Myosin-binding protein C regulates the sarcomere lattice and stabilizes the OFF states of myosin heads.

Muscle contraction is produced via the interaction of myofilaments and is regulated so that muscle performance matches demand. Myosin-binding protein C (MyBP-C) is a long and flexible protein that is tightly bound to the thick filament at its C-terminal end (MyBP-CC8C10), but may be loosely bound at its middle- and N-terminal end (MyBP-CC1C7) to myosin heads and/or the thin filament. MyBP-C is thought to control muscle contraction via the regulation of myosin motors, as mutations lead to debilitating disease. We use a combination of mechanics and small-angle X-ray diffraction to study the immediate and selective removal of the MyBP-CC1C7 domains of fast MyBP-C in permeabilized skeletal muscle. We show that cleavage leads to alterations in crossbridge kinetics and passive structural signatures of myofilaments that are indicative of a shift of myosin heads towards the ON state, highlighting the importance of MyBP-CC1C7 to myofilament force production and regulation.

Remodelling of Skeletal Muscle Myosin Metabolic States in Hibernating Mammals.

Hibernation is a period of metabolic suppression utilized by many small and large mammal species to survive during winter periods. As the underlying cellular and molecular mechanisms remain incompletely understood, our study aimed to determine whether skeletal muscle myosin and its metabolic efficiency undergo alterations during hibernation to optimize energy utilization. We isolated muscle fibers from small hibernators, Ictidomys tridecemlineatus and Eliomys quercinus and larger hibernators, Ursus arctos and Ursus americanus. We then conducted loaded Mant-ATP chase experiments alongside X-ray diffraction to measure resting myosin dynamics and its ATP demand. In parallel, we performed multiple proteomics analyses. Our results showed a preservation of myosin structure in U. arctos and U. americanus during hibernation, whilst in I. tridecemlineatus and E. quercinus, changes in myosin metabolic states during torpor unexpectedly led to higher levels in energy expenditure of type II, fast-twitch muscle fibers at ambient lab temperatures (20°C). Upon repeating loaded Mant-ATP chase experiments at 8°C (near the body temperature of torpid animals), we found that myosin ATP consumption in type II muscle fibers was reduced by 77-107% during torpor compared to active periods. Additionally, we observed Myh2 hyper-phosphorylation during torpor in I. tridecemilineatus, which was predicted to stabilize the myosin molecule. This may act as a potential molecular mechanism mitigating myosin-associated increases in skeletal muscle energy expenditure during periods of torpor in response to cold exposure. Altogether, we demonstrate that resting myosin is altered in hibernating mammals, contributing to significant changes to the ATP consumption of skeletal muscle. Additionally, we observe that it is further altered in response to cold exposure and highlight myosin as a potentially contributor to skeletal muscle non-shivering thermogenesis.

Strong Evidence for

The boundaries of the chart of nuclides contain exotic isotopes that possess extreme proton-to-neutron asymmetries. Here we report on strong evidence of ^{9}N, one of the most exotic proton-rich isotopes where more than one half of its constitute nucleons are unbound. With seven protons and two neutrons, this extremely proton-rich system would represent the first-known example of a ground-state five-proton emitter. The invariant-mass spectrum of its decay products can be fit with two peaks whose energies are consistent with the theoretical predictions of an open-quantum-system approach; however, we cannot rule out the possibility that only a single resonancelike peak is present in the spectrum.

Titin-based force regulates cardiac myofilament structures mediating length-dependent activation.

The Frank-Starling law states that the heart's stroke volume increases with greater preload due to increased venous return, allowing the heart to adapt to varying circulatory demands. Molecularly, increasing preload increases sarcomere length (SL), which alters sarcomere structures that are correlated to increased calcium sensitivity upon activation. The titin protein, spanning the half-sarcomere, acts as a spring in the I-band, applying a SL-dependent force suggested to pull against and alter myofilaments in a way that supports the Frank-Starling effect. To evaluate this, we employed the titin cleavage (TC) model, where a tobacco-etch virus protease recognition site is inserted into distal I-band titin and allows for rapid, specific cleavage of titin in an otherwise-healthy sarcomere. Here, we evaluated the atomic-level structures of amyopathic cardiac myofilaments following 50% titin cleavage under passive stretch conditions using small-angle X-ray diffraction, which measures these structures under near-physiological (functional) conditions. We report that titin-based forces in permeabilized papillary muscle regulate both thick and thin myofilament structures clearly supporting titin's role in the Frank-Starling mechanism.

Community Involvement in Response to Ebola Virus Disease Epidemic in North Kivu and Ituri, Democratic Republic of Congo: A Mixed-Methods Study.

We investigated the involvement of community members in response to the Ebola Virus Disease (EVD) epidemic in the North Kivu and Ituri provinces of the Democratic Republic of Congo. This cross-sectional study, conducted using mixed methods of data collection, included a uniformly structured questionnaire survey, which was administered to 800 randomly selected adults (aged ≥ 18 years). Further, we used qualitative tools of inquiry-focus group discussions (FGD) and in-depth interviews (IDI)-to guide the context of the information collected in the survey. Community leaders, religious leaders, and Ebola survivors were interviewed using the IDI guide, while young men (≤ 30 years), young women (≤30 years), adult community males (<30 years), and adult community females (<30 years) were in separate FGD sessions. The results revealed that the urban area was the most affected by the epidemic (79.2%) compared to 20.8% in rural areas. The χ2 calculated was 18.183 (P<0.001). Community members exhibited varying degrees of involvement in response to the EVD epidemic in the two provinces. Community members were mostly engaged in information dissemination. However, they believe they could have contributed more if they had been fully engaged. These findings were derived from the qualitative data. The study contributes to evidence on how community involvement could help response to public health events globally, hence this study provides valuable insights for future public health interventions and response.

Perceptions and Rumors About the Ebola Virus Disease Vaccine in the Ituri and Kivu Provinces of the Democratic Republic of Congo.

Perceptions and rumors about vaccinations can contribute to vaccine hesitancy. This study aimed to examine perceptions and rumors about the Ebola vaccine during the 10th Ebola Virus Disease outbreak in the Ituri and North Kivu provinces of the Democratic Republic of Congo. Eight hundred randomly selected respondents were surveyed with a uniform structured questionnaire. Further, we collected qualitative data through focus group discussions and using in-depth interview guides. Results revealed several misperceptions and rumors about the vaccine, which led to some level of vaccine hesitancy and refusal among the people. The acceptance rate of the vaccine was 67.3% (below the 80% threshold needed to create herd immunity in the population). More of the urban population (31.3%) than the rural population (10.4%) accepted the vaccine. Refusals were largely due to fear that the vaccine could activate other diseases in the body and could even kill. Some feared that it was a conspiracy of the government to reduce the population in the study area through forced fertility control and death, among other such concerns. In conclusion, these rumors increased mistrust, which challenged the efforts of the government and its partners to safeguard the health of the people.

Perceptions, Disease Representations, and Response Obstacles Regarding the Ebola Virus Disease Epidemic in the North Kivu and Ituri Provinces of the Democratic Republic of the Congo.

We explored the perceptions and representations of diseases in the North Kivu and Ituri provinces of the Democratic Republic of Congo to identify perceived obstacles regarding responses to the country 's Ebola virus disease (EVD) outbreak using a mix-methods approach. We surveyed a representative sample including 800 adults aged 18 years and older, held in-depth interviews with 17 community leaders, and conducted 10 focus group discussions with community members (using same-sex interviewers/discussion leaders). The results revealed the existence of several health conditions among members of the two communities. Locals consider nearly 80 of these ailments as untreatable by orthodox medicines and methods, even when symptoms are similar to EVD. Creating awareness must be considered a critical goal of community education to further educate these populations about EVD and other health problems and their respective treatments.

Survivors and the Response to the Ebola Virus Disease in the Provinces of North Kivu and Ituri in the Democratic Republic of Congo.

We explored issues around the integration of survivors in communities and the implications for the Ebola Virus Disease (EVD) response in the Democratic Republic of Congo (DRC). We conducted a survey with 800 randomly selected respondents using a structured questionnaire. Respondents were persons aged 18 years and above. Focus group discussions (FGDs) and in-depth interviews (IDIs) were employed to obtain contextual data on the issues. Community leaders, health workers, and response pillar leads engaged in IDIs, while community members were involved in FGDs. The results revealed that the survivors suffered stigmatization and, upon return to the communities, were avoided by the community members due to fear of contamination. Some thought that the survivors should be supported in adjusting to the community, while some recommended engaging the survivors in EVD response activities.

Description of the Proton-Decaying 0_{2}

The recent precise experimental determination of the monopole transition form factor from the ground state of ^{4}He to its 0_{2}^{+} resonance via electron scattering has reinvigorated discussions about the nature of this first excited state of the α particle. The 0_{2}^{+} state has been traditionally interpreted in the literature as the isoscalar monopole resonance (breathing mode) or, alternatively, as a particle-hole shell-model excitation. To better understand the nature of this state, which lies only ∼410 keV above the proton emission threshold, we employ the coupled-channel representation of the no-core Gamow shell model. By considering the [^{3}H+p], [^{3}He+n], and [^{2}H+^{2}H] reaction channels, we explain the excitation energy and monopole form factor of the 0_{2}^{+} state. We argue that the continuum coupling strongly impacts the nature of this state, which carries characteristics of the proton decay threshold.

Involvement of Civil Society Organizations and Other Community Groups in the Response to the Ebola Virus Disease Outbreak in the North Kivu and Ituri Provinces of the Democratic Republic of Congo.

We reviewed the involvement of civil society organizations as well as other community level organizations and structures in the response to the Ebola Virus Disease (EVD) outbreak in the Democratic Republic of Congo. A total of 800 randomly selected adults were surveyed using a uniform set of structured questionnaires. An in-depth interview guide was employed to collect information from community members and religious leaders, while focus group discussions were held with community members. The results revealed some involvement of the different organizations in the communities in the response to the EVD outbreak. However, several challenges were encountered, namely security issues, poor awareness, and non-compliance to safety measures. The findings underscore that despite considerable experience over a long period with outbreaks in the DRC, people still need to be educated about the disease.

Cardiopulmonary Arrest After COVID-19 Vaccination: A Case Report.

Coronavirus disease 2019 (COVID-19) emerged in Wuhan in 2019 and by far has affected the whole world, and many people have succumbed to the disease. Vaccination programs introduced around the globe are aiming to reduce morbidity, mortality, and disease spread. We report the case of a 59-year-old male who suffered from cardiopulmonary arrest post-COVID-19 mRNA booster vaccination with no history of any other cardiopulmonary disease. Association between myocarditis and mRNA COVID-19 vaccines have been previously reported. However, this is the first case of cardiopulmonary arrest post-COVID-19 booster vaccination. Further research and cases should be described to confirm if this relationship exists. We need further cases to find this temporal association as such cases can also increase vaccine hesitancy. However, vaccination-associated adverse events should be vigilantly monitored and evaluated from time to time as further reports emerge.

Efficacy of magnesium sulfate in the chronic obstructive pulmonary disease population: a systematic review and meta-analysis.

INTRODUCTION: Magnesium sulfate has been extensively used to treat asthma exacerbations, but its efficacy remains questionable in the chronic obstructive pulmonary disease (COPD) population. The aim of the study was to compare the efficacy of intravenous (IV) magnesium sulfate in COPD. A systemic review search was conducted on PubMed, Embase, and the Central Cochrane Registry. Randomized clinical trials were included with magnesium sulfate as an intervention arm in the COPD population. MATERIALS AND METHODS: For continuous variables, standardized mean difference (SMD) and difference in means (MD) were calculated. For discrete variables, the Mantel-Haenszel (MH) odds ratio was used. For effect sizes, a confidence interval of 95% was used. A p-value of less than 0.05 was used for statistical significance. Analysis was done using both random and fixed effect models. Heterogeneity was evaluated using the I² statistic. RESULTS: Seven studies were included in the final analysis. In patients with acute exacerbations of COPD treated with IV magnesium, a significant increase in forced expiratory volume in one second (FEV1) was observed (MD = 2.537 [0.717 to 4.357], p = 0.006), as well as in peak expiratory flow rate (PEFR) (SMD = 1.073 [0.748 to 1.397], p < 0.001) using the fixed model. Similarly, residual volume decreased significantly in the IV magnesium group (MD = -0.470 [-0.884 to -0.056], p = 0.026). The hospitalization rate was also lower in the magnesium group, (MH odds ratio 0.453 [0.233 to 0.882], p = 0.020). No statistically significant difference was noted in FEV1 in the stable COPD population. CONCLUSION: IV magnesium was associated with a favorable deviation of FEV1 and PEFR, decreased residual volume, and decreased odds of admission in the COPD exacerbation population. Therefore, magnesium sulfate can be used as an adjunctive therapy in the treatment of acute exacerbations of COPD.

Causes de stress chez les médecins en milieux hospitaliers dans la ville de Lubumbashi / NA

ntroduction.Les stress sont cliniquement sous-estimés pourtant ils ont des répercussions non négligeables sur la qualité de vie et sur le travail du médecin et de son entourage. L'objectif est de déterminer les causesde stress chez lesmédecins de l'Hôpital Provincial de Référence (HPR) Jason Sendwe de Lubumbashi.Matérieletméthodes.Nous avons mené une étude descriptive transversale auprès des 36 médecins de l'HPR Jason Sendwe de Lubumbashi ayant donné un consentement éclairé pour répondre à nos questions pendant la période allant de Janvier à Mars 2022.Résultats.L'analyse des données montre que l'âge moyen des médecins interrogés était de 46 ± 5,4ans dont les extrêmesétaient de 34 et 66 ans. Les médecins de sexe masculin représentaient 66,7% et 44,4% étaient mariés. Parmi eux 30,6% avaient une expérience professionnelle > 10 ans et 41,7% œuvraient dans le département de chirurgie. Les causes principales de stress des médecins étaient la surcharge du travail dans 33,3% des cas et l'impuissance de sauver un patient par manque des médicaments dans 22,2%. La perte de certaines habilités techniques était la conséquenceprincipaledans 44,4% des cas. Les signes de stress étaient caractérisés par l'insomnie, céphalées et vertiges respectivement dans 25%, 22,2% et 19,4%. Se confier à un ami en dehors du service était le mécanisme d'adaptation adopté par les médecins en cas de stress dans 27,8% des cas.Conclusion.La profession médicale expose aux circonstances qui provoquent les stress. Ainsi les médecins devront bénéficier des meilleures conditions de travail pour leur équilibre et leur sérénité au quotidien.

Autodétermination des femmes dans la santé sexuelle et reproductive à Lubumbashi, République Démocratique du Congo / NA

ntroduction.La santé reproductive est caractérisée par une vie sexuelle satisfaisante, sûre et la capacité de se reproduire et de prendre des décisions. La vie de beaucoup de femmes estmarquée par les capacités d'action réduites quant aux décisions portant sur leur propre vie. L'objectif était d'évaluer l'autodétermination des femmes en matière de la santésexuelle et reproductive.Matérieletméthodes.Il s'agit d'une étude descriptive transversale effectuée dans 5 maternités de la ville de Lubumbashi au mois de juillet 2021 au près des 46 accouchées ayant accepté librement de participer à cette étude basée sur le questionnaire préétabli. Résultats.L'analyse des données montre que la moyenne d'âge était de 27,8 ± 3,6 ans avec les extrêmes entre 17 et 41 ans, dont 58,7% d'entre elles avaient le niveau de secondaire et paucipares dans 52,17%. La décision des rapports sexuels revenait au couple dans 58,70%. La décision d'avoir les enfantsrevenait au couple alors que celle de nommer les enfants revenait au mari dans 45,65% et 45,65%. Le nombre d'enfants était déterminé par le couple dans 45,65%. L'espacement des naissances était déterminé par la femme dans 45,65%. Le début de la CPN était décidé par la femme dans 86,6% et le choix du lieu des consultation prénatales(CPN) étaient décidés par la femme dans 89,13%. Le moment de se rendre à la maternité était décidé par la femme dans 73,91%. Le retour à domicile était décidé par le couple dans 39,13% et la décision des rapports sexuels après l'accouchement revenait à l'homme dans 52,17%.Conclusion.La femme congolaise n'a pas toujours une autodétermination maximale dans la santé reproductive. Ainsi des efforts supplémentaires sont nécessairespour laisser la liberté aux femmes de prendre des décisions qui conviennent mieux pour leur santé

Detectability and impact of repetitive surveys on threatened West African crocodylians.

West African crocodylians are among the most threatened and least studied crocodylian species globally. Assessing population status and establishing a basis for population monitoring is the highest priority action for this region. Monitoring of crocodiles is influenced by many factors that affect detectability, including environmental variables and individual- or population-level wariness. We investigated how these factors affect detectability and counts of the critically endangered Mecistops cataphractus and the newly recognized Crocodylus suchus. We implemented 195 repetitive surveys at 38 sites across Côte d'Ivoire between 2014 and 2019. We used an occupancy-based approach and a count-based GLMM analysis to determine the effect of environmental and anthropogenic variables on detection and modeled crocodile wariness over repetitive surveys. Despite their rarity and level of threat, detection probability of both species was relatively high (0.75 for M. cataphractus and 0.81 for C. suchus), but a minimum of two surveys were required to infer absence of either species with 90% confidence. We found that detection of M. cataphractus was significantly negatively influenced by fishing net encounter rate, while high temperature for the previous 48 h of the day of the survey increased C. suchus detection. Precipitation and aquatic vegetation had significant negative and positive influence, respectively, on M. cataphractus counts and showed the opposite effect for C. suchus counts. We also found that fishing encounter rate had a significant negative effect on C. suchus counts. Interestingly, survey repetition did not generally affect wariness for either species, though there was some indication that at least M. cataphractus was more wary by the fourth replicate. These results are informative for designing future survey and monitoring protocols for these threatened crocodylians in West Africa and for other endangered crocodylians globally.

Technical Modifications That Might Improve Long-term Outcomes of the Ross Procedure in Children.

BACKGROUND: Failure of the pulmonary valve autograft (PVA) after the Ross procedure (RP) has discouraged its widespread use and has led to modifications or alternatives to the procedure. We sought to analyze whether certain technical modifications could improve results of the RP in children. METHODS: Sixty-nine patients (median age, 12 years; range, 0.25-17.9) underwent the RP between January 1996 and December 2018. A concomitant Konno procedure was performed on 20 of 69 patients (29%). Prior interventions included balloon valvuloplasty in 30 (44%) and/or surgical valvuloplasty in 39 (57%). Technical modifications included using the native aortic root for external annuloplasty, implanting the autograft using uniplanar horizontal sutures through the aortic wall, normalizing the sinotubular junction, and wrapping the native root remnant around the PVA. RESULTS: Operative mortality was 1 of 69 patients (1.5%), with no late deaths. No patient had neoaortic valvar stenosis and 7 of 68 (10%) had mild regurgitation on discharge echocardiogram. At latest follow-up (median, 9.4 years; range, 0.4-21.3) there was no significant change in Z scores of annulus, sinus, or sinotubular junction diameters when compared with those at discharge. Three patients (4.4%) required late autograft replacement, 2 PVA repair, and 2 resection of a pseudoaneurysm. Actuarial freedom from PVA replacement was 87% at 20 years. Freedom from right ventricular outflow tract catheter reintervention or reoperation was 83% and 80%, respectively. CONCLUSIONS: Technical modifications of the RP used in this cohort might successfully prolong the life of the PVA without compromising its growth, an important advantage in pediatric patients.

Vagus nerve stimulation promotes extinction generalization across sensory modalities.

Traumatic experiences involve complex sensory information, and individuals with trauma-related psychological disorders, such as posttraumatic stress disorder (PTSD), can exhibit abnormal fear to numerous different stimuli that remind them of the trauma. Vagus nerve stimulation (VNS) enhances extinction of auditory fear conditioning in rat models for PTSD. We recently found that VNS-paired extinction can also promote extinction generalization across different auditory cues. Here we tested whether VNS can enhance extinction of olfactory fear and promote extinction generalization across auditory and olfactory sensory modalities. Male Sprague Dawley rats were implanted with a stimulating cuff on the cervical vagus nerve. Rats then received two days of fear conditioning where olfactory (amyl acetate odor) and auditory (9 kHz tones) stimuli were concomitantly paired with footshock. Twenty-four hours later, rats were given three days of sham or VNS-paired extinction (5 stimulations, 30-sec trains at 0.4 mA) overlapping with presentation of either the olfactory or the auditory stimulus. Two days later, rats were given an extinction retention test where avoidance of the olfactory stimulus or freezing to the auditory stimulus were measured. VNS-paired with exposure to the olfactory stimulus during extinction reduced avoidance of the odor in the retention test. VNS-paired with exposure to the auditory stimulus during extinction also decreased avoidance of the olfactory cue, and VNS paired with exposure to the olfactory stimulus during extinction reduced freezing when the auditory stimulus was presented in the retention test. These results indicate that VNS enhances extinction of olfactory fear and promotes extinction generalization across different sensory modalities. Extinction generalization induced by VNS may therefore improve outcomes of exposure-based therapies.

Quasifree Neutron Knockout Reaction Reveals a Small s-Orbital Component in the Borromean Nucleus

A kinematically complete quasifree (p,pn) experiment in inverse kinematics was performed to study the structure of the Borromean nucleus ^{17}B, which had long been considered to have a neutron halo. By analyzing the momentum distributions and exclusive cross sections, we obtained the spectroscopic factors for 1s_{1/2} and 0d_{5/2} orbitals, and a surprisingly small percentage of 9(2)% was determined for 1s_{1/2}. Our finding of such a small 1s_{1/2} component and the halo features reported in prior experiments can be explained by the deformed relativistic Hartree-Bogoliubov theory in continuum, revealing a definite but not dominant neutron halo in ^{17}B. The present work gives the smallest s- or p-orbital component among known nuclei exhibiting halo features and implies that the dominant occupation of s or p orbitals is not a prerequisite for the occurrence of a neutron halo.

First Observation of the Four-Proton Unbound Nucleus

^{18}Mg was observed, for the first time, by the invariant-mass reconstruction of ^{14}O+4p events. The ground-state decay energy and width are E_{T}=4.865(34) MeV and Γ=115(100) keV, respectively. The observed momentum correlations between the five particles are consistent with two sequential steps of prompt 2p decay passing through the ground state of ^{16}Ne. The invariant-mass spectrum also provides evidence for an excited state at an excitation energy of 1.84(14) MeV, which is likely the first excited 2^{+} state. As this energy exceeds that for the 2^{+} state in ^{20}Mg, this observation provides an argument for the demise of the N=8 shell closure in nuclei far from stability. However, in open systems this classical argument for shell strength is compromised by Thomas-Ehrman shifts.