A single center experience on PI3K/AKT/MTOR signaling defects: Towards pathogenicity assessment for four novel defects.

BACKGROUND: Phosphoinositide 3 kinases (PI3K) are lipid kinases expressed in lymphocytes/myeloid cells. PI3K/AKT/mTOR signaling defects present with recurrent infections, autoimmunity, lymphoproliferation, and agammaglobulinemia. OBJECTIVE: To characterize the PI3K/AKT/mTOR pathway defects and perform pathway analyses to assess novel variant pathogenicity. METHODS: We included 12 patients (heterozygous PIK3CD (n = 9) and PIK3R1 (n = 1) (activated PI3K delta syndrome (APDS) with gain-of-function mutations) and homozygous PIK3R1 variant (n = 2)), performed clinical/laboratory/genetic evaluation, and flow cytometric PI3K/AKT/mTOR pathway analyses. RESULTS: Median age at onset of complaints was 17.5 months (3 months to 12 years) and at diagnosis was 15.7 years (2.5-37) in APDS. Median diagnostic delay was 12.9 years (1.6-27). Recurrent respiratory tract infections (90%), lymphoproliferation (70%), autoimmune/inflammatory findings (60%), and allergy (40%) were common in APDS. Recurrent viral infections were present in 4/10 and malignancy (non-Hodgkin lymphoma and testicular yolk sac tumor) was present in 2/10 in APDS. Low CD4+ T cells(5/8) with increased CD4+ effector memory (8/8) and CD4+ TEMRA cells (6/8) were present in the given number of APDS patients. We diagnosed tubulointerstitial nephritis, Langerhans cell histiocytosis, and late-onset congenital adrenal hyperplasia in APDS. Allergic findings, lymphoproliferation/malignancy, and high IgM were present in the APDS but not in PIK3R1 deficiency. Low IgM/IgG/CD19+ B cell counts were characteristic in patients with PIK3R1 homozygous loss-of function mutations. CONCLUSION: Differential diagnosis with combined immunodeficiency and diseases of immune dysregulation make molecular genetic analysis crucial for diagnosing mTOR pathway defects. It is easy to differentiate APDS and homozygous PIK3R1 defects with specific laboratory features. Additionally, mTOR pathway functional analysis is a definitive diagnostic and pathogenicity assessment tool for novel APDS mutations.

Protective Effect of Fasudil on Testicular Ischemia-Reperfusion Injury in Rats.

Background: Ischemia-reperfusion (I/R) injury to the testis can lead to organ damage, infertility, and subfertility. The goal of this study was to investigate the effects of fasudil on this devastating condition. Methods: Thirty male Long-Evans rats were divided into five groups: a control group (no torsion), rats administered fasudil (30 mg/kg, no torsion), rats subject to ischemia with no treatment (I) (I/R injury), injured rats that received treatment 1 (T1) (I/R with 30 mg/kg fasudil before detorsion), and injured rats that received treatment 2 (T2) (I/R with 30 mg/kg fasudil after detorsion). Serum levels of TNF-ɑ and IL-6, along with tissue levels of glutathione (GSH), malondialdehyde (MDA), caspase-3, and Johnsen Tubular Biopsy Score (JTBS), were measured. Results: Group I exhibited significantly higher levels of MDA and caspase-3 than all other groups except T2 (p ˂ 0.05). Although the difference was not statistically significant, Group T2 exhibited lower MDA and caspase-3 levels than Group I (p ˃ 0.05). Additionally, Group I displayed significantly higher TNF-ɑ and IL-6 levels, and lower GSH and JTBS values, than the other groups (p ˂ 0.05). Conclusion: Our findings indicate that fasudil protects the testis from I/R injury, particularly when administered early.

Chenodeoxycholic acid (CDCA) treatment during pregnancy in women with cerebrotendinous xanthomatosis (CTX): Lessons learned from 19 pregnancies.

PURPOSE: Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive bile acid synthesis disorder. Biallelic pathogenic variants in CYP27A1, encoding for sterol 27-hydroxylase, impair cholic acid (CA) and chenodeoxycholic acid (CDCA) synthesis and lead to accumulation of cholestanol and C27 bile alcohols. Treatment with CDCA decreases the accumulation of these harmful metabolites and slows disease progression. Currently, CDCA is contraindicated for use during pregnancy based on animal studies that showed that high-dose CDCA may cause fetal harm when administered to pregnant animals. Data regarding the safety of CDCA treatment in humans are lacking. METHODS: We present a case series of 19 pregnancies in 9 women with CTX who either received CDCA treatment throughout pregnancy or did not. RESULTS: In 11 pregnancies where mothers continued CDCA treatment, no complications were reported, and newborns were born at or near full term, with normal birth weight and Apgar scores. In 8 pregnancies where mothers did not receive CDCA, 2 newborns experienced elevated bilirubin soon after birth. One woman who stopped treatment during her pregnancy deteriorated neurologically while off treatment. CONCLUSION: The data we present support the benefit of continued CDCA treatment in pregnant women with CTX for both the affected women and their offspring.

The effect of vibrating cold application and puppet use on pain and fear during phlebotomy in children: A randomized controlled study.

BACKGROUND: Non-pharmacological methods are often used as a creative strategy to reduce pain and fear in children during a painful procedure such as phlebotomy. OBJECTIVES: This study was conducted to evaluate the effects of Bee Buzzy and puppet use on pain and fear during phlebotomy in children. METHODS: This randomized controlled study was conducted in the pediatric phlebotomy unit of a university hospital. The CONSORT checklist was used in this study. The sample of 3-6 years children (n = 105) was divided into groups by block randomization. Children's pain and fear scores were evaluated with the Wong-Baker Faces Pain Rating Scale and Children's Fear Scale by the parents and the nurse who attempted phlebotomy during phlebotomy. RESULTS: A statistically significant difference was found between the Bee Buzzy and puppet and Bee Buzzy and control groups in pain scores (p < .05). Pain scores were lower in the Bee Buzzy group than in the puppet and control groups. A statistical difference was found between Bee Buzzy and the control group or puppet and control group according to all fear scores (p < .05). Fear scores were lower in the Bee Buzzy and puppet group (p < .05). CONCLUSIONS: The results show that the use of Bee Buzzy during phlebotomy has a pain-relieving effect, and the use of Bee Buzzy and puppet has an anti-fear effect in 3-6-year-old children. IMPLICATIONS FOR PRACTICES: The use of Bee-Buzzy and puppets is effective in reducing pain and fear in children as they increase effective communication and distract attention. CLINICAL TRIAL REGISTRATION: National Institutes of Health (NIH), ClinicalTrials.gov, NCT05827783.

Effects of oxytocin induction on early postpartum hemorrhage, perineal integrity, and breastfeeding: a case-control study

SUMMARY OBJECTIVE: The aim of this study was to evaluate the postpartum hemorrhage, perineal integrity, and breastfeeding results of mothers who underwent oxytocin induction in the first stage of labor in the early postpartum period. METHODS: This single-center observational case-control study was conducted in the obstetric unit of a public hospital in Istanbul. The study sampling included 44 pregnant women who received oxytocin induction (case group) and 44 pregnant women who did not receive oxytocin (control group). The Personal Information Form, LATCH Breastfeeding Assessment Tool, Breastfeeding Self-Efficacy Scale, Redness, Edema, Ecchymosis, Discharge, and Approximation Scale, and Postpartum Hemorrhage Collection Bag were used in data collection, and pad follow-up was carried out. RESULTS: The amount of hemorrhage in the first 24 h of the postpartum period and the mean Redness, Edema, Ecchymosis, Discharge, and Approximation Scale score were significantly higher in the case group. While 47.7% of the oxytocin-induced women had 1st or 2nd, and 11.4% had 3rd or 4th degrees of lacerations, 20.5% of the control group had 1st or 2nd, and 2.3% had 3rd or 4th degrees of lacerations. There was no significant difference between the mean scores of the Breastfeeding Self-Efficacy Scale and LATCH Breastfeeding Assessment Tool in both groups. CONCLUSION: According to the study findings, it was determined that oxytocin induction administered in the first stage of labor increased hemorrhage and perineal trauma in the early postpartum period but did not affect the results of breastfeeding. Clinical Trial Registration Number: NCT04441125.

Validity and reliability of the baby Eating behaviour Questionnaire in a Turkey sample.

The research was centered on developing a Turkish version of the Baby Eating Behaviour Questionnaire (BEBQ), ensuring cultural and linguistic adaptation while upholding its reliability and validity. Employing a methodological approach, the study encompassed 202 mothers whose infants were aged between 0 and 6 months. Data collection took place from December 2022 to January 2023, utilizing the Parent Demographic Questionnaire and BEBQ. Statistical analysis incorporated descriptive statistics, assessing reliability through Cronbach's alpha, test-retest, and item-total score analysis. Explanatory and confirmatory factor analyses were conducted, revealing 18 items across 4 sub-dimensions, explaining 58.3% of total variance. The scale demonstrated high reliability with a Cronbach's alpha of 0.81, while Confirmatory Factor Analysis validated the model with a Root Mean Square Error of Approximation at 0.074. Test-retest results exhibited a strong correlation (Pearson Correlation of 0.97, p < 0.001). The adapted BEBQ serves as a valid, reliable tool for evaluating infant feeding behavior in the Turkish context.

Comprehensively analyzing the genetic alterations, and identifying key genes in ovarian cancer.

Though significant improvements have been made in the treatment methods for ovarian cancer (OC), the prognosis for OC patients is still poor. Exploring hub genes associated with the development of OC and utilizing them as appropriate potential biomarkers or therapeutic targets is highly valuable. In this study, the differentially expressed genes (DEGs) were identified from an independent GSE69428 Gene Expression Omnibus (GEO) dataset between OC and control samples. The DEGs were processed to construct the protein-protein interaction (PPI) network using STRING. Later, hub genes were identified through Cytohubba analysis of the Cytoscape. Expression and survival profiling of the hub genes were validated using GEPIA, OncoDB, and GENT2. For exploring promoter methylation levels and genetic alterations in hub genes, MEXPRESS and cBioPortal were utilized, respectively. Moreover, DAVID, HPA, TIMER, CancerSEA, ENCORI, DrugBank, and GSCAlite were used for gene enrichment analysis, subcellular localization analysis, immune cell infiltration analysis, exploring correlations between hub genes and different diverse states, lncRNA-miRNA-mRNA co-regulatory network analysis, predicting hub gene-associated drugs, and conducting drug sensitivity analysis, respectively. In total, 8947 DEGs were found between OC and normal samples in GSE69428. After STRING and Cytohubba analysis, 4 hub genes including TTK (TTK Protein Kinase), (BUB1 mitotic checkpoint serine/threonine kinase B) BUB1B, (Nucleolar and spindle-associated protein 1) NUSAP1, and (ZW10 interacting kinetochore protein) ZWINT were selected as the hub genes. Further, it was validated that these 4 hub genes were significantly up-regulated in OC samples compared to normal controls, but overexpression of these genes was not associated with overall survival (OS). However, genetic alterations in those genes were found to be linked with OS and disease-free (DFS) survival. Moreover, this study also revealed some novel links between TTK, BUB1B, NUSAP1, and ZWINT overexpression and promoter methylation status, immune cell infiltration, miRNAs, gene enrichment terms, and various chemotherapeutic drugs. Four hub genes, including TTK, BUB1B, NUSAP1, and ZWINT, were revealed as tumor-promotive factors in OC, having the potential to be utilized as novel biomarkers and therapeutic targets for OC management.

Parent Quality of Life scale in Type 1 Diabetes: a scale development and validation study.

The study aimed to develop and evaluate the psychometric properties of the Parental Quality of Life Scale in Type 1 Diabetes for parents. This research was a methodological study. The data of the study were collected between May and July 2021. The study included 201 parents who have a child with type 1 diabetes. Descriptive statistics, Cronbach's alpha, item-total score analysis, and factor analysis were used to evaluate the research data. In line with the suggestions of the experts, a total of 20 items were removed from the scale and a 12-item scale was created. The scale consists of 12 items and 2 sub-dimensions and shows 62.7% of the total variance. The Cronbach's alpha value of the scale was found to be 0.91 and its sub-dimensions were more significant than 0.85. According to both explanatory factor analysis and confirmatory factor analysis, all factor loads were more significant than 0.60.  Conclusion: The Parental Quality of Life Scale in Type 1 Diabetes was found to be valid and reliable. The scale can be used as a measurement tool in experimental or qualitative studies to be conducted on children with type 1 diabetes and their families. It is recommended to adapt the scale's psychometric properties to different cultures. What is Known: • The quality of life of parents who have a child with type 1 diabetes may be affected due to the burden of care for the disease. Parents' low quality of life can negatively affect pediatric patients' health.. • There is no measurement tool in the literature that directly measures the quality of life of parents who have a child with type 1 diabetes, whose validity and reliability studies have been conducted. What is New: • A measurement tool was developed to evaluate the quality of life of parents with a child with type 1 diabetes. • This measurement tool is valid and reliable.

Clinical and Osteopetrosis-Like Radiological Findings in Patients with Leukocyte Adhesion Deficiency Type III.

BACKGROUND: Leukocyte and platelet integrin function defects are present in leukocyte adhesion deficiency type III (LAD-III) due to mutations in FERMT3. Additionally, osteoclast/osteoblast dysfunction develops in LAD-III. AIM: To discuss the distinguishing clinical, radiological, and laboratory features of LAD-III. METHODS: This study included the clinical, radiological, and laboratory characteristics of twelve LAD-III patients. RESULTS: The male/female ratio was 8/4. The parental consanguinity ratio was 100%. Half of the patients had a family history of patients with similar findings. The median age at presentation and diagnosis was 18 (1-60) days and 6 (1-20) months, respectively. The median leukocyte count on admission was 43,150 (30,900-75,700)/µL. The absolute eosinophil count was tested in 8/12 patients, and eosinophilia was found in 6/8 (75%). All patients had a history of sepsis. Other severe infections were pneumonia (66.6%), omphalitis (25%), osteomyelitis (16.6%), gingivitis/periodontitis (16%), chorioretinitis (8.3%), otitis media (8.3%), diarrhea (8.3%), and palpebral conjunctiva infection (8.3%). Four patients (33.3%) received hematopoietic stem cell transplantation (HSCT) from HLA-matched-related donors, and one deceased after HSCT. At initial presentation, 4 (33.3%) patients were diagnosed with other hematologic disorders, three patients (P5, P7, and P8) with juvenile myelomonocytic leukemia (JMML), and one (P2) with myelodysplastic syndrome (MDS). CONCLUSION: In LAD-III, leukocytosis, eosinophilia, and bone marrow findings may mimic pathologies such as JMML and MDS. In addition to non-purulent infection susceptibility, patients with LAD-III exhibit Glanzmann-type bleeding disorder. In LAD-III, absent integrin activation due to kindlin-3 deficiency disrupts osteoclast actin cytoskeleton organization. This results in defective bone resorption and osteopetrosis-like radiological changes. These are distinctive features compared to other LAD types.

Assessing COVID-19 pandemic policies and behaviours and their economic and educational trade-offs across US states from Jan 1, 2020, to July 31, 2022: an observational analysis.

BACKGROUND: The USA struggled in responding to the COVID-19 pandemic, but not all states struggled equally. Identifying the factors associated with cross-state variation in infection and mortality rates could help to improve responses to this and future pandemics. We sought to answer five key policy-relevant questions regarding the following: 1) what roles social, economic, and racial inequities had in interstate variation in COVID-19 outcomes; 2) whether states with greater health-care and public health capacity had better outcomes; 3) how politics influenced the results; 4) whether states that imposed more policy mandates and sustained them longer had better outcomes; and 5) whether there were trade-offs between a state having fewer cumulative SARS-CoV-2 infections and total COVID-19 deaths and its economic and educational outcomes. METHODS: Data disaggregated by US state were extracted from public databases, including COVID-19 infection and mortality estimates from the Institute for Health Metrics and Evaluation's (IHME) COVID-19 database; Bureau of Economic Analysis data on state gross domestic product (GDP); Federal Reserve economic data on employment rates; National Center for Education Statistics data on student standardised test scores; and US Census Bureau data on race and ethnicity by state. We standardised infection rates for population density and death rates for age and the prevalence of major comorbidities to facilitate comparison of states' successes in mitigating the effects of COVID-19. We regressed these health outcomes on prepandemic state characteristics (such as educational attainment and health spending per capita), policies adopted by states during the pandemic (such as mask mandates and business closures), and population-level behavioural responses (such as vaccine coverage and mobility). We explored potential mechanisms connecting state-level factors to individual-level behaviours using linear regression. We quantified reductions in state GDP, employment, and student test scores during the pandemic to identify policy and behavioural responses associated with these outcomes and to assess trade-offs between these outcomes and COVID-19 outcomes. Significance was defined as p<0·05. FINDINGS: Standardised cumulative COVID-19 death rates for the period from Jan 1, 2020, to July 31, 2022 varied across the USA (national rate 372 deaths per 100 000 population [95% uncertainty interval [UI] 364-379]), with the lowest standardised rates in Hawaii (147 deaths per 100 000 [127-196]) and New Hampshire (215 per 100 000 [183-271]) and the highest in Arizona (581 per 100 000 [509-672]) and Washington, DC (526 per 100 000 [425-631]). A lower poverty rate, higher mean number of years of education, and a greater proportion of people expressing interpersonal trust were statistically associated with lower infection and death rates, and states where larger percentages of the population identify as Black (non-Hispanic) or Hispanic were associated with higher cumulative death rates. Access to quality health care (measured by the IHME's Healthcare Access and Quality Index) was associated with fewer total COVID-19 deaths and SARS-CoV-2 infections, but higher public health spending and more public health personnel per capita were not, at the state level. The political affiliation of the state governor was not associated with lower SARS-CoV-2 infection or COVID-19 death rates, but worse COVID-19 outcomes were associated with the proportion of a state's voters who voted for the 2020 Republican presidential candidate. State governments' uses of protective mandates were associated with lower infection rates, as were mask use, lower mobility, and higher vaccination rate, while vaccination rates were associated with lower death rates. State GDP and student reading test scores were not associated with state COVD-19 policy responses, infection rates, or death rates. Employment, however, had a statistically significant relationship with restaurant closures and greater infections and deaths: on average, 1574 (95% UI 884-7107) additional infections per 10 000 population were associated in states with a one percentage point increase in employment rate. Several policy mandates and protective behaviours were associated with lower fourth-grade mathematics test scores, but our study results did not find a link to state-level estimates of school closures. INTERPRETATION: COVID-19 magnified the polarisation and persistent social, economic, and racial inequities that already existed across US society, but the next pandemic threat need not do the same. US states that mitigated those structural inequalities, deployed science-based interventions such as vaccination and targeted vaccine mandates, and promoted their adoption across society were able to match the best-performing nations in minimising COVID-19 death rates. These findings could contribute to the design and targeting of clinical and policy interventions to facilitate better health outcomes in future crises. FUNDING: Bill & Melinda Gates Foundation, J Stanton, T Gillespie, J and E Nordstrom, and Bloomberg Philanthropies.

A Bibliometric Analysis of Publications on Tinnitus: A Study Based on Web of Science Data From 1980 to 2020.

BACKGROUND: The incidence of tinnitus has been increasing together with its patient impact and societal costs. Much research has been conducted in the field of tinnitus, especially on treatment modalities because there still is no cure. This study aims to analyze the evolutions and developments in the scientific output relating to tinnitus. METHODS: We analyzed the Science Citation Index Expanded featured articles in the Web of Science Core Collection relating to tinnitus from 1980 to 2020. The publications were analyzed by characteristics such as the countries and institutions, journals, the most cited articles and references, and the most frequently used words in the abstracts and keywords. RESULTS: In total, 8282 articles relating to tinnitus were identified in the Web of Science. The number of publications has been significantly increasing after the 1990s. Of the 8282 articles, a major part originated from the American and European institutions. Most articles originated from high-impact journals, which consequently also covered the most cited papers. A major interest was seen in areas about treatment and pathogenic mechanisms. CONCLUSION: This bibliometric analysis here indicated an increasing trend in tinnitus research from 1980 to 2020, particularly with the increase in tinnitus burden and the societal costs by it. Specific interest has been seen in the specific tinnitus pathophysiological mechanisms and treatment. Individual researchers and institutions will gain a new perspective on their future studies based on the bibliometric data in our paper.

Evaluation of periodontal status and cytokine response in children with familial Mediterranean fever or systemic juvenile idiopathic arthritis.

OBJECTIVES: Familial Mediterranean fever (FMF) and systemic juvenile idiopathic arthritis (sJIA) are chronic inflammatory diseases and anti-inflammatory agents are used in their treatment. This study evaluates the periodontal status and cytokine response in pediatric patients with FMF or sJIA. MATERIALS AND METHODS: Forty-eight FMF/sJIA patients were under treatment/control and in attack-free period; 20 systemically healthy children participated in the study. FMF/sJIA patients were divided into two subgroups based on the treatment they received: receiving anti-IL-1 therapy (anti-IL-1 ( +)) and not receiving anti-IL-1 therapy (anti-IL-1 ( -)). The clinical periodontal indices were recorded. Gingival crevicular fluid (GCF) and serum samples were collected. Cytokine levels (IL-1ß, IL-1α, TNF-α, IL-6, IL-8, IL-10, IL-17, IL-33) in GCF and serum were measured using ELISA kits. RESULTS: There was no significant difference between the groups in terms of GCF IL-1ß and IL-1α levels although, BoP and GI were significantly lower in the anti-IL-1 ( +) group compared to the control group. GCF IL-10 level was higher in the anti-IL-1 ( -) group than in the control group; GCF IL-8 levels were lower in both FMF/sJIA subgroups versus controls. There was no significant difference between serum cytokine levels of FMF/sJIA subgroups. CONCLUSIONS: Considering the significant decrease in GI, BoP, and GCF IL-8 levels in the anti-IL-1 ( +) group, it can be concluded that anti-IL-1 medications may suppress periodontal inflammation clinically and immunologically. CLINICAL RELEVANCE: Anti-IL agents are not currently used in periodontal therapy. However, this study demonstrated the positive effect of anti-IL-1 medications on periodontal inflammation in pediatric patients with FMF or sJIA.

Primary lateral sclerosis natural history study - planning, designing, and early enrollment.

Introduction/Aims. Primary lateral sclerosis (PLS) is exceedingly rare and has been an enigmatic disease. Recent progress has drastically changed this perception, with early biomarkers being investigated and potential medications for PLS emerging at the preclinical stage. The aim of this paper is to describe a study of PLS natural history and discuss the limitations and proposed solutions to the study of a rare and slowly progressive disease. Methods. The PLS Natural History Study is a 30-site, 24-month, prospective study that is supported by multiple funding sources. The study aims to enroll 50 early PLS (disease duration ≤4 years) and 50 definite PLS (disease duration 4 to 15 years) participants using modified PLS Diagnostic Criteria. Smartphone-based assessments including semi-quantitative and quantitative measures and patient-reported outcomes are utilized. In-person quantitative measures are also completed during site visits. The change in the PLS Functional Rating Scale score is the primary outcome. The study utilizes the NeuroBANK® patient-centric data capture and management platform. The biostatistical analysis plan has been developed. Results. In one year, 28 participants have been recruited. Enrollment has been much slower than anticipated due to the COVID-19 pandemic, the rarity of PLS, and potential study competition for internal resources from ALS clinical trials. Discussion. We discuss the need for more innovative methods to enroll and study individuals with such rare diseases and propose a number of mechanisms by which more efficient enrollment could be facilitated.

Metastatic diffuse follicular variant papillary thyroid cancer without cervical lymph node metastasis presenting with symptoms related to hypopituitarism

ABSTRACT In this article, we present a case of diffuse follicular variant papillary thyroid carcinoma with pituitary metastasis, which is a rare cause of pituitary metastasis. The follicular variant of papillary thyroid carcinoma is an uncommon variant of papillary carcinoma. A 74-year-old male was presented with weakness, fatigue, and a decreased appetite. The patient was diagnosed with secondary adrenal and thyroid insufficiencies. Imaging revealed a pituitary mass with suprasellar extension, right cavernous sinus invasion, and optic chiasm compression. Thyroid ultrasonography revealed a nodule with a maximum size of 7.2cm in the right lobe. Cytological examination via fine-needle aspiration suggested papillary thyroid cancer. Total thyroidectomy with central and right lateral neck dissection confirmed the diagnosis of diffuse follicular variant of papillary thyroid carcinoma. Owing to visual field defects, the patient underwent transsphenoidal surgery. Histological and immunohistochemical evaluations confirmed pituitary metastasis from the papillary thyroid cancer. Radioactive iodine treatment and gamma knife radiotherapy of the pituitary gland were performed. The initiation of sorafenib treatment was deemed appropriate during the follow-up. A significant decrease in the thyroglobulin levels was observed after sorafenib treatment. Pituitary metastasis should be considered in patients diagnosed with hypopituitarism and pituitary lesions at initial evaluation. The presence of visual field defects may be an indication for neurosurgical intervention and guide both diagnosis and treatment. The management of papillary thyroid cancer and the role of treatment modalities in prognosis depend on the biological behavior of the tumor. Early diagnosis and multidisciplinary management are crucial for the treatment of these patients.

Effect of Transurethral Thermotherapy on Storage Symptoms Associated with Lower Urinary System Complaints in Elderly

Background: Storage symptoms are pathology with increasing frequency and importance among elderly men. The efficacy and advantages of the new bipolar radiofrequency prostate thermotherapy method were investigated for storage symptoms in elderly. Methods: The outcomes for 150 elderly patients with significant storage symptoms accompanying voiding symptoms were investigated. The patients’ Qmax (maximum urinary flow rate), prostate volumes, OAB-V8 (overactivebladder-Validated 8) and quality of life scores were questioned before the procedure and 1st month and 6th month. Results: OAB-V8 total score had mean value of 26.3, with values identified as 16.2 (p < 0.001) at the end of the 1st month and 13.9 (p = 0.001) at the end of the 6th month. There were significant reductions in daytime frequent urination, uncomfortable urgency and sudden feeling of urgency complaints (p < 0.001). Thirty-five patients had significant fall in urgency with incontinence (p = 0.016). Conclusions: The bipolar radiofrequency thermotherapy method provides significant improvement of storage symptoms in elderly men. It is thought that this method has advantages in terms of its effects on storage and voiding symptoms in the elderly (AU)

Valproate, obesity and other causes of clozapine poor metabolism in the context of rapid titration may explain clozapine-induced myocarditis: A re-analysis of a Turkish case series / El valproato, la obesidad y otras causas de metabolismo deficiente de la clozapina en el contexto de una titulación rápida de las dosis pueden explicar la miocarditis inducida por clozapina: un nuevo análisis de una serie de casos turca

Introduction: Clozapine-induced myocarditis or any clozapine-induced inflammation may be a hypersensitivity reaction due to titration that was too rapid for the patient's clozapine metabolism. Clozapine metabolism is influenced by ancestry, sex, smoking and the presence of confounders including obesity, infections, and inhibitors (e.g., valproate) causing the patient to behave as a clozapine poor metabolizer (PM). A published study in a Turkish hospital identified 1 case of clozapine-induced pancreatitis and hepatitis and 9 cases of clozapine-induced myocarditis. To explore the hypothesis that the 10 patients were clozapine PMs, their serum clozapine concentrations were investigated using concentration-to-dose (C/D) ratios and their titrations carefully reviewed. Methods: Dividing the trough serum concentration by the dose produces the clozapine C/D ratio. The dose required to reach 350ng/ml was considered the minimum therapeutic dosage and was used to classify patients according to clozapine PM status. Titration speed was assessed. Results: All 10 patients were possibly clozapine PMs (3 of them had as minimum therapeutic doses: 72, 82 or 83mg/day). Nine of the 10 patients may have behaved as clozapine PMs due to obesity and/or valproate co-prescription during titration. One also had an undiagnosed infection. Of the 10 patients, 9 had at least 1 of 3 factors: too-rapid titration in the first or second weeks, or a final dosage that was too high. Conclusions: Future studies using clozapine levels and considering the role of clozapine PM status should explore whether or not all cases of clozapine-induced inflammation could be explained by lack of individualized titration. (AU)

Introducción: Cualquier inflamación inducida por la clozapina, incluida la miocarditis, podría ser una reacción de hipersensibilidad asociada a una titulación demasiado rápida de del fármaco para el metabolismo del paciente. El metabolismo de la clozapina está influenciado por la ascendencia, el sexo, el tabaquismo, y por la presencia de factores de confusión como obesidad, infecciones e inhibidores, como el valproato, que hacen que el paciente se comporte como un metabolizador lento (PM). Un estudio publicado identificó un caso de pancreatitis y hepatitis, y 9 casos de miocarditis inducidos por clozapina. Para explorar la hipótesis de que los 10 pacientes eran PM de clozapina, se investigaron sus concentraciones séricas de clozapina utilizando relaciones concentración/dosis (C/D) y revisando sus titulaciones. Métodos: La dosis necesaria para alcanzar 350ng/ml se consideró la dosis terapéutica mínima y clasificó a los pacientes según el estado de PM de clozapina. Se evaluó la velocidad de titulación. Resultados: Los 10 pacientes eran posiblemente PM de clozapina (3 tenían dosis terapéuticas mínimas: 72, 82 u 83mg/día). Nueve pacientes pueden haberse comportado como PM de clozapina debido a obesidad y/o prescripción conjunta de valproato durante la titulación. Uno también tenía una infección no diagnosticada. Nueve de los 10 pacientes tenían al menos uno de los 3 factores siguientes: titulación demasiado rápida en la primera o segunda semana, o una dosis final excesiva. Conclusiones: Futuros estudios que utilicen niveles de clozapina y consideren el PM deberían explorar si la inflamación inducida por clozapina podría explicarse por la falta de titulaciones individualizadas. (AU)

Dental caries and associated salivary biomarkers in patients with cystic fibrosis.

PURPOSE: To evaluate the caries status of the Cystic fibrosis (CF) children and adolescents with the comparation of some biochemical markers, secretory-immunoglobulin-A (sIgA), and antimicrobial peptides in the saliva. METHODS: In this cross-sectional descriptive study, the approval Ethics Board was obtained. Unstimulated saliva samples were collected from CF and healthy control children (non-CF) patients. Both groups underwent the same dental and periodontal evaluation scheme of the assessment. Human beta defensin (HBD1), human alpha defensin (HNP-1), cathelicidin (LL-37), sIgA in saliva were evaluated by enzyme-linked immunoassay method. A general biochemical analysis was performed. Statistical analysis was performed by using Statistical Package for the Social Sciences Version 20.0 (SPSS Inc.). RESULTS: A total of 21 (9 male, 12 female) CF and 23 (11 male, 12 female) control patients were participated with the mean age of 10.17 ± 3.38 and 9.52 ± 2.15 years, respectively. In control children, DMFT/S (decayed-missing-filled-tooth/surface-in-permanent-dentition), dmft/s (decayed-missing-filled-tooth/surface-in-primary-dentition) values were higher; DT (decayed-tooth in permanent dentition), ft (filled-tooth in primary dentition) and plaque index values were statistically significantly higher (p = 0.042, p = 0.005, p = 0.038, respectively) than CF patients. Bicarbonate was higher in control group; sodium, chloride, and total protein were higher in CF group; magnesium, calcium and phosphate levels were similar in each group (p > 0.05). Alpha and beta defensin-1 levels in control group was statistically significantly higher (p = 0.037 and p = 0.020, respectively), while LL37 and sIgA were not statistically significantly higher (p > 0.05) than CF group. CONCLUSIONS: Children with CF had lower caries in permanent teeth, filling in primary teeth, and an altered salivary biomarker profile, especially in HNB1, HNP1. Therefore, it is important to conduct periodic oral-dental controls among CF patients during their childhood.

The Effects of Using Hearing Aids and Hearing Assistive Technologies on Programmable Ventriculoperitoneal Shunt.

BACKGROUND: To investigate interaction between behind-the-ear (BTE) hearing aids, hearing assistive technologies, and programmable shunt valve to understand how use of BTE hearing aids in patients who underwent ventriculoperitoneal shunt (VPS) surgery affects the settings of a programmable shunt valve. METHODS: In this study, we investigated the magnetic field (MF) generation of 3 BTE hearing aids made by different companies, 1 frequency modulated system using telecoil technology, and 1 wireless microphone technology and their interactions with 2 programmable shunt valves. All measurements were made in a silent booth using 2 different models. The influence of MF strength in the distance modeling was investigated based on the distance from source auditory prostheses. The measurements were recorded using a Gauss meter. In the anatomical modeling, the change in the settings and interaction of the valve in a bust mannequin were investigated. RESULTS: No MF created by BTE hearing aids was detected in the distance modeling. The highest value measured was 32.67 µT (<90 dB noise) when BTE hearing aids and frequency modulated systems were used, and this value decreased as the distance increased. No MF generation was observed at measurements done for distances >10 mm. In the anatomical modeling, the settings of both programmable valves did not change under all acoustic conditions. CONCLUSIONS: This is the first study to our knowledge examining the MF created by hearing aids and hearing assistive technologies and its impact on programmable valves and variations in their settings. Our findings showed that it is safe to use BTE hearing aids, frequency modulated systems, and wireless microphone technologies in patients with a programmable VPS.

Evaluating the impact and cost-effectiveness of chlamydia management strategies in Hong Kong: A modeling study.

Objectives: To illustrate the epidemiologic and cost-effectiveness impact of shifting the focus from population-based screening toward a targeted management approach for genital chlamydia infection. Design: Modeling study, implementing an individual-based, stochastic, dynamic network model. Setting: Hong Kong. Population: A hypothetical sample network of 10,000 people with a partnership distribution based on Hong Kong's sexually active population of reproductive age (age 18-49 years). Interventions: In this study, we present several scenarios with different implementations of universal vs. targeted screening (based on partner numbers). We also explored the impact of (1) screening only, (2) screening plus expedited partner therapy, and (3) screening plus partner testing. Primary outcome measures: Change of chlamydia prevalence before and after implementing the different strategies. The cost-effectiveness analysis reports total direct cost from a health provider perspective, the QALYs gained, and incremental cost-effectiveness ratios (ICER). Results: In comparing the effects of universal screening only and targeted screening of the high-risk population, the mean prevalence during the 10th year of intervention was 2.75 ± 0.30% and 2.35 ± 0.21%, respectively (compared with 3.24 ± 0.30% and 3.35 ± 0.21% before the interventions, respectively). The addition of contact tracing to the latter targeted screening scenario reduces the mean prevalence during the 10th year of intervention to 1.48 ± 0.13% (compared with 3.31 ± 0.33% at baseline) in the best-case of testing before treatment and maximal contact-tracing effectiveness (40%). Overall, the most effective scenarios were those for which interventions focused on the high-risk population defined by the number of partners, with contact tracing included. The ICER for targeted screening with contact tracing at 20% and 40% efficiency was $4,634 and $7,219 per QALY gained, respectively (10-year time horizon). Expedited partner therapy did not significantly impact overall chlamydia prevalence and caused overtreatment. Conclusions: Our study suggests that targeted screening with strengthened contact tracing efforts is the most cost-effective strategy to reduce the prevalence of chlamydia in Hong Kong.