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•The alternative synthesis of afatinib (BIBW2992) is presented.•The work is presenting a new route with good yield that could be suitable for industrial use.•Ullmann-Goldberg reaction ...for CN coupling on position 6 of quinazoline.•The synthesis provides direct access to afatinib analogues of and similar quinazoline type of kinase inhibitors.
Afatinib (BIBW2992) is the anticancer drug developed by Boehringer Ingelheim. This work is reporting the synthesis of the afatinib using a new route by Ullmann-Goldberg reaction from corresponding 4-anilinoquinazoline iodide as the last step in the synthesis. This route was not described previously and it could be used for synthesis of afatinib analogues.
BackgroundInsomnia is a widespread disease in adults and has a high prevalence rate. As sleep disturbances are a risk factor concerning mental and physical health, prevention and early intervention ...are necessary. Thus, the aim of this study was to implement a self-learning prevention and early intervention training for university staff members. We adapted an established cognitive behavioral therapy for insomnia (CBT-I) intervention as an online version for use during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) crisis.MethodsDevelopment and adaptation procedure of the internet-based CBT‑I (iCBT-I) prevention and early intervention training is described. Sessions and topics are shown in detail. The Online Sleep Prevention and Treatment Acceptance questionnaire (OSTA) and the Online Sleep Prevention and Treatment Feedback questionnaire (OSTF) were used to assess acceptance. Sleep problems of university staff members were assessed using the Pittsburgh Sleep Questionnaire (PSQI).ResultsThe online-adapted version consisted of seven modules. Contents of sessions and topics were implemented based on video clips. Drawings were added to information regarding sleep and sleep hygiene as well as addressing stress and cognitions. In all, 15 individuals participated in this pilot study. The new iCBT‑I self-learning prevention training was well accepted. In addition, participants scored the online version as helpful based on the OSTA. Prior to online training, 89% of the participants reported impaired sleep quality or insomnia symptoms, and 56% had a PSQI score over 10. After training 78% of participants showed reduced sleep problems according to PSQI and 56% reached clinically significant enhancement. In addition, after training 44% were healthy sleepers.DiscussionThis is the first iCBT‑I prevention and early intervention training for university staff members. The training by participants was very well accepted and they scored the videos as very helpful. Sleep problems decreased after online training. However, further studies with larger samples and more sleep-related assessment strategies, e.g., actigraphy and sleep log, are necessary.
The goal of this research was to examine the contribution of traditional games to the quality of relations and to the frequency of students' socialization in primary education. A modified version of ...the School Violence Questionnaire was implemented on a sample of 232 students in the second, third and fourth grades in four primary schools in Karlovac. The first testing determined the quality of students' relations and the frequency of their socialization. After applying the traditional games, in June 2010, a final test was implemented. Two hypotheses assumed the existence of a statistically significant difference in the quality of relations and the frequency of students' socializations before and after the implementation of traditional games. The research results have shown an improvement of human relations between students in class, and an increase of students' socialization outside classes, after implementing traditional games in school. Adapted from the source document.
Background
Insomnia is a widespread disease in adults and has a high prevalence rate. As sleep disturbances are a risk factor concerning mental and physical health, prevention and early intervention ...are necessary. Thus, the aim of this study was to implement a self-learning prevention and early intervention training for university staff members. We adapted an established cognitive behavioral therapy for insomnia (CBT-I) intervention as an online version for use during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) crisis.
Methods
Development and adaptation procedure of the internet-based CBT‑I (iCBT-I) prevention and early intervention training is described. Sessions and topics are shown in detail. The Online Sleep Prevention and Treatment Acceptance questionnaire (OSTA) and the Online Sleep Prevention and Treatment Feedback questionnaire (OSTF) were used to assess acceptance. Sleep problems of university staff members were assessed using the Pittsburgh Sleep Questionnaire (PSQI).
Results
The online-adapted version consisted of seven modules. Contents of sessions and topics were implemented based on video clips. Drawings were added to information regarding sleep and sleep hygiene as well as addressing stress and cognitions. In all, 15 individuals participated in this pilot study. The new iCBT‑I self-learning prevention training was well accepted. In addition, participants scored the online version as helpful based on the OSTA. Prior to online training, 89% of the participants reported impaired sleep quality or insomnia symptoms, and 56% had a PSQI score over 10. After training 78% of participants showed reduced sleep problems according to PSQI and 56% reached clinically significant enhancement. In addition, after training 44% were healthy sleepers.
Discussion
This is the first iCBT‑I prevention and early intervention training for university staff members. The training by participants was very well accepted and they scored the videos as very helpful. Sleep problems decreased after online training. However, further studies with larger samples and more sleep-related assessment strategies, e.g., actigraphy and sleep log, are necessary.
Background
Recurrent aphthous stomatitis (RAS) is one of the most common oral mucosal diseases in many parts of the world. However, there is very limited published clinical evidence for the therapies ...used in this condition. This could be partly due to the difficulty in evaluating the efficacy of oral ulcer treatment objectively. In this paper, we present a method for assessing and monitoring the severity of oral ulcers before and after treatment.
Methods
Six ulcer characteristics, number, size, duration, ulcer‐free period, site and pain, were used to generate an ulcer severity score (USS). The scores for 223 RAS patients were determined, and 79 were scored again after 3‐month therapy with topical betamethasone.
Results
The scores for the minor RAS group were between 18 and 43 (mean 29.2 ± 5.3). The mean score in the major ulcers group (range: 28–60, mean 39.9 ± 6.1) was significantly greater than in the minor group (P < 0.001). The herpetiform recurrent ulcers score range was wide (range: 18–57, mean 36.6 ± 8.4). The mean severity score decreased significantly after treatment (P < 0.001).
Conclusions
The USS was indicative of the disease activity in recurrent oral ulceration. It helped in assessing the efficacy of therapy, as the change in the numerical score reflected the change in ulcer severity in response to treatment. This tool may well prove to be of value in clinical management, research and in clinical trials.
At onset of generalized seizures, focal electroclinical features are commonly seen, while generalized onset seizures with focal evolution (GOFE) are largely unknown bearing the risk of ...misclassification.
In two German epilepsy-centers, patients with GOFE documented by video-EEG monitoring (VEM) between 2017 and 2022 were identified retrospectively. In addition to analysis of ictal electroclinical features, detailed epilepsy and family history, response to antiseizure medication (ASM), and findings from neuroimaging were considered.
We identified five patients with GOFE, three females, age 14 to 22 years. All patients developed genetic generalized epilepsy in childhood or adolescence, each presenting with two or three generalized seizure types. In each of the five patients, one GOFE was recorded by VEM. At onset, EEG seizure patterns were characterized by generalized spike-wave discharges at 2.5 to 3.5/sec for 9 to 16 s followed by focal evolution of the discharges. Interictally, all patients presented with generalized spike-wave discharges without focal abnormalities. Semiology at onset was behavioral arrest in two patients and generalized increase in tone in one, while two onsets were clinically inapparent. Semiological signs during focal evolution were variable, comprising head and body version, figure 4 sign, unilateral arm clonic activity, and staring with oral automatisms. In one case, focality involved both hemispheres successively.
Prominent focal semiological features in GOFE carry a high risk of misclassification as focal seizures and epilepsy and thus wrong choice of ASM. This calls for low-threshold VEM if any doubts of focal genesis of seizures exist.
The reconstruction of fullthickness nasal alla defects is challenging procedure. Use of local flaps is acceptable approach. Flap based on infraorbital artery could be used for primary reconstruction ...of nasal ala defects.
The prospective study include consecutive series of 15 patients with advanced skin carcinoma of the nasal ala and medial cheek staged T4 by TNM, in whom the turn in infraorbital flap was used. The patient characteristics, type of carcinoma and complications were analyzed.
The turn in infraorbital flap was used mostly in male patients (80%), mean age 64 years. The basal cell skin carcinoma was found in 60%. Skin layer was skin grafted. All flaps survived, but in one case a partial wound dehiscence in one partial skin graft loss was found, and in two patients partial nasal obstruction occurred. These three complications were solved as secondary procedures under local anesthesia.
Full-thickness defect of the nasal ala can be properly reconstructed using flap based on infraorbital artery providing exceptional esthetic and functional results, as single stage procedure.
Cilj ovog istraživanja bio je ispitati doprinos tradicijskih igara kvaliteti međuljudskih odnosa i učestalosti druženja učenika primarnog obrazovanja. Modificirana verzija Upitnika o školskom nasilju ...(Buljan Flander, Karlović, Štimac, 2003) primijenjena je na uzorku od 232 učenika drugih, trećih i četvrtih razreda u četiri karlovačke osnovne škole. Prvim je ispitivanjem utvrđena kvaliteta međuljudskih odnosa i učestalost druženja učenika, a nakon primjene deset tradicijskih igara, u lipnju 2010. godine, provedeno je finalno ispitivanje. Dvjema hipotezama pretpostavljeno je postojanje statistički značajne razlike u kvaliteti međuljudskih odnosa i učestalosti druženja učenika prije i nakon provođenja tradicijskih igara. Rezultati istraživanja pokazali su poboljšanje međuljudskih odnosa među učenicima u razredu te porast druženja učenika izvan nastave nakon provođenja tradicijskih igara u školi.
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