Stretch‐Induced Increase in Cardiac Contractility Is Independent of Myocyte Ca\u3csup\u3e2+\u3c/sup\u3e While Block of Stretch Channels by Streptomycin Improves Contractility After Ischemic Stunning

Stretching the cardiac left ventricle (LV) enhances contractility but its effect on myoplasmic [Ca2+] is controversial. We measured LV pressure (LVP) and [Ca2+] as a function of intra-LV stretch in guinea pig intact hearts before and after 15 min global stunning ± perfusion with streptomycin (STM), a stretch activated channel blocker. LV wall [Ca2+] was measured by indo-1 fluorescence and LVP by a saline-filled latex balloon inflated in 50 μL steps to stretch the LV. We implemented a mathematical model to interpret crossbridge dynamics and myofilament Ca2+ responsiveness from the instantaneous relationship between [Ca2+] and LVP ± stretching. We found that: (1) stretch enhanced LVP but not [Ca2+] before and after stunning in either control (CON) and STM groups, (2) after stunning [Ca2+] increased in both groups although higher in STM versus CON (56% vs. 39%), (3) STM-enhanced LVP after stunning compared to CON (98% vs. 76% of prestunning values), and (4) stretch-induced effects on LVP were independent of [Ca2+] before or after stunning in both groups. Mathematical modeling suggested: (1) cooperativity in cross-bridge kinetics and myofilament Ca2+ handling is reduced after stunning in the unstretched heart, (2) stunning results in depressed myofilament Ca2+ sensitivity in the presence of attached cross-bridges regardless of stretch, and (3) the initial mechanism responsible for increased contractility during stretch may be enhanced formation of cross-bridges. Thus stretch-induced enhancement of contractility is not due to increased [Ca2+], whereas enhanced contractility after stunning in STM versus CON hearts results from improved Ca2+ handling and/or enhanced actinomyosin cross-bridge cycling

Mg\u3csup\u3e2+\u3c/sup\u3e Differentially Regulates Two Modes of Mitochondrial Ca\u3csup\u3e2+\u3c/sup\u3e Uptake in Isolated Cardiac Mitochondria: Implications for Mitochondrial Ca\u3csup\u3e2+\u3c/sup\u3e Sequestration

The manner in which mitochondria take up and store Ca2+ remains highly debated. Recent experimental and computational evidence has suggested the presence of at least two modes of Ca2+ uptake and a complex Ca2+ sequestration mechanism in mitochondria. But how Mg2+ regulates these different modes of Ca2+ uptake as well as mitochondrial Ca2+ sequestration is not known. In this study, we investigated two different ways by which mitochondria take up and sequester Ca2+ by using two different protocols. Isolated guinea pig cardiac mitochondria were exposed to varying concentrations of CaCl2 in the presence or absence of MgCl2. In the first protocol, A, CaCl2 was added to the respiration buffer containing isolated mitochondria, whereas in the second protocol, B, mitochondria were added to the respiration buffer with CaCl2 already present. Protocol A resulted first in a fast transitory uptake followed by a slow gradual uptake. In contrast, protocol B only revealed a slow and gradual Ca2+ uptake, which was approximately 40 % of the slow uptake rate observed in protocol A. These two types of Ca2+ uptake modes were differentially modulated by extra-matrix Mg2+. That is, Mg2+ markedly inhibited the slow mode of Ca2+ uptake in both protocols in a concentration-dependent manner, but not the fast mode of uptake exhibited in protocol A. Mg2+ also inhibited Na+-dependent Ca2+ extrusion. The general Ca2+ binding properties of the mitochondrial Ca2+ sequestration system were reaffirmed and shown to be independent of the mode of Ca2+ uptake, i.e. through the fast or slow mode of uptake. In addition, extra-matrix Mg2+ hindered Ca2+ sequestration. Our results indicate that mitochondria exhibit different modes of Ca2+ uptake depending on the nature of exposure to extra-matrix Ca2+, which are differentially sensitive to Mg2+. The implications of these findings in cardiomyocytes are discussed

Evaluation of the health-related quality of life of children in Schistosoma haematobium-endemic communities in Kenya: a cross-sectional study.

BACKGROUND: Schistosomiasis remains a global public health challenge, with 93% of the ~237 million infections occurring in sub-Saharan Africa. Though rarely fatal, its recurring nature makes it a lifetime disorder with significant chronic health burdens. Much of its negative health impact is due to non-specific conditions such as anemia, undernutrition, pain, exercise intolerance, poor school performance, and decreased work capacity. This makes it difficult to estimate the disease burden specific to schistosomiasis using the standard DALY metric. METHODOLOGY/PRINCIPAL FINDINGS: In our study, we used Pediatric Quality of Life Inventory (PedsQL), a modular instrument available for ages 2-18 years, to assess health-related quality of life (HrQoL) among children living in a Schistosoma haematobium-endemic area in coastal Kenya. The PedsQL questionnaires were administered by interview to children aged 5-18 years (and their parents) in five villages spread across three districts. HrQoL (total score) was significantly lower in villages with high prevalence of S. haematobium (-4.0%, p<0.001) and among the lower socioeconomic quartiles (-2.0%, p<0.05). A greater effect was seen in the psychosocial scales as compared to the physical function scale. In moderate prevalence villages, detection of any parasite eggs in the urine was associated with a significant 2.1% (p<0.05) reduction in total score. The PedsQL reliabilities were generally high (Cronbach alphas ≥0.70), floor effects were acceptable, and identification of children from low socioeconomic standing was valid. CONCLUSIONS/SIGNIFICANCE: We conclude that exposure to urogenital schistosomiasis is associated with a 2-4% reduction in HrQoL. Further research is warranted to determine the reproducibility and responsiveness properties of QoL testing in relation to schistosomiasis. We anticipate that a case definition based on more sensitive parasitological diagnosis among younger children will better define the immediate and long-term HrQoL impact of Schistosoma infection

The efficacy and safety of a new fixed-dose combination of amodiaquine and artesunate in young African children with acute uncomplicated Plasmodium falciparum

<p>Abstract</p> <p>Background</p> <p>Artesunate (AS) plus amodiaquine (AQ) is one artemisinin-based combination (ACT) recommended by the WHO for treating <it>Plasmodium falciparum </it>malaria. Fixed-dose AS/AQ is new, but its safety and efficacy are hitherto untested.</p> <p>Methods</p> <p>A randomized, open-label trial was conducted comparing the efficacy (non-inferiority design) and safety of fixed (F) dose AS (25 mg)/AQ (67.5 mg) to loose (L) AS (50 mg) + AQ (153 mg) in 750, <it>P</it>. <it>falciparum</it>-infected children from Burkina Faso aged 6 months to 5 years. Dosing was by age. Primary efficacy endpoint was Day (D) 28, PCR-corrected, parasitological cure rate. Recipients of rescue treatment were counted as failures and new infections as cured. Documented, common toxicity criteria (CTC) graded adverse events (AEs) defined safety.</p> <p>Results</p> <p>Recruited and evaluable children numbered 750 (375/arm) and 682 (90.9%), respectively. There were 8 (AS/AQ) and 6 (AS+AQ) early treatment failures and one D7 failure (AS+AQ). Sixteen (AS/AQ) and 12 (AS+AQ) patients had recurrent parasitaemia (PCR new infections 10 and 6, respectively). Fourteen patients per arm required rescue treatment for vomiting/spitting out study drugs. Efficacy rates were 92.1% in both arms: AS/AQ = 315/342 (95% CI: 88.7–94.7) vs. AS+AQ = 313/340 (95% CI: 88.6–94.7). Non-inferiority was demonstrated at two-sided α = 0.05: Δ (AS+AQ – AS/AQ) = 0.0% (95% CI: -4.1% to 4.0%). D28, Kaplan Meier PCR-corrected cure rates (all randomized children) were similar: 93.7% (AS/AQ) vs. 93.2% (AS+AQ) Δ = -0.5 (95% CI -4.2 to 3.0%). By D2, both arms had rapid parasite (F & L, 97.8% aparasitaemic) and fever (97.2% [F], 96.0% [L] afebrile) clearances.</p> <p>Both treatments were well tolerated. Drug-induced vomiting numbered 8/375 (2.1%) and 6/375 (1.6%) in the fixed and loose arms, respectively (<it>p </it>= 0.59). One patient developed asymptomatic, CTC grade 4 hepatitis (AST 1052, ALT 936). Technical difficulties precluded the assessment and risk of neutropaenia for all patients.</p> <p>Conclusion</p> <p>Fixed dose AS/AQ was efficacious and well tolerated. These data support the use of this new fixed dose combination for treating <it>P. falciparum </it>malaria with continued safety monitoring.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN07576538</p

Ischemia reperfusion dysfunction changes model-estimated kinetics of myofilament interaction due to inotropic drugs in isolated hearts

BACKGROUND: The phase-space relationship between simultaneously measured myoplasmic [Ca(2+)] and isovolumetric left ventricular pressure (LVP) in guinea pig intact hearts is altered by ischemic and inotropic interventions. Our objective was to mathematically model this phase-space relationship between [Ca(2+)] and LVP with a focus on the changes in cross-bridge kinetics and myofilament Ca(2+ )sensitivity responsible for alterations in Ca(2+)-contraction coupling due to inotropic drugs in the presence and absence of ischemia reperfusion (IR) injury. METHODS: We used a four state computational model to predict LVP using experimentally measured, averaged myoplasmic [Ca(2+)] transients from unpaced, isolated guinea pig hearts as the model input. Values of model parameters were estimated by minimizing the error between experimentally measured LVP and model-predicted LVP. RESULTS: We found that IR injury resulted in reduced myofilament Ca(2+ )sensitivity, and decreased cross-bridge association and dissociation rates. Dopamine (8 μM) reduced myofilament Ca(2+ )sensitivity before, but enhanced it after ischemia while improving cross-bridge kinetics before and after IR injury. Dobutamine (4 μM) reduced myofilament Ca(2+ )sensitivity while improving cross-bridge kinetics before and after ischemia. Digoxin (1 μM) increased myofilament Ca(2+ )sensitivity and cross-bridge kinetics after but not before ischemia. Levosimendan (1 μM) enhanced myofilament Ca(2+ )affinity and cross-bridge kinetics only after ischemia. CONCLUSION: Estimated model parameters reveal mechanistic changes in Ca(2+)-contraction coupling due to IR injury, specifically the inefficient utilization of Ca(2+ )for contractile function with diastolic contracture (increase in resting diastolic LVP). The model parameters also reveal drug-induced improvements in Ca(2+)-contraction coupling before and after IR injury

Fall Armyworm (Spodoptera frugiperda)

The fall armyworm (FAW), Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), originated from America but is reported recently from Africa and the Asia-Pacific. FAW has caused huge international concern since its outbreak in Africa since 2016 and in Asia since mid-2018. The chapter mainly reviews its global distribution, life cycle, identification characters, strains, host plants, nature of damage, economic damage, and integrated pest management strategies available. The pest completes its life cycle on maize in 30 days (in warm summer months); in cooler temperatures, it may extend up to 60–90 days. For effective management of fall armyworm, different tools, viz., cultural control, agronomic management, breeding for resistance, natural enemies, and eco-friendly insecticides, should be used in an integrated approach. As the insect is recently introduced to Africa and the Asia-Pacific, possible management strategies and future cases of action are discussed

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Caracteristiques Sociodemographiques Du Begaiement En Milieu Scolaire A Lome (Togo)

Introduction : L’objectif de cette étude était d’évaluer la prévalence du bégaiement et de décrire le profil épidémiologique du bègue en milieu scolaire à Lomé au Togo. Matériel et méthodes : Notre travail a eu pour cadre 5 établissements primaires publics de la capitale dont 2 à la commune de Lomé et 3 dans la banlieue nord. Il s’était agi d’une étude transversale, descriptive et analytique qui s’était déroulée du 5 janvier au 31mai 2012.Résultats : Cette étude a permis de dépister 203 enquêtés souffrant de bégaiement, soit une prévalence de 2,1%. L’âge moyen était de 9,4 ans et un sex-ratio de 2,6. La tranche d’âge la plus représentative était de 10 à 14 ans dans une proportion de 57,6%. Les antécédents familiaux de bégaiement au premier degré (parents direct et fratrie) avaient été retrouvé chez 112 (55,2%) et au deuxième degré (oncles et cousins) chez 72 (35,5%). Le bégaiement avait débuté dans plus de 75,3% des cas avant l’âge de 7 ans. Sur l’ensemble de notre série 16 élèves étaient orphelin de père, 9 de mère et 6 des deux parents. Les élèves vivant avec les parents dans un foyer monogamique étaient de 58,1%. Par rapport aux possibilités thérapeutiques 86,7% des élèves n’avaient aucune information sur les moyens de prise en charge moderne, 6,9% d’entre eux décrivaient des moyens traditionnels de prise en charge et 6,4% étaient informés des méthodes de prise en charge moderne.Conclusion : Le niveau de connaissance en matière de la disponibilité des soins moderne était très faible ceci devrait obliger aux actions de sensibilisation de grande masse de population.Mots clés : bégaiement, langage,parole, école primaire, Togo.Introduction: The objective of this study was to look for the prevalence of stuttering and describe the epidemiological profile of the stutterer in school environment in Lome in Togo.Material and methods: our work was to frame 5 official public primary schools of the capital including the municipality of Lome 2 and 3 in the northern suburbs. It had been a cross-sectional, descriptive and analytical study which was held from January 5th to May 31st, 2012.Results: This study has identified 203 respondents suffering from stuttering, either a prevalence of 2.1%. The average age was 9.4 years and a sex ratio of 2.6. The age group most representative was 10-14 years in 57.6%. Family history of stuttering in the first degree (parents direct and siblings) had found in 112 (55.2%) and the second degree (uncles and cousins) in 72 (35.5%). Stuttering began in over 75.3% of the cases before the age of 7. Throughout our series 16 pupils were fatherless, 9were motherless and 6 of both parents. Students living with parents in a monogamous household were 58.1%. Concerning the therapeutic possibilities 86.7% of students had no information on modern care, 6.9% of them described traditional means of care, and 6.4% were aware of the methods of modern care.Conclusion: The level of knowledge in the field of the availability of moderncare was very low this should require awareness-raising of large mass of population.Key words: Stuttering, language, talk, primary school, Togo.Article in Frenc

Seropositivite au vih et grossesse au Togo: vecu et representation a propos de 250 cas au Togo.

Introduction : Ce travail avait pour objectifs d’identifier les indicateurs de la représentation et du vécu des femmes enceintes séropositives d’une part, et de rechercher un lien entre ces indicateurs chez ces femmes au sud du Togo.Méthodologie : Le cadre de notre étude ont été l’hôpital de Bè, le centre de santé de Lomé, le centre de la protection maternelle et infantile de Tsévié, le CHR de Tsévié et le CHP de Vogan. Il s’est agi d’une étude transversale, multicentrique, descriptive et analytique qui s’était déroulée du 4 janvier au 31 octobre 2012.Résultat : Avant la découverte de la séropositivité, les femmes vivaient la grossesse comme une satisfaction et un accomplissement dans 78,0% de cas, comme recherchée et précieuse dans 18,0% de cas et comme non désirée dans 1% des cas. La représentation du nouveau-né et de l’enfant de bas âge par la femme avant le test de sérologie au VIH était une adoration dans 74,0% de cas et 26,0% de femmes décrivaient la place précieuse de l’enfant dans leur vie personnelle et sociétale. De même 72% de femmes avaient une représentation de « maladie mortelle » du VIH ; et 55,6% de « maladie des prostitués ». L’angoisse du devenir du foetus existait dans 55% de cas. Le vécu de la grossesse a été le bonheur dans 80,4% avant la découverte de la séropositivité mais comme une punition ou une malédiction respectivement dans 169 et 120 cas après. La représentation de la séropositivité en fonction du vécu psychologique de ce statut a monté un Chi2 = 81,53 et un coefficient de contingence = 0,88 ce qui a explicité leur forte corrélation.Conclusion : Notre étude a révélé un lien entre les variables de la représentation et du vécu.Mots clés : Séropositivité, grossesse, Togo, culture, VIH