Abstract Background Knowledge transfer of Middle East respiratory syndrome coronavirus (MERS-CoV) involves the dissemination of created/acquired information on MERS-CoV in hospitals, making this information accessible to all healthcare workers (HCWs). This study evaluated the perceived effectiveness of MERS-CoV educational programs and knowledge transfer among primary care HCWs at a hospital in Saudi Arabia that witnessed the largest outbreak of confirmed MERS-CoV cases in this country. Methods A survey was distributed among primary care HCWs at five clinics in Saudi Arabia in 2016. Those with non-direct patient care responsibilities were excluded. Their knowledge was evaluated against facts published by Mayo Clinic Foundation, and its percentage mean score (PMS) ± standard deviation was calculated. HCWs’ perceived effectiveness of educational programs and knowledge transfer was classified as negative or positive. Results Sample comprised of 404 HCWs, of which 64% were females and 36% were males. Almost 26% were ≤ 30 years old, and 42% had > 10 years of work experience. Almost 46.5% were nurses, 23.0% physicians, 18.1% were pharmacists, and 12.4% were technical staff. PMS for knowledge was 71.1 ± 19.4. The prevalence of negative perceptions towards educational programs was 22.5% and of knowledge transfer was 20.8%. Older(> 40 years of age) and more experienced(> 10 years) HCWs had the highest PMS for knowledge(73.4 ± 18.9,P = 0.005 and 76.9 ± 15.7,P 

Kitazato, K., Milliken, R. E., Iwata, T., Abe, M., Ohtake, M., Matsuura, S., Arai, T., Nakauchi, Y., Nakamura, T., Matsuoka, M., Senshu, H., Hirata, N., Hiroi, T., Pilorget, C., Brunetto, R., Poulet, F., Riu, L., Bibring, J.- P., Takir, D., Domingue, D. L., Vilas, F., Barucci, M. A., Perna, D., Palomba, E., Galiano, A., Tsumura, K., Osawa, T., Komatsu, M., Nakato, A., Arai, T., Takato, N., Matsunaga, T., Takagi, Y., Matsumoto, K., Kouyama, T., Yokota, Y., Tatsumi, E., Sakatani, N., Yamamoto, Y., Okada, T.,

The near-Earth asteroid 162173 Ryugu, the target of Hayabusa2 sample return mission, is thought to be a primitive carbonaceous object. We report reflectance spectra of Ryugu’s surface acquired with the Near Infrared Spectrometer (NIRS3) on Hayabusa2, to provide direct measurements of the surface composition and geological context for the returned samples. A weak, narrow absorption feature centered at 2.72 μm was detected across the entire observed surface, indicating that hydroxyl (OH)-bearing minerals are ubiquitous there. The intensity of the OH feature and low albedo are similar to thermally- and/or shock-metamorphosed carbonaceous chondrite meteorites. There are few variations in the OH-band position, consistent with Ryugu being a compositionally homogeneous rubble-pile object, generated from impact fragments of an undifferentiated aqueously altered parent body.…

Coulehan J.

Ayako Sumi, Nobumichi Kobayashi

by Ayako Sumi, Nobumichi Kobayashi Background Understanding seasonality of tuberculosis (TB) epidemics may lead to identify potentially modifiable risk factors. Studies conducted outside Japan have found seasonal variation among reported TB cases, with peaks in spring and summer and low prevalence in fall and winter. One hypothesis regarding spring or summer peaks in TB epidemics is that TB transmission likely increases in winter because of indoor crowding and poor ventilation, with development of primary TB among socially vulnerable people in spring and summer. Another plausible explanation is that vitamin D deficiency in winter depresses immunity, increasing the TB reactivation risk in these seasons. Previous studies suggest latitude-dependent factors, including reduced winter sunlight and its effect on vitamin D levels. Here, we investigated mechanisms of seasonality in TB epidemics in Japan, according to the effects of crowding and latitude. Methods We used time-series analysis consisting of spectral analysis and least-squares method, to analyse geographically specific monthly number of newly registered cases of all forms of active TB in all 47 prefectures of Japan during 1998–2015. Results In all power spectral densities for the 47 prefectures, spectral lines were observed at frequency positions corresponding to a 1-year cycle. The degree of this seasonality was associated with population density. We did not detect greater amplitude of seasonality at higher latitudes, suggesting that latitude-dependent factors, including reduced winter sunlight and its potential effect on vitamin D levels, do not contribute significantly to seasonality in Japan. Discussion and conclusion In districts with high population density, measures are needed to address two specific types of active infection risk in adolescents and middle-aged adults: (i) public transport use, and (ii) irregular employment with no periodic medical examinations. To control active TB epidemics, investigating periodic structures in the temporal patterns of active TB in each district and each age group is important.…

Grijalva C, de St. Maurice A.

Dong-Hyun Lee, Jin Hyun Kim, Myeong Hee Jung, Min-Chul Cho

by Dong-Hyun Lee, Jin Hyun Kim, Myeong Hee Jung, Min-Chul Cho Epidemiological investigations have suggested that serum 25-hydroxyvitamin D [25(OH)D] level has significantly inverse associations with various neurological and neurodegenerative diseases. However, little is known about 25(OH)D level in human cerebrospinal fluid (CSF). Thus, the aim of this study was to determine correlations of 25(OH)D level in CSF with serum total, bioavailable, and free 25(OH)D levels. This observational study enrolled a total of 117 subjects (58 patients with non-neurologic disease and 59 patients with neurologic disease) from 2017 to 2018. CSF and blood samples were collected in pairs. Total 25(OH)D levels in CSF and serum and vitamin D binding protein (VDBP) levels in serum were measured. We also performed GC genotyping for polymorphisms of rs4588 and rs7041 to calculate bioavailable and free 25(OH)D levels. CSF total 25(OH)D levels were compared with serum total, bioavailable, and free 25(OH)D levels. Mean total 25(OH)D concentrations in CSF and serum of all patients were 37.14 ± 7.71 and 25.72 ± 12.37 ng/mL, respectively. The mean total 25(OH)D concentration in CSF was generally 1.4-fold higher than that in the serum. Total 25(OH)D concentrations in CSF showed weakly positive but significant correlations with serum total, bioavailable, and free 25(OH)D concentrations (P = 0.022, P = 0.033, and P = 0.026, respectively). Serum total 25(OH)D concentration was also correlated with serum VDBP concentration (P = 0.017). However, total 25(OH)D levels in CSF of non-neurologic disease group and neurologic disease group were similar. Total 25(OH)D level in CSF has weakly positive but significant correlations with serum total, bioavailable, and free 25-hydroxy vitamin D levels in the Korean population. The distribution of CSF total 25(OH)D in Korean neurologic and non-neurologic disease patients was presented.

Pospisilova, T., Urbanova, V., Hes, O., Kopacek, P., Hajdusek, O., Sima, R.

Quantitative and microscopic tracking of Borrelia afzelii transmission from infected Ixodes ricinus nymphs has shown transmission cycle different from Borrelia burgdorferi and Ixodes scapularis. Borrelia afzelii are abundant in the guts of unfed I. ricinus nymphs and their numbers continuously decrease during feeding. Borrelia afzelii spirochetes are present in murine skin within 1 day of tick attachment. In contrast, spirochetes were not detectable in salivary glands at any stage of tick feeding. Further experiments demonstrated that tick saliva is not essential for B. afzelii infectivity, the most important requirement for successful host colonization being a change in expression of outer surface proteins that occurs in the tick gut during feeding. Spirochetes in vertebrate mode are then able to survive within the host even in the absence of tick saliva. Taken together, our data suggest that the tick gut is the decisive organ that determines the competence of I. ricinus to vector B. afzelii. We discuss possible transmission mechanisms of B. afzelii spirochetes that should be further tested in order to design effective preventive and therapeutic strategies against Lyme disease.…

Li, Chunyan; Chiluwal, Amrit; Afridi, Adil; Chaung, Wayne; Powell, Keren; Yang, Weng-Lang; Wang, Ping; Narayan, Raj K.

Objectives: To determine if trigeminal nerve stimulation can ameliorate the consequences of acute blood loss and improve survival after severe hemorrhagic shock. Design: Animal study. Setting: University research laboratory. Subjects: Male Sprague-Dawley rats. Interventions: Severe hemorrhagic shock was induced in rats by withdrawing blood until the mean arterial blood pressure reached 27 ± 1 mm Hg for the first 5 minutes and then maintained at 27 ± 2 mm Hg for 30 minutes. The rats were randomly assigned to either control, vehicle, or trigeminal nerve stimulation treatment groups. The effects of trigeminal nerve stimulation on survival rate, autonomic nervous system activity, hemodynamics, brain perfusion, catecholamine release, and systemic inflammation after severe hemorrhagic shock in the absence of fluid resuscitation were analyzed. Measurements and Main Results: Trigeminal nerve stimulation significantly increased the short-term survival of rats following severe hemorrhagic shock in the absence of fluid resuscitation. The survival rate at 60 minutes was 90% in trigeminal nerve stimulation treatment group whereas 0% in control group (p < 0.001). Trigeminal nerve stimulation elicited strong synergistic coactivation of the sympathetic and parasympathetic nervous system as measured by heart rate variability. Without volume expansion with fluid resuscitation, trigeminal nerve stimulation significantly attenuated sympathetic hyperactivity paralleled by increase in parasympathetic tone, delayed hemodynamic decompensation, and improved brain perfusion following severe hemorrhagic shock. Furthermore, trigeminal nerve stimulation generated sympathetically mediated low-frequency oscillatory patterns of systemic blood pressure associated with an increased tolerance to central hypovolemia and increased levels of circulating norepinephrine levels. Trigeminal nerve stimulation also decreased systemic inflammation compared with the vehicle. Conclusions: Trigeminal nerve stimulation was explored as a novel resuscitation strategy in an animal model of hemorrhagic shock. The results of this study showed that the stimulation of trigeminal nerve modulates both sympathetic and parasympathetic nervous system activity to activate an endogenous pressor response, improve cerebral perfusion, and decrease inflammation, thereby improving survival. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by the U.S. Army Medical Research and Materiel Command under award number W81XWH-18-1-0773 and U.S. Department of Defense Congressionally Directed Medical Research Programs Psychological Health and Traumatic Brain Injury Research Program under award number W81XWH-10-1-0978. Drs. Li and Narayan are inventors of the patent application No. PCT/US18/28622: “Systems and methods for delivering non-invasive neuromodulation to reduce the effects of shock and traumatic brain injury in animals and humans and to prolong life.” This patent application covers the fundamental concept of using trigeminal nerve stimulation for the treatment of shock and traumatic brain injury. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, Email: cli11@northwell.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Abstract Over the last two decades there has been a renaissance in the pipeline of new drugs targeting malaria, with the launch of new products that help save the lives of children throughout the world. In addition, there is a wealth of new molecules both entering and progressing through clinical development. These bring hope for a new generation of simpler and more effective cures that could overcome the emerging threat of drug resistance. In addition, there is hope that some of these medicines will have prophylactic activity and can be used to protect vulnerable populations, given the absence of a highly effective vaccine. Switzerland has played a key role in the development of these medicines. First, the country has a long history of understanding the biology of parasites and the pharmacology of drug responses through the leadership of the Swiss Tropical and Public Health Institute in Basel. Second, the highly successful Swiss pharmaceutical industry brings, beyond excellence, a strong interest in neglected diseases, building on work at Hoffmann-La Roche in the last century and with more recent products from Novartis and other Swiss companies. Third, the emergence of product-development-partnerships, in this case led by the Medicines for Malaria Venture, based in Geneva, has helped to catalyze the development of new medicines and bring the community together within Switzerland and beyond. Finally, this progress would not have been possible without the engagement of the Swiss people and the support of the federal government through the Swiss Agency for Development and Cooperation (SDC), the State Secretariat of Education, Research and Innovation (SERI) and the Swiss Republic and Canton of Geneva.…

Emmanuel Njeuhmeli, Melissa Schnure, Andrea Vazzano, Elizabeth Gold, Peter Stegman, Katharine Kripke, Michel Tchuenche, Lori Bollinger, Steven Forsythe, Catherine Hankins

by Emmanuel Njeuhmeli, Melissa Schnure, Andrea Vazzano, Elizabeth Gold, Peter Stegman, Katharine Kripke, Michel Tchuenche, Lori Bollinger, Steven Forsythe, Catherine Hankins Background Modeling contributes to health program planning by allowing users to estimate future outcomes that are otherwise difficult to evaluate. However, modeling results are often not easily translated into practical policies. This paper examines the barriers and enabling factors that can allow models to better inform health decision-making. Description The Decision Makers’ Program Planning Tool (DMPPT) and its successor, DMPPT 2, are illustrative examples of modeling tools that have been used to inform health policy. Their use underpinned Voluntary Medical Male Circumcision (VMMC) scale-up for HIV prevention in southern and eastern Africa. Both examine the impact and cost-effectiveness of VMMC scale-up, with DMPPT used initially in global advocacy and DMPPT 2 then providing VMMC coverage estimates by client age and subnational region for use in country-specific program planning. Their application involved three essential steps: identifying and engaging a wide array of stakeholders from the outset, reaching consensus on key assumptions and analysis plans, and convening data validation meetings with critical stakeholders. The subsequent DMPPT 2 Online is a user-friendly tool for in-country modeling analyses and continuous program planning and monitoring. Lessons learned Through three iterations of the DMPPT applied to VMMC, a comprehensive framework with six steps was identified: (1) identify a champion, (2) engage stakeholders early and often, (3) encourage consensus, (4) customize analyses, (5), build capacity, and (6) establish a plan for sustainability. This framework could be successfully adapted to other HIV prevention programs to translate modeling results to policy and programming. Conclusions Models can be used to mobilize support, strategically plan, and monitor key programmatic elements, but they can also help inform policy environments in which programs are conceptualized and implemented to achieve results. The ways in which modeling has informed VMMC programs and policy may be applicable to an array of other health interventions.…

Kohoutova, Michaela; Horak, Jan; Jarkovska, Dagmar; Martinkova, Vendula; Tegl, Vaclav; Nalos, Lukas; Vistejnova, Lucie; Benes, Jan; Sviglerova, Jitka; Kuncova, Jitka; Matejovic, Martin; Stengl, Milan

Objectives: To investigate the potential benefits of vagus nerve stimulation in a clinically-relevant large animal model of progressive sepsis. Design: Prospective, controlled, randomized trial. Setting: University animal research laboratory. Subjects: Twenty-five domestic pigs were divided into three groups: 1) sepsis group (eight pigs), 2) sepsis + vagus nerve stimulation group (nine pigs), and 3) control sham group (eight pigs). Interventions: Sepsis was induced by cultivated autologous feces inoculation in anesthetized, mechanically ventilated, and surgically instrumented pigs and followed for 24 hours. Electrical stimulation of the cervical vagus nerve was initiated 6 hours after the induction of peritonitis and maintained throughout the experiment. Measurements and Main Results: Measurements of hemodynamics, electrocardiography, biochemistry, blood gases, cytokines, and blood cells were collected at baseline (just before peritonitis induction) and at the end of the in vivo experiment (24 hr after peritonitis induction). Subsequent in vitro analyses addressed cardiac contractility and calcium handling in isolated tissues and myocytes and analyzed mitochondrial function by ultrasensitive oxygraphy. Vagus nerve stimulation partially or completely prevented the development of hyperlactatemia, hyperdynamic circulation, cellular myocardial depression, shift in sympathovagal balance toward sympathetic dominance, and cardiac mitochondrial dysfunction, and reduced the number of activated monocytes. Sequential Organ Failure Assessment scores and vasopressor requirements significantly decreased after vagus nerve stimulation. Conclusions: In a clinically-relevant large animal model of progressive sepsis, vagus nerve stimulation was associated with a number of beneficial effects that resulted in significantly attenuated multiple organ dysfunction and reduced vasopressor and fluid resuscitation requirements. This suggests that vagus nerve stimulation might provide a significant therapeutic potential that warrants further thorough investigation. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Drs. Kohoutova’s, Horak’s, Jarkovska’s, Martinkova’s, Tegl’s, Nalos’s, Vistejnova’s, Benes’s, Sviglerova’s, Kuncova’s, Matejovic’s, and Stengl’s institutions received funding from Grant Agency of the Czech Republic (project No. 15-15716S). Dr. Benes received funding from Edwards Lifesciences (consulting) and CNSystems Medizintechnik Graz (consulting and open access publication grant) (unrelated to this study). For information regarding this article, E-mail: milan.stengl@lfp.cuni.cz Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Friedrich MJ.

Venezuela’s plunge into an economic crisis and the collapse of its health care system appear to have taken a toll on newborns. The country’s infant mortality rate has increased by 40% since 2008, according to a recent study.

Just as skill in perspective drawing is necessary for proficiency in painting and sculpture, a mastership in anatomy opens the door to all purposeful work in medicine. The period of Galen, emphasizing rational anatomy and physiology as a corrective to even the brightest hippocratic philosophies of form and function, significantly runs synchronously with the highest development in Greek art. Galen’s inductive school dominated practically all natural and medical science until the advent of the Renaissance, when medicine, till then a unit, burst into the cluster of component disciplines natural history, physiology, geology, chemistry, physics, astronomy and mechanics. When Vesalius in the sixteenth century instituted the teaching of anatomy by dissections of the human body, the laboratory method recorded its first victory over the didactic. No wonder, then, that the name of Andreas Vesalius took a high place in medical consciousness.

Friedrich MJ.

In its list of the top 10 global health threats for 2019, the World Health Organization (WHO) identified noncommunicable diseases such as diabetes, cancer, and heart disease as a grave danger, causing more than 70% of deaths worldwide and disproportionately affecting low- and middle-income countries. The WHO noted that these illnesses sometimes exacerbate mental health issues among young people, which can lead to suicide.