Olanzapine induced reproductive toxicity in male rats.

Although it is reported that olanzapine (OLZ), which is an atypical antipsychotic drug, causes sexual dysfunction in men, it is noteworthy that there is not any study evaluating the toxic effects of OLZ on the male reproductive system. In the scope of this research, it was aimed to assess the reproductive toxic effects of OLZ by oral administration of 2.5, 5, or 10 mg/kg of it to male rats for 28 days. For this purpose, sperm concentration, motility and morphology, and DNA damage were determined, and histopathological examination of testis tissue was carried out in rats. Also, the levels of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone, which play roles in the regulation of reproductive functions, and the levels of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA) which play roles in reproductive pathologies as oxidative stress biomarkers, were determined. According to the results, normal sperm morphology was decreased in 5 ve 10 mg/kg OLZ-administered groups, and pathological findings were evident in the testicular structure of the OLZ-administered group when compared with the control group. It was determined that serum LH, FSH, and testosterone levels were decreased in the OLZ-administered group. Also, decreases of GSH levels in testis tissue were determined and evaluated as the markers of the oxidative stress induced by OLZ in the testis. In conclusion, it was determined that reproductive toxic effects were induced in rats by OLZ administration. This pathology was accompanied by alterations of the hormone levels and testicular oxidative stress.

Manual ability and upper limb performance in nonambulatory stage of Duchenne muscular dystrophy.

PURPOSE: The functional use of the upper extremities in daily living activities has become important in the later ages with the increasing life expectancy of patients with Duchenne muscular dystrophy (DMD). This study aimed to assess manual ability and upper limb performance of nonambulatory children with DMD, and to determine their relationship with factors that might affect ability and performance. METHODS: Manual ability was determined via the ABILHAND-Kids questionnaire and upper limb performance was assessed with the Performance of Upper Limb (PUL) test. Possible related factors such as functional level, steroid usage, upper limb range of motion (ROM), thumb opposition, upper limb muscular strength, and grip strength were evaluated. Correlations of related factors with manual ability and upper limb performance were analyzed. RESULTS: The mean age of 23 nonambulatory DMD children was 13.04±1.39 years. Moderate impairments were determined according to the ABILHAND-Kids and PUL, with scores of 26.30±10.74 and 46.22±15.02, respectively. The functional level, steroid usage, duration of wheelchair use, upper extremity ROM, and global upper limb muscle strength of children were weak-to-strongly correlated with at least one score of ABILHAND-Kids and PUL (P<0.05). CONCLUSION: Children with DMD may already have severe proximal and mid-level upper extremity involvement, even reflected in distal functions, at the time when they progress to the nonambulatory stage. Besides muscular strength, many related factors should be taken into account for therapists to assess and treat upper limb performance at later stages of DMD.

Indeterminate cell histiocytosis in a patient with systemic lupus erythematosus and antiphospholipid antibody syndrome: an unusual association.

Indeterminate cell histiocytosis (ICH) is an extremely rare clonal proliferative disorder of dendritic cells which presents with skin lesions in the majority of cases. Although extra-cutaneous manifestations are very rare, ICH may involve the mucosa, cornea, and conjunctiva as well as the visceral organs. Since the clinical appearance of cutaneous lesions of ICH is not distinctive, it is diagnosed with histopathological and immunohistochemical findings after clinical suspicion. Herein, we report a 27-year-old man with a two-year history of asymptomatic reddish papules and papulonecrotic lesions on his face, arms and buttocks. He was previously diagnosed with systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome (APS), and he had been treated with hydroxychloroquine and low-dose aspirin. Diffuse dermal infiltration of a mixture of histiocytes and lymphocytes accompanied with multinuclear giant cells, the positive CD68 and Factor XIIIa and negative Langerin immunoreactions, along with the positive staining with CD1a and S100, led us to the diagnosis of ICH. To the best of our knowledge, this is the first case of ICH associated with SLE and APS.

Reproductive toxic effects and possible mechanisms of zonisamide in male rats.

Zonisamide (ZNS) is an anticonvulsant which is used to treat the symptoms of epilepsy. Although it is frequently used during reproductive ages, studies that investigated the effects of ZNS on reproductive system are limited. Therefore, we aimed to assess the effects of ZNS on male reproductive system by oral administration to rats in 25, 50, and 100 mg/kg doses for 28 days. After the exposure period, sperm concentration, motility, morphology, and DNA damage, as biomarkers of reproductive toxic effects, were determined, and histopathological examination of testis was performed. In addition, levels of the hormones that play a role in the regulation of reproductive functions, such as follicle-stimulating hormone, luteinizing hormone (LH), and testosterone were measured and the levels of oxidative stress biomarkers that take part in the reproductive pathologies such as catalase, superoxide dismutase, glutathione, and malondialdehyde, were determined. Reproductive toxic effects related to ZNS administration were shown by the significant decrease of sperm concentration and normal sperm morphology in ZNS groups. Additionally, pathological findings were observed in the testicular tissues of ZNS-administered groups dose dependently. In addition, serum LH and testosterone levels were significantly decreased in the ZNS groups. Decreased catalase activities and increased malondialdehyde levels in ZNS groups were evaluated as oxidative stress findings in the testis tissue. It could be expressed that ZNS administration induced dose-dependent reproductive toxic effects in rats, and pathological findings associated with the reproductive system could be the result of that hormonal changes and testicular oxidative stress, which in turn might be considered as possible mechanisms of male reproductive toxicity.

Design and evaluation of biological activities of 1,3-oxazolidinone derivatives bearing amide, sulfonamide, and thiourea moieties.

1,3-Oxazolidine-2-one is an important heterocyclic ring participating in the chemical structure of many drugs. In this research, 22 new amide/sulfonamide/thiourea derivatives (1-22) were obtained by the reaction of (S)-4-(4-aminobenzyl)-2(1H)-1,3-oxazolidinone with 4-substituted benzoyl chlorides, 4-substituted benzene sulfonyl chlorides, and 4-substituted phenyl isothiocyanates. The structures of all synthesized compounds were clarified by FT-IR, NMR, and mass spectroscopic and elemental analysis techniques. The synthesized compounds were screened for their antimicrobial activity. Antimicrobial susceptibility and cellular physiology were evaluated using the microbroth dilution assay and the flow cytometry method. As a result, it was determined that compound 16 displayed better antimicrobial activity than chloramphenicol against Gram-positive bacteria, especially Staphylococcus aureus. In order to understand the mechanism of effect of the compounds on the cell membrane, fluorescence microscopy was used. Cell membrane damage of the Gram positive bacteria treated with compound 16 was observed as a result of intense staining with propidium iodide. In addition, genotoxicity, cytotoxicity, and absorption, distribution, metabolism, and excretion (ADME) parameters of compound 16 were examined and it was found as non-mutagenic and non-cytotoxic at the concentration at which it showed antimicrobial activity. According to the calculated ADME parameters and drug likeness scores, the compounds can be good drug candidates, especially compound 16.

Reliability and validity of the Karaduman Chewing Performance Scale in paediatric neuromuscular diseases: A system for classification of chewing disorders.

Chewing disorders can be seen in children with neuromuscular diseases (NMDs), which may cause swallowing difficulties such as choking, retching and food stuck feeling in the throat. Due to these effects, it is important to determine chewing disorders early with appropriate assessment methods to plan appropriate therapies in NMDs. The aim of this study was to investigate reliability and validity of the Karaduman Chewing Performance Scale (KCPS) in children with NMDs. Age, sex and diagnosis were recorded. Children were asked to chew a standardised biscuit while video-recording. Two physical therapists scored each video according to the KCPS. The correlation between the KCPS scores of 2 therapists was analysed for interobserver reliability. One therapist rescored the recordings after an interval of 2 weeks for intra-observer reliability. The Pediatric Version of the Eating Assessment Tool (PEDI-EAT-10) was used for criterion-based validity. Sixty-eight children with a mean age of 8.34 ± 3.73 (min = 2.5, max = 14.5) years were included, of which 94.1% were male. Karaduman Chewing Performance Scale scores were found to be level 0 in 20 cases, level 1 in 35 cases, level 2 in 12 cases and level 3 in 1 case. A positive, very strong correlation was detected between 2 therapists (r = .93, P < .001) and between 2 examinations of 1 therapist (r = .83, P < .001). A good correlation between the KCPS and PEDI-EAT-10 was detected (r = .62, P < .001). Chewing function, especially food processing phase, deteriorated in children with NMDs. The KCPS could be used as a reliable and valid instrument in determining chewing performance level for children with NMDs.

Is elevated triglyceride high density lipoprotein cholesterol ratio a risk factor that causes acute coronary syndrome to appear earlier?

BACKGROUND: The purpose of this study was to assess the relationship between the triglyceride/high density lipoprotein cholesterol ratio and the risk of acute myocardial infarction in young adults. PATIENTS AND METHODS: A total of 621 patients, who underwent coronary angiography (CAG) due to Myocardial Infarction (MI) at our hospital were included in this study. Demographic characteristics, risk factor profile, laboratory test results, electrocardiographic and CAG findings were assessed in the selected groups. RESULTS: Total cholesterol, triglyceride/high density lipoprotein cholesterol (Tg/HDL) ratio, Tg levels, were higher in younger patients with MI, while glucose and high-density lipoprotein levels were lower. Using propensity score matching in the matched population comparing young patients to the older ones, serum triglyceride levels [179 (145-231) vs 148 (101-197)] and triglyceride to high density lipoprotein cholesterol ratio [5.8 (4.1-9.1) vs 3.0 (1.8-4.6)] were significantly higher, whereas high density lipoprotein levels were observed dramatically lower (32.6 ± 8.2 vs 41.7 ± 8.8). CONCLUSION: This study demonstrated that Tg/HDL ratio may be an important predictor for an acute coronary syndrome in the young adult population. Tg/HDL ratio can be used to prevent MI in young adults (Tab. 3, Fig. 1, Ref. 32.).

Clinical Outcomes in Duchenne Muscular Dystrophy: A Study of 5345 Patients from the TREAT-NMD DMD Global Database.

BACKGROUND: Recent short-term clinical trials in patients with Duchenne Muscular Dystrophy (DMD) have indicated greater disease variability in terms of progression than expected. In addition, as average life-expectancy increases, reliable data is required on clinical progression in the older DMD population. OBJECTIVE: To determine the effects of corticosteroids on major clinical outcomes of DMD in a large multinational cohort of genetically confirmed DMD patients. METHODS: In this cross-sectional study we analysed clinical data from 5345 genetically confirmed DMD patients from 31 countries held within the TREAT-NMD global DMD database. For analysis patients were categorised by corticosteroid background and further stratified by age. RESULTS: Loss of ambulation in non-steroid treated patients was 10 years and in corticosteroid treated patients 13 years old (p = 0.0001). Corticosteroid treated patients were less likely to need scoliosis surgery (p < 0.001) or ventilatory support (p < 0.001) and there was a mild cardioprotective effect of corticosteroids in the patient population aged 20 years and older (p = 0.0035). Patients with a single deletion of exon 45 showed an increased survival in contrast to other single exon deletions. CONCLUSIONS: This study provides data on clinical outcomes of DMD across many healthcare settings and including a sizeable cohort of older patients. Our data confirm the benefits of corticosteroid treatment on ambulation, need for scoliosis surgery, ventilation and, to a lesser extent, cardiomyopathy. This study underlines the importance of data collection via patient registries and the critical role of multi-centre collaboration in the rare disease field.

Effect of Functional Chewing Training on tongue thrust and drooling in children with cerebral palsy: a randomised controlled trial.

Tongue thrust, which is an oral reflex associated with sucking behaviour, may cause problems in swallowing, speech, oro-facial development and also drooling. We aimed to examine the effect of Functional Chewing Training (FuCT) on tongue thrust and drooling in children with cerebral palsy. The study included 32 children with a mean age of 58·25 ± 9·58 months who had tongue thrust. Children were divided into two groups: the FuCT group and control group receiving classical oral motor exercises. Each group received training for 12 weeks. Oral motor assessment was performed. Chewing performance level was determined with the Karaduman Chewing Performance Scale. Tongue thrust severity was evaluated with the Tongue Thrust Rating Scale. The Drooling Severity and Frequency Scale was used to evaluate drooling severity and frequency. The evaluations were performed before and after treatment. Groups were well matched in age, gender and oral motor assessment. No significant difference was found between groups in terms of pre-treatment chewing function, tongue thrust severity, drooling severity and frequency (P > 0·05). The FuCT group showed improvement in chewing performance (P = 0·001), tongue thrust severity (P = 0·046) and drooling severity (P = 0·002), but no improvement was found in terms of drooling frequency (P = 0·082) after treatment. There was no improvement in chewing performance, tongue thrust, drooling severity and frequency in the control group. A significant difference was found between groups in favour of FuCT group in tongue thrust severity (P = 0·043). This study showed that the FuCT is an effective approach on the severity of tongue thrust and drooling in children with CP.

The Anxiety Level of Caregivers of Neurological Patients with Dysphagia.

We aimed to investigate anxiety level of caregivers of neurological patients with dysphagia, and the relationship of patient-related factors to anxiety level of dysphagia caregivers. A total of 103 adult neurological patients with dysphagia (study group), 30 without dysphagia (control group), and their primary caregivers were included. Types of feeding, condition of dependency in eating and drinking, dysphagia duration, and history of previous dysphagia treatment were recorded for study group. In study group, the Turkish version of the Eating Assessment Tool-10 (T-EAT-10) was used to determine dysphagia symptom severity. Penetration and aspiration severity was determined with the penetration-aspiration scale (PAS). The Spielberger State-Trait Anxiety Inventory (STAI) that has two subscales including state anxiety (S-STAI) and trait anxiety (T-STAI) was used to determine anxiety level of caregivers. There was no difference between groups in terms of age, gender, weight, and height. The mean S-STAI was 42.56 ± 10.10 for the study group and 29.20 ± 6.64 for the control group (p < 0.001). The mean T-STAI was 44.81 ± 8.98 for the study group and 29.37 ± 6.46 for the control group (p < 0.001). Significant correlation was detected between only T-STAI and history of previous dysphagia treatment (p = 0.01, r = 0.25). No correlation was found between STAI (in terms of both S-STAI and T-STAI) and T-EAT-10, PAS, types of feeding, condition of dependency in eating and drinking, dysphagia duration (p > 0.05). Caregivers of neurological patients with dysphagia have greater anxiety level than caregivers of neurological patients without dysphagia.

Reliability and validity of a tool to measure the severity of tongue thrust in children: the Tongue Thrust Rating Scale.

This study aimed to develop a scale called Tongue Thrust Rating Scale (TTRS), which categorised tongue thrust in children in terms of its severity during swallowing, and to investigate its validity and reliability. The study describes the developmental phase of the TTRS and presented its content and criterion-based validity and interobserver and intra-observer reliability. For content validation, seven experts assessed the steps in the scale over two Delphi rounds. Two physical therapists evaluated videos of 50 children with cerebral palsy (mean age, 57·9 ± 16·8 months), using the TTRS to test criterion-based validity, interobserver and intra-observer reliability. The Karaduman Chewing Performance Scale (KCPS) and Drooling Severity and Frequency Scale (DSFS) were used for criterion-based validity. All the TTRS steps were deemed necessary. The content validity index was 0·857. A very strong positive correlation was found between two examinations by one physical therapist, which indicated intra-observer reliability (r = 0·938, P < 0·001). A very strong positive correlation was also found between the TTRS scores of two physical therapists, indicating interobserver reliability (r = 0·892, P < 0·001). There was also a strong positive correlation between the TTRS and KCPS (r = 0·724, P < 0·001) and a very strong positive correlation between the TTRS scores and DSFS (r = 0·822 and r = 0·755; P < 0·001). These results demonstrated the criterion-based validity of the TTRS. The TTRS is a valid, reliable and clinically easy-to-use functional instrument to document the severity of tongue thrust in children.

Effect of a new treatment protocol called Functional Chewing Training on chewing function in children with cerebral palsy: a double-blind randomised controlled trial.

Cerebral palsy (CP) is a group of permanent sensorimotor impairments. Children with CP have various feeding difficulties including chewing disorder, which may affect their nutritional status. Functional Chewing Training (FuCT) was designed as a holistic approach to improve chewing function by providing postural alignment, sensory and motor training, and food and environmental adjustments. This study aimed to investigate the effect of FuCT on chewing function in children with CP. This study was designed as a double-blind, randomised controlled trial. Eighty CP children with chewing disorder were randomised and split between the FuCT group (31 males, 19 females; mean age 3·5 ± 1·9 years) and the control group (16 males, 14 females; 3·4 ± 2·3 years) receiving traditional oral motor exercises. Each group received the training programme for 12 weeks with weekly follow-up and with two evaluations at baseline and end of 12 weeks. Chewing function was evaluated by analysing video recordings and scored with the Karaduman Chewing Performance Scale (KCPS). The Behavioral Pediatrics Feeding Assessment Scale (BPFAS) was used to evaluate feeding behaviours of children. A significant improvement was observed in KCPS scores at 12 weeks after training in the FuCT group (P < 0·001), but no change was found in the control group (P = 0·07). A significant improvement was detected in all parameters of BPFAS at 12 weeks after training in the FuCT group (P < 0·001) and in four parameters of BPFAS in the control group (P = 0·02, P = 0·02). FuCT is an effective method to improve chewing function compared with traditional oral motor exercises.

Reliability and Validity of the Turkish Eating Assessment Tool (T-EAT-10).

The purpose of this study was to test the reliability and validity of the Turkish Eating Assessment Tool (T-EAT-10) among patients with swallowing disorders. One hundred and five patients completed the T-EAT-10 and Functional Oral Intake Scale (FOIS). The internal consistency, test-retest reliability, and criterion validity of T-EAT-10 were investigated. The internal consistency was assessed using Cronbach's alpha. Intraclass correlation coefficient (ICC) value with 95 % confidence intervals was calculated for test-retest reliability. The criterion validity of the T-EAT-10 was determined by assessing the correlation between T-EAT-10 and FOIS. All the patients in the study completed the T-EAT-10 without assistance. The mean time to complete the instrument was 1.8 ± 0.9 min. The internal consistency of the T-EAT-10 was found to be high with 0.90 Cronbach's alpha for test and 0.91 Cronbach's alpha for retest reproducibility. No difference between the test and retest scores of the T-EAT-10 was found (p = 0.14). A negative, moderate correlation between T-EAT-10 and FOIS was detected (r = -0.365, p < 0.001). The T-EAT-10 is a reliable and valid symptom-specific outcome tool for dysphagia in adult Turkish patients. It can be used in clinical practice and research.

Development of a new instrument for determining the level of chewing function in children.

This study aimed to develop a chewing performance scale that classifies chewing from normal to severely impaired and to investigate its validity and reliability. The study included the developmental phase and reported the content, structural, criterion validity, interobserver and intra-observer reliability of the chewing performance scale, which was called the Karaduman Chewing Performance Scale (KCPS). A dysphagia literature review, other questionnaires and clinical experiences were used in the developmental phase. Seven experts assessed the steps for content validity over two Delphi rounds. To test structural, criterion validity, interobserver and intra-observer reliability, two swallowing therapists evaluated chewing videos of 144 children (Group I: 61 healthy children without chewing disorders, mean age of 42·38 ± 9·36 months; Group II: 83 children with cerebral palsy who have chewing disorders, mean age of 39·09 ± 22·95 months) using KCPS. The Behavioral Pediatrics Feeding Assessment Scale (BPFAS) was used for criterion validity. The KCPS steps arranged between 0-4 were found to be necessary. The content validity index was 0·885. The KCPS levels were found to be different between groups I and II (χ(2) = 123·286, P < 0·001). A moderately strong positive correlation was found between the KCPS and the subscales of the BPFAS (r = 0·444-0·773, P < 0·001). An excellent positive correlation was detected between two swallowing therapists and between two examinations of one swallowing therapist (r = 0·962, P < 0·001; r = 0·990, P < 0·001, respectively). The KCPS is a valid, reliable, quick and clinically easy-to-use functional instrument for determining the level of chewing function in children.

The relationship between recurrent aphthous stomatitis, and periodontal disease and Helicobacter Pylori infection.

OBJECTIVE: Recurrent aphthous stomatitis (RAS) is a common oral mucosal disease with unknown etiology. This cross-sectional study aimed to test the hypothesis that Helicobacter pylori and periodontal disease might play an etiological role in RAS. METHODS: Dental plaque samples obtained from 38 patients with RAS and 43 healthy individuals via periodontal examinations were examined for H. pylori colonization. H. pylori was identified using the rapid urease test (RUT). The periodontal status of the patients and controls was based on the following periodontal parameters: periodontal pocket depth (PPD), the plaque index (PI), the gingival index (GI), and clinical attachment loss (CAL). RESULTS: RUT results were positive in 34 (89.5 %) of the 38 patients and 24 (55.8 %) of the 43 controls (P = 0.002). There were not any significant differences in mean PPD, PI, GI, or CAL between the patient and control groups (P > 0.05). Mean PPD, PI, GI, and CAL were higher in the RUT-positive RAS patients than in the RUT-negative patients (P > 0.05, for all). CONCLUSIONS: The present findings show that H. pylori might have played an etiological role in RAS and might have caused periodontal disease, but RAS was not associated with any of the periodontal parameters examined in this study. CLINICAL RELEVANCE: The present study indicates that H. pylori plays a role in the development of RAS, but periodontal diseases have no effect on it. Eradicating H. pylori might be useful to prevent RAS.

The TREAT-NMD DMD Global Database: analysis of more than 7,000 Duchenne muscular dystrophy mutations.

Analyzing the type and frequency of patient-specific mutations that give rise to Duchenne muscular dystrophy (DMD) is an invaluable tool for diagnostics, basic scientific research, trial planning, and improved clinical care. Locus-specific databases allow for the collection, organization, storage, and analysis of genetic variants of disease. Here, we describe the development and analysis of the TREAT-NMD DMD Global database (http://umd.be/TREAT_DMD/). We analyzed genetic data for 7,149 DMD mutations held within the database. A total of 5,682 large mutations were observed (80% of total mutations), of which 4,894 (86%) were deletions (1 exon or larger) and 784 (14%) were duplications (1 exon or larger). There were 1,445 small mutations (smaller than 1 exon, 20% of all mutations), of which 358 (25%) were small deletions and 132 (9%) small insertions and 199 (14%) affected the splice sites. Point mutations totalled 756 (52% of small mutations) with 726 (50%) nonsense mutations and 30 (2%) missense mutations. Finally, 22 (0.3%) mid-intronic mutations were observed. In addition, mutations were identified within the database that would potentially benefit from novel genetic therapies for DMD including stop codon read-through therapies (10% of total mutations) and exon skipping therapy (80% of deletions and 55% of total mutations).

Cutaneous mastocytosis: demographic aspects and clinical features of 55 patients.

BACKGROUND: Mastocytosis is a rare, heterogeneous group of disorder with abnormal increase of mast cells in one or more organ systems. OBJECTIVE: To evaluate the demographic and clinical features of cutaneous mastocytosis (CM). METHODS: Records of 55 patients with cutaneous mastocytosis were retrospectively analysed. RESULTS: Of the 22 females and 33 males, 80% had urticaria pigmentosa/maculopapular CM and 20% had mastocytoma. Of all cases, 81.8% had first lesions in childhood. The most common presentation was involvement of trunk together with extremities. Thirteen (23.6%) patients had history of bulla; Darier's sign was positive in 34 of 38 patients. Itching was the most common complaint, provocated by hot weather/bath. CONCLUSION: Clinical presentations of urticaria pigmentosa/maculopapular CM and mastocytoma are similar regarding gender, age of onset, age of diagnosis, and presence of Darier's sign and history of bulla. In contrast to mastocytoma, urticaria pigmentosa/maculopapular CM lesions were frequently located on trunk together with extremities.

Acute aortic dissection provoked by sneeze: a case report.

The response of the abdominal viscera and the contraction of the intercostal muscles during the respiratory phase of sneezing increases intrathoracic pressure, which may lead to several complications. However, there are no reports in the literature concerning aortic dissection after sneezing. We report a patient in whom the development of dissection was secondary to sneezing, although hypertension was present as a risk factor, and we discuss the relationship between sneezing and aortic dissection. To our knowledge, this is the first report of aortic dissection provoked by sneezing in the literature.