Comprehensive phenotypic analysis of diverse FOXN1 variants.

BACKGROUND: Thymus hypoplasia due to stromal cell problems has been linked to mutations in several transcription factors, including Forkhead box N1 (FOXN1). FOXN1 supports T-cell development by regulating the formation and expansion of thymic epithelial cells (TECs). While autosomal recessive FOXN1 mutations result in a nude and severe combined immunodeficiency phenotype, the impact of single-allelic or compound heterozygous FOXN1 mutations is less well-defined. OBJECTIVE: With more than 400 FOXN1 mutations reported, their impact on protein function and thymopoiesis remains unclear for most variants. We developed a systematic approach to delineate the functional impact of diverse FOXN1 variants. METHODS: Selected FOXN1 variants were tested with transcriptional reporter assays and imaging studies. Thymopoiesis was assessed in mouse lines genocopying several human FOXN1 variants. Reaggregate thymus organ cultures were used to compare the thymopoietic potential of the FOXN1 variants. RESULTS: FOXN1 variants were categorized into benign, loss- or gain-of-function, and/or dominant-negatives. Dominant negative activities mapped to frameshift variants impacting the transactivation domain. A nuclear localization signal was mapped within the DNA binding domain. Thymopoiesis analyses with mouse models and reaggregate thymus organ cultures revealed distinct consequences of particular Foxn1 variants on T-cell development. CONCLUSIONS: The potential effect of a FOXN1 variant on T-cell output from the thymus may relate to its effects on transcriptional activity, nuclear localization, and/or dominant negative functions. A combination of functional assays and thymopoiesis comparisons enabled a categorization of diverse FOXN1 variants and their potential impact on T-cell output from the thymus.

The Antibiotic Efflux Protein TolC Is a Highly Evolvable Target under Colicin E1 or TLS Phage Selection.

Bacteriophages and bacterial toxins are promising antibacterial agents to treat infections caused by multidrug-resistant (MDR) bacteria. In fact, bacteriophages have recently been successfully used to treat life-threatening infections caused by MDR bacteria (Schooley RT, Biswas B, Gill JJ, Hernandez-Morales A, Lancaster J, Lessor L, Barr JJ, Reed SL, Rohwer F, Benler S, et al. 2017. Development and use of personalized bacteriophage-based therapeutic cocktails to treat a patient with a disseminated resistant Acinetobacter baumannii infection. Antimicrob Agents Chemother. 61(10); Chan BK, Turner PE, Kim S, Mojibian HR, Elefteriades JA, Narayan D. 2018. Phage treatment of an aortic graft infected with Pseudomonas aeruginosa. Evol Med Public Health. 2018(1):60-66; Petrovic Fabijan A, Lin RCY, Ho J, Maddocks S, Ben Zakour NL, Iredell JR, Westmead Bacteriophage Therapy Team. 2020. Safety of bacteriophage therapy in severe Staphylococcus aureus infection. Nat Microbiol. 5(3):465-472). One potential problem with using these antibacterial agents is the evolution of resistance against them in the long term. Here, we studied the fitness landscape of the Escherichia coli TolC protein, an outer membrane efflux protein that is exploited by a pore forming toxin called colicin E1 and by TLS phage (Pagie L, Hogeweg P. 1999. Colicin diversity: a result of eco-evolutionary dynamics. J Theor Biol. 196(2):251-261; Andersen C, Hughes C, Koronakis V. 2000. Chunnel vision. Export and efflux through bacterial channel-tunnels. EMBO Rep. 1(4):313-318; Koronakis V, Andersen C, Hughes C. 2001. Channel-tunnels. Curr Opin Struct Biol. 11(4):403-407; Czaran TL, Hoekstra RF, Pagie L. 2002. Chemical warfare between microbes promotes biodiversity. Proc Natl Acad Sci U S A. 99(2):786-790; Cascales E, Buchanan SK, Duché D, Kleanthous C, Lloubès R, Postle K, Riley M, Slatin S, Cavard D. 2007. Colicin biology. Microbiol Mol Biol Rev. 71(1):158-229). By systematically assessing the distribution of fitness effects of ∼9,000 single amino acid replacements in TolC using either positive (antibiotics and bile salts) or negative (colicin E1 and TLS phage) selection pressures, we quantified evolvability of the TolC. We demonstrated that the TolC is highly optimized for the efflux of antibiotics and bile salts. In contrast, under colicin E1 and TLS phage selection, TolC sequence is very sensitive to mutations. Finally, we have identified a large set of mutations in TolC that increase resistance of E. coli against colicin E1 or TLS phage without changing antibiotic susceptibility of bacterial cells. Our findings suggest that TolC is a highly evolvable target under negative selection which may limit the potential clinical use of bacteriophages and bacterial toxins if evolutionary aspects are not taken into account.

The Effects of High-Pressure Processing on pH, Thiobarbituric Acid Value, Color and Texture Properties of Frozen and Unfrozen Beef Mince.

In this study, beef mince (approximately 4% fat longissmus costarum muscle of approximately 2-year-old Holstein cattle) was used as a material. High-pressure processing (HPP) was applied to frozen and unfrozen, vacuum-packed minced meat samples. The pH and thiobarbituric acid (TBA) values of the samples were examined during 45 days of storage. Color values (L*, a* and b*) and texture properties were examined during 30 days of storage. After freezing and HPP (350 MPa, 10 min, 10 °C), the pH value of minced meat increased (p > 0.05) and its TBA value decreased (p < 0.05). The increase in pH may be due to increased ionization during HPP. Some meat peptides, which are considered antioxidant compounds, increased the oxidative stability of meat, so a decrease in TBA may have been observed after freezing and HPP. While the color change in unpressurized samples was a maximum of 3.28 units during storage, in the pressurized sample, it exceeded the limit of 10 units on the first day of storage and exceeded the limit of 10 units on the third day of storage in the frozen and pressurized sample. Freezing and HPP caused the color of beef mince to be retained longer. The hardness, gumminess, chewability, adherence, elasticity, flexibility values of the pressurized and pressurized after freezing samples were higher than those of the unpressurized samples during storage. On the other hand, the opposite was the case for the adhesiveness values. In industrial applications, meat must be pressurized after being vacuum packed. If HPP is applied to frozen beef mince, some of its properties such as TBA, color, and texture can be preserved for a longer period of time without extreme change.

Age-Related Co-Expression of BCOR and BCORL1 mRNA in Acute Myeloid Leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is an aggressive hematological malignancy caused by a variety of genetic abnormalities and epigenetic dysregulation. The incidence of AML is strongly related to age, with the highest incidence rates being in older adults. The loss of function mutations in BCOR and BCORL1 genes have been identified in AML. BCL6 corepressor (BCOR) and BCL6 corepressor like 1 (BCORL1) are important epigenetic regu-lators as a member of Polycomb repressive complex 1 (PRC1.1), involved in histone modification processes. METHODS: We analyzed the BCOR and BCORL1 mRNA expression in 74 adult and 22 pediatric patients with AML by Real-Time quantitative PCR in this study. RESULTS: Our results indicated that both BCOR and BCORL1 mRNA expressions decrease with age (p = 0.009 and p = 0.008, respectively) and there is a positive correlation between BCOR and BCORL1 mRNA expression (p < 0.001). BCOR and BCORL1 mRNA expressions were not significantly different in both adult and pediatric patients with AML compared to control (p > 0.05). CONCLUSIONS: Our findings indicate that expression of BCOR and BCORL1 mRNA are down-regulated with age. The increase in AML incidence with age suggests that age-associated BCOR and BCORL1 down-regulation might potentially contribute to age-related epigenetic alterations and form a predisposing condition for the development of elderly AML.

The effect of attention deficit/hyperactivity disorder and other psychiatric disorders on the treatment of pediatric diabetes mellitus.

OBJECTIVE: Psychiatric diagnoses of patients with type 1 diabetes mellitus (T1DM), the severity of attention deficit/hyperactivity disorder (ADHD) symptoms of the patients and their primary caregivers, and the effects of these factors on treatment were investigated. METHODS: Sixty-one patients with T1DM were included in the study along with their parents. Psychiatric diagnoses of the patients were determined using a semistructured psychiatric interview, and their depression and ADHD symptom severities were evaluated with self-report scales. The ADHD symptom severities of the parents were evaluated using self-report scales. The relationships among the psychiatric symptoms and the hemoglobin A1c (HbA1c), fasting blood glucose (FBG), and postprandial blood glucose (PBG) levels of the patients were investigated. RESULTS: HbA1c levels were found to correlate with the hyperactivity levels of children and the number of diagnoses they had. FBG and PBG values of patients diagnosed with ADHD were found to be higher than in those who did not have ADHD. HbA1c, FBG, and PBG values of the patients who had any disruptive behavior disorder were found to be higher than in those who did not. ADHD total scores, gender (being female), having diagnoses of ADHD or depression were found to be predictive of HbA1c levels according to the regression analyses. No relationship between the clinical findings of the children and their parents' ADHD levels was found. CONCLUSIONS: The findings of this study implicate that children with T1DM should be evaluated in terms of ADHD which could have negative effects on the treatment.

Evaluation of ventricular repolarization features with Tp-e, Tp-e/QTc, JTc and JTd during electroconvulsive therapy.

OBJECTIVE: The purpose of this study was to investigate the influence of electrical stimulation transmitted through the body during electroconvulsive therapy on traditional and relatively new ventricular repolarization parameters (Rate corrected QT interval (QTc), QT dispersion (QTd), rate corrected JT interval (JTc), JT dispersion (JTd), T-peak to T-end interval (Tp-e) and Tp-e/QTc ratio) under propofol anaesthesia. METHODS: Twenty-two patients (aged 18-50 years) who were each scheduled for ECT for major depression, bipolar disorder or schizophrenia enrolled to the study. Electrocardiography (ECG) recordings were obtained before anaesthesia and within 3-5 min after electrical stimulus of ECT for measurements. QTc, QTd, JTc, JTd, Tp-e and Tp-e/QTc were measured as repolarization indices. RESULTS: The study included twenty-two patients, 9(40.9%) females and 13(59.1%) males, and the mean age accounted for 33.57 ±â€¯9.95 years. The comparison of the measured parameters before and after ECT, which were not statistically different, were as follows: QTc (416.52 ±â€¯46.64 vs 430.00 ±â€¯34.00msn; p = 0.18), JTc (308.09 ± 25.09 vs 315.47 ±â€¯26.89msn; p = 0.30), QTd (22.27 ±â€¯11.51 vs 20.45 ±â€¯9.9msn; p = 0.52) and JTd (22.72 ±â€¯11.2 vs 17.72 ±â€¯10.20msn; p = 0.06). Also, no significant difference was detected at the following parameters Tp-e (80.0 ±â€¯13.45 vs 78.63 ±â€¯15.21msn; p = 0.65) and Tp-e/QTc ratio (0.19 ±â€¯0.03 vs 0.18 ±â€¯0.07; p = 0.08). On the other hand, HR showed a significant increase after ECT at 88.13 ±â€¯13.74 vs 93.0 ±â€¯15.2 bpm; p = 0.03. CONCLUSION: QTc, QTd, JTc, JTd, Tp-e interval and Tp-e/QTc ratio, which are thought to be potential repolarisation markers for ventricular arrhythmias, did not demonstrate significant change within 3-5 min of electrical stimulation during ECT.

Plasma microRNA profiling of children with idiopathic dilated cardiomyopathy.

CONTEXT: Dilated cardiomyopathy (DCM) is the most common cardiomyopathy in children. MicroRNAs (miRNA) are small RNAs which have regulatory functions in many biological processes. OBJECTIVE: We aimed to determine miRNA expression levels in plasma of children with DCM. MATERIALS AND METHODS: Plasma expression levels of 379 miRNAs were compared between 23 DCM and 26 healthy children. RESULTS: The expression levels of miR-618, miR-875-3p, miR-205, miR-194, miR-302a, miR-147, and miR-544 were found decreased. The expression levels of miR-518f and miR-454 were found increased in DCM patients. DISCUSSION: miRNA level differences may provide the chance of using these miRNAs as new biomarkers.

Relationship between Neurocardiogenic Syncope and Ventricular Repolarization.

BACKGROUND: We aimed to analyze ventricular repolarization in neurocardiogenic syncope (NCS) patients by using T-peak-T-end interval, T-peak-T-end/QT ratio, T-peak-T-end/QTc ratio and corrected QT interval (QTc), QT dispersion (QTd), QT index (QTI) and corrected QT interval index (QTcI) comparing with the corrected JT dispersion (JTcd), and corrected JT (JTc) and the corrected JT interval index (JTcI), by inspecting ventricular activation until termination of repolarization. These parameters are used as an index of potential ventricular arrhythmogenesis. METHODS: We have studied patients with head-up tilt table test (HUTT) (+) (33 patients; mean age: 28 ± 11 years) and HUTT (-) as control group (33 patients; mean age: 30 ± 11 years). In all patients, T-peak-T-end interval, T-peak-T-end/QT ratio, T-peak-T-end/QTc ratio, QT, QTd, QTI, QTc, QTcI, JTd, JTc, and JTcI were measured on electrocardiogram. RESULTS: The following parameters were statistically significant between groups: QTd (22.72 ± 17.54 msn; 11.21 ± 13.40 msn; P = 0.004), QTc (424.27 ± 33.75 msn; 403.66 ± 38.08 msn; P = 0.023), QTcI (114.09 ± 14, 29%; 106.71 ± 15.33%, P = 0.047), and QTI (100.72 ± 7.19%; 97.14 ± 7.13%, P = 0.046). Furthermore, T-peak-T-end interval was significantly prolonged in the study group (93.78 ± 20.27 msn; 81.21 ± 11.66 msn; P = 0.003). T-peak-T-end/QT ratio was significantly higher in the study group (0.24 ± 0.04 msn; 0.22 ± 0.04 msn; P = 0.030). T-peak-T-end/QTc ratio was significantly higher in the study group (0.22 ± 0.04 msn; 0.20 ± 0.03 msn; P = 0.015). The JTc and JTd were also significantly higher in the study group ([103.00 ± 9, 72%; 95.44 ± 10.26%, P = 0.003], [27.57 ± 16.01 msn; 10.45 ± 16.08 msn; P < 0.001], respectively). CONCLUSIONS: Electrocardiographic ventricular repolarization parameters including T-peak-T-end interval, T-peak-T-end/QT ratio, T-peak-T-end/QTc ratio, QTc, QTd, QTI, QTcI, JTc, JTd, and JTI are prolonged in NCS.

Streptomyces use umbrella toxins to gently compete with kin.

In a recent issue of Nature, Zhao et al. have demonstrated that Streptomyces spp. produce "umbrella"-shaped polymorphic toxin particles, a novel class of non-lethal toxins that gently inhibit competitors by arresting hyphal growth in closely related bacteria, unveiling a unique bacterial defense strategy in microbial ecological interactions.1.

Classification of Student Leadership Profiles in Diverse Governance Settings: Insights from Pisa 2022.

Student leadership prepares students for responsibilities, such as taking on specific tasks and assuming leadership roles in their future personal and professional lives. Developing students' leadership profiles is among the important goals of educational systems aiming for future generations to take responsibility and advance their countries. With this perspective in mind, the PISA assessment includes items to measure students' leadership behaviors. This study aims to extract student leadership profiles from the leadership-related items in the PISA 2022 application, using data from Cambodia, Peru, Paraguay, and Guatemala, which have different governance systems and cultural characteristics. The second purpose of the research is to determine the distribution of the identified leadership profiles in these countries and explain them in the context of governance and cultural characteristics. Latent class analysis was used to determine student leadership profiles. Accordingly, two-class and three-class latent models were found to be the most suitable models to explain student profiles. While the distinction between student profiles is more pronounced in the two-class model, the three-class model provides more detailed information about student profiles. In this respect, two-class and three-class latent models are reported comparatively. In the two-class latent model, students are labeled as the "Shy or Lack of Self-Confidence Group" and the "Active Leader or Influential Group". In the three-class latent model, students are labeled as the "Moderate or Passive Leader Group", the "Strong Leader or Influential Group", and the "Avoidant or Leadership-Uncomfortable Group". In both models, it is one of the striking findings that Cambodian students are in the low leadership profile, and Peruvian students are in the high leadership profile.

Comparison of serum thrombospondin-1 and thrombospondin-2 levels among children with autism spectrum disorder and healthy controls.

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder, the etiology of which has not been clearly determined yet. There is increasing evidence that synaptic and dendritic changes are involved in the etiology of ASD. The aim of this study is to determine whether serum Thrombospondin-1 and Thrombospondin-2 differ between ASD patients and healthy controls. This study also investigates possible correlations between clinical symptomatology of ASD and serum Thrombospondin-1 and Thrombospondin-2 levels. Method: A total of 44 children with ASD and 21 healthy controls under 6 years of age were included in the study. Symptom severity and behavioral problems among children with ASD were evaluated by using Childhood Autism Rating Scale and Abnormal Behavior Checklist. Serum levels of Thrombospondin-1 and Thrombospondin-2 were measured by using commercial enzyme-linked immunosorbent assay kits. Result: No statistically significant differences were found between the two groups in terms of serum Thrombospondin-1 and Thrombospondin-2 levels. In addition, no correlation was determined between Thrombospondin-2 levels and clinical symptomatology and severity of ASD. However, the Thrombospondin-1 level was found to negatively correlated with the total score of Childhood Autism Rating Scale, inappropriate speech and stereotype subscale scores of Aberrant Behavior Checklist scale. Conclusion: Thrombospondin-1 might have a potential role in the etiopathogenesis of ASD. Further studies are required to clearly elucidate the association between Trombospondin-1 and ASD.

Psychological risk factors for upper extremity fractures in preschool children: A case-control study.

BACKGROUND: In school-age children, upper extremity fractures are associated with both parental and child-related factors and represent a multifactorial entity. This study aims to explore the psychological risk factors associated with upper extremity fractures in preschool children. METHODS: This single-center, hospital-based, age-matched case-control study involved 55 cases of upper extremity fractures and 55 controls experiencing growing pains. Parents of the children participated in face-to-face interviews. We examined the potential as-sociations between scores on the Mother-to-Infant Bonding Scale (MIBS), Adult Attention Deficit Hyperactivity Disorder Self-Report Scale (ASRS), Autism-Spectrum Quotient (AQ), State-Trait Anxiety Inventory (STAI), and Strengths and Difficulties Questionnaire (SDQ), and the risk of upper extremity fractures. RESULTS: Advanced parental age and lower household income emerged as risk factors for upper extremity fractures, while longer maternal educational attainment was identified as a protective factor. In the univariate analyses, elevated scores on the Autism-Spec-trum Quotient Communication subscale (AQ-C), overall AQ score, Strengths and Difficulties Questionnaire Hyperactivity subscale (SDQ-H), and Strengths and Difficulties Questionnaire Emotional and Peer Problems subscale (SDQ-Int) were associated with an increased fracture risk (Odds Ratio [OR] (95% Confidence Interval [CI]): 1.15 (1.05-1.27), OR: 1.05 (1.01-1.09), OR: 1.25 (1.01-1.54), and OR: 1.19 (1.04-1.37), respectively). The AQ-C and SDQ-Int scales remained statistically significant as risk factors for upper ex-tremity fractures (OR: 1.15 (1.02-1.28) and OR: 1.21 (1.02-1.43), respectively) in the multivariate regression analyses. CONCLUSION: Our findings suggest that psychological factors affecting both parents and children could potentially increase the risk of upper extremity fractures in preschool children.

The role of the psychological attributes of parents and children, and fracture history in upper extremity fractures in school-age and adolescents: A case-control study.

OBJECTIVES: This study aims to investigate the influence of parents and children's psychological attributes and previous fracture history on upper extremity fractures in school-aged and adolescent children. PATIENTS AND METHODS: Between January 2022 and January 2023, a total of 194 participants consisting of 97 cases with upper extremity fractures (23 males, 74 females; median age: 10 years; range, 6 to 16 years) and 97 age-matched controls suffering from growing pains (47 males, 50 females; median age: 10 years; range, 6 to 16 years) were included in this case-control study. Both cases and controls were of school-age or over. The parents of the children were interviewed face-to-face using psychological scales including the Adult Attention Deficit Hyperactivity Disorder Self-Report Scale (ASRS), the Autism-Spectrum Quotient (AQ), the Short Form of the Conners' Parent Rating Scale-Revised (CPRS-R:S), and the Developmental Coordination Disorder Questionnaire 2007 (DCDQ'07). The results derived from these scales and the demographics of the participants were evaluated in terms of their association with the risk of upper extremity fractures. RESULTS: A household income below the official minimum monthly wage (MMW) and a previous fracture history showed a higher risk for upper extremity fractures (odds ratio [OR]=2.38, 95% confidence interval [CI]: 1.07-5.26 and OR=24.93, 95% CI: 3.27-189.98, respectively). In the univariate analyses, elevated scores on the hyperactivity subscale of CPRS-R:S (CPRS-R:SHS) were associated with a higher fracture risk (OR=1.14, 95% CI: 1.05-1.24). Furthermore, both a household income below MMW, a previous fracture history, and higher CPRS-R:S-HS scores were found as independent risk factors for upper extremity fractures in the multivariate regression analysis (OR=2.78, 95% CI: 1.13-6.86, OR=21.79, 95% CI: 2.73-174.03), and OR=1.11, 95% CI: 1.02-1.22, respectively). CONCLUSION: Our study results highlight the importance of known risk factors for upper extremity fractures such as lower monthly wage and the presence of previous fractures. The psychological states of parents and children should be evaluated together.

Evaluation of vitamin D levels in children and adolescents after the first year of the COVID-19 pandemic: 1-year results of a secondary-level state hospital.

BACKGROUND: The COVID-19 pandemic caused a global public health problem with high morbidity and mortality rates. In this study, we aimed to evaluate the 25-hydroxyvitamin D (25(OH)D) status of patients presenting to the Pediatrics Department of Gaziantep Maternity and Children's Hospital in the 1-year period after the onset of the COVID-19 pandemic according to ethnicity, age, and gender. METHOD: This cross-sectional study included the data of 7640 patients whose 25(OH)D levels were assessed at our hospital between March 2021 and March 2022. Vitamin D levels, age, gender, and the ethnic origin of the patients were retrospectively scanned and recorded from the laboratory results system. Based on the World Health Organization (WHO) classification of vitamin D levels, patients were divided into three groups: <10 ng/mL = vitamin D deficiency; 10-19 ng/mL = vitamin D insufficiency, and 20 ng/mL and over = normal vitamin D status. RESULTS: The mean age of the 7640 patients who presented to the pediatrics department was 7.47 (±5.3) years. Of these patients, 48 % (3665) were male and 52 % (3975) were female. The mean vitamin D level of girls was 18.1 (±15.2) ng/mL, and of boys it was 20.2 (±15.4) ng/mL, with a statistically significant difference (p < 0.001). In total, 21.2 % (1650) of patients had deficient, 43.3 % (3310) of patients had insufficient, and 35.5 % (2710) of patients had normal 25(OH)D levels. Overall, 21.8 % of the patients (1667) were immigrants, and in this group the deficiency was found to be statistically significantly higher at 27.4 % (n = 456; p < 0.001). There was a low negative correlation between the age of the patients and their 25(OH)D levels (r=-0.35; p < 0.001). CONCLUSIONS: Vitamin D deficiency remains a serious public health problem. Since the most important production source is exposure to the sun, it must be kept in mind that vitamin D should be supported during lockdown pandemic processes.

Association of Epicardial Adipose Tissue Thickness with Cardiovascular Risk in Acromegaly.

Objective: Acromegaly is a rare disease associated with increased mortality. Reports on coronary artery disease in acromegaly are controversial. This study aimed to investigate the possible association of epicardial adipose tissue thickness with cardiovascular risk in patients with acromegaly. Methods: The study included 38 patients followed up with the diagnosis of acromegaly and 29 healthy controls. Patients with acromegaly were divided into controlled and uncontrolled acromegaly groups based on insulin-like growth factor-1 levels. Epicardial adipose tissue thickness measurements were obtained from chest computed tomography, and laboratory data were extracted from patient files. Results: Twenty-nine patients (76.3%) had controlled acromegaly. Eleven patients with acromegaly had diabetes mellitus (28.9%), 18 (47.4%) had hypertension, and 27 (71%) had a concomitant chronic disease. Epicardial adipose tissue thickness was significantly increased in the acromegaly group (p<0.001). No significant difference was observed between the controlled and uncontrolled acromegaly groups in terms of the epicardial adipose tissue thickness. Age was the only parameter that was significantly correlated with the epicardial adipose tissue thickness. When the Framingham risk score was calculated, the 10-year cardiovascular risk of patients with acromegaly was 5.63%. Conclusions: The epicardial adipose tissue thickness is increased in acromegaly. However, this increase may not have clinical relevance in terms of cardiovascular risk.

The Validity and Reliability of Borderline Personality Features Scale for Children-Short Form in Turkish Adolescents. / Borderline Kisilik Özellikleri Çocuk Ölçegi­Kisa Formunun Türk Ergenlerinde Geçerlik ve Güvenirlik Çalismasi.

OBJECTIVE: This study has aimed to investigate the validity and reliability of the Borderline Personality Features Scale for Children-Short Form (BPFSC-SF-TR) in Turkish adolescents. METHOD: The study was carried out with adolescents between the ages of 12-18 from clinical (N=168) and community (N=181) backgrounds. All participants were asked to complete the BPFSC-SF-TR, the Personality Belief Questionaire - Short Form (PBQ-SF), the Brief Symptom Inventory (BSI) and the Personality Inventory for DSM-5- Short Form (PID-5-SF) scales. Also, the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version-Turkish Version (K-SADS-PL-TR) was administered to the participants in the clinical group and their parents were asked to complete the Pediatric Quality of Life Inventory (PEDsQL). Test-retest correlations and the Cronbach's α coefficients were calculated. RESULTS: BPFSC-SF-TR scores of both groups of participants positively correlated with the PBQ-BF borderline subscale, the PID-5-SF borderline related facets and the BSI scores, and negatively correlated with the PedsQL in the clinical group. Furthermore, the clinical group had higher total BPFSC-SF-TR scores than the community group, and their scores positively correlated with the number of diagnoses and psychiatric symptoms determined by using the KSADS-PL-TR. Exploratory and multi-group confirmatory factor analyses of the data of both groups supported a single factor structure. The Cronbach's α of the scale was 0.84 in the clinical group, and 0.79 in the community group. The test-retest reliability correlation coefficient of the scale was 0.71. CONCLUSION: The BPFSC-SF-TR is a valid and reliable tool for Turkish adolescents.

Can serum 8-hydroxy-2'-deoxyguanosine levels reflect the severity of pulmonary arterial hypertension?

OBJECTIVE: Oxidative stress plays a pivotal role in the pathogenesis of pulmonary arterial hypertension. 8-Hydroxy-2'-deoxyguanosine is a sensitive biomarker that reflects the degree of oxidative damage to DNA. We investigated whether serum 8-Hydroxy-2'-deoxyguanosine is a clinically useful biomarker for the severity of pulmonary arterial hypertension. METHODS: We measured serum 8-Hydroxy-2'-deoxyguanosine levels in 25 patients (age 37±13 years, 68% women) diagnosed with idiopathic pulmonary arterial hypertension, familial pulmonary arterial hypertension, or pulmonary arterial hypertension associated with congenital heart disease. The severity of pulmonary arterial hypertension was evaluated by six-min walking distance, World Health Organization functional class, and serum brain natriuretic peptide levels. Age and gender-matched 22 healthy subjects served as the control group. RESULTS: The comparison of 8-Hydroxy-2'-deoxyguanosine levels between patients and controls was not statistically different [(19.86±9.79) versus (18.80±3.94) ng/mL, p=0.622)]. However, there was a significant negative correlation between 8-Hydroxy-2'-deoxyguanosine levels and six-min walking distance (r= -0.614, p=0.001). Additionally, serum 8-Hydroxy-2'-deoxyguanosine levels in patients with functional class III-IV were significantly higher than those with functional class I-II (functional class III-IV 32.31±10.63 ng/mL versus functional class I-II 16.74±6.81 ng/mL, respectively, p=0.003). CONCLUSION: The 8-Hydroxy-2'-deoxyguanosine levels were significantly correlated with exercise capacity (six-min walking distance) and symptomatic status (functional class), both of which show the severity of pulmonary arterial hypertension in patients.

Small RNAs Asserting Big Roles in Mycobacteria.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), with 10.4 million new cases per year reported in the human population. Recent studies on the Mtb transcriptome have revealed the abundance of noncoding RNAs expressed at various phases of mycobacteria growth, in culture, in infected mammalian cells, and in patients. Among these noncoding RNAs are both small RNAs (sRNAs) between 50 and 350 nts in length and smaller RNAs (sncRNA) < 50 nts. In this review, we provide an up-to-date synopsis of the identification, designation, and function of these Mtb-encoded sRNAs and sncRNAs. The methodological advances including RNA sequencing strategies, small RNA antagonists, and locked nucleic acid sequence-specific RNA probes advancing the studies on these small RNA are described. Initial insights into the regulation of the small RNA expression and putative processing enzymes required for their synthesis and function are discussed. There are many open questions remaining about the biological and pathogenic roles of these small non-coding RNAs, and potential research directions needed to define the role of these mycobacterial noncoding RNAs are summarized.

Manipulation of IRE1-Dependent MAPK Signaling by a Vibrio Agonist-Antagonist Effector Pair.

Diverse bacterial pathogens employ effector delivery systems to disrupt vital cellular processes in the host (N. M. Alto and K. Orth, Cold Spring Harbor Perspect Biol 4:a006114, 2012, https://doi.org/10.1101/cshperspect.a006114). The type III secretion system 1 of the marine pathogen Vibrio parahaemolyticus utilizes the sequential action of four effectors to induce a rapid, proinflammatory cell death uniquely characterized by a prosurvival host transcriptional response (D. L. Burdette, M. L. Yarbrough, A Orvedahl, C. J. Gilpin, and K. Orth, Proc Natl Acad Sci USA 105:12497-12502, 2008, https://doi.org/10.1073/pnas.0802773105; N. J. De Nisco, M. Kanchwala, P. Li, J. Fernandez, C. Xing, and K. Orth, Sci Signal 10:eaa14501, 2017, https://doi.org/10.1126/scisignal.aal4501). Herein, we show that this prosurvival response is caused by the action of the channel-forming effector VopQ that targets the host V-ATPase, resulting in lysosomal deacidification and inhibition of lysosome-autophagosome fusion. Recent structural studies have shown how VopQ interacts with the V-ATPase and, while in the ER, a V-ATPase assembly intermediate can interact with VopQ, causing a disruption in membrane integrity. Additionally, we observed that VopQ-mediated disruption of the V-ATPase activates the IRE1 branch of the unfolded protein response (UPR), resulting in an IRE1-dependent activation of ERK1/2 MAPK signaling. We also find that this early VopQ-dependent induction of ERK1/2 phosphorylation is terminated by the VopS-mediated inhibitory AMPylation of Rho GTPase signaling. Since VopS dampens VopQ-induced IRE1-dependent ERK1/2 activation, we propose that IRE1 activates ERK1/2 phosphorylation at or above the level of Rho GTPases. This study illustrates how temporally induced effectors can work as in tandem as agonist/antagonist to manipulate host signaling and reveals new connections between V-ATPase function, UPR, and MAPK signaling.IMPORTANCE Vibrio parahaemolyticus is a seafood-borne pathogen that encodes two type 3 secretion systems (T3SS). The first system, T3SS1, is thought to be maintained in all strains of V. parahaemolyticus to maintain survival in the environment, whereas the second system, T3SS2, is linked to clinical isolates and disease in humans. Here, we found that first system targets evolutionarily conserved signaling systems to manipulate host cells, eventually causing a rapid, orchestrated cells death within 3 h. We have found that the T3SS1 injects virulence factors that temporally manipulate host signaling. Within the first hour of infection, the effector VopQ acts first by activating host survival signals while diminishing the host cell apoptotic machinery. Less than an hour later, another effector, VopS, reverses activation and inhibition of these signaling systems, ultimately leading to death of the host cell. This work provides example of how pathogens have evolved to manipulate the interplay between T3SS effectors to regulate host signaling pathways.

Assessment of subclinical left ventricular dysfunction with speckle-tracking echocardiography in hyperthyroid and euthyroid Graves' disease and its correlation with serum TIMP-1.

BACKGROUND: Graves' disease has a multitude of effects on the cardiovascular system. In the detection of subclinical left ventricular dysfunction, speckle-tracking echocardiography is more useful than conventional echocardiography. The aim of the present study was to compare the longitudinal global strain values and venous blood concentration of (tissue inhibitor of metalloproteinase-1) TIMP-1, a regulator of the extracellular matrix, among hyperthyroid patients with Graves' disease, euthyroid patients with Graves' disease and healthy control subjects. MATERIALS AND METHODS: The study enrolled 40 hyperthyroid patients with newly diagnosed Graves' disease, 40 patients with Graves' disease who were euthyroid for at least 6 months and 40 control subjects with normal thyroid function. Participants underwent conventional echocardiography and speckle-tracking echocardiography to obtain segmental and global longitudinal strain values. In addition, the serum TIMP-1 value was assessed in the venous blood samples of the participants. RESULTS: The hyperthyroid Graves' patients showed greater serum TIMP-1 levels versus the control group and the euthyroid Graves' group. Compared to the control group, the TIMP-1 level was also significantly higher in the euthyroid Graves' group. Lower GLS (global longitudinal strain) average and GLS2C, GLS3C, GLS4C values were observed in both the hyperthyroid and euthyroid Graves' patients compared to the control group. The euthyroid Graves' patients and hyperthyroid Graves' patients had similar GLS values. The serum TIMP-1 level was negatively correlated with global strain values. CONCLUSION: Graves' disease coexists with impaired segmental and global longitudinal strain and increased TIMP-1 levels. This coexistence seems to be independent of serum thyroid hormone levels.