What Drives Knowledge Seeking, Sharing, and Use Among Family Planning Professionals? Behavioral Evidence From Africa, Asia, and the United States.

OBJECTIVE: To contribute to strengthening family planning and reproductive health (FP/RH) programs by identifying behavioral factors that influence FP/RH professionals' knowledge management (KM) behaviors. METHODS: We conducted an online survey, in-depth interviews, and cocreation workshops between July 2019 and June 2020 with a convenience sample of FP/RH professionals in Africa, Asia, and the United States to explore their KM behaviors. We used descriptive statistics to analyze the survey data and inductive thematic analysis for the interviews, and we synthesized participant inputs from selected cocreation activities. RESULTS: The samples consisted of 273 survey respondents, 23 interviewees, and 69 cocreation workshop participants. There were no significant differences in how professionals seek and share information by gender, role, or geographic region, except related to language barriers among Francophone professionals. FP/RH professionals reported using both digital sources and their professional networks to seek and share information. Choice overload and cognitive overload (when people are presented with too much information and in a way that is hard to understand, respectively) act as barriers as they seek and use information. Too many information sources lead to frustration and inaction and best practices are often not contextualized or specific enough for application. Positive KM organizational cultures help facilitate effective information sharing, but reluctance to share information persists due to fear of losing comparative advantage. FP/RH professionals noted that such barriers result in duplication of effort and lack of advancement in FP/RH programs. CONCLUSION: To improve overall program impact, KM interventions in FP/RH and global health should reduce cognitive and choice overload, especially by curating and sharing practical, actionable information with essential details on context and how programs are implemented so that others can apply or adapt the learnings. Programs should use incentives to foster motivation to share this type of information.

Evaluation of laser speckle flowmetry for imaging cortical perfusion in experimental stroke studies: quantitation of perfusion and detection of peri-infarct depolarisations.

Laser speckle imaging of the exposed cerebral cortex allows detailed examination of the time course and topography of perfusion under different experimental conditions. Here we examine the quantitative capacity of the method and its sensitivity for the detection of peri-infarct depolarisations (PIDs). In four cats anaesthetised with chloralose, the right hemisphere was exposed and the right middle cerebral artery was occluded. The brain was illuminated with a laser diode, the speckle pattern was imaged, and images of inverse speckle correlation time (ICT) were derived from the calculated speckle contrast images. We examined the relationship of ICT with perfusion, as imaged quantitatively using umbelliferone clearance (CBF(umb)). Values of ICT and CBF(umb) were compared and regression parameters were calculated for each experiment. In eight cats, cortical surface direct current (DC) potential was monitored at two locations and detection of PIDs by DC potential and ICT change was compared. ICT- and CBF(umb)-derived values of perfusion were closely correlated, with a high degree of significance (P<0.0001). Overall, monitoring of DC potential detected 90% of PIDs, whereas ICT detected 56%. We conclude that (1) laser speckle imaging provides an index of perfusion that has a linear relationship with the clearance rate of umbelliferone within the range of levels of perfusion examined; (2) this relationship is relatively stable between experiments; and (3) the method's ability to detect blood flow changes associated with PIDs likely depends on the noise level of the speckle measurements.

Transient changes in cortical glucose and lactate levels associated with peri-infarct depolarisations, studied with rapid-sampling microdialysis.

Peri-infarct depolarisations (PIDs) contribute to infarct expansion in experimental focal ischaemia; furthermore, depolarisations propagate in the injured human brain. Glucose utilisation is increased under both conditions, and depletion of brain glucose carries a poor prognosis. We studied dynamics of cerebral glucose and lactate in relation to PID patterns in experimental stroke. The middle cerebral artery was occluded for 3 h in 23 cats under terminal chloralose anaesthesia. We used fluorescence imaging to detect occurrence of PIDs, and rapid-sampling online microdialysis (rsMD), coupled to a flow-injection assay, to examine changes in cerebral cortical extracellular glucose and lactate at intervals of 30 sec each. After 30 min' ischaemia, lactate had increased by 43.6+/-s.d. 45.9 micromol/L, and stabilised in that range for 3 h. In contrast, glucose fell only slightly initially (11.9+/-9.7 micromol/L), but progressively decreased to a reduction of 56.7+/-47.2 micromol/L at 3 h, with no evidence of stabilisation. There was a highly significant inverse relationship of frequency of PIDs with plasma glucose (P<0.001). The results also characterise a metabolic signature for PIDs for possible application in clinical work, and emphasise potential risks in the use of insulin to control plasma glucose in patients with brain injury.

Dynamic changes in brain glucose and lactate in pericontusional areas of the human cerebral cortex, monitored with rapid sampling on-line microdialysis: relationship with depolarisation-like events.

The pathophysiology of peri-lesion boundary zones in acute brain injury is highly dynamic, and it is now clear that spreading-depression-like events occur frequently in areas of cerebral cortex adjacent to contusions in the injured human brain. An automated method to assay microdialysate from peri-lesion cerebral cortex in 11 patients with intracranial haematomas requiring surgery was used. Perfusate (2 microL/min) flowed directly into a flow-injection system for assay of glucose and lactate at intervals typically of 30 secs each. Four channels of electrocorticogram (ECoG) were recorded from a subdural strip adjacent to the catheter. Several patterns of change in metabolites were identified in different time domains. Overall, the number of transient lactate events was significantly correlated with the number of glucose events (r2=0.48, P=0.027, n=10). Progressive reduction in dialysate glucose was very closely correlated with the aggregate number of ECoG events (r2=0.76, P=0.0004, n=11). It is proposed that the recently documented adverse impact of low dialysate glucose on clinical outcome may be because of recurrent, spontaneous spreading-depression-like events in the perilesion cortex.

Spreading and synchronous depressions of cortical activity in acutely injured human brain.

BACKGROUND AND PURPOSE: Cortical spreading depression (CSD) has been much studied experimentally but never demonstrated unequivocally in human neocortex by direct electrophysiological recording. A similar phenomenon, peri-infarct depolarization, occurs in experimental models of stroke and causes the infarct to enlarge. Our current understanding of the mechanisms of deterioration in the days after major traumatic or ischemic brain injury in humans has not yielded any effective, novel drug treatment. This study sought clear evidence for the occurrence and propagation of CSD in the injured human brain. METHODS: In 14 patients undergoing neurosurgery after head injury or intracranial hemorrhage, we placed electrocorticographic (ECoG) electrodes near foci of damaged cortical tissue. RESULTS: Transient episodes of depressed ECoG activity that propagated across the cortex at rates in the range of 0.6 to 5.0 mm/min were observed in 5 patients; this rate of propagation is characteristic of CSD. We also observed, in 8 of the 14 patients, transient depressions of ECoG amplitude that appeared essentially simultaneous in all recording channels, without clear evidence of spread. CONCLUSIONS: These results indicate that CSD or similar events occur in the injured human brain and are more frequent than previously suggested. On the basis of these observations, we suggest that the related phenomenon, peri-infarct depolarization, is indeed likely to occur in boundary zones in the ischemic human cerebral cortex.

An empirical test of the Theory of Planned Behaviour applied to contraceptive use in rural Uganda.

There is a high unmet need for contraceptives in developing countries such as Uganda, with high population growth, where efforts are needed to promote family planning and contraceptive use. Despite this high need, little research has investigated applications of health-behaviour-change theories to contraceptive use among this population. This study tested the Theory of Planned Behaviour's ability to predict contraceptive-use-related behaviours among post-partum women in rural Uganda. Results gave modest support to the theory's application and suggest an urgent need for improved theory-based interventions to promote contraceptive use in the populations of developing countries.

Application of rapid-sampling, online microdialysis to the monitoring of brain metabolism during aneurysm surgery.

OBJECTIVE: To introduce rapid-sampling microdialysis for the early detection of adverse metabolic changes in tissue at risk during aneurysm surgery. METHODS: A microdialysis catheter was inserted under direct vision into at-risk cortex at the start of surgery. This monitoring was sustained throughout the course of the operation, during which intraoperative events, for example, temporary arterial occlusion or lobe retraction, were precisely documented. A continuous online flow of dialysate was fed into a mobile bedside glucose and lactate analyser. This comprises flow-injection dual-assay enzyme-based biosensors capable of determining values of metabolites every 30 seconds. RESULTS: Eight patients underwent clipping or wrapping of intracranial aneurysms and were monitored. Time between events and detection: 9 minutes. Mean change in metabolite value +/- standard deviation: temporal lobe retraction lactate, +656 +/- 562 micromol/L (n = 7, P < 0.05); glucose, -123 +/- 138 micromol/L (n = 6, P = 0.08). Glucose intravenous bolus infusion glucose, +512 +/- 244 micromol/L (n = 5, P < 0.01); peak at mean time after bolus, 16 minutes. Temporary proximal clip lactate, +731 +/- 346 micromol/L (n = 6, P < 0.01); glucose, -139 +/- 96 micromol/L (n = 5, P < 0.05); mean clip time, 8.6 minutes. CONCLUSION: The technique detects changes 9 minutes after intraoperative events occur (limited only by probe-to-sensor tubing length and dialysate flow rate). This provides reliable information to the surgeon and anesthetist promptly. It is a useful method for monitoring glucose and lactate in dialysate, particularly when rapid, transient changes in brain analyte levels need to be determined and the alternative offline methodology would be inadequate.

TASK-like K+ channels mediate effects of 5-HT and extracellular pH in rat dorsal vagal neurones in vitro.

Dorsal vagal neurones (DVN) receive serotonergic projections from the medullary raphé nuclei, suggesting that 5-HT modulates vagal activity. A previous study has shown that 5-HT excites DVN in part by inhibition of a K+ current via postsynaptic 5-HT2A receptors. As mRNA for the two-pore-domain K+ channels TASK-1 (KCNK3) and TASK-3 (KCNK9) has been found in DVN, we investigated the possibility that 5-HT exerts its effects via inhibition of these K+ channels using whole-cell patch-clamp techniques. In current clamp, 5-HT (20 microM) elicited a depolarization by 5.1+/-1.5 mV and an increase in firing rate. In voltage clamp, 5-HT reduced the standing outward current (ISO) at -20 mV by 106+/-17 pA, inhibiting a conductance (reversal, -95+/-4 mV) which displayed Goldman-Hodgkin-Katz outward rectification, supportive of a TASK-like K+ current. Since TASK channels are modulated by extracellular pH (pHo), we next investigated the pH sensitivity of ISO in Hepes-buffered ACSF. At pHo 7.3, DVN exhibited an ISO of 147+/-15 pA at -20 mV. Acidification to pHo 6.3 reduced ISO to 85+/-13 pA, whereas raising pHo to 8.5 increased ISO to 216+/-26 pA. At pHo 7.3, ISO was inhibited by BaCl2 (IC50 465 microM), but unaffected by ZnCl2 (100 microM). 5-HT (10 microM) reduced ISO by 114+/-17 pA at pHo 7.3, but at pHo 6.3 the 5-HT-induced inhibition of ISO was significantly smaller. The present data suggest that the excitatory effects of 5-HT on DVN are mediated in part by inhibition of a TASK-like, pH-sensitive K+ conductance. The pharmacological profile of this conductance excludes TASK-3 homomers, but rather implicates TASK-1-containing channels.

Altered presynaptic function in monoaminergic neurons of monoamine oxidase-A knockout mice.

Monoamine oxidase-A knockout (MAO-A KO) mice have elevated brain serotonin (5-HT) and noradrenaline (NA) levels, and one would therefore anticipate increased monoamine release and compensatory changes in other aspects of presynaptic monoamine function. In this study we used voltammetry in brain slices from the locus coeruleus (LC), dorsal raphe (DRN) and striatum (CPu) in 7-week-old MAO-A KO and C3H control mice to measure stimulated monoamine efflux and its control by amine transporters and autoreceptors. In LC, peak NA efflux on stimulation (99 pulses, 100 Hz) was higher in MAO-A KO than C3H mice (938 +/- 58 nm cf. 511 +/- 42 nm; P < 0.001). The NA uptake half time (t(1/2)) was longer in MAO-A KO than in C3H mice (6.0 +/- 0.9 s cf. 1.9 +/- 0.3 s; P < 0.001) and the selective NA reuptake inhibitor desipramine (50 nm) had a smaller effect in MAO-A KO mice. NA transporter binding was significantly lower in the LC of MAO-A KO mice compared to C3H controls (P < 0.01) but not in the DRN. The alpha 2 agonist dexmedetomidine (10 nm) decreased stimulated NA efflux more in C3H than in MAO-A KO mice (73.3% cf. 29.6% inhibition, P < 0.001). In DRN, peak 5-HT efflux on stimulation (99 pulses, 100 Hz) was greater (P < 0.01) in MAO-A KO (262 +/- 44 nm) than C3H mice (157 +/- 16 nm). Moreover, 5-HT uptake t(1/2) was longer (P < 0.05) in MAO-A KO than in C3H mice (8.8 +/- 1.1 s cf. 4.9 +/- 0.6 s, P < 0.05) and the effect of citalopram (75 nm) was attenuated in MAO-A KOs. Serotonin transporter binding was also lower in both the DRN and LC of MAO-A KO mice. The 5-HT(1A) agonist 8-OH-DPAT (1 microm) decreased 5-HT efflux more in C3H than in MAO-A KO mice (38.3% inhibition cf. 21.6%, P < 0.001). In contrast, there were no significant differences between MAO-A KO and C3H mice in CPu dopamine efflux and uptake and the effect of the D(2/3) agonist quinpirole was similar in the two strains. In summary, MAO-A KO mice show major dysregulation of monoaminergic presynaptic mechanisms such as autoreceptor control and transporter kinetics.