A new class of insecticide for malaria vector control: evaluation of mosquito nets treated singly with indoxacarb (oxadiazine) or with a pyrethroid mixture against Anopheles gambiae and Culex quinquefasciatus.

BACKGROUND: Universal coverage with long-lasting insecticidal mosquito nets (LLIN) or indoor residual spraying (IRS) of houses remain the primary strategies for the control of mosquito vectors of malaria. Pyrethroid resistant malaria vectors are widespread throughout sub-Saharan Africa and new insecticides with different modes of action are urgently needed if malaria vector control is to remain effective. Indoxacarb is an oxadiazine insecticide that is effective as an oral and contact insecticide against a broad spectrum of agricultural pests and, due to its unique site of action, no cross-resistance has been detected through mechanisms associated with resistance to insecticides currently used in public health. METHODS: WHO tunnel tests of host seeking mosquitoes were carried out as a forerunner to experimental hut trials, to provide information on dosage-dependent mortality, repellency, and blood-feeding inhibition. A dosage range of indoxacarb treated netting (100-1000 mg/m(2)) was tested against a pyrethroid susceptible strain of Anopheles gambiae. In addition, efficacy of indoxacarb 500 mg/m(2) was compared with a standard pyrethroid formulation against pyrethroid susceptible and resistant Culex quinquefasciatus. Dosages between 25 and 300 mg/m(2) indoxacarb were tested in tunnel tests and in ball-frame bioassays as mixtures with alphacypermethrin 25 mg/m(2) and were compared with singly applied treatments against an insectary reared pyrethroid resistant strain of Cx. quinquefasciatus originally collected in Cotonou, Benin. RESULTS: There was a dosage-dependent response in terms of indoxacarb induced mortality, with dosages >100 mg/m(2) producing the best mortality response. In tunnel tests indoxacarb 500 mg/m(2) exceeded WHOPES thresholds with >80 % mortality of adult An. gambiae and blood-feeding inhibition of 75 %. No cross-resistance to indoxacarb was detected through mechanisms associated with resistance to pyrethroid insecticides and was equally effective against susceptible and resistant strains of Cx. quinquefasciatus. Indoxacarb 500 mg/m(2) killed 75 % of pyrethroid resistant Cx. quinquefasciatus compared with only 21 % mortality with alphacypermethrin 40 mg/m(2). Mixtures of indoxacarb with pyrethroid produced an additive response for both mortality and blood-feeding inhibition. The best performing mixture (indoxacarb 200 mg/m(2) + alphacypermethrin 25 mg/m(2)) killed 83 % of pyrethroid resistant Cx. quinquefasciatus and reduced blood-feeding by 88 %, while alphacypermethrin only killed 36 % and inhibited blood-feeding by 50 %. CONCLUSIONS: New insecticides with different modes of action to those currently used in mosquito vector control are urgently needed. Indoxacarb shows great promise as a mixture with a pyrethroid and should be evaluated in experimental hut trials to determine performance against wild free-flying, pyrethroid resistant An. gambiae and wash-resistant formulations developed

Global and regional cardiac function in lifelong endurance athletes with and without myocardial fibrosis

The aim of the present study was to compare cardiac structure as well as global and regional cardiac function in athletes with and without myocardial fibrosis (MF). Cardiac magnetic resonance imaging with late gadolinium enhancement was used to detect MF and global cardiac structure in nine lifelong veteran endurance athletes (58 ± 5 years, 43 ± 5 years of training). Transthoracic echocardiography using tissue-Doppler and myocardial strain imaging assessed global and regional (18 segments) longitudinal left ventricular function. MF was present in four athletes (range 1–8 g) and not present in five athletes. MF was located near the insertion points of the right ventricular free wall on the left ventricle in three athletes and in the epicardial lateral wall in one athlete. Athletes with MF demonstrated a larger end diastolic volume (205 ± 24 vs 173 ± 18 ml) and posterior wall thickness (11 ± 1 vs 9 ± 1 mm) compared to those without MF. The presence of MF did not mediate global tissue velocities or global longitudinal strain and strain rate; however, regional analysis of longitudinal strain demonstrated reduced function in some fibrotic regions. Furthermore, base to apex gradient was affected in three out of four athletes with MF. Lifelong veteran endurance athletes with MF demonstrate larger cardiac dimensions and normal global cardiac function. Fibrotic areas may demonstrate some co-localised regional cardiac dysfunction, evidenced by an affected cardiac strain and base to apex gradient. These data emphasize the heterogeneous phenotype of MF in athletes

The Activityof the Pyrrole Insecticide Chlorfenapyr in Mosquito Bioassay: Towards a More Rational Testing and Screening of Non-neurotoxic Insecticides for Malaria\ud vector control

The rapid selection of pyrethroid resistance throughout sub-Saharan Africa is a serious threat to malaria vector control. Chlorfenapyr is a pyrrole insecticide which shows no cross resistance to insecticide classes normally used for vector control and is effective on mosquito nets under experimental hut conditions. Unlike neurotoxic insecticides, chlorfenapyr owes its toxicity to disruption of metabolic pathways in mitochondria that enable cellular respiration. A series of experiments explored whether standard World Health Organization (WHO) guidelines for evaluation of long-lasting insecticidal nets, developed through testing of pyrethroid insecticides, are suitable for evaluation of non-neurotoxic insecticides. The efficacy of WHO recommended cone, cylinder and tunnel tests was compared for pyrethroids and chlorfenapyr. To establish bioassay exposure times predictive of insecticidetreated net (ITN) efficacy in experimental hut trials, standard three-minute bioassays of pyrethroid and chlorfenapyr ITNs were compared with longer exposures. Mosquito behaviour and response to chlorfenapyr ITN in bioassays conducted at night were compared to day and across a range of temperatures representative of highland and lowland transmission. Standard three-minute bioassay of chlorfenapyr produced extremely low levels of mortality compared to pyrethroids. Thirty-minute day-time bioassay produced mortality closer to hut efficacy of chlorfenapyr ITN but still fell short of the WHO threshold. Overnight tunnel test with chlorfenapyr produced 100% mortality and exceeded the WHO threshold of 80%. The endogenous circadian activity rhythm of anophelines results in inactivity by day and raised metabolism and flight activity by night. A model which explains improved toxicity of chlorfenapyr ITN when tested at night, and during the day at higher ambient temperature, is that activation of chlorfenapyr and disruption of respiratory pathways is enhanced when the insect is more metabolically and behaviourally active. Testing according to current WHO guidelines is not suitable for certain types of nonneurotoxic insecticide which, although highly effective in field trials, would be overlooked at the screening stage of evaluation through bioassay. Testing methods must be tailored to the characteristics and mode of action of each insecticide class. The WHO tunnel test on nightactive anophelines is the most reliable bioassay for identifying the toxicity of nove

Left and right ventricular longitudinal strain-volume/area relationships in elite athletes.

We propose a novel ultrasound approach with the primary aim of establishing the temporal relationship of structure and function in athletes of varying sporting demographics. 92 male athletes were studied [Group IA, (low static-low dynamic) (n = 20); Group IC, (low static-high dynamic) (n = 25); Group IIIA, (high static-low dynamic) (n = 21); Group IIIC, (high static-high dynamic) (n = 26)]. Conventional echocardiography of both the left ventricles (LV) and right ventricles (RV) was undertaken. An assessment of simultaneous longitudinal strain and LV volume/RV area was provided. Data was presented as derived strain for % end diastolic volume/area. Athletes in group IC and IIIC had larger LV end diastolic volumes compared to athletes in groups IA and IIIA (50 ± 6 and 54 ± 8 ml/(m(2))(1.5) versus 42 ± 7 and 43 ± 2 ml/(m(2))(1.5) respectively). Group IIIC also had significantly larger mean wall thickness (MWT) compared to all groups. Athletes from group IIIC required greater longitudinal strain for any given % volume which correlated to MWT (r = 0.4, p < 0.0001). Findings were similar in the RV with the exception that group IIIC athletes required lower strain for any given % area. There are physiological differences between athletes with the largest LV and RV in athletes from group IIIC. These athletes also have greater resting longitudinal contribution to volume change in the LV which, in part, is related to an increased wall thickness. A lower longitudinal contribution to area change in the RV is also apparent in these athletes

Left ventricular speckle tracking-derived cardiac strain and cardiac twist mechanics in athletes: a systematic review and meta-analysis of controlled studies

Background: The athlete’s heart is associated with physiological remodeling as a consequence of repetitive cardiac loading. The effect of exercise training on left ventricular (LV) cardiac strain and twist mechanics are equivocal, and no meta-analysis has been conducted to date. Objective: The objective of this systematic review and meta-analysis was to review the literature pertaining to the effect of different forms of athletic training on cardiac strain and twist mechanics and determine the influence of traditional and contemporary sporting classifications on cardiac strain and twist mechanics. Methods: We searched PubMed/MEDLINE, Web of Science, and ScienceDirect for controlled studies of aged-matched male participants aged 18–45 years that used two-dimensional (2D) speckle tracking with a defined athlete sporting discipline and a control group not engaged in training programs. Data were extracted independently by two reviewers. Random-effects meta-analyses, subgroup analyses, and meta-regressions were conducted. Results: Our review included 13 studies with 945 participants (controls n = 355; athletes n = 590). Meta-analyses showed no athlete–control differences in LV strain or twist mechanics. However, moderator analyses showed greater LV twist in high-static low-dynamic athletes (d = –0.76, 95% confidence interval [CI] –1.32 to –0.20; p < 0.01) than in controls. Peak untwisting velocity (PUV) was greater in high-static low-dynamic athletes (d = –0.43, 95% CI –0.84 to –0.03; p < 0.05) but less than controls in high-static high-dynamic athletes (d = 0.79, 95% CI 0.002–1.58; p = 0.05). Elite endurance athletes had significantly less twist and apical rotation than controls (d = 0.68, 95% CI 0.19–1.16, p < 0.01; d = 0.64, 95% CI 0.27–1.00, p = 0.001, respectively) but no differences in basal rotation. Meta-regressions showed LV mass index was positively associated with global longitudinal (b = 0.01, 95% CI 0.002–0.02; p < 0.05), whereas systolic blood pressure was negatively associated with PUV (b = –0.06, 95% CI –0.13 to –0.001; p = 0.05). Conclusion: Echocardiographic 2D speckle tracking can identify subtle physiological differences in adaptations to cardiac strain and twist mechanics between athletes and healthy controls. Differences in speckle tracking echocardiography-derived parameters can be identified using suitable sporting categorizations

Left ventricular morphology and function in adolescents: Relations to fitness and fatness.

BACKGROUND: Obesity in childhood predisposes individuals to cardiovascular disease and increased risk of premature all-cause mortality. The aim of this study was to determine differences in LV morphology and function in obese and normal-weight adolescents. Furthermore, relationships between LV outcomes, cardiorespiratory fitness (CRF) and adiposity were explored. METHODS: LV morphology was assessed using magnetic resonance imaging (MRI) in 20 adolescents (11 normal-weight [BMI equivalent to 18kg/m(2)-25kg/m(2)] and 9 obese [BMI equivalent to ≥30kg/m(2)]); 13.3±1.1years, 45% female, Tanner puberty stage 3 [2-4]) using magnetic resonance imaging (MRI). Global longitudinal strain (GLS), strain rate (SR) and traditional echocardiographic indices were used to assess LV function. CRF (peak oxygen consumption), percent body fat (dual-energy x-ray absorptiometry), abdominal adipose tissue (MRI), and blood biochemistry markers were also evaluated. RESULTS: Adolescents with obesity showed significantly poorer LV function compared to normal-weight adolescents (P0.05). Moderate to strong associations between myocardial contractility and relaxation, adiposity, arterial blood pressure and cardiorespiratory fitness were noted (r=0.49-0.71, P<0.05). CONCLUSION: Obesity in adolescence is associated with altered LV systolic and diastolic function. The notable relationship between LV function, CRF and adiposity highlights the potential utility of multidisciplinary lifestyle interventions to treat diminished LV function in this population. CLINICAL TRIAL REGISTRATION: NCT01991106

Speckle Tracking Echocardiography for the Assessment of the Athlete's Heart: Is It Ready for Daily Practice?

PURPOSE OF REVIEW: To describe the use of speckle tracking echocardiography (STE) in the biventricular assessment of athletes' heart (AH). Can STE aid differential diagnosis during pre-participation cardiac screening (PCS) of athletes? RECENT FINDINGS: Data from recent patient, population and athlete studies suggest potential discriminatory value of STE, alongside standard echocardiographic measurements, in the early detection of clinically relevant systolic dysfunction. STE can also contribute to subsequent prognosis and risk stratification. Despite some heterogeneity in STE data in athletes, left ventricular global longitudinal strain (GLS) and right ventricular longitudinal strain (RV ɛ) indices can add to differential diagnostic protocols in PCS. STE should be used in addition to standard echocardiographic tools and be conducted by an experienced operator with significant knowledge of the AH. Other indices, including left ventricular circumferential strain and twist, may provide insight, but further research in clinical and athletic populations is warranted. This review also raises the potential role for STE measures performed during exercise as well as in serial follow-up as a method to improve diagnostic yield

Concentric and eccentric remodelling of the left ventricle and its association to function in the male athletes heart:an exploratory study

Aims: To compare (1) conventional left ventricular (LV) functional parameters, (2) LV peak strain and strain rate and (3) LV temporal strain and strain rate curves in age, ethnicity and sport-matched athletes with concentric, eccentric and normal LV geometry. Methods: Forty-five male athletes were categorised according to LV geometry including concentric remodelling/hypertrophy (CON), eccentric hypertrophy (ECC) or normal (NORM). Athletes were evaluated using conventional echocardiography and myocardial speck tracking, allowing the assessment of myocardial strain and strain rate; as well as twist mechanics. Results: Concentric remodelling was associated with an increased ejection fraction (EF) compared to normal geometry athletes (64% (48–78%) and 56% (50–65%), respectively; p &lt; 0.04). No differences in peak myocardial strain or strain rate were present between LV geometry groups including global longitudinal strain (GLS; CON −16.9% (−14.9–20.6%); ECC −17.9% (−13.0–22.1%); NORM −16.9% (−12.8–19.4%)), global circumferential strain (GCS; CON −18.1% (−13.5–24.5%); ECC −18.7% (−15.6–22.4%); NORM −18.0% (−13.5–19.7%)), global radial strain (GRS; CON 42.2% (30.3–70.5%); ECC 50.0% (39.2–60.0%); NORM 40.6 (29.9–57.0%)) and twist (CON 14.9° (3.7–25.3°); ECC 12.5° (6.3–20.8°); NORM 13.2° (8.8–24.2°)). Concentric and eccentric remodelling was associated with alterations in temporal myocardial strain and strain rate as compared to normal geometry athletes. Conclusion: Physiological concentric and eccentric remodelling in the athletes heart is generally associated with normal LV function; with concentric remodelling associated with an increased EF. Physiological concentric and eccentric remodelling in the athletes heart has no effect on peak myocardial strain but superior deformation and untwisting is unmasked when assessing the temporal distribution

Impact of ECG data format on the performance of machine learning models for the prediction of myocardial infarction

Background We aim to determine which electrocardiogram (ECG) data format is optimal for ML modelling, in the context of myocardial infarction prediction. We will also address the auxiliary objective of evaluating the viability of using digitised ECG signals for ML modelling. Methods Two ECG arrangements displaying 10s and 2.5 s of data for each lead were used. For each arrangement, conservative and speculative data cohorts were generated from the PTB-XL dataset. All ECGs were represented in three different data formats: Signal ECGs, Image ECGs, and Extracted Signal ECGs, with 8358 and 11,621 ECGs in the conservative and speculative cohorts, respectively. ML models were trained using the three data formats in both data cohorts. Results For ECGs that contained 10s of data, Signal and Extracted Signal ECGs were optimal and statistically similar, with AUCs [95% CI] of 0.971 [0.961, 0.981] and 0.974 [0.965, 0.984], respectively, for the conservative cohort; and 0.931 [0.918, 0.945] and 0.919 [0.903, 0.934], respectively, for the speculative cohort. For ECGs that contained 2.5 s of data, the Image ECG format was optimal, with AUCs of 0.960 [0.948, 0.973] and 0.903 [0.886, 0.920], for the conservative and speculative cohorts, respectively. Conclusion When available, the Signal ECG data should be preferred for ML modelling. If not, the optimal format depends on the data arrangement within the ECG: If the Image ECG contains 10s of data for each lead, the Extracted Signal ECG is optimal, however, if it only uses 2.5 s, then using the Image ECG data is optimal for ML performance.</p

The influence of age and exercise training status on left ventricular systolic twist mechanics in healthy males—an exploratory study

Age-related differences in twist may be mitigated with exercise training, although this remains inconclusive. Moreover, temporal left ventricular (LV) systolic twist mechanics, including early-systolic (twistearly), and beyond peak twist (twistpeak) alone, have not been considered. Therefore, further insights are required to ascertain the influence of age and training status on twist mechanics across systole. Forty males were included and allocated into 1 of 4 groups based on age and training status: young recreationally active (YRA, n = 9; 28 ± 5 years), old recreationally active (ORA, n = 10; 68 ± 6 years), young trained (YT, n = 10; 27 ± 6 years), and old trained (OT, n = 11, 64 ± 4 years) groups. Two-dimensional speckle-tracking echocardiography was performed to determine LV twist mechanics, including twistearly, twistpeak, and total twist (twisttotal), by considering the nadir on the twist time-curve during early systole. Twisttotal was calculated by subtracting twistearly from their peak values. LV twistpeak was higher in older than younger men (p = 0.036), while twistpeak was lower in the trained than recreationally-active (p = 0.004). Twistpeak is underestimated compared with twisttotal (p &lt; 0.001), and when early-systolic mechanics were considered, to calculate twisttotal, the age effect (p = 0.186) was dampened. LV twist was higher in older than younger age, with lower twist in exercise-trained than recreationally-active males. Twistpeak is underestimated when twistearly is not considered, with novel observations demonstrating that the age effect was dampened when considering twistearly. These findings elucidated a smaller age effect when early phases of systole are considered, while lower LV systolic mechanics were observed in older aged trained than recreationally-active males