Maternal Periodontal Status as a Factor Influencing Obstetrical Outcomes.

Background and Objectives: Preterm birth as a complex phenomenon is influenced by numerous endogenic and exogenic factors, although its exact cause often remains obscure. According to epidemiological studies, maternal periodontal diseases, in addition to affecting general health, can also cause adverse pregnancy outcomes. Nonetheless, the existing results in the literature regarding this topic remain controversial. Consequently, our study aimed to determine the connection between poor maternal periodontal status and neonatal birth weight. Materials and Methods: A total of 111 primigravida-primiparous pregnant, healthy women underwent a periodontal examination in the second trimester of their pregnancies. Probing depth (PD) and bleeding on probing (BOP) were determined, and based on these diagnostic measurements, the patients were divided into three subgroups according to their dental status: healthy (H, n = 17), gingivitis (G, n = 67), and periodontitis (P, n = 27). Results: Considering that poor maternal oral status is an influencing factor for obstetrical outcomes, the presence of PD and BOP (characterized by the sulcus bleeding index, SBI) was evaluated. In the case of P, defined as PD ≥ 4 mm in at least one site and BOP ≥ 50% of the teeth, a significant correlation between BOP and a low neonatal birth weight at delivery (p = 0.001) was found. An analysis of the relationship between SBI and gestational age (GA) at the time of the periodontal examination in the different dental status groups showed a significant correlation between these parameters in the G group (p = 0.04). Conclusions: Our results suggest that a worse periodontal status during pregnancy may negatively affect obstetrical outcomes, especially the prematurity rate and newborn weight. Therefore, the importance of periodontal screening to prevent these complications is undeniable.

Decision curve analysis apropos of choice of preferable treatment positioning during breast irradiation.

BACKGROUND: Radiotherapy is a standard treatment option for breast cancer, but it may lead to significant late morbidity, including radiation heart damage. Breast irradiation performed individually in the supine or prone position may aid in minimizing the irradiation dose to the heart and LAD coronary artery. A series of CT scans and therapy plans are needed in both positions for the 'gold standard' decision on the preferable treatment position. This method is expensive with respect to technology and physician workload. Our ultimate goal is to develop a predictive tool to identify the preferable treatment position using easily measurable patient characteristics. In this article, we describe the details of how model building and consequently validation of the best model are done. METHODS: Different models were used: both logistic regression and multiple linear regressions were used to estimate the LAD mean dose difference (the difference between the mean dose to the LAD in the supine position versus prone position); predicted dose differences were analysed compared to the 'gold standard' values, and the best model was selected accordingly. The final model was checked by random cross-validation. In addition to generally used measures (ROC and Brier score), decision curves were employed to evaluate the performance of the models. RESULTS: ROC analysis demonstrated that none of the predictors alone was satisfactory. Multiple logistic regression models and the linear regression model lead to high values of net benefit for a wide range of threshold probabilities. Multiple linear regression seemed to be the most useful model. We also present the results of the random cross-validation for this model (i.e. sensitivity of 80.7% and specificity of 87.5%). CONCLUSIONS: Decision curves proved to be useful to evaluate our models. Our results indicate that any of the models could be implemented in clinical practice, but the linear regression model is the most useful model to facilitate the radiation treatment decision. In addition, it is in use in everyday practice in the Department of Oncotherapy, University of Szeged, Hungary.

[A clinicopathological retrospective epidemiological analysis of benign tumors and tumor-like lesions in the oral and maxillofacial region, diagnosed at the University of Szeged, Department of Oral Medicine (1960-2014)]. / A szegedi Fogászati és Szájsebészeti Klinikán diagnosztizált, az orofacialis régiót érinto jóindulatú daganatok és daganatszeru laesiók klinikopatológiai retrospektív epidemiológiai analízise (1960­2014).

INTRODUCTION: In a clinicopathological retrospective epidemiological study we investigated benign tumors and tumor-like lesions located in the orofacial region, diagnosed at the Universiy of Szeged, Department of Oral Medicine. METHOD: During a 54-year period (1960-2014), 14 661 biopsies were taken. The included subjects were 7491 patients diagnosed with benign tumors and tumor-like lesions. RESULTS: The average age of patients was 55.3 years, 2823 (37.7%) patients were male and 4668 (62.3%) female. The male : female ratio was 1 : 1.65. Most of the patients included in the study were aged 51-60 (1280, 17.1%). The number of children was 1014 (13.6%) and the number of adults was 6477 (86.3%). The number of non-neoplasms was 6420 (85.7%), being significantly higher than the number of neoplasms (1071, 14.3%). Most of the lesions were of mesenchymal origin (5574, 77.4%); the number of lesions of non-mesenchymal origin was 982 (13.1%). The most prevalent type of lesions was traumatic fibroma (fibrosis): 1806 (32.4%). The most common lesion type in the group of lesions of infectious/inflammational origin was pyogenic granuloma, the number of which was 465 (8.3%). The most common cystic lesion was mucocele (805, 10.7%). Hemangioma was the most frequent lesion type among developmental anomalies with the number of 815 (14.6%). The most common location of the lesions was the lip in 2081 cases (27.8%), followed by the gingiva in 2024 cases (27.0%), bucca in 1069 cases (14.3%), tongue in 981 cases (13.1%), and the facial skin in 695 cases (9.3%). After taking biopsy, the majority of benign lesions were treated with cryo-, laser-, or combined (cryo and laser) surgery. CONCLUSION: The present computer-aided study showed that irritational fibroma was the most common orofacial benign tumor, and the lip was the most frequent location. The diagnostic classification and the methodology are considerably different in the majority of the studies, which may hinder the exact comparison with other surveys from different regions of the world. Orv Hetil. 2018; 159(37): 1516-1524.

Individualized positioning for maximum heart protection during breast irradiation.

BACKGROUND: Prone positioning has been found feasible and appropriate for the reduction of radiation exposure of the lungs, but its effects on the heart dose remain controversial. Individual anatomical features were sought for the selection of optimal treatment positioning. MATERIAL AND METHODS: In 138 left-sided breast cancer cases awaiting postoperative whole-breast radiotherapy, conformal radiotherapy plans were generated in both prone and supine positions. RESULTS: The radiation doses to the left anterior descending coronary artery (LAD) and heart in the two positions differed individually, and were strongly related to the body mass index (BMI). Image fusion of the CT scans revealed that prone positioning was detrimental if the heart was situated distant from the chest wall in the supine position, but moved to the chest wall in the prone position. For characterization of the geography of the heart and the breast, the median distance between the LAD and the chest wall (dmedian), and the heart area included in the radiation field on a single CT scan at the middle of the heart in the supine position (Aheart) proved most appropriate. CONCLUSION: A validated statistical model, utilizing the BMI, dmedian and Aheart, permits individualized positioning for maximum heart protection.

Respiratory impedance in healthy subjects: baseline values and bronchodilator response.

Because of the minimal demand for cooperation by the subject, the forced oscillation technique is increasingly employed in routine lung function testing. However, comprehensive and device-independent values of respiratory impedance at baseline and after bronchodilation have not been established for healthy adults. The aim of this multicentre study was to collect impedance data from 4 to 26 Hz in healthy Caucasian subjects between 18 and 80 years of age. Five different devices were employed to assess baseline values and the bronchodilator response. Altogether, 368 subjects were examined. Despite adjustment for anthropometry, the impedance spectra differed in frequency dependence between the centres, and hence could not be pooled. However, resistance at all frequencies except 20 and 25 Hz, and the low-frequency (≤14 Hz) values of reactance did not exhibit a centre dependence. The regression equations for resistance reflected a greater height dependence in males and a greater weight dependence in both males and females than those published previously. Bronchodilation resulted in a statistically significant decrease (11%) in resistance and a 95th percentile equal to a 32% decrease in resistance at low frequency. We conclude that rigorous calibration procedures should be developed to ensure data compatibility. Furthermore, new reference equations based on different setups are recommended to replace those established with a single device.

[Early Mental Test--developing a screening test for mild cognitive impairment]. / Korai Mentális Teszt: az enyhe kognitív zavar szurotesztjének fejlesztése.

BACKGROUND AND PURPOSE: Mild cognitive impairment (MCI) is a heterogenous syndrome considered as a prodromal state of dementia with clinical importance in the early detection of Alzheimer's Disease. We are currently developing an MCI screening instrument, the Early Mental Test (EMT) suitable to the needs of primary care physicians. The present study describes the validation process of the 6.2 version of the test. METHODS: Only subjects (n = 132, female 95, male 37) over the age of 55 (mean age 69.2 years (SD = 6.59)) scoring at least 20 points on Mini-Mental State Examination (MMSE), mean education 11.17 years (SD = 3.86) were included in the study. The psychometric evaluation consisted of Alzheimer's Disease Assessment Scale Cognitive subscale (ADAS-Cog) and the 6.2 version of EMT. The statistical analyses were carried out using the 17.00 version of SPSS statistical package. RESULTS: The optimalised cut-off point was found to be 3.45 points with corresponding 69% sensitivity, 69% specificity and 69% accuracy measures. The Cronbach-alpha, that describes the internal consistence of the test was 0.667, which is higher as compared with the same category in the case of the ADAS-Cog (0.446). A weak negative rank correlation was found between the total score of EMT 6.2 and the age of probands (rs = -0.25, p = 0.003). Similarly, only a weak correlation was found between the education levels and the total score of EMT 6.2 (rs = 0.31, p < 0.001). Two of the subtests, the repeated delayed short-time memory and the letter fluency test with a motorical distraction task had significantly better power to separate MCI and control groups than the other subtests of the EMT. CONCLUSION: The 6.2 version of EMT is a fast and simple detector of MCI with a similar sensitivity-specificity profile to the MMSE, but this version of the test definitely needs further development.

Oxyhemoglobin and Cerebral Blood Flow Transients Detect Infarction in Rat Focal Brain Ischemia.

Spreading depolarizations (SD) refer to the near-complete depolarization of neurons that is associated with brain injuries such as ischemic stroke. The present gold standard for SD monitoring in humans is invasive electrocorticography (ECoG). A promising non-invasive alternative to ECoG is diffuse optical monitoring of SD-related flow and hemoglobin transients. To investigate the clinical utility of flow and hemoglobin transients, we analyzed their association with infarction in rat focal brain ischemia. Optical images of flow, oxy-hemoglobin, and deoxy-hemoglobin were continuously acquired with Laser Speckle and Optical Intrinsic Signal imaging for 2 h after photochemically induced distal middle cerebral artery occlusion in Sprague-Dawley rats (n = 10). Imaging was performed through a 6 × 6 mm window centered 3 mm posterior and 4 mm lateral to Bregma. Rats were sacrificed after 24 h, and the brain slices were stained for assessment of infarction. We mapped the infarcted area onto the imaging data and used nine circular regions of interest (ROI) to distinguish infarcted from non-infarcted tissue. Transients propagating through each ROI were characterized with six parameters (negative, positive, and total amplitude; negative and positive slope; duration). Transients were also classified into three morphology types (positive monophasic, biphasic, negative monophasic). Flow transient morphology, positive amplitude, positive slope, and total amplitude were all strongly associated with infarction (p < 0.001). Associations with infarction were also observed for oxy-hemoglobin morphology, oxy-hemoglobin positive amplitude and slope, and deoxy-hemoglobin positive slope and duration (all p < 0.01). These results suggest that flow and hemoglobin transients accompanying SD have value for detecting infarction.

Single Nucleotide Polymorphisms of Indoleamine 2,3-Dioxygenase 1 Influenced the Age Onset of Parkinson's Disease.

BACKGROUND: Earlier studies reported alterations of the kynurenine (KYN) pathway of tryptophan (TRP) metabolism in Parkinson's disease (PD). The first rate-limiting enzymes indoleamine 2,3-dioxygenase (IDO) and tryptophan dioxygenase were observed upregulated, resulting elevated KYN/TRP ratios in the serum and cerebrospinal fluid samples of patients with PD. More and more single nucleotide polymorphisms (SNPs) have been identified in a population of PD. However, little is known about the impact of genetic variations of the IDO on the pathogenesis of PD. METHODS: SNP analysis of IDO1 was performed by allelic discrimination assay with fluorescently labelled TaqMan probes and a subgroup analysis was conducted according to the age of PD onset. The frame shifts variant rs34155785, intronic variant rs7820268, and promotor region variant rs9657182 SNPs of 105 PD patients without comorbidity were analyzed and compared to 129 healthy controls. RESULTS: No significant correlation was found in three SNPs between PD patients and healthy controls. However, the subgroup analysis revealed that A alleles of rs7820268 SNP or rs9657182 SNP carriers contribute to later onset of PD than non-carriers. CONCLUSIONS: The study suggested that SNPs of IDO1 influenced the age onset of PD and genotyping of SNPs in certain alleles potentially serves as a risk biomarker of PD.

Pulmonary congestion during Exercise stress Echocardiography in Hypertrophic Cardiomyopathy.

BACKGROUND: B-lines detected by lung ultrasound (LUS) during exercise stress echocardiography (ESE), indicating pulmonary congestion, have not been systematically evaluated in patients with hypertrophic cardiomyopathy (HCM). AIM: To assess the clinical, anatomical and functional correlates of pulmonary congestion elicited by exercise in HCM. METHODS: We enrolled 128 HCM patients (age 52 ± 15 years, 72 males) consecutively referred for ESE (treadmill in 46, bicycle in 82 patients) in 10 quality-controlled centers from 7 countries (Belgium, Brazil, Bulgaria, Hungary, Italy, Serbia, Spain). ESE assessment at rest and peak stress included: mitral regurgitation (MR, score from 0 to 3); E/e'; systolic pulmonary arterial pressure (SPAP) and end-diastolic volume (EDV). Change from rest to stress was calculated for each variable. Reduced preload reserve was defined by a decrease in EDV during exercise. B-lines at rest and at peak exercise were assessed by lung ultrasound with the 4-site simplified scan. B-lines positivity was considered if the sum of detected B-lines was ≥ 2. RESULTS: LUS was feasible in all subjects. B-lines were present in 13 patients at rest and in 38 during stress (10 vs 30%, p < 0.0001). When compared to patients without stress B-lines (n = 90), patients with B-lines (n = 38) had higher resting E/e' (14 ± 6 vs. 11 ± 4, p = 0.016) and SPAP (33 ± 10 vs. 27 ± 7 mm Hg p = 0.002). At peak exercise, patients with B-lines had higher peak E/e' (17 ± 6 vs. 13 ± 5 p = 0.003) and stress SPAP (55 ± 18 vs. 40 ± 12 mm Hg p < 0.0001), reduced preload reserve (68 vs. 30%, p = 0.001) and an increase in MR (42 vs. 17%, p = 0.013) compared to patients without congestion. Among baseline parameters, the number of B-lines and SPAP were the only independent predictors of exercise pulmonary congestion. CONCLUSIONS: Two-thirds of HCM patients who develop pulmonary congestion on exercise had no evidence of B-lines at rest. Diastolic impairment and mitral regurgitation were key determinants of pulmonary congestion during ESE. These findings underscore the importance of evaluating hemodynamic stability by physiological stress in HCM, particularly in the presence of unexplained symptoms and functional limitation.

Risk assessment for respiratory complications in paediatric anaesthesia: a prospective cohort study.

BACKGROUND: Perioperative respiratory adverse events in children are one of the major causes of morbidity and mortality during paediatric anaesthesia. We aimed to identify associations between family history, anaesthesia management, and occurrence of perioperative respiratory adverse events. METHODS: We prospectively included all children who had general anaesthesia for surgical or medical interventions, elective or urgent procedures at Princess Margaret Hospital for Children, Perth, Australia, from Feb 1, 2007, to Jan 31, 2008. On the day of surgery, anaesthetists in charge of paediatric patients completed an adapted version of the International Study Group for Asthma and Allergies in Childhood questionnaire. We collected data on family medical history of asthma, atopy, allergy, upper respiratory tract infection, and passive smoking. Anaesthesia management and all perioperative respiratory adverse events were recorded. FINDINGS: 9297 questionnaires were available for analysis. A positive respiratory history (nocturnal dry cough, wheezing during exercise, wheezing more than three times in the past 12 months, or a history of present or past eczema) was associated with an increased risk for bronchospasm (relative risk [RR] 8.46, 95% CI 6.18-11.59; p<0.0001), laryngospasm (4.13, 3.37-5.08; p<0.0001), and perioperative cough, desaturation, or airway obstruction (3.05, 2.76-3.37; p<0.0001). Upper respiratory tract infection was associated with an increased risk for perioperative respiratory adverse events only when symptoms were present (RR 2.05, 95% CI 1.82-2.31; p<0.0001) or less than 2 weeks before the procedure (2.34, 2.07-2.66; p<0.0001), whereas symptoms of upper respiratory tract infection 2-4 weeks before the procedure significantly lowered the incidence of perioperative respiratory adverse events (0.66, 0.53-0.81; p<0.0001). A history of at least two family members having asthma, atopy, or smoking increased the risk for perioperative respiratory adverse events (all p<0.0001). Risk was lower with intravenous induction compared with inhalational induction (all p<0.0001), inhalational compared with intravenous maintenance of anaesthesia (all p<0.0001), airway management by a specialist paediatric anaesthetist compared with a registrar (all p<0.0001), and use of face mask compared with tracheal intubation (all p<0.0001). INTERPRETATION: Children at high risk for perioperative respiratory adverse events could be systematically identified at the preanaesthetic assessment and thus can benefit from a specifically targeted anaesthesia management. FUNDING: Department of Anaesthesia, Princess Margaret Hospital for Children, Swiss Foundation for Grants in Biology and Medicine, and the Voluntary Academic Society Basel.

Impaired vascular responses of insulin-resistant rats after mild subarachnoid hemorrhage.

Insulin resistance (IR) impairs cerebrovascular responses to several stimuli in Zucker obese (ZO) rats. However, cerebral artery responses after subarachnoid hemorrhage (SAH) have not been described in IR. We hypothesized that IR worsens vascular reactions after a mild SAH. Hemolyzed blood (300 µl) or saline was infused (10 µl/min) into the cisterna magna of 11-13-wk-old ZO (n = 25) and Zucker lean (ZL) rats (n = 25). One day later, dilator responses of the basilar artery (BA) and its side branch (BA-Br) to acetylcholine (ACh, 10(-6) M), cromakalim (10(-7) M, 10(-6) M), and sodium nitroprusside (10(-7) M) were recorded with intravital videomicroscopy. The baseline diameter of the BA was increased both in the ZO and ZL rats 24 h after the hemolysate injection. Saline-injected ZO animals showed reduced dilation to ACh (BA = 9 ± 3 vs. 22 ± 4%; and BA-Br = 23 ± 5 vs. 37 ± 7%) compared with ZL rats. Hemolysate injection blunted the response to ACh in both the ZO (BA = 4 ± 2%; and BA-Br = 12 ± 3%) and ZL (BA = 7 ± 2%; and BA-Br = 11 ± 3%) rats. Cromakalim (10(-6) M)-induced dilation was significantly reduced in the hemolysate-injected ZO animals compared with the saline control (BA = 13 ± 3 vs. 26 ± 5%; and BA-Br = 28 ± 8 vs. 44 ± 9%) and in the hemolysate-injected ZL rats compared with their saline control (BA = 24 ± 4 vs. 32 ± 4%; but not BA-Br = 39 ± 6 vs. 59 ± 9%). No significant difference in sodium nitroprusside reactivity was observed. Western blot analysis of the BA showed a lower baseline level of neuronal nitric oxide synthase expression and an enhanced cyclooxygenase-2 level in the hemolysate-injected ZO animals. In summary, cerebrovascular reactivity to both endothelium-dependent and -independent stimuli is severely compromised by SAH in IR animals.

Sevoflurane and desflurane protect cholinergic-induced bronchoconstriction of hyperreactive airways in rabbits.

PURPOSE: The potential of desflurane to alter respiratory mechanics in the presence of bronchial hyperresponsiveness (BHR) is still a subject of debate. Accordingly, we evaluated the bronchoprotective potential of desflurane compared with sevoflurane following cholinergic lung constriction in rabbits with normal and hyperreactive airways. METHODS: The input impedance of the respiratory system (Zrs) was measured during midazolam-based anesthesia before and during intravenous infusions of increasing doses of methacholine (MCh). The rabbits in the control group (Group C) were then randomized to receive either sevoflurane 1 MAC followed by desflurane 1 MAC or vice versa, whereas ovalbumin-sensitized rabbits received sevoflurane followed by desflurane (Group S-SD) or vice versa (Group S-DS). Baseline Zrs measurements and the MCh provocations were repeated under the maintenance of each volatile agent. Airway resistance (Raw), tissue damping (G), and elastance data were obtained from Zrs by model fitting. RESULTS: Similar bronchoprotective effects of sevoflurane and desflurane against MCh-induced bronchoconstriction were observed independently of the severity of the bronchospasm and the presence of BHR. With sevoflurane, the decreases in Raw ranged from 22 (8.8)% to 44 (12)%, and with desflurane, they ranged from 22 (8.7)% to 50 (12)%. The increases in G reflecting the enhanced ventilation heterogeneities in the lung periphery were not affected by the volatile agents. CONCLUSIONS: If the contractile stimulus is cholinergic in origin, sevoflurane and desflurane exert similar bronchoprotective potentials to act against lung constriction independent of the presence of BHR. These volatile anesthetics otherwise lack a potential to improve the enhanced ventilation heterogeneities that develop particularly in the presence of BHR.

Calcaneo-stop procedure for paediatric flexible flatfoot.

BACKGROUND: Flexible flatfoot is a frequent deformity found in children. The aim of this study is to evaluate the pedographic outcome of the percutaneous arthroereisis with the use of a screw through the sinus tarsi into the talus. MATERIALS AND METHODS: 43 calcaneo-stop procedures of 25 patients (18 bilateral, seven unilateral) were evaluated. Mean age at surgery was 10 years (7-14, SD 2.2) (SD: standard deviation), mean follow-up time was 9.7 months (3-19, SD 5.5). Patient satisfaction rate was recorded, the Meary's talus-first metatarsal angle was measured with lateral radiograms, and a dynamic pedographic assessment was also performed. RESULTS: Patient satisfaction rate was excellent for 33 feet of 19 children, good for eight feet of five children, and poor for either feet of one child. We did not observe any complications during or following the surgery.The mean rest heel valgus decreased from 13.4° (10°-17°, SD 1.5) to 2.8° (0°-6°, SD 1.7) post op. The Meary's angle improved from 160.2° (148°-177°, SD 6.8) to 175.9° (167°-179°, SD 3.5). By pedographic analysis, the area and the pressure-time integral (load amount, PTI) values increased on the lateral regions of the sole (except for the lesser toes) and decreased on the medial areas (except for the hallux). The relative contact time in the lateral midfoot increased from 63.8% (39.6-78.4%, SD 10.6) to 75.1% (50-86.1%, SD 9.4), and that in the lateral forefoot region from 81.2% (60.4-89.2%, SD 6.6) to 86.8% (78.1-97.1%, SD 4.8). CONCLUSION: The calcaneo-stop procedure is a simple and reliable method for the correction of severe flexible paediatric flatfoot. Our prospective, short-term results following the anterograde screw implantation into the talus correlate well with the results of similar or different arthroereisis methods. Further investigations are required to evaluate the long-term outcome of the screw calcaneo-stop method, including the conditions following implant removal.

Two subgroups of schizophrenia identified by systematic cognitive neuropsychiatric mapping.

The description of the heterogeneous phenomenological, pathophysiological, and etiological nature of schizophrenia is under way; however, the relationships between heterogeneity levels are still unclear. We performed a robust cross-sectional study, including a systematic neuropsychological battery, assessment of clinical symptoms, neurological soft signs, morphogenetic anomalies and smell identification, and measurement of event-related potentials on 50 outpatients with schizophrenia in their compensated states. An explorative fuzzy cluster analysis revealed two subgroups in this sample that could be distinguished from each other on symptomatological, cognitive and neurological levels. The patterns of cognitive dysfunctions and neurological developmental anomalies equally indicate that there may be hemispherical differences between the patients belonging to the different clusters.

Does inspiration efficiency influence the stability limits of the trunk in patients with chronic low back pain?

OBJECTIVE: To determine the effects of diaphragm-strengthening training on the stability limits of the trunk and inspiratory function in patients with low back pain. DESIGN: A randomized comparative trial including a diaphragm training group that took part in conventional training together with diaphragm strengthening, and a control group that took part in conventional training only. Both groups participated in an 8-week training, 2 times/week. All subjects underwent the same measurement protocol before and after the intervention. PATIENTS: The study included 52 subjects with chronic low back pain. METHODS: The inspiratory functions (chest excursion, maximal inspiratory pressure, peak inspiratory flow, and volume of inspired air) and stability limits of the trunk with the subject in the sitting position (modified functional and lateral reach test) were assessed. RESULTS: Maximal inspiratory pressure and stability limit tests showed a statistically significant improvement only in the diaphragm training group. Statistically significant improvements in chest excursion and peak expiratory flow tests were found in both groups; however, the improvement was more greater in the diaphragm training group. CONCLUSION: Conventional exercises together with diaphragm training result in a greater improvement than conventional exercises alone in patients with chronic low back pain.

Cloud-Based Multicenter Data Collection and Epidemiologic Analysis of Bisphosphonate-Related Osteonecrosis of the Jaws in a Central European Population.

Objective: Bisphosphonate-related osteonecrosis of the jaws is considered to be a rare but severe complication of bisphosphonate therapy. To understand this condition better, data collection is essential. Although the number of scientific papers about this subject is large, to date only a few multicenter reports have been published. Study design: We present a novel cloud-based data collection system for the evaluation of the risk factors of bisphosphonate-related osteonecrosis of the jaws. Web-based questionnaire and database have been set up and made available to voluntary researchers and clinicians in oral and maxillofacial surgery in Hungary and Slovakia. Results: To date, fifteen colleagues from eight maxillofacial units have joined the study. Data of 180 patients have been recorded. Collected data were statistically analysed and evaluated from an epidemiological point of view. Conclusions: Authors consider cloud-based multicenter data collection a useful tool that allows for real-time collaboration between users, facilitates fast data entry and analysis, and thus considerably contributes to widening our knowledge of bisphosphonate-related osteonecrosis of the jaws.

Long-term follow-up of inflammatory bowel disease patients receiving anti-tumor necrosis factor-alpha therapy / Anti-TNFα-terápiában részesülo gyulladásos bélbetegek hosszú távú utánkövetése.

Összefoglaló. Bevezetés: A gyulladásos bélbetegségek kezelésében a tumornekrózisfaktor-alfa-ellenes (anti-TNFα) antitestek elsodleges választási lehetoséget jelentenek a kortikoszteroid- és immunmoduláns kezelésre refrakter páciensek kezelési stratégiájában. Ezek a hatóanyagok hatékonyak, ám hosszú távú hatásosságukkal kapcsolatban sok az ellentmondás. Célkituzés: Vizsgálatunk célja megvizsgálni az anti-TNFα-terápia (infliximab [IFX], adalimumab [ADA]) hosszú távú hatékonyságát gyulladásos bélbetegek körében. Módszerek: Retrospektív, adatgyujtéses vizsgálatunkba a Szegedi Tudományegyetem I. Sz. Belgyógyászati Klinikáján gondozott, 18-65 év közötti gyulladásos bélbetegeket vontunk be. Az adatgyujtést a Klinika informatikai rendszerébol végeztük a betegek ambuláns megjelenéseinek kezelolapjaiból, illetve a zárójelentésekbol. Eredmények: 102 beteg adatait elemeztük (Crohn-beteg: 67 fo, colitis ulcerosás: 35 fo). A Crohn-betegség diagnózisát követoen átlagosan 7,84 év, a colitis ulcerosa diagnózisát követoen átlagosan 9,86 év telt el az elso anti-TNFα-terápia elkezdéséig. Az elso kezelési ciklus átlagosan 2,64 évig tartott, a ciklus végén az IFX-t kapó betegek 50%-ánál, az ADA-t kapó betegek 46%-ánál volt remisszióban a betegség. A második kezelési ciklus átlagosan 4,67 évig tartott, a ciklus végén az IFX-t kapó betegek 36%-a, az ADA-t kapó betegek 40%-a volt remisszióban. Az elso, illetve a második kezelési ciklus alatt az allergiás reakciók gyakorisága IFX esetében 13% és 18%, ADA esetében 4% és 3% volt. A primer hatástalanság és a másodlagos hatásvesztés az elso ciklusban IFX esetében 4% és 10,5%, ADA esetében 11,5% és 19% volt. A második kezelési ciklusban IFX esetében 9%-ban és 18%-ban, ADA esetében 23%-ban és 10%-ban jelentették a ciklus végét. Következtetés: Az anti-TNFα-terápiák eredményeink alapján hosszú távon is hatékonynak és biztonságosnak bizonyultak. Másodlagos hatásvesztés kisebb arányban fordult elo a vizsgált populációban az irodalmi adatokhoz képest. Orv Hetil. 2020; 161(47): 1989-1994. INTRODUCTION: Anti-tumor necrosis factor-alpha (anti-TNFα) treatment is reserved for steroid-dependent or steroid/immunomodulator-refractory inflammatory bowel diseases patients. These agents are effective, however, their long-term safety is still questionable. OBJECTIVE: We aimed to assess the long-term efficacy and safety of two anti-TNFα therapies. METHODS: In our retrospective study, we reviewed medical records via the administration system of the First Department of Medicine, University of Szeged. Female and male patients, aged between 18-65 years who received anti-TNFα therapy between 2010-2019 were enrolled. RESULTS: 102 patients with inflammatory bowel disease were enrolled (Crohn's disease: 67, ulcerative colitis: 35). The first anti-TNFα therapy was introduced after an average 7.84 and 9.86 years from diagnosis of Crohn's disease and ulcerative colitis. The first treatment period lasted for 2.64 years; 50% of patients receiving IFX and 46% of patients receiving ADA were in remission at the end of the period. The second treatment period lasted for 4.67 years, 36% of IFX-treated patients and 40% of ADA-treated patients were in remission at the end of the period. 13% and 18% of patients treated by IFX and 4% and 3% of patients treated by ADA experienced infusion reaction during the first and the second treatment period. Primary non-response and loss of response rates were 4% and 10.5% (IFX) and 11.5% and 19% (ADA) during the first treatment period. These rates were 9% and 18% (IFX) and 23% and 10% (ADA) during the second treatment period. CONCLUSION: Our study confirmed the long-term efficacy and safety of the anti-TNFα therapies. Loss of response rate is lower in our population compared to the literature. Orv Hetil. 2020; 161(47): 1989-1994.

Second-generation de novo design: a view from a medicinal chemist perspective.

For computational de novo design, a general retrospective validation work is a very challenging task. Here we propose a comprehensive workflow to de novo design driven by the needs of computational and medicinal chemists and, at the same time, we propose a general validation scheme for this technique. The study was conducted combining a suite of already published programs developed within the framework of the NovoBench project, which involved three different pharmaceutical companies and four groups of developers. Based on 188 PDB protein-ligand complexes with diverse functions, the study involved the ligand reconstruction by means of a fragment-based de-novo design approach. The structure-based de novo search engine FlexNovo showed in five out of eight total cases the ability to reconstruct native ligands and to rank them in four cases out of five within the first five candidates. The generated structures were ranked according to their synthetic accessibilities evaluated by the program SYLVIA. This investigation showed that the final candidate molecules have about the same synthetic complexity as the respective reference ligands. Furthermore, the plausibility of being true actives was assessed through literature searches.

Distribution of oxytocin-immunoreactive neuronal elements in the rat spinal cord.

We investigated the distribution of oxytocin in rat spinal cord using immunocytochemistry and radioimmunoassay (RIA). Each segment of the spinal cord from cervical to coccygeal contained oxytocin-immunoreactive fibers. The Rexed laminae I and II of the dorsal horn showed moderate to intense immunoreactivity. A dense network was found around the central canal where some fibers apposed the ependyma. The autonomic centers of the spinal cord at the thoracolumbar and sacral segments were heavily innervated. Few fibers were found around the motoneurons. In the white matter, the immunoreactivity was localized mainly in the dorsal part of the lateral funiculus, in the pars funicularis of the nucleus intermediolateralis and in a longitudinal network of the lateral funiculus below the spinal cord surface. Some fibers from this network entered the pia mater. RIA measurements revealed that the cervical spinal cord had lower oxytocin content than that found in either the thoracic, lumbar, sacral or coccygeal region. Our results show that the distribution of oxytocin-immunoreactive fibers in the spinal cord correlates with anatomic locations related to nociceptive, autonomic and motor functions. We assume that oxytocin-containing axons play a role in secreting oxytocin directly into the liquor space of the spinal cord.

Utilization of in Vitro Anther Culture in Spelt Wheat Breeding.

The efficiency of in vitro anther culture was screened in a full diallel population of four spelt wheat genotypes and ten F1 hybrids. Genotype dependency was observed based on the data of embryo-like structures (ELS), green-, albino plantlets. In the diallel population and ten F1 hybrids, the green plantlets production ranged from 13.75 to 85.00 and from 6.30 to 51.00, respectively. The anther culture-derived plants of F1 hybrids were grown up in the nursery. At the harvest, 436 spontaneous doubled haploid (DH) plants were identified among the 1535 anther culture-derived transplanted and grown up individual plants. The mean of spontaneous rediploidization was 28.4% which ranged from 9.76% to 54.24%. In two consecutive years, the agronomic values of 'Tonkoly.pop1' advanced line were compared with seven DH lines of 'Tonkoly.pop1' in the nursery. The DH lines achieved competitive values in comparison with 'Tonkoly.pop1' advanced line based on the 11 measured parameters (heading date, plant height, yield, hardness, width and length of seed, TKW, hulling yield, flour yield, protein and wet gluten content). These observations presage the efficient utilization of anther culture in spelt wheat breeding.