Labeling Dual Presynaptic Inputs using cFork Anterograde Tracing System

Understanding brain function-related neural circuit connectivity is essential for investigating how cognitive functions are decoded in neural circuits. Trans-synaptic viral vectors are useful for identifying neural synaptic connectivity because of their ability to be transferred from transduced cells to synaptically connected cells. However, concurrent labeling of multisynaptic inputs to postsynaptic neurons is impossible with currently available trans-synaptic viral vectors. Here, we report a neural circuit tracing system that can simultaneously label postsynaptic neurons with two different markers, the expression of which is defined by presynaptic input connectivity. This system, called “cFork (see fork)”, includes delivering serotype 1-packaged AAV vectors (AAV1s) containing Cre or flippase recombinase (FlpO) into two different presynaptic brain areas, and AAV5 with a dual gene expression cassette in postsynaptic neurons. Our in vitro and in vivo tests showed that selective expression of two different fluorescence proteins, EGFP and mScarlet, in postsynaptic neurons could be achieved by AAV1-mediated anterograde trans-synaptic transfer of Cre or FlpO constructs. When this tracing system was applied to the somatosensory barrel field cortex (S1BF) or striatum innervated by multiple presynaptic inputs, postsynaptic neurons defined by presynaptic inputs were simultaneously labeled with EGFP or mScarlet. Our new anterograde tracing tool may be useful for elucidating the complex multisynaptic connectivity of postsynaptic neurons regulating diverse brain functions.

Clinical Characteristics Associated with Electrocardiographic Left Ventricular Hypertrophy in Clinical Normotensives without a History of Hypertension: a Cross-Sectional Study / 가정의학회지

BACKGROUND: This study evaluated factors independently associated with electrocardiographic left ventricular hypertrophy (ECG-LVH) in subjects who were normotensive on clinical measurement and had no prior history of hypertension. METHODS: This cross-sectional study analyzed cases and controls in the Comprehensive Medical Examination Center of Hallym University Sacred Heart Hospital. Eligible case participants presented ECG-LVH according to the Sokolow- Lyon or Cornell criteria, were normotensive on clinical measurement, and had never received a diagnosis of hypertension. The control group comprised subjects with normal sinus rhythm who were normotensive on clinical measurement with no history of hypertension. RESULTS: A multiple logistic regression model showed male sex, age and systolic blood pressure to be positively related to the presence of ECG-LVH. A positive relation of smoking and regular exercise; an inverse relation of pulse rate to the presence of ECG-LVH were found only in men. An inverse relation of uric acid level was found only in women. Detailed analyses of relatively healthy and young men according to whether or not to exercise regularly showed that positive relations of age and systolic blood pressure; an inverse relation of obesity to the presence of ECG-LVH were apparent in the non-regular exercise group but not in the regular exercise group. In the regular exercise group, only pulse rate showed significant (inverse) association with the presence of ECG-LVH. CONCLUSION: The varying risk factor profiles associated with ECG-LVH according to sex and the participation in regular exercise may help to elucidate the ECG-LVH in clinical normotensives with no prior history of hypertension.

Association of Time to First Morning Cigarette and Chronic Obstructive Pulmonary Disease Measured by Spirometry in Current Smokers / 가정의학회지

BACKGROUND: Time to first cigarette after waking is an indicator of nicotine dependence. We aimed to identify the association between time to first cigarette and spirometry-proven obstructive respiratory impairment, especially chronic obstructive pulmonary disease, in current smokers. METHODS: We included 392 subjects who visited the comprehensive medical examination center of Hallym University Sacred Heart Hospital between July 2014 and September 2015. Subjects with lung disease or anemia were excluded. Obstructive pulmonary impairment was defined as 30 minutes) groups based on the time to first cigarette. Logistic regression and linear regression analyses were used for data analysis. RESULTS: Ninety-eight subjects (25%) were classified into the early group. After adjusting for smoking behaviors (cigarettes per day and smoking duration), socioeconomic status (education and income), age, and physical activity, an early time to first cigarette was found to be associated with an increased risk of obstructive pulmonary impairment measured using spirometry (adjusted odds ratio, 2.84; 95% confidence interval, 1.22–6.61). CONCLUSION: Compared to current smokers with a late time to first cigarette, those with an early time to first cigarette had a higher risk of obstructive pulmonary impairment, especially chronic obstructive pulmonary disease. Classifying smoking-related behaviors, especially time to first cigarette, may help target clinical screening for chronic obstructive pulmonary disease.