High-resolution SNP mapping by denaturing HPLC

With the availability of complete genome sequences, new rapid and reliable strategies for positional cloning become possible. Single-nucleotide polymorphisms (SNPs) permit the mapping of mutations at a resolution not amenable to classical genetics. Here we describe a SNP mapping procedure that relies on resolving polymorphisms by denaturing HPLC without the necessity of determining the nature of the SNPs. With the example of mapping mutations to the Drosophila nicastrin locus, we discuss the benefits of this method, evaluate the frequency of closely linked and potentially misleading second site mutations, and demonstrate the use of denaturing high-performance liquid chromatography to identify mutations in the candidate genes and to fine-map chromosomal breakpoints. Furthermore, we show that recombination events are not uniformly dispersed over the investigated region but rather occur at hot spots.     

Low melatonin secretion associates with albedo in circumpolar environments

To clarify how seasonal changes of environmental luminosity affect melatonin secretion in human beings, nocturnal urine samples were collected every 2 months throughout the year from 20 outdoor workers living in an area, for which exact data on solar irradiance and temperature were available (67-68 degrees N). Melatonin secretion rates, determined by melatonin-specific radioimmunoassays, were found to be twice as high in December as in April, i.e. 0.88 +/- 0.16 nmol/12 hr (mean +/- S.E.) versus 0.43 +/- 0.09 nmol/12 hr, P < 0.05. Regression analyses showed that melatonin values correlated best inversely with solar irradiance reflected off the ground (albedo). A 10-fold increase in albedo for 1-4 weeks prior to the date of urine sampling was associated with a ca. 50% reduction in melatonin secretion. Association with global irradiance was weaker and did not correlate with temperature. Thus, light reaching the eyes via snow or other reflecting surfaces appears to be most effective. These results assist us in understanding some of the mechanisms involved in certain biological phenomena that exhibit seasonal variations as, for instance, reproduction and self-destructive behavior.     

SARS-CoV-2 Disinfection of Air and Surface Contamination by TiO2 Photocatalyst-Mediated Damage to Viral Morphology,RNA, and Protein

SARS-CoV-2 is the causative agent of COVID-19, which is a global pandemic. SARS-CoV-2 is transmitted rapidly via contaminated surfaces and aerosols, emphasizing the importance of environmental disinfection to block the spread of virus. Ultraviolet C radiation and chemical compounds are effective for SARS-CoV-2 disinfection, but can only be applied in the absence of humans due to their toxicities. Therefore, development of disinfectants that can be applied in working spaces without evacuating people is needed. Here we showed that TiO₂-mediated photocatalytic reaction inactivates SARS-CoV-2 in a time-dependent manner and decreases its infectivity by 99.9% after 20 min and 120 min of treatment in aerosol and liquid, respectively. The mechanistic effects of TiO₂ photocatalyst on SARS-CoV-2 virion included decreased total observed virion count, increased virion size, and reduced particle surface spike structure, as determined by transmission electron microscopy. Damage to viral proteins and genome was further confirmed by western blotting and RT-qPCR, respectively. The multi-antiviral effects of TiO₂-mediated photocatalytic reaction implies universal disinfection potential for different infectious agents. Notably, TiO₂ has no adverse effects on human health, and therefore, TiO₂-induced photocatalytic reaction is suitable for disinfection of SARS-CoV-2 and other emerging infectious disease-causing agents in human habitation.     

Intravenous coronary angiography using electron beam computed tomography

Intravenous coronary angiography with electron beam computed tomography (EBCT) allows for the noninvasive visualisation of coronary arteries. With dedicated computer hardware and software, three-dimensional renderings of the coronary arteries, veins, and other cardiac structures can be constructed from the individual transaxial tomograms. Interest in this technique is growing, and recently a number of clinical studies have been published comparing EBCT coronary angiography with conventional cine-coronary angiography. In this article, image acquisition, postprocessing techniques, and the results of recently published clinical studies are discussed. EBCT coronary angiography is a promising imaging technique of coronary arteries. Currently, it is a reasonably robust technique for the visualization and assessment of the left main and left anterior descending coronary artery. However, at the moment a relatively high proportion of the right and circumflex coronary angiograms are noninterpretable. Improvements in image acquisition and postprocessing techniques are expected to improve visualization and diagnostic accuracy of the technique.     

Choroidal blood flow during exercise-induced changes in the ocular perfusion pressure

PURPOSE: The high metabolic rate of the human retina is supported by the choroidal vasculature. Knowledge of the normal choroidal blood flow (ChBF) responses to various physiological stimuli is therefore highly important if the pathophysiology of ocular diseases involving the choroid is to be understood better. In the present study, the hemodynamic responses of the subfoveal ChBF were examined during and after an exercise-induced increase in the ocular perfusion pressure (OPP). METHODS: Twenty-six healthy volunteers, 19 to 55 years of age participated in this two-phase study. Each subject increased resting OPP through stationary biking at a heart rate (HR) of 140 beats per minute (bpm) over 20 minutes. The ChBF was measured by laser Doppler flowmetry (LDF), the systemic BP by electronic sphygmomanometry, and the resting intraocular pressure (IOP) by applanation tonometry. RESULTS: The OPP increased by approximately 43% at the onset of biking, and then decreased biphasically to approximately 12% above resting value by the end of biking. The ChBF remained within 10% of its basal value throughout biking. Immediately after biking, the OPP decreased twice as much as the ChBF in the same time frame. CONCLUSIONS: The dissociation between the OPP and the ChBF during biking and recovery suggests that some mechanism keeps the ChBF close to its basal value, an observation that indicates blood flow regulation.     

The First‐Episode Psychosis Outcome Study: premorbid and baseline characteristics of an epidemiological cohort of 661 first‐episode psychosis patients

Aims: Studies conducted in first‐episode psychosis (FEP) samples avoid many biases. However, very few studies are based on epidemiological cohorts treated in specialized FEP services. The aim of this file audit study was to examine premorbid and baseline characteristics of a large epidemiological sample of FEP. Methods: File audit study of all patients admitted to the Early Psychosis Prevention and Intervention Centre between 1998 and 2000 using a specialized questionnaire. Results: There were 661 patient files included in the study. Premorbid evaluation revealed high rates of substance use disorder (74.1%), history of psychiatric disorder (47.5%), past traumatic events (82.7%) suicide attempts (14.3%) and family history of psychiatric illness (55.6%). Baseline characteristics revealed high intensity of illness (mean CGI 5.5), high prevalence of lack of insight (62%) and high rate of comorbidity (70%). Conclusion: High rates of traumatic events or episodes of mental illness before treatment for FEP must be considered when designing treatment approaches because a too narrow focus on positive psychotic symptoms will inevitably lead to incomplete treatment. Additionally, early intervention programmes need sufficient range of resources to address the multiple challenges presented by FEP patients such as high severity of illness, comorbidities and functional impairment. Finally, observation of an important degree of functional impairment despite short duration of untreated psychosis suggests that while early detection of FEP is a necessary step in early intervention, it may not be sufficient to improve functional recovery in psychosis and that efforts aimed at identifying people during the prodromal phase of psychotic disorders should be pursued.     

Estrogen, menstrual cycle phases, and psychopathology in women suffering from schizophrenia

BACKGROUND: Estrogen has been hypothesized to have a protective and antipsychotic-like effect in women at risk for schizophrenia. The aim of the present study was to evaluate the association between menstrual cycle and/or estrogen levels and psychotic symptoms in a sample of women with schizophrenia. METHOD: One hundred and twenty-five premenopausal women with schizophrenia and regular menses were examined. The levels of 17beta-estradiol and other hormones of the gonadal axis were assessed in the follicular, peri-ovulatory, and luteal phases of the menstrual cycle. The effects of the menstrual cycle phase and/or the estradiol level on the Positive and Negative Syndrome Scale (PANSS) and the Brief Psychiatric Rating Scale (BPRS) scores were calculated by means of regression analyses. RESULTS: Significant improvement in psychotic, but not depressive, symptoms was observed during the luteal phase, compared with other days of the menstrual cycle. CONCLUSIONS: The present findings indicate that estradiol may have specific antipsychotic-like effects on the symptoms of schizophrenia. Thus further investigation into the therapeutic effect of estrogen may be worthwhile.