A novel technique to quantify the instantaneous mitral regurgitant rate

Background

The systolic variation of mitral regurgitation (MR) is a pitfall in its quantification. Current recommendations advocate using quantitative echocardiographic techniques that account for this systolic variation. While prior studies have qualitatively described patterns of systolic variation no study has quantified this variation.

Methods

This study includes 41 patients who underwent cardiovascular magnetic resonance (CMR) evaluation for the assessment of MR. Systole was divided into 3 equal parts: early, mid, and late. The MR jets were categorized as holosystolc, early, or late based on the portions of systole the jet was visible. The aortic flow and left ventricular stroke volume (LVSV) acquired by CMR were plotted against time. The instantaneous regurgitant rate was calculated for each third of systole as the difference between the LVSV and the aortic flow.

Results

The regurgitant rate varied widely with a 1.9-fold, 3.4-fold, and 1.6-fold difference between the lowest and highest rate in patients with early, late, and holosystolic jets respectively. There was overlap of peak regurgitant rates among patients with mild, moderate and severe MR. The greatest variation of regurgitant rate was seen among patients with mild MR.

Conclusion

CMR can quantify the systolic temporal variation of MR. There is significant variation of the mitral regurgitant rate even among patients with holosystolic MR jets. These findings highlight the need to use quantitative measures of MR severity that take into consideration the temporal variation of MR.     

Randomized controlled trial of an internet-based versus face-to-face dyspnea self-management program for patients with chronic obstructive pulmonary disease: pilot study

Background

People with chronic obstructive pulmonary disease (COPD) continue to experience dyspnea with activities of daily living (ADL) despite optimal medical management. Information and communication technologies may facilitate collaborative symptom management and could potentially increase the reach of such interventions to those who are unable to attend face-to-face pulmonary rehabilitation or self-management programs.

Objective

The purpose of this randomized study was to test the efficacy of two 6-month dyspnea self-management programs, Internet-based (eDSMP) and face-to-face (fDSMP), on dyspnea with ADL in people living with COPD.

Methods

We randomly assigned 50 participants with moderate to severe COPD who were current Internet users to either the eDSMP (n = 26) or fDSMP (n = 24) group. The content of the two programs was similar, focusing on education, skills training, and ongoing support for dyspnea self-management, including independent exercise. The only difference was the mode (Internet/personal digital assistant [PDA] or face-to-face) in which the education sessions, reinforcement contacts, and peer interactions took place. Participants returned to one of two academic clinical sites for evaluation at 3 and 6 months. The primary outcome of dyspnea with ADL was measured with the Chronic Respiratory Questionnaire. Secondary outcomes of exercise behavior, exercise performance, COPD exacerbations, and mediators, such as self-efficacy and social support, were also measured. A satisfaction survey was administered and a semistructured exit interview was conducted at the final visit.

Results

The study was stopped early due to multiple technical challenges with the eDSMP, but follow-up was completed on all enrolled participants. Data were available for 39 participants who completed the study (female: 44%; age: 69.5 ± 8.5 years; percent predicted forced expiratory volume in 1 s: 49.6 ± 17.0%). The fDSMP and eDSMP showed similar clinically meaningful changes in dyspnea with ADL from baseline to 3 months (fDSMP: + 3.3 points; eDSMP: + 3.5 points) and sustained these improvements at 6 months (fDSMP: + 4.0 points; eDSMP: + 2.5 points; time effects P < .001; group by time P = .51). Self-reported endurance exercise time (P = .001), physical functioning (P = .04), and self-efficacy for managing dyspnea (P = .02) also showed positive improvements over time in both groups with no significant differences with respect to program modality. Participants who completed the study reported favorable satisfaction with the programs.

Conclusions

Although there were numerous technical challenges with the eDSMP, both dyspnea self-management programs were effective in reducing dyspnea with ADL in the short term. Our findings will need to be confirmed in a larger randomized trial with more mature Web and personal digital assistant tools, use of a control group, and longer follow-up.

Trial registration

clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00102401","term_id":"NCT00102401"}}NCT00102401, http://www.webcitation.org/5X8CX4gLC     

Naturally acquired immunity and reduced susceptibility to falciparum malaria in two subpopulations of endemic eastern India

This study was aimed to assess the prevalence of naturally acquired humoral immune responses and their association with reduced susceptibility to malaria in children and adults with differential clinical conditions from an Indian zone where malaria is endemic. The study was undertaken in an eastern province of India (Keonjhar, Orissa) in a group of 341 children (both younger and older) and 98 adults living in two different areas, Town area and Forest area. They were studied for their parasitological and immunological profiles. Sera from different age-matched groups were screened by ELISA to measure IgG reactivities for characterizing humoral immune responses to the B-cell epitopes of Plasmodium falciparum MSP1, AMA1, RAP1 and EBA175 peptides and P. falciparum -infected erythrocyte lysate. In Town area, overall P. falciparum cases were 5.5%, whereas those in Forest area were 26.7%. We observed an age-wise increasing trend of immunity in these two populations. It was also noticed that the frequency of responders to stage-specific antigens was higher in individuals from the Town area where the frequency of malaria was lower. The naturally acquired humoral immune responses to different stage-specific antigens of P. falciparum reflect the reduced risk of malaria in the study groups. The higher frequency of seroresponders showed correlation with lower risk of developing malaria.     

Timing of extinction relative to acquisition: a parametric analysis of fear extinction in humans

Fear extinction is a reduction in conditioned fear following repeated exposure to the feared cue in the absence of any aversive event. Extinguished fear often reappears after extinction through spontaneous recovery. Animal studies suggest that spontaneous recovery can be abolished if extinction occurs within minutes of acquisition. However, a limited number of human extinction studies have shown that short interval extinction does not prevent the return of fear. For this reason, we performed an in-depth parametric analysis of human fear extinction using fear-potentiated startle. Using separate single-cue and differential conditioning paradigms, participants were fear conditioned and then underwent extinction either 10 min (Immediate) or 72 hr (Delayed) later. Testing for spontaneous recovery occurred 96 hr after acquisition. In the single cue paradigm, the Immediate and Delayed groups exhibited differences in context, but not fear, conditioning. With differential conditioning, there were no differences in context conditioning and the Immediate group displayed less spontaneous recovery. Thus, the results remain inconclusive regarding spontaneous recovery and the timing of extinction and are discussed in terms of performing translational studies of fear in humans.     

Motor variability: within-subject correlations during separate and simultaneous contractions

To determine the similarity of motor variability in proximal muscles, young and elderly adults performed steady elbow flexor (EF) and knee extensor (KE) contractions separately (SEP; at 2.5, 30, and 65% of maximum) and simultaneously (SIM; at 2.5 and 30% of maximum), with (VIS) and without (NVIS) visual feedback. Between-muscle correlations of fluctuation amplitude (SD, CV of force), time-based cross-correlations (CC), force power spectra, and frequency-based coherence (COH) values were computed from the concurrent force records. Correlations of fluctuation amplitude ranged from r = 0.34 to 0.86 (P < 0.05) across forces, SEP/SIM, and vision conditions, but were absent for 2.5% NVIS. The relatively low CC values for SIM (r = 0.22–0.33) were stronger for elderly than young adults. The vast majority of the power in the force fluctuations was <4 Hz for all records. Weak COH peaks were only observed <2 Hz for elderly and between 3 and 4 Hz for young, and COH was slightly stronger for elderly below 3 Hz for the 30% MVC target force. The correlations in force fluctuation amplitude suggest that the EF and KE motor neuron pools similarly transform the oscillating synaptic input and may influence each other. The cross-correlations suggest the remote motor neuron pools are influenced similarly in time by a common source of excitation, perhaps more coherently for elderly adults at low frequencies.     

Adaptation of Francisella tularensis to the mammalian environment is governed by cues which can be mimicked in vitro

The intracellular bacterium Francisella tularensis survives in mammals, arthropods, and freshwater amoeba. It was previously established that the conventional media used for in vitro propagation of this microbe do not yield bacteria that mimic those harvested from infected mammals; whether these in vitro-cultivated bacteria resemble arthropod- or amoeba-adapted Francisella is unknown. As a foundation for our goal of identifying F. tularensis outer membrane proteins which are expressed during mammalian infection, we first sought to identify in vitro cultivation conditions that induce the bacterium's infection-derived phenotype. We compared Francisella LVS grown in brain heart infusion broth (BHI; a standard microbiological medium rarely used in Francisella research) to that grown in Mueller-Hinton broth (MHB; the most widely used F. tularensis medium, used here as a negative control) and macrophages (a natural host cell, used here as a positive control). BHI- and macrophage-grown F. tularensis cells showed similar expression of MglA-dependent and MglA-independent proteins; expression of the MglA-dependent proteins was repressed by the supraphysiological levels of free amino acids present in MHB. We observed that during macrophage infection, protein expression by intracellular bacteria differed from that by extracellular bacteria; BHI-grown bacteria mirrored the latter, while MHB-grown bacteria resembled neither. Naïve macrophages responding to BHI- and macrophage-grown bacteria produced markedly lower levels of proinflammatory mediators than those in cells exposed to MHB-grown bacteria. In contrast to MHB-grown bacteria, BHI-grown bacteria showed minimal delay during intracellular replication. Cumulatively, our findings provide compelling evidence that growth in BHI yields bacteria which recapitulate the phenotype of Francisella organisms that have emerged from macrophages.     

Placental expression of ceruloplasmin in pregnancies complicated by severe preeclampsia

There is consensus that ischemia/reperfusion injury associated with preeclampsia (PE) promotes both placental damage and the release of factors leading to maternal endothelium dysfunction, a hallmark of this potentially life-threatening syndrome. These factors include plasminogen activator inhibitor-1 (PAI-1) and soluble fms-like tyrosine kinase-1 (sFlt-1). The goal of this study was to further characterize placental factors involved in the pathophysiology of PE. Thus, DNA microarray gene profiling was utilized to identify mRNA differentially regulated in placentas from women with severe PE compared to both preterm (PC) and term control (TC) groups. Microarray studies detected an upregulation of mRNA for ceruloplasmin, a copper-containing iron transport protein with antioxidant ferroxidase properties, in PE compared to PC and TC placentas, respectively. Quantitative real-time PCR confirmed these results by demonstrating significant increases in ceruloplasmin mRNA in PE vs PC and TC placentas. Supporting previous reports, the expression of sFlt-1 and PAI-1 were also upregulated in PE placentas. Immunohistochemistry localized ceruloplasmin to the intervillous space in PE and PC placentas, whereas stronger syncytial staining was noted in PE. Western blotting confirmed a significant increase in ceruloplasmin levels in placental tissue in PE compared to PC groups. PCR identified the presence of mRNA for ceruloplasmin in primary cultures of syncytiotrophoblasts, but not villous-derived fibroblasts, suggesting that syncytium is the site of ceruloplasmin synthesis in placenta. Hypoxic treatment (1% O(2)) of syncytiotrophoblasts enhanced levels of ceruloplasmin mRNA approximately 25-fold, a significantly greater upregulation than that noted for PAI-1 and sFlt-1, suggesting that enhanced ceruloplasmin expression is a sensitive marker of syncytial hypoxia. We suggest that syncytial ceruloplasmin and its associated ferroxidase activity, induced by the hypoxia accompanying severe PE, is important in an endogenous cellular program to mitigate the damaging effects of subsequent reperfusion injury at this site.     

Memory loss resulting from fornix and septal damage: impaired supra-span recall but preserved recognition over a 24-hour delay

Despite increasing evidence that the fornix is important for memory, uncertainty remains about the exact nature of subsequent impairments arising from damage to this tract. This uncertainty is often created by pathology in additional brain structures. The present study involved a young man, DN, who had almost complete bilateral loss of the rostral columns of the fornix and much of the surrounding septum in the left hemisphere following the surgical removal of a cavernous angioma. Quantitative MRI analyses of structure size, normalized to intracranial volume, showed no difference in any of the additional brain regions measured, apart from those areas removed to expose the tumor. DN showed a marked, stable anterograde memory impairment that was still present 4 years postsurgery. In contrast, DN performed within normal levels on most tests of recognition memory. This sparing was most striking when given a 24-hr delay between study and test of the Warrington Recognition Memory Test. This recall/recognition dissociation provides further evidence for neuroanatomical divisions within recognition memory processes.     

Effect of temperature on development,eclosion, longevity and survivorship of malathion-resistant and malathion-susceptible strain of <Emphasis Type="Italic">Culex quinquefasciatus</Emphasis>

Density of vectors and development of resistance against insecticides are two important aspects in the control of vector-borne diseases. Here, effect of temperature on different aspects of development of malathion-resistant and susceptible strains of Culex quinquefasciatus was evaluated in the laboratory. Fourth-instar larvae of C. quinquefasciatus were exposed to 37 degrees C, 39 degrees C, 40 degrees C, and 41 degrees C, and their LT(50) values calculated. The fourth-instar larvae were subjected to heat for 4 h at 39 degrees C and live larvae were reared until the completion of life cycle. The larvae of malathion-resistant strain were more tolerant to heat than the larvae of malathion-susceptible ones. The difference in mortality between 37 degrees C, 39 degrees C, 40 degrees C, and 41 degrees C of both the strains of C. quinquefasciatus were highly significant. Pupation percentage of heat-exposed larvae of both the strains was higher and delayed than the control ones. The percentage of adult emergence from the heat-exposed larvae was significantly lower than the control. The adult female of malathion-resistant strain showed increased longevity when exposed to heat at larval stage but reverse was true in case of malathion-susceptible. The highlights of the study would help in the management of resistance of mosquito vectors in the tropics where variable climatic condition is observed.