A-raf oncogene localizes on mouse X chromosome to region some 10–17 centimorgans proximal to hypoxanthine phosphoribosyltransferase gene

The localization of the A-rafcellular oncogene on the mouse X chromosome has been determined using Xbal-restricted DNAs prepared from progeny of an interspecies backcross between the B6.CBA.R1 and the Spe/Pas mouse strains. This localization to the proximal part of the mouse X chromosome has been confirmed by the use of somatic cell hybrids, carrying partially deleted X chromosomes and suggests that the A-raf oncogene localizes to a region lying some 10–17 centimorgans proximal to the hypoxanthine phosphoribosyltransferase (Hprt) gene between the locus DXPas4and the locus DXPas7defined by the cross-reacting human X chromosome-specific probe DXS32 (M2C). This localization on the mouse X chromosome is compatible with the presence of the A-rafoncogene on the short arm of the human X chromosome between the centromere and Xp21.     

Report on two patients with Costello syndrome and sialuria

We report on 2 unrelated patients with Costello syndrome. The first is a 5-year-old girl with “coarse” face, nasal papillomata, redundant skin of feet and hands, hyperextensible hand and finger joints, curly hair, feeding problems due to oral motor apraxia, growth and psychomotor retardation. The second is a 3-year-old boy with “coarse” face, loose skin on hands and feet, curly hair, oral motor apraxia, severe growth and psychomotor retardation. In both patients urine sialic acid levels were found to be repeatedly high. The meaning of this biochemical abnormality is discussed. © 1993 Wiley-Liss, Inc.     

Screening for antibacterial activity in 72 species of wood-colonizing fungi by the Vibrio fisheri bioluminescence method

Resistance of pathogenic bacteria to antibiotics leads scientists to discover new antibacterial drugs. Ninety samples of wood-colonizing fungi were cultivated on agar plates, and their extracts tested for antibacterial activity using the Vibrio fischeri bioluminescence test. Two fungi species, Serpula lacrymans and Nectria vilior, were found to be a potential new source of thermostable antibiotics. Vibrio fischeri bioluminescence test was found to be a useful method for antibacterial activity screening from the samples of natural origin.     

Phase I pharmacological and bioavailability study of oral diflomotecan (BN80915), a novel E-ring-modified camptothecin analogue in adults with solid tumors.

PURPOSE: Diflomotecan (BN80915) is an E-ring modified camptothecin analogue that possesses greater lactone stability in plasma compared with other topoisomerase I inhibitors, a potential advantage for antitumor activity. As with other camptothecins, oral administration has pharmacological and clinical advantages. This Phase I study was performed to assess the feasibility of the administration of oral diflomotecan, to determine the maximum-tolerated, dose its bioavailability, and to explore the pharmacokinetics. EXPERIMENTAL DESIGN: An initial i.v. bolus was administered to assess the bioavailability of diflomotecan. Fourteen days later, diflomotecan was administered p.o. once daily for 5 days to adult patients with solid malignant tumors and repeated every 3 weeks. BN80915 and its open lactone form BN80942 were measured. RESULTS: Twenty-two patients entered the study and received a total of 57 cycles of oral diflomotecan at flat dose levels of 0.10, 0.20, 0.27, and 0.35 mg. The main toxicity was hematological, but some patients experienced alopecia, mild gastrointestinal toxicity, and fatigue. At the 0.35-mg dose level, 2 of 4 patients experienced dose-limiting toxicity comprising grade 3 thrombocytopenia with epistaxis and febrile neutropenia in 1 patient and uncomplicated grade 4 neutropenia lasting for >7 days in another. Toxicity was acceptable at the 0.27-mg dose level at which dose-limiting toxicities were observed in 3 of 12 patients (grade 4 neutropenia > 7 days, complicated by fever in 1 patient but without other signs of infection). After two cycles of diflomotecan, 6 patients had disease stabilization, which was maintained in 2 patients for 9 months and >1 year, respectively. Diflomotecan pharmacokinetics were linear over the dose range studied. Systemic exposure correlated with the fall in WBC counts. The mean oral bioavailability (+/-SD) was 72.24 +/- 59.2% across all dose levels. Urinary excretion of BN80915 was very low. CONCLUSIONS: The recommended oral diflomotecan dose for Phase II studies is 0.27 mg/day x 5 every 3 weeks. This regimen is convenient and generally well tolerated with a favorable pharmacokinetic profile and high but variable bioavailability.     

The construction of the Split Sleep Questionnaire on sleep habits during the COVID-19 pandemic in the general population

AimTo construct a single-format questionnaire on sleep habits and mood before and during the COVID-19 pandemic in the general population.MethodsWe constructed the Split Sleep Questionnaire (SSQ) after a literature search of sleep, mood, and lifestyle questionnaires, and after a group of sleep medicine experts proposed and assessed questionnaire items as relevant/irrelevant. The study was performed during 2021 in 326 respondents distributed equally in all age categories. Respondents filled out the SSQ, the Pittsburgh Sleep Quality Index (PSQI), and State Trait Anxiety Inventory (STAI), and kept a seven-day sleep diary.ResultsWorkday and work-free day bedtime during the COVID-19 pandemic assessed with SSQ were comparable to the sleep diary assessment (P = 0.632 and P = 0.203, respectively), as was the workday waketime (P = 0.139). Work-free day waketime was significantly later than assessed in sleep diary (8:19 ± 1:52 vs 7:45 ± 1:20; P < 0.001). No difference in sleep latency was found between the SSQ and PSQI (P = 0.066). Cronbach alpha for Sleep Habits section was 0.819, and 0.89 for Mood section. Test-retest reliability ranged from 0.45 (P = 0.036) for work-free day bedtime during the pandemic to 0.779 (P < 0.001) for sleep latency before the pandemic.ConclusionThe SSQ provides a valid, reliable, and efficient screening tool for the assessment of sleep habits and associated factors in the general population during the COVID-19 pandemic.

The COVID-19 pandemic, along with its multiple adverse effects on various aspects of mental health, has significantly affected sleep. Sleep habits alterations and newly developed sleep disturbances during the COVID-19 pandemic may influence the overall well-being and health (1). Since the beginning of the pandemic, several studies reported a delay in bedtimes and waketimes, and an associated shift in chronotype toward eveningness (2-5).Even though actigraphy and sleep diaries provide a valid and reliable assessment of sleep habits (6,7), to achieve the highest reliability and validity, these methods require an assessment during seven consecutive days including weekends (8). Daily reporting may be perceived by the respondents as an additional burden (6,9), a limitation that may be overcome by the use of single-administration questionnaires (9,10). Since sleep disturbances recognized in the first pandemic outbreak remained stable during new waves of the COVID-19 pandemic (5), single-administration questionnaires may enable screening of large population groups and an extended assessment of sleep disturbances during the pandemic.So far, validated sleep questionnaires have most often aimed at sleep disorders or symptoms associated with sleep disorders (9). Studies commonly report the Pittsburgh sleep Quality Index (PSQI) (11), which provides data on sleep duration, sleep disturbances, and sleep latency during the previous month. However, PSQI reflects mainly sleep quality on workdays (12), while not collecting information on sleep habits on weekends. The Sleep Timing Questionnaire (STQ) has been developed as an alternative to the sleep diary for the healthy adult population, showing good reliability and validity (10). Still, although sleep habits are associated with mood (13), social media use (14-16), learning time in students (17-19), sports or exercise (20), and symptoms of insomnia (21), the STQ does not assess variables such as mood and lifestyle habits.Large studies objectively assessing sleep with wearable devices have recognized sleep timing and sleep duration to be modifiable risk factors for adverse mental health during the current pandemic (22). Young adults are especially at risk for increased mood disorder symptoms, higher levels of perceived stress, and more common alcohol use during the pandemic (23). Even though mood disorders are often reported in pandemic studies on sleep habits, mood itself has been less commonly measured and associated with sleep parameters (24). A review of the literature showed a transactional relationship between mood and emotion (25), indicating that mood is characterized by longer duration than emotion (26). Mood is often assessed with the Brief Mood Introspection Scale (27), the Profile of Mood States (28), or the Visual Analogue Mood Scale (29). A relevant aspect of mood measurement is a hierarchical structure with two broad dimensions in positive and negative affect, and multiple specific states (30). Commonly used mood assessment scales evaluate the basic negative mood of fear/anxiety, sadness/depression, and anger/hostility, as well as at least one positive mood. Therefore, it has been strongly recommended that mood researchers assess a broad range of both positive and negative emotions (30).Linking mood changes and lifestyle habits during the pandemic has been relevant in order to recognize possible predictors of mood changes, especially due to a reported increase in depression (31). Since sleep is often intertwined with mood and lifestyle changes (31), we assumed that a single-format questionnaire comprehensively assessing these variables and sleep may be applicable and timely.The aim of this study was to construct a single-format Split Sleep Questionnaire (SSQ) comprehensively assessing sleep habits, lifestyle habits, and mood changes, as well as to evaluate its reliability and validity in the general population. Sleep habits were validated by using standard instruments such as sleep diary, PSQI, and STAI questionnaires as the measures of construct validity. Additionally, we aimed to assess the psychometric properties of the Mood section and to explore the effects of the COVID-19 pandemic on sleep habits and mood alterations in the general population of Croatia.