Presynaptic inhibition produced by an identified presynaptic inhibitory neuron. I. Physiological mechanisms

We have examined the synaptic conductance mechanisms underlying presynaptic inhibition in Aplysia californica in a circuit in which all the neural elements are identified cells (Fig. 1). L10 makes connections to identified follower cells (RB and left upper quadrant cells, L2-L6). These connections are presynaptically inhibited by stimulating cells of the L32 cluster (4). L32 cells produce a slow inhibitory synaptic potential on L10. This inhibitory synaptic potential is associated with an apparent increased membrane conductance in L10. Both the inhibitory postsynaptic potential (IPSP) and the conductance increase are voltage dependent; the IPSP could not be reversed by hyperpolarizing the membrane potentials to - 120 mV. The hyperpolarization of L10 induced by L32 reduces the transmitter output of L10 and thereby contributes to presynaptic inhibition. However, this hyperpolarization accounts for about 30% of the effect because presynaptic inhibition can still be observed even when the hyperpolarization of L10 by L32 is prevented by voltage clamping. When L10 is voltage clamped, stimulation of L32 produces a slow outward synaptic current associated with an apparent increased conductance. Both the synaptic current and conductance change measured under clamp are voltage dependent, and the outward current could not be reversed. This synaptic current is not mediated by an increase in C1- conductance. It is sensitive to external K+ concentration, especially at hyperpolarized membrane potentials. With L10 under voltage clamp, stimulation of L32 also reduces a slow inward current in L10. This current has time and voltage characteristics similar to those of the Ca2+ current. Presynaptic inhibition is still produced by L32 when L10 is voltage clamped, and transmitter release is elicited by depolarizing voltage-clamp pulses. This component of presynaptic inhibition, which accounts for approximately 70% of the inhibition, appears to be due to a decrease in the Ca2+ current in the presynaptic neuron.     

STOP Questionnaire: A Tool to Screen Patients for Obstructive Sleep Apnea

Background: Obstructive sleep apnea (OSA) is a major risk factor for perioperative adverse events. However, no screening tool for OSA has been validated in surgical patients. This study was conducted to develop and validate a concise and easy-to-use questionnaire for OSA screening in surgical patients.

Methods: After hospital ethics approval, preoperative patients aged 18 yr or older and without previously diagnosed OSA were recruited. After a factor analysis, reliability check, and pilot study; four yes/no questions were used to develop this screening tool. The four questions were respectively related to snoring, tiredness during daytime, observed apnea, and high blood pressure (STOP). For validation, the score from the STOP questionnaire was evaluated versus the apnea-hypopnea index from monitored polysomnography.

Results: The STOP questionnaire was given to 2,467 patients, 27.5% classified as being at high risk of OSA. Two hundred eleven patients underwent polysomnography, 34 for the pilot test and 177 for validation. In the validation group, the apnea-hypopnea index was 20 +/- 6. The sensitivities of the STOP questionnaire with apnea-hypopnea index greater than 5, greater than 15, and greater than 30 as cutoffs were 65.6, 74.3, and 79.5%, respectively. When incorporating body mass index, age, neck circumference, and gender into the STOP questionnaire, sensitivities were increased to 83.6, 92.9, and 100% with the same apnea-hypopnea index cutoffs.     

Disruption of ejaculates by male copulation in deer mice (Peromyscus maniculatus)

Six experiments were conducted to analyze possible disruption of sperm transport occurring when one male deer mouse copulates soon after another male ejaculates. When a second male mated soon after the first, females had significantly fewer uterine sperm 1 hr later than when a delay of 7 or 15 min was imposed between males. However, it was impossible to detect any effect of such disruption on pregnancy initiation. Similarly, artificial stimulation soon after an ejaculation was ineffective in disrupting pregnancy initiation. No effect of a rapid resumption of copulation could be detected on litter composition in a sperm competition situation. Although it is clear, from these and other data, that the phenomenon of ejaculate disruption occurs in deer mice, technical difficulties may interfere with experimental analysis.     

Arterial oxygenation during sleep in patients with right-to-left cardiac or intrapulmonary shunts.

We have studied arterial oxygen saturation (SaO2), breathing patterns, and electroencephalographic (EEG) sleep stage during nocturnal sleep in six patients with right-to-left cardiac or intrapulmonary shunts and six patients with chronic bronchitis and emphysema, chosen because they were equally hypoxaemic when awake (SaO2 during wakefulness: bronchitis 74-90%, mean 83%; shunt 77-89%, mean 83%). The patients with bronchitis had far greater falls in SaO2 when asleep than those with shunts (maximum fall in SaO2 during sleep: bronchitis 14-47%, mean 29%; shunt 5-10%, mean 8%; p less than 0.01). Significant episodes of hypoxaemia (defined as SaO2 falls greater than 10%) occurred in all six bronchitic patients, from once to seven times per night, but in none of the patients with shunts (p less than 0.05). Twenty-four of the 27 episodes of hypoxaemia occurred in rapid-eye-movement (REM) sleep and 24 were associated with hypopnoea. The two groups of patients had similar EEG sleep patterns and the same amount of hypopnoea during sleep. Thus the level of arterial oxygenation when the patient is awake is not the sole determinant of the degree of nocturnal hypoxaemia; the pathological process is also important.     

Predicting patient follow-through on telephone nursing advice

Although use of telephone advice nursing services continues to grow, little research has addressed factors that affect crucial call outcomes like follow-through on the advice given. This article describes aspects of the advice call process and examines predictors of caller follow-through, using a conceptual model derived from the literature and the authors' preliminary work. Calls to call centers and medical offices of a large health maintenance organization were taped, then content was coded and matched with caller questionnaire (CQ) data. Out of 1,863 participants, 1,489 reported following all the advice. In the final multivariate predictive model, statistically significant predictors of follow-through were patient health status, caller's rating of nurse helpfulness, and the extent to which caller expectations for collaboration were met and the caller understood the advice given. Results suggest that nurses should receive continuous training on effective communication techniques, and advice nurse performance standards that create barriers to communication should be modified.     

Starch-based microparticles as vehicles for the delivery of active platelet-derived growth factor

In a previous work, we described the use of starch-based microparticles as vehicles for the controlled release of corticosteroids. The goal of the present work is to evaluate the potential of these microparticles to incorporate and release platelet-derived growth factor (PDGF). The loading efficiency and release profile were evaluated, and PDGF was incorporated into and released from the matrix of starch-based microparticles. The release profile shows rapid release of PDGF in the first 24 h, after which there was a slow but constant release for up to 8 weeks. The maintenance of the PDGF biological activity after incorporation and release was evaluated by its mitogenic effect over osteoblastic cells, and it was shown to be comparable to that of PDGF supplemented to the culture medium. This proves that the incorporation and release did not affect the biological activity of the growth factor (GF). The results clearly demonstrate that starch-based microparticles are suitable vehicles for the incorporation and release of GFs. When combined with previous results, these materials also suggest their ability to enhance the regenerating potential of tissue engineering hybrid constructs.     

Polyomavirus BK non-coding control region rearrangements in health and disease

BACKGROUND: BK virus is an increasingly recognized pathogen in transplanted patients. DNA sequencing of this virus shows considerable genomic variability. METHODS: To understand the clinical significance of rearrangements in the non-coding control region (NCCR) of BK virus (BKV), we report a meta-analysis of 507 sequences, including 40 sequences generated in our own laboratory, for associations between rearrangements and disease, tissue tropism, geographic origin, and viral genotype. RESULTS: NCCR rearrangements were less frequent in (a) asymptomatic BKV viruria compared to patients viral nephropathy (1.7% vs. 22.5%), and (b) viral genotype 1 compared to other genotypes (2.4% vs. 11.2%). Rearrangements were commoner in malignancy (78.6%), and Norwegians (45.7%), and less common in East Indians (0%), and Japanese (4.3%). A surprising number of rearranged sequences were reported from mononuclear cells of healthy subjects, whereas most plasma sequences were archetypal. This difference could not be related to potential recombinase activity in lymphocytes, as consensus recombination signal sequences could not be found in the NCCR region. CONCLUSIONS: NCCR rearrangements are neither required nor a sufficient condition to produce clinical disease. BKV nephropathy and hemorrhagic cystitis are not associated with any unique NCCR configuration or nucleotide sequence.     

Hepatitis B vaccination of newborn infants in rural China: evaluation of a village-based, out-of-cold-chain delivery strategy

OBJECTIVE: To prevent perinatal transmission of hepatitis B virus (HBV), WHO recommends that the first dose of hepatitis B (HepB) vaccine be given within 24 hours after birth. This presents a challenge in remote areas with limited cold-chain infrastructure and where many children are born at home. METHODS: Rural townships in three counties in China's Hunan Province were randomized into three groups with different strategies for delivery of the first dose of HepB vaccine. In group 1, vaccine was stored within the cold chain and administered in township hospitals. In group 2, vaccine was stored out of the cold chain in villages and administered by village-based health workers to infants at home. Group 3 used the same strategy as group 2, but vaccine was packaged in a prefilled injection device. Training of immunization providers and public communication conveying the importance of the birth dose was performed for all groups. FINDINGS: Among children born at home, timely administration (within 24 hours after birth) of the first dose of HepB vaccine increased in all groups after the study: group 1, from 2.4% to 25.2%; group 2, from 2.6% to 51.8%; and group 3, from 0.6% to 66.7%; P < 0.001 in each case. No significant difference in antibody response to vaccine was observed between the groups. CONCLUSION: Timely administration of the first dose of HepB vaccine was improved by communication and training activities, and by out-of-cold-chain storage of vaccine and administration at the village level, especially among children born at home.