccharide (LPS) group, hyperoxia + LPS + astaxhantin group, and control: no treatment group (21% O2). Pups in the hyperoxia + LPS + astaxanthin group were given 100 mg/kg/day oral astaxanthin from the first day to the fifth day. Histopathologic and biochemical evaluations, including glutathione (GSH), total anti-oxidant status (TAS), total oxidant status (TOS), lipid hydroperoxide (LPO), 8-hydroxydeoxyguanosine (8-OHdG), advanced oxidation protein products (AOPP), myeloperoxidase (MPO), total thiol, tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), and caspase-3 activities, were performed. RESULTS: Better survival rates and weight gain were demonstrated in the hyperoxia + LPS + astaxanthin group (p <0.001). In the histopathologic evaluation, the severity of lung damage was significantly reduced in the hyperoxia+LPS+astaxanthin group, as well as decreased apoptosis (ELISA for caspase-3) (p <0.001). The biochemical analyses of lung tissues showed that TAS, GSH, and Total thiol levels were significantly higher in the astaxanthin treated group compared to the hyperoxia + LPS group (p <0.05) while TOS, AOPP, LPO, 8-OHdG, MPO levels were significantly lower (p <0.001). In addition, unlike the hyperoxia + LPS group, TNF-α and IL-1ß levels in lung tissue were significantly lower in the astaxanthin-treated group (p <0.001). CONCLUSION: Astaxanthin was shown to reduce lung damage caused by inflammation and hyperoxia with its anti-inflammatory, anti-oxidant, anti-apoptotic properties, and to protect the lung from severe destruction.

Thiol/Disulfide Homeostasis as an Early Biomarker to Differentiate Sepsis from Pneumonia in Intensive Care Units.

BACKGROUND: It is possible that patients with pneumonia may also have sepsis and the separation of these two clinical entities may cause some trouble to clinicians. OBJECTIVE: In order to separate a patient with pneumonia and a patient with sepsis, we qualify thiol/disulfide homeostasis as a potential biomarker. METHODS: This study was designed between February 2018 - February 2019 prospectively. All patients in the intensive care unit with pneumonia and sepsis were enrolled in the study. At the time of hospitalization, thiol/disulfide homeostasis was measured. Patients diagnosed with sepsis and pneumonia were compared, in regards to thiol/disulfide homeostasis. RESULTS: During research period, 103 patients with sepsis and 120 patients with pneumonia were enrolled into the study. When we compared native-thiol, total-thiol, and disulfide levels in both sepsis and pneumonia patients, we had similar results (p>0.05). In sepsis group, index-1 (disulfide/native thiol ratio) and index-2 (disulfide/total thiol ratio) were found to be statistically higher than the pneumonia group, and index-3 (native thiol/total thiol ratio) was statistically lower than the pneumonia group (p=0.020, p= 0.021, p=0.021, respectively). CONCLUSION: In this study, we showed that thiol/disulfide homeostasis could be used as new markers in the early period in order to separate patients with sepsis and patients with pneumonia.

Preventative and therapeutic effects of fennel (Foeniculum vulgare) seed extracts against necrotizing enterocolitis.

We aimed to understand the efficacy of fennel (Foeniculum vulgare: FV) extract in an experimental necrotizing enterocolitis (NEC) model. Forty-two rat pups were divided into three groups as NEC, NEC treated with fennel extract, and control. At the end of the experiment, tissue samples were taken from the proximal colon and ileum for biochemical and immuno-histological studies including hematoxylin-eosin and Caspase-3-8-9 immunohistochemical staining. Bowel damage and apoptosis were found to be less in the NEC + FV group. Oxidant stress, caspase 3, TNF-α, and IL-6 levels were considerably decreased in the NEC + FV group. Antioxidants were significantly higher in the NEC + FV group more than in the NEC group. Moreover, protein, DNA damage, and lipid peroxidation were found to be decreased in the NEC + FV group compared to the NEC group. PRACTICAL APPLICATIONS: Intense inflammation, oxidant stress, apoptosis, and infection are important in the development of NEC. Fennel has anti-oxidant, anti-inflammatory, antibacterial, antifungal, antiviral, immunomodulatory effects. Fennel extract might be a novel option in the treatment of NEC through its anti-oxidant, anti-inflammatory, anti-apoptotic, and cytoprotective features.

Favorable Effects of Astaxanthin on Brain Damage due to Ischemia- Reperfusion Injury.

BACKGROUND: Activated inflammation and oxidant stress during cerebral ischemia reperfusion injury (IRI) lead to brain damage. Astaxanthin (ASX) is a type of carotenoid with a strong antioxidant effect. OBJECTIVE: The aim of this study was to investigate the role of ASX on brain IRI. METHODS: A total of 42 adult male Sprague-Dawley rats were divided into 3 groups as control (n=14) group, IRI (n=14) group and IRI + ASX (n=14) group. Cerebral ischemia was instituted by occluding middle cerebral artery for 120 minutes and subsequently, reperfusion was performed for 48 hours. Oxidant parameter levels and protein degradation products were evaluated. Hippocampal and cortex cell apoptosis, neuronal cell count, neurological deficit score were evaluated. RESULTS: In the IRI group, oxidant parameter levels and protein degradation products in the tissue were increased compared to control group. However, these values were significantly decreased in the IRI + ASX group (p<0.05). There was a significant decrease in hippocampal and cortex cell apoptosis and a significant increase in the number of neuronal cells in the IRI + ASX group compared to the IRI group alone (p<0.05). The neurological deficit score which was significantly lower in the IRI group compared to the control group was found to be significantly improved in the IRI + ASX group (p<0.05). CONCLUSION: Astaxanthin protects the brain from oxidative damage and reduces neuronal deficits due to IRI injury.

Sumac (Rhus coriaria) for the prevention and treatment of necrotizing enterocolitis.

Leukotrienes, free oxygen radicals, tumor necrosis factor-alpha, and inflammatory mediators play major roles in the development of necrotizing enterocolitis (NEC). Rhus coriaria (RC: sumac) extracts may enhance cell viability by reinforcing defenses against free radical species in several progressive diseases as well as inflammatory diseases. The aim of the present study was to evaluate the effects of RC in a rat NEC model in terms of intestinal damage. Newborn pups were separated into three groups: control, NEC, and NEC treated with RC. Mortality and clinical sickness scores were evaluated. At the end of the study, ileum and proximal colon were obtained from all rats and histopathological and immunohistochemical studies were performed. In this study, the anti-inflammatory, antioxidant, immunomodulatory, and anti-apoptotic activities of RC were demonstrated in a rat NEC model, which suggests RC as a promising treatment option for preventing intestinal tissue damage. PRACTICAL APPLICATIONS: Free oxygen radicals, tumor necrosis factor-alpha, and inflammatory mediators play major roles in the development of NEC. Intestinal tissue damage is caused by necrosis and apoptosis as a result of intestinal inflammation and release of pro-inflammatory cytokines. Anti-inflammatory, antioxidant, immunomodulatory, and anti-apoptotic activities of RC are especially due to its phenolic compounds. In this study, the anti-inflammatory, antioxidant, immunomodulatory, and anti-apoptotic activities of RC were demonstrated in a rat NEC model. RC can suggest as a new treatment option for preventing intestinal injury.

Brain Deaths and Donors in an Education and Research Hospital.

BACKGROUND: We aimed to define the causes of brain death (BD), criteria, and tests used for diagnosis, rates of family consent, and rates of organ donation in intensive care units (ICUs) of an education and research hospital. METHODS: The data of patients with BD diagnosis in 7 years in our hospital was collected from an electronic database and archives retrospectively consisting of the demographic data, the causes of BD, criteria, and the tests used for diagnosis, family consent, and organ donation rates. RESULTS: A total of 210 patients with BD diagnosis were enrolled in the study. There was a decline in number of patients with BD diagnosis between 2012 (54.76%) and 2018 (17.64%) in the neurology and neurosurgery ICU, while it increased from 35.71% in 2012 to 70.6% in 2018 in the general ICU. The most common cause of hospitalization for BD was spontaneous intracranial hemorrhage (43.8%). A total of 47.6% of brain-dead patients who did not qualify for organ donation were resuscitated unnecessarily after cardiac death. In 2012, diagnosis was always supported by ancillary tests, while in 2018, a total of 35.29% of the patients were diagnosed solely by clinical examination; 23.8% of patients' families had given consent for organ donation, and 19.53% of 210 patients became donors. CONCLUSION: Physicians should be aware that patients with poor neurologic outcome can be candidates of BD donation, and careful examination and rapid diagnosis is crucial. All segments of society and the health care professionals should be informed and updated about organ donation and BD regularly to raise the numbers of organ donation.