Rapid Biocatalytic Synthesis of Aromatic Acid CoA Thioesters by Using Microbial Aromatic Acid CoA Ligases.

Chemically labile ester linkages can be introduced into lignin by incorporation of monolignol conjugates, which are synthesized in planta by acyltransferases that use a coenzyme A (CoA) thioester donor and a nucleophilic monolignol alcohol acceptor. The presence of these esters facilitates processing and aids in the valorization of renewable biomass feedstocks. However, the effectiveness of this strategy is potentially limited by the low steady-state levels of aromatic acid thioester donors in plants. As part of an effort to overcome this, aromatic acid CoA ligases involved in microbial aromatic degradation were identified and screened against a broad panel of substituted cinnamic and benzoic acids involved in plant lignification. Functional fingerprinting of this ligase library identified four robust, highly active enzymes capable of facile, rapid, and high-yield synthesis of aromatic acid CoA thioesters under mild aqueous reaction conditions mimicking in planta activity.

Sociodemographic, clinical, laboratory, treatment and prognostic characteristics of 156 generalized pustular psoriasis patients in Turkey: a multicentre case series.

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare and severe inflammatory disease characterized by widespread and superficial sterile pustules on an erythematous background. OBJECTIVES: This multicentre study aimed to determine the clinical profile and course in a large cohort of patients with GPP. METHODS: One hundred and fifty-six GPP patients (mean age, 44.2 ± 18.7 years) who met the diagnostic criteria of the European Consensus Report of GPP were included in the study. Sociodemographic characteristics, quality of life, triggering factors of the disease, clinical, laboratory, treatment and prognostic features were evaluated. RESULTS: 61.5% of the patients were female. The rate of working at or below the minimum wage (≤$332.5/month) was 44.9%. Drugs (36.5%) were the most common trigger. While hypocalcaemia (35.7%) was the most important cause of GPP during pregnancy, systemic steroid withdrawal (20%) was the most frequently reported trigger for infantile/juvenile and mixed-type GPP (15%) (P < 0.05). Acute GPP (53.8%) was the most common clinic. Nails were affected in 43.6% of patients, and subungual yellow spots (28.2%) were the most common change. In annular GPP, fever (P < 0.001) and relapse frequency (P = 0.006) were lower than other subtypes, and the number of hospitalizations (P = 0.002) was lower than acute GPP. GPP appeared at a later age in those with a history of psoriasis (P = 0.045). DLQI score (P = 0.049) and joint involvement (P = 0.016) were also higher in this group. Infantile/juvenile GPP was observed in 16.02% of all patients, and arthritis was lower in this group (24.4 vs. 16%). GPP of pregnancy had the worst prognosis due to abortion observed in three patients. CONCLUSIONS: Recent advances in treatment have improved mortality associated with GPP, but abortion remains a significant complication. Although TNF-α inhibitors have proven efficacy in GPP, they can also trigger the disease. Mixed-type GPP is more similar to acute GPP than annular GPP with systemic manifestations and course.

The usability of the ratio of bi-humerus breadth to maximum pelvic breadth in sex estimation.

BACKGROUND: Although sex can be determined with high accuracy in forensic anthropology, additional parameters are still required. AIM: To estimate with known simple statistical methods, the usability of the bi-humerus/maximum pelvic breadth ratio in sex estimation. SUBJECTS AND METHODS: Bi-humerus breadth and maximum pelvic breadth were measured using the topogram images (196 males, 171 females), the ratio between them was calculated. We examined the usability of the ratio of the distance between the lateral edges of the right and left humeral heads to the maximum distance between the two most lateral parts of the iliac crests in sex estimation. RESULTS: There was significant difference in the bi-humerus breadth and "bi-humerus breadth/maximum pelvic breadth" according to sex. The greatest breadth of the pelvis was higher in females, yet the difference was not statistically significant. The ratio yielded 80.6%-90.3% accuracy for females and 73.6%-74.7% for males, depending on arm position. CONCLUSIONS: The obtained data may contribute to the development of formulas created with metric measurements used in sex estimation. This can be used as a parameter to help in estimating the sex of skeletal remains found as a whole or excavated without losing their integrity, and also in the reconstruction of body structure.

Intraoperative and postoperative complications of gynecological laparoscopic interventions: incidence and risk factors.

PURPOSE: The aims of this study were to determine the incidence of intraoperative and postoperative complications of laparoscopic gynecological interventions and to identify risk factors for such complications. METHODS: All patients who underwent laparoscopic interventions from September 2013 to September 2017 at the Department of Gynecology, Obstetrics and Reproductive Medicine, Saarland University Hospital were identified retrospectively using a prospectively compiled clinical database. Binary logistic regression analysis was used to identify independent risk factors for intra- and postoperative complications. RESULTS: Data from 3351 patients were included in the final analysis. Overall, 188 (5.6%) intraoperative and 219 (6.5%) postoperative complications were detected. On multivariate analysis, age [odds ratio (OR), 1.03; 95% confidence interval (CI) 1.01-1.04], surgery duration (OR, 1.02; 95% CI 1.02-1.03), carbon dioxide use (OR, 0.99; 95% CI 0.99-1.00), and surgical indication (all p ≤ 0.01) were independent risk factors for intraoperative and duration of surgery (OR, 1.01; 95% CI 1.01-1.02; p ≤ 0.01), carbon dioxide use (OR, 0.99; 95% CI 0.99-1.00; p ≤ 0.01), hemoglobin drop (OR, 1.41; 95% CI 1.21-1.65; p ≤ 0.01), and ASA status (p = 0.04) for postoperative complications. CONCLUSION: In this large retrospective analysis with a generally low incidence of complications (5.6% intraoperative and 6.5% postoperative complications), a representative risk collective was identified: Patients aged > 38 years, surgery duration > 99 min, benign or malignant adnex findings were at higher risk for intraoperative and patients with surgery duration > 94 min, hemoglobin drop > 2 g/dl and ASA status III at higher risk for postoperative complications.

THE EFFECT OF DIABETES SYMPTOMS ON QUALITY OF LIFE IN INDIVIDUALS WITH TYPE 2 DIABETES.

OBJECTIVE: This study aimed to investigate the effect of symptoms of diabetes on the quality of life of individuals with Type 2 diabetes. METHOD: The study used a cross-sectional design. No sampling procedure was employed in the study; instead, 410 individuals presenting to the Balikesir Atatürk City Hospital Endocrinology and Internal Medicine Polyclinics between December 2016 and July 2017, diagnosed with Type 2 diabetes, and meeting the inclusion criteria were enrolled in the study sample. The study data were collected with a "Socio-demographic Characteristics Questionnaire", the "Diabetes Symptom Checklist", and the "SF-36 Quality of Life Questionnaire". RESULTS: The participants obtained the highest mean scores from the hyperglycemia subscale of the Diabetes Symptoms Checklist (3.35±0.60) and the mental health subscale of the SF-36 Quality of Life Questionnaire (50.65±8.10). The hypoglycemia, cardiology, psychology, and neurology variables included in the model were statistically significant and predicted 35% of the mental subscale score of the SF 36 questionnaire. SF 36 physical subscale score increased as the hypoglycemia, cardiology, psychology, and neurology scores decreased (p<0.05). CONCLUSION: The participants obtained high scores from the hyperglycemia subscale of the diabetes symptom checklist and mental health subscale of the quality of life questionnaire. Diabetes symptoms were found to affect the quality of life of individuals with diabetes.

Uncovering sperm metabolome to discover biomarkers for bull fertility.

BACKGROUND: Subfertility decreases the efficiency of the cattle industry because artificial insemination employs spermatozoa from a single bull to inseminate thousands of cows. Variation in bull fertility has been demonstrated even among those animals exhibiting normal sperm numbers, motility, and morphology. Despite advances in research, molecular and cellular mechanisms underlying the causes of low fertility in some bulls have not been fully elucidated. In this study, we investigated the metabolic profile of bull spermatozoa using non-targeted metabolomics. Statistical analysis and bioinformatic tools were employed to evaluate the metabolic profiles high and low fertility groups. Metabolic pathways associated with the sperm metabolome were also reported. RESULTS: A total of 22 distinct metabolites were detected in spermatozoa from bulls with high fertility (HF) or low fertility (LF) phenotype. The major metabolite classes of bovine sperm were organic acids/derivatives and fatty acids/conjugates. We demonstrated that the abundance ratios of five sperm metabolites were statistically different between HF and LF groups including gamma-aminobutyric acid (GABA), carbamate, benzoic acid, lactic acid, and palmitic acid. Metabolites with different abundances in HF and LF bulls had also VIP scores of greater than 1.5 and AUC- ROC curves of more than 80%. In addition, four metabolic pathways associated with differential metabolites namely alanine, aspartate and glutamate metabolism, ß-alanine metabolism, glycolysis or gluconeogenesis, and pyruvate metabolism were also explored. CONCLUSIONS: This is the first study aimed at ascertaining the metabolome of spermatozoa from bulls with different fertility phenotype using gas chromatography-mass spectrometry. We identified five metabolites in the two groups of sires and such molecules can be used, in the future, as key indicators of bull fertility.

Transcatheter aortic valve replacement alters ascending aortic blood flow and wall shear stress patterns: A 4D flow MRI comparison with age-matched, elderly controls.

BACKGROUND: With the implementation of transcatheter aortic valve replacement (TAVR) in lower-risk patients, evaluation of blood flow characteristics and the effect of TAVR on aortic dilatation becomes of considerable interest. We employed 4D flow MRI in the ascending aorta of patients after TAVR to assess wall shear stress (WSS) and compare blood flow patterns with surgical aortic valve replacement (SAVR) and age- and gender-matched controls. METHODS: Fourteen post-TAVR patients and ten age- and gender-matched controls underwent kt-PCA accelerated 4D flow MRI of the thoracic aorta at 3.0 Tesla. Velocity and wall shear stress was compared between the two groups. In addition, aortic flow eccentricity and displacement was assessed and compared between TAVR patients, controls and 14 SAVR patients recruited as part of an earlier study. RESULTS: Compared to controls, abnormally elevated WSS was present in 30±10% of the ascending aortic wall in TAVR patients. Increased WSS was present along the posterior mid-ascending aorta and the anterior distal-ascending aorta in all TAVR patients. TAVR results in eccentric and displaced flow in the mid- and distal-ascending aorta, whereas blood flow displacement in SAVR patients occurs only in the distal-ascending aorta. CONCLUSION: This study shows that TAVR results in increased blood flow velocity and WSS in the ascending aorta compared to age- and gender-matched elderly controls. This finding warrants longitudinal assessment of aortic dilatation after TAVR in the era of potential TAVR in lower-risk patients. Additionally, TAVR results in altered blood flow eccentricity and displacement in the mid- and distal-ascending aorta, whereas SAVR only results in altered blood flow eccentricity and displacement in the distal-ascending aorta. KEY POINTS: • TAVR results in increased blood flow velocity and WSS in the ascending aorta. • Longitudinal assessment of aortic dilatation after TAVR is warranted in the era of potential TAVR in lower-risk patients. • Both TAVR and SAVR result in altered blood flow patterns in the ascending aorta when compared to age-matched controls.

Soluble fms-like tyrosine kinase-1 and placental growth factor kinetics during and after pregnancy in women with suspected or confirmed pre-eclampsia.

OBJECTIVES: To assess the evolution of the soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio in women with suspected or confirmed pre-eclampsia (PE), and to investigate the changes in sFlt-1 and PlGF levels in pre-eclamptic women after delivery. METHODS: This was an exploratory study in which secondary analysis was performed on a prospective cohort study that enrolled women with a singleton pregnancy and suspected or confirmed PE from 18 weeks' gestation, carried out between December 2013 and April 2016 at the Department of Obstetrics of the Erasmus Medical Center in Rotterdam. sFlt-1 and PlGF were determined using Roche Diagnostics Elecsys assays in two groups of patients. In the first group, patients with suspected or confirmed PE had sFlt-1 and PlGF levels measured at least twice during their pregnancy. Changes in these biomarkers over the course of pregnancy were compared for patients in this group with a baseline sFlt-1/PlGF ratio of ≤ 38 and for those with a ratio > 38. In the second group, sFlt-1 and PlGF levels of women with PE or HELLP syndrome were measured before and after delivery. For this group, pre- and postpartum sFlt-1 and PlGF levels were compared and half-lives were calculated. RESULTS: Women with suspected or confirmed PE for whom sFlt-1 and PlGF levels were measured at least twice during pregnancy (n = 46) had a median gestational age at inclusion of 26 weeks (range, 18-40 weeks). In 27 of the 30 patients with sFlt-1/PlGF ratio ≤ 38 at baseline, thereby ruling out PE, the sFlt-1/PlGF ratio remained stable for up to 100 days. In the remaining three patients with a ratio ≤ 38 and in most of the 16 patients with a ratio > 38, the ratio increased further. For women diagnosed with PE or HELLP syndrome for whom sFlt-1 and PlGF levels were measured before and after delivery (n = 26), median gestational age at inclusion was 29 weeks (range, 16-37 weeks) and median time between antepartum measurement and delivery was 2 days (range, 1-17 days). In this group, after delivery, sFlt-1 dropped to < 1% of its pre-delivery value, with a half-life of 1.4 ± 0.3 days, while PlGF dropped to ∼30% of its pre-delivery value, with a half-life of 3.7 ± 4.3 days. CONCLUSIONS: Based on this small cohort, up to 10% of pregnant women admitted with suspected or confirmed PE presenting with a sFlt-1/PlGF ratio of ≤ 38 display a rise in sFlt-1/PlGF ratio in subsequent weeks, implying that repeat determination of the sFlt-1/PlGF ratio is required to exclude definitively a diagnosis of PE. Furthermore, the rapid and pronounced decline in sFlt-1 levels after delivery in patients with PE/HELLP syndrome suggests that sFlt-1, in contrast to PlGF, is almost entirely derived from the placenta. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

RASopathic comedone-like or cystic lesions induced by vemurafenib: a model of skin lesions similar but not identical to those induced by dioxins MADISH.

BACKGROUND: Patients treated with vemurafenib for metastatic melanoma often develop skin lesions similar to those observed after exposure to dioxin-like compounds. We previously called these lesions MADISH (metabolizing acquired dioxin-induced skin hamartoma) when analysing a case of acute dioxin poisoning. OBJECTIVE: We performed a clinical trial aimed at comparing the skin lesions observed under vemurafenib treatment with MADISH in order to bring to light a possible crosstalk between vemurafenib and dioxin pathways. METHODS: In this case series study, we explored the histological aspect of skin lesions in 10 cases treated with vemurafenib for malignant melanoma. We also analysed the ability of vemurafenib and tyrosine kinase inhibitors to induce dioxin-AhR pathway. RESULTS: All patients had skin lesions diagnosed as 'non-inflammatory acneiform eruption' by dermatologists. These were predominantly facial with notable retroauricular involvement and clinically compatible with chloracne/MADISH when assessed by dioxin expert. Histological analysis showed mostly comedone-like lesions and dermal cysts containing epithelial wall with basal or lateral epithelial projections and lamellar keratinization and alterations of remaining sebaceous glands. The expression of CYP1A1, a gene highly induced following dioxin exposure, was not observed in these lesions. Vemurafenib and the tyrosine kinase inhibitors erlotinib and gefitinib did not induce CYP1A1 activity. DISCUSSION: Although the skin lesions under vemurafenib treatment were morphologically similar to MADISH, the absence of CYP1A1 expression in dermal cysts of patients and the absence of CYP1A1 activation by vemurafenib led us consider that these skin lesions were different from true MADISH and not mediated by a crosstalk of AhR signalling, but rather to a hyperactivation of PI3K-Akt pathway as a consequence of vemurafenib treatment. A strong expression of CYP1A1 in the epithelial wall of dermal cysts must be required, parallel to the morphology of the lesions, to make the diagnosis of MADISH, the hallmark of an exposure to dioxin-like/chloracnegen compounds.

Acetylation and methylation of sperm histone 3 lysine 27 (H3K27ac and H3K27me3) are associated with bull fertility.

Epigenetic modifications in histones are crucial for proper sperm physiology, egg activation and reproductive development of males. The objectives of this study were to determine the conservation and interactomes of histone three (H3) and ascertain the expression dynamics of acetylated and methylated H3 lysine 27 (H3K27ac and H3K27me3) in spermatozoa from Holstein bulls with different fertility. Methods in immunocytochemistry and flow cytometry were used to evaluate the expression dynamics of H3K27ac and H3K27me3 in spermatozoa from 10 bulls with different in vivo fertility. Computational biology methods including Clustal Omega and Cytoscape were performed to determine the evolutionary conservation and interactome of H3. The post-translational modifications (PTM) of H3 (H3K27ac and H3K27me3) had different spatiotemporal dynamics in the sperm head. Intensities of methylation were higher than those of acetylation and inversely correlated between the two fertility groups (p = .0032). The interacting proteins of H3 are involved in critical subcellular processes such as regulation of methylation, nucleosome assembly, regulation of DNA replication and chromatin assembly. These results are significant because they help advance fundamental science and biotechnology of mammalian reproduction.

Trends in patient characteristics and clinical outcome over 8 years of transcatheter aortic valve implantation.

AIM: In the evolving field of transcatheter aortic valve implantations (TAVI) we aimed to gain insight into trends in patient and procedural characteristics as well as clinical outcome over an 8­year period in a real-world TAVI population. METHODS: We performed a single-centre retrospective analysis of 1,011 consecutive patients in a prospectively acquired database. We divided the cohort into tertiles of 337 patients; first interval: January 2009-March 2013, second interval: March 2013-March 2015, third interval: March 2015-October 2016. RESULTS: Over time, a clear shift in patient selection was noticeable towards lower surgical risks including Society of Thoracic Surgeons predicted risk of mortality score and comorbidity. The frequency of transfemoral TAVI increased (from 66.5 to 77.4%, p = 0.0015). Device success improved (from 62.0 to 91.5%, p < 0.0001) as did the frequency of symptomatic relief (≥1 New York Heart Association class difference) (from 73.8 to 87.1%, p = 0.00025). Complication rates decreased, including in-hospital stroke (from 5.0 to 2.1%, p = 0.033) and pacemaker implantations (from 10.1 to 5.9%, p = 0.033). Thirty-day mortality decreased (from 11.0 to 2.4%, p < 0.0001); after adjustment for patient characteristics, a mortality-risk reduction of 72% was observed (adjusted hazard ratio [HR]: 0.28, 95% confidence interval [CI]: 0.13-0.62). One-year mortality rates decreased (from 23.4 to 11.4%), but this was no longer significant after a landmark point was set at 30 days (mortality from 31 days until 1 year) (adjusted HR: 0.69, 95% CI: 0.41-1.16, p = 0.16). CONCLUSION: A clear shift towards a lower-risk TAVI population and improved clinical outcome was observed over an 8­year period. Survival after TAVI improved impressively, mainly as a consequence of decreased 30-day mortality.

Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience.

BACKGROUND: Reed-Sternberg cells of classical Hodgkin's lymphoma (cHL) are characterized by genetic alterations at the 9p24.1 locus, leading to over-expression of programmed death-ligand 1 and 2. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed or refractory cHL, with an acceptable safety profile. PATIENTS AND METHODS: We present a retrospective analysis of 82 patients (median age: 30 years; range: 18-75) with relapsed/refractory HL treated with nivolumab in a named patient program from 24 centers throughout Turkey. The median follow-up was 7 months, and the patients had a median of 5 (2-11) previous lines of therapy. Fifty-seven (70%) and 63 (77%) had been treated by stem-cell transplantation and brentuximab vedotin, respectively. RESULTS: Among 75 patients evaluated after 12 weeks of nivolumab treatment, the objective response rate was 64%, with 16 complete responses (CR; 22%); after 16 weeks, it was 60%, with 16 (26%) patients achieving CR. Twenty patients underwent subsequent transplantation. Among 11 patients receiving allogeneic stem-cell transplantation, 5 had CR at the time of transplantation and are currently alive with ongoing response. At the time of analysis, 41 patients remained on nivolumab treatment. Among the patients who discontinued nivolumab, the main reason was disease progression (n = 19). The safety profile was acceptable, with only four patients requiring cessation of nivolumab due to serious adverse events (autoimmune encephalitis, pulmonary adverse event, and two cases of graft-versus-host disease aggravation). The 6-month overall and progression-free survival rates were 91.2% (95% confidence interval: 0.83-0.96) and 77.3% (0.66-0.85), respectively. Ten patients died during the follow-up; one of these was judged to be treatment-related. CONCLUSIONS: Nivolumab represents a novel option for patients with cHL refractory to brentuximab vedotin, and may serve as a bridge to transplantation; however, it may be associated with increased toxicity.

A novel and useful predictive indicator of prognosis in ST-segment elevation myocardial infarction, the prognostic nutritional index.

BACKGROUND AND AIM: The prognostic impact of poor nutritional status and cardiac cachexia in myocardial infarction is not clearly understood. Recent studies have implied a prognostic value of the prognostic nutritional index (PNI) in colorectal surgeries and postoperative septic complications. The present study aimed to evaluate the prognostic value of PNI in ST-segment elevation myocardial infarction (STEMI) patients. METHODS AND RESULTS: We evaluated the in-hospital and long-term (3 years) prognostic impact of PNI on 1823 patients with STEMI undergoing primary percutaneous coronary intervention. Patients with lower PNI had significantly higher in-hospital and long-term mortality and major adverse cardiac events. After adjustment for all confounders, the in-hospital mortality rates were 7.9 times higher at the lower PNI level (95% CI: 5.0-15.8) than those at the higher PNI level. The long-term mortality rates were also 6.4 times higher at the lower PNI level (95% CI: 4.4-12.4) than those at the higher PNI level. CONCLUSION: The present study demonstrated that the PNI, calculated based on the serum albumin level and lymphocyte count, is an independent prognostic factor for mortality in patients with STEMI.

Knowledge and attitudes among patients with asthma and parents and physicians towards influenza vaccination.

BACKGROUND: Influenza is an infectious disease, dangerous for all people, especially for some risk groups such as patients with chronic diseases and health care workers. But most of the people under the risk of influenza, including health care workers are not immunised because of misinformation. In this study, we aimed to determine the knowledge, beliefs and attitudes of patients with allergic rhinitis and asthma and parents of such children related to influenza vaccination. Attitudes and beliefs of physicians treating these patients about influenza vaccination were also investigated. METHODS: Two different questionnaires consisting of various items related to influenza vaccine were distributed to physicians and patients and parents of children with asthma and allergic disease. RESULTS: The physicians group consisted of 189 physicians from various branches. About one third of physicians from various branches reported that they did not believe the vaccine's effectiveness. Most of the participating physicians did not immunise themselves with influenza vaccination despite the fact that any patient of theirs had died due to influenza infection. Although nearly half of the 183 patients had been vaccinated with influenza vaccine, only 27% of adults and 11.7% of children had been vaccinated annually. CONCLUSIONS: Asthmatic patients are not immunised regularly with influenza vaccine due to misperceptions about vaccine effectiveness and fear of adverse effects. Another important reason of this is that most the physicians caring for these patients neither immunise themselves nor recommend the vaccine to their patients.

Comparison of the effects of dietary supplementation of flavonoids on laying hen performance, egg quality and egg nutrient profile.

1. The aim of this experiment was to compare the effects of dietary supplementation of hesperidin, naringin and quercetin on laying hen performance, egg quality and egg yolk lipid and protein profiles. 2. A total of 96 Lohmann White laying hens weighing an average of 1500 g at 28 weeks of age were randomly assigned to a basal diet and the basal diet supplemented (0.5 g/kg) with either hesperidin, naringin or quercetin. Each treatment was replicated in 6 cages in an 8-week experimental period. Data were analysed using one-way analysis of variance. 3. None of the dietary flavonoids affected laying performance and eggshell quality. Hesperidin and quercetin supplementations decreased albumen and yolk indexes. 4. As compared to the control group, egg yolk cholesterol content decreased and egg yolk protein content increased in response to dietary hesperidin and quercetin supplementation. The mean egg yolk cholesterol (mg/g) and protein (g/100 g) contents were 10.08/14.28, 16.12/14.08, 14.75/15.04 and 15.15/14.85 for the control group and groups supplemented with naringin, hesperidin and quercetin, respectively. 5. Egg yolk lipid and protein profiles were variable. 6. In conclusion, dietary supplementation of hesperidin or quercetin could be used in the diets during the early laying period to reduce egg yolk cholesterol and increase egg yolk protein, which may be attractive to consumers.

Kinetic and in silico studies of hydroxy-based inhibitors of carbonic anhydrase isoforms I and II.

A series of hydroxy and phenolic compounds have been assayed for the inhibition of two physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isozymes, the cytosolic human isozymes I and II. The investigated molecules showed inhibition constants in the range of 1.07-4003 and 0.09-31.5 µM at the hCA I and hCA II enzymes, respectively. In order to investigate the binding mechanisms of these inhibitors, in silico studies were also applied. Molecular docking scores of the studied compounds are compared using three different scoring algorithms, namely Glide/SP, Glide/XP and Glide/IFD. In addition, different ADME (absorption, distribution, metabolism and excretion) analysis was performed. All the examined compounds were found within the acceptable range of pharmacokinetic profiles.

Vitamin D status in children with Crimean-Congo hemorrhagic fever.

BACKGROUND & OBJECTIVES: Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral disease, causing severe viral hemorrhagic fever outbreaks. This study aimed at determining the serum vitamin D levels and investigated the association between Crimean-Congo hemorrhagic fever (CCHF) and serum vitamin D levels in children with CCHF. METHODS: A total of 45 children aged between 5 and 15 yr, viz. 15 healthy control (HC) and 30 pediatric patients diagnosed with CCHF with real-time polymerase chain reaction (PCR) (patient group) were selected for the study. RESULTS: Analysis of the blood serum samples taken from the said individuals revealed that vitamin D, parathyroid hormone and calcium levels of the patients and the control groups were statistically different. INTERPRETATION & CONCLUSION: It was found that the serum vitamin D levels of the pediatric patients with CCHF were lower when compared to those of the controls, and that a low vitamin D level could negatively affect the reaction of the body to infections in children having CCHF.

Doppler ultrasonographic evaluation of the carotid and vertebral arteries in children with Crimean-Congo hemorrhagic fever.

AIM: In children with Crimean-Congo hemorrhagic fever (CCHF), the aim of present study was to determine the cerebral hemodynamic changes assessed with Doppler ultrasonography with measurements of lumen diameter (LD), peak systolic velocity (PSV), end-diastolic velocity (EDV), resistive index (RI), pulsatility index (PI), and total cerebral blood flow volume (tCBFV) of common carotid artery (CCA), internal carotid artery (ICA, and vertebral artery (VA). METHODS: This case-control study examined children with clinically defined CCHF as cases (N.=24) and healthy children as controls (N.=17). The CCHF and healthy children underwent ultrasonography of the CCA, ICA and VA for the measurements of flow velocity and cerebral blood flow volume. Doppler ultrasonography were performed in the CCHF children if vital signs were stable and fever lower than 37.5 °C. RESULTS: There was no significant difference between the CCHF and healthy children in the lumen diameter of study arteries (P>0.05). PSV and EDV values were significantly higher in the CCHF children compared to the controls (P<0.05). Overall, the CCHF did not cause considerable change in RI and PI values (P>0.05). tCBFV values of CCHF children was found higher compared to healthy controls (P<0.05). CONCLUSION: Overall, in children, CCHF causes an increase in the cerebral blood flow as determined by Doppler ultrasonography with flow velocity and cerebral blood flow volume measurements; however, this increase need to be accepted as mild to moderate degree. Several pathophysiological derangements may be contributory to the increased cerebral blood flow in children with CCHF.

An Examination of the Effects of Leuprolide Acetate Used in the Treatment of Central Precocious Puberty on Bone Mineral Density and 25-Hydroxy Vitamin D.

AIM: Leuprolide acetate is a gonadotropin-releasing hormone (GnRH) analogue frequently used in the treatment of central precocious puberty. Research is currently taking place into its effects on endocrine systems. The aim of this study is to investigate the effect of leuprolide acetate on vitamin D and bone mineral density. METHODS: Twenty-three children diagnosed with central precocious puberty and receiving leuprolide acetate therapy for at least 12 months, and a control group of 17 healthy children were enrolled. In the study group, calcium, phosphorus, alkaline phosphatase, parathormone and 25-hydroxy vitamin D levels and bone mineral density were measured. The results were compared with those of the control group. RESULTS: 25-Hydroxy vitamin D levels in the study and control groups were 15.17 ± 7 mg/dL and 22.2 ± 6.1 mg/dL, respectively (p < 0.05). In terms of bone mineral density, osteopenia was determined in 13 (56.5%) patients in the study group and osteoporosis in one (4.3%), while osteopenia was identified in seven patients in the control group, with no osteoporosis being identified (p > 0.05). CONCLUSION: Gonadotropin-releasing hormone agonists may have an adverse effect on bone health. They may exhibit these effects by impacting on vitamin D levels. These levels should be periodically monitored in patients receiving treatment, and vitamin D support should be given in cases where the deficiency is identified.