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The vestibular system is integral to behavior; the loss of peripheral vestibular function leads to disabling consequences, such as blurred vision, dizziness, and unstable posture, severely limiting activities of daily living. Fortunately, the vestibular system’s well-defined peripheral structure and well-understood encoding strategies offer unique opportunities for developing sensory prostheses to restore vestibular function. While these devices show promising results in both animal models and implanted patients, substantial room for improvement remains. Research from an engineering perspective has largely focused on optimizing stimulation protocol to improve outcomes. However, this approach has often been pursued in isolation from research in neuroscience that has enriched our understanding of neural responses at the synaptic, cellular, and circuit levels. Accordingly, this review bridges the domains of neuroscience and engineering to consider recent progress and challenges in vestibular prosthesis development. We advocate for interdisciplinary approaches that leverage studies of neural circuits at the population level, especially in light of recent advancement in large-scale recording technology, to identify impediments still to overcome and to develop more naturalistic stimulation strategies. Fully integrating neuroscience and engineering in the context of prosthesis development will help advance the field forward and ultimately improve patient outcomes.

Early blastomeres of mouse preimplantation embryos exhibit bi-potential cell fate, capable of generating both embryonic and extra-embryonic lineages in blastocysts. Here we identify three major two-cell-stage (2C)-specific endogenous retroviruses (ERVs) as the molecular hallmark of this bi-potential plasticity. Using the long terminal repeats (LTRs) of all three 2C-specific ERVs, we identify Krüppel-like factor 5 (Klf5) as their major upstream regulator. Klf5 is essential for bi-potential cell fate; a single Klf5-overexpressing embryonic stem cell (ESC) generates terminally differentiated embryonic and extra-embryonic lineages in chimeric embryos, and Klf5 directly induces inner cell mass (ICM) and trophectoderm (TE) specification genes. Intriguingly, Klf5 and Klf4 act redundantly during ICM specification, whereas Klf5 deficiency alone impairs TE specification. Klf5 is regulated by multiple 2C-specific transcription factors, particularly Dux, and the Dux/Klf5 axis is evolutionarily conserved. The 2C-specific transcription program converges on Klf5 to establish bi-potential cell fate, enabling a cell state with dual activation of ICM and TE genes.

ABSTRACTThe development of biosurveillance programs with strong analytical performance and economically accessible protocols is essential for monitoring viral pathogens. Throughout the COVID-19 pandemic, whole-genome sequencing (WGS) has been the prevailing technology for SARS-CoV-2 variant of concern (VOC) detection. While WGS offers benefits, it is a lengthy process, financially and technically straining for scalable viral tracking. The aim of this study was to compare the analytical performance and economic feasibility of WGS and PCR mutation panels for distinguishing six known VOCs: Alpha (B.1.1.7 and Q.4), Gamma (P.1), Delta (B.1.617.2 and AY.4.2), and Omicron. (B.1.1.529.1). In all, 78 SARS-CoV-2-positive samples were collected from April to December 2021 at Northeastern University (Cabot Testing Site, Boston, MA, USA) for genotyping PCR and WGS analysis. MagMax Viral/Pathogen II Nucleic Acid Isolation and TaqPath COVID-19 Combo Kits were used for RNA extraction and SARS-CoV-2 confirmation. VOC discrimination was assessed using two TaqMan SARS-CoV-2 single nucleotide polymorphism (SNP) assay layouts, and Ion Torrent WGS. In November 2021, the mutation panel demonstrated marked versatility by detecting the emerging Omicron variant reported by South Africa. SNP panel analysis yielded the following 78 VOC identifications: Alpha B.1.1.7 (N = 20), Alpha Q.4 (N = 3), Gamma P.1 (N = 1), Delta B.1.617.2 (N = 30), Delta AY.4.2 (N = 3), and Omicron B.1.1.529.1 (N = 20) with one undetermined (N = 1) sample. Genotyping mutation panels designated lineages in 77 of 78 samples, 46/78 were confirmed by WGS, while 32 samples failed WGS lineage assignment. RT-PCR genotyping panels offer pronounced throughput and sensitivity and provide an economically advantageous technique for SARS-CoV-2 biosurveillance.IMPORTANCEThe results presented in our manuscript demonstrate how the value of simplistic and reliable molecular assays coupled with the core scientific principle of standardization can be overlooked by the charm of more sophisticated assays and instrumentation. This effect can often be amplified during tumultuous public health events, such as the COVID-19 pandemic. By adapting standardized PCR mutation panels to detect prominently circulating SARS-CoV-2 variants, we were able to better assess the potential health impacts of rising positivity rates and transmission clusters within the Northeastern University population. While several literature publications utilizing genotyping PCR and NGS have a similar scope to ours, many investigations lack sufficiently standardized genotyping PCR and NGS bioinformatics inclusionary/exclusionary criteria for SARS-CoV-2 variant identification. Finally, the economic benefits of standardized PCR mutation panels would allow for global implementation of biosurveillance, rather than reserving biosurveillance to more economically developed nations.

BackgroundClustering lifestyle risk behaviors is important for predicting cardiovascular disease risk. However, it is unclear which behavior mediates other ones to influence cardiovascular disease risk. We aimed to assess the causal inference of each lifestyle risk behavior for the atherosclerotic cardiovascular disease (ASCVD) risk of the general population.MethodsWe performed a Bayesian network mediation analysis using data from the Korea National Health and Nutrition Examination Survey from 2014 to 2019. The main exposure was a combination of lifestyle risk behaviors including unhealthy weight, heavy alcohol consumption, inadequate sleep, physical inactivity, excessive sodium intake, and current smoking among subjects 40 to 79 years of age. The high risk of ASCVD (≥7.5% for the 10-year risk) was assessed using logistic regression, Bayesian networks, and structural equational models to examine the causal relationships between these six lifestyle risk behaviors.ResultsAmong all participants, the most prevalent lifestyle risk behavior for those at high risk for ASCVD was excessive sodium intake (95.6%), followed by inadequate sleep (49.9%) and physical inactivity (43.8%). Older age (65-79 years) and male sex were directly associated with a high risk for ASCVD. Physical inactivity, current smoking, excessive sodium intake, and unhealthy weight indirectly mediated the effects of older age (8.2% of the older age) and male sex (39.9% of males) to high ASCVD risk. Physical inactivity, current smoking, excessive sodium intake, and unhealthy weight particularly mediated the high ASCVD risk sequentially. Heavy alcohol consumption and inadequate sleep were not directly associated with high ASCVD risk and did not indirectly mediate the effects of older age and males on the high ASCVD risk.ConclusionLifestyle risk behaviors mediated the atherosclerotic cardiovascular disease risk in a different manner. Especially, physical inactivity preceded current smoking, excessive sodium intake, and unhealthy weight in relation to high ASCVD risk, and this causal relationship was different according to age and sex. Therefore, tailored strategies according to specific target populations may be needed to effectively reduce the high ASCVD risk.

Abstract Background Cardiac rehabilitation (CR) is a prognostic management strategy to help patients with CVD achieve a good quality of life and lower the rates of recurrence, readmission, and premature death from disease. Globally, cardiac rehabilitation is poorly established in hospitals and communities. Hence, this study aimed to investigate the discrepancies in the perceptions of the need for CR programs and relevant health policies between directors of hospitals and health policy personnel in South Korea to shed light on the status and to establish practically superior and effective strategies to promote CR in South Korea. Methods We sent a questionnaire to 592 public health policy managers and directors of selected hospitals, 132 of whom returned a completed questionnaire (response rate: 22.3%). The participants were categorized into five types of organizations depending on their practice of PCI (Percutaneous Coronary Intervention), establishment of cardiac rehabilitation, director of hospital, and government's policy makers. Differences in the opinions between directors of hospitals that perform/do not perform PCI, directors of hospitals with/without cardiac rehabilitation, and between hospital directors and health policy makers were analyzed. Results Responses about targeting diseases for cardiac rehabilitation, patients’ roles in cardiac rehabilitation, hospitals’ roles in cardiac rehabilitation, and governmental health policies’ roles in cardiac rehabilitation were more positive among hospitals that perform PCI than those that do not. Responses to questions about the effectiveness of cardiac rehabilitation and hospitals’ roles in cardiac rehabilitation tended to be more positive in hospitals with cardiac rehabilitation than in those without. Hospital directors responded more positively to questions about targeting diseases for cardiac rehabilitation and governmental health policies’ roles in cardiac rehabilitation than policy makers, and both hospitals and public organizations provided negative responses to the question about patients’ roles in cardiac rehabilitation. Responses to questions about targeting diseases for cardiac rehabilitation, patients’ roles in cardiac rehabilitation, and governmental health policies’ roles in cardiac rehabilitation were more positive in hospitals that perform PCI than those that do not and public organizations. Conclusions Hospitals must ensure timely referral, provide education, and promote the need for cardiac rehabilitation. In addition, governmental socioeconomic support is needed in a varity of aspects.

Background Whether the early use of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors have cardioprotective effects following acute myocardial infarction is unknown. Thus, we aimed to evaluate the association between the early initiation of SGLT2 inhibitors and cardiac event rates in patients with diabetes with acute myocardial infarction undergoing percutaneous coronary intervention. Methods and Results Based on the National Health Insurance claims data in South Korea, patients who received percutaneous coronary intervention for acute myocardial infarction between 2014 and 2018 were analyzed. Patients given SGLT2 inhibitors or other glucose‐lowering drugs were matched based on a propensity score. The primary end point was a composite of all‐cause mortality and hospitalizations for heart failure. Major adverse cardiac events (a composite of all‐cause death, nonfatal myocardial infarction, and ischemic stroke) were compared as the secondary end point. After 1:2 propensity score matching, the SGLT2 inhibitors group (938 patients) and the no use of SGLT2 inhibitors group (1876 patients) were compared. During a median follow‐up of 2.1 years, the early use of SGLT2 inhibitors was associated with lower risks of both the primary end point (9.8% versus 13.9%; adjusted hazard ratio [HR], 0.68 [95% CI, 0.54–0.87]; P=0.002) and secondary end point (9.1% versus 11.6%; adjusted HR, 0.77 [95% CI, 0.60–0.99]; P=0.04). All‐cause mortality and hospitalizations for heart failure were also significantly lower in early users of SGLT2 inhibitors. Conclusions The early use of SGLT2 inhibitors in patients with diabetes treated with percutaneous coronary intervention for acute myocardial infarction was associated with a significantly lower risk of cardiovascular events, including all‐cause mortality, hospitalizations for heart failure, and major adverse cardiac events.

Intro: Rodent-borne hantaviruses are pathogenic in humans and remain a threat for public health. In Asia, data are available mostly from oriental countries, but limited in South-East Asia. In Cambodia, the presence of hantavirus was reported in rodents since 1998. Nevertheless, burden of infection in humans remains unknown. In our study, we aimed to document the presence and diversity of hantaviruses in rodents and to assess hantavirus seroprevalence in people living in urban and rural settings in Cambodia. Methods: This is a retrospective study conducted using pooled organs collected from 750 rodents in urban and rural settings in 2020 (rainy season) and 2022 (dry season). Concurrently, 788 people working or living at the vicinity of rodent trapping locations were requested for blood collection. Hantavirus RNA in rodents was assessed using RT-PCR and confirmed by Sanger sequencing. Human sera were tested for anti-Thailand hantavirus IgG and IgM using in-house ELISA. Findings: In rodents, hantavirus RNA was detected in 25 (3.3%) caught rodents all originated from urban area. Seoul orthohantavirus was the most predominant virus detected in 23 Rattus norvegicus and 1 Rattus rattus. Thottapalayam virus was detected in one Suncus murinus. In humans, the initial seroprevalence of anti-hantavirus IgG was 10.0% (79/788) in 2020. For 70.4% (555/788) of these study participants, a follow-up blood collection was performed in 2022. Out of these, six (1.1%) individuals turned seroconverted, and one even was positive for hantavirus IgM antibodies. Overall, the hantavirus seroprevalence was significantly higher in urban compared to rural area (13.8% vs. 8.9%, p=0.03). Conclusion: Our findings highlighted a new insight of hantavirus circulation at the rodent-human interface in Cambodia. Additional analyses are ongoing to identify potential factors associated with human exposure to hantavirus. Further investigations are also needed to determine the impact of hantavirus infection on human health in Cambodia.

Parental environments have profound consequences for offspring fitness through transgenerational transmission of resources and epigenetic factors. Locomotor activity is a functional trait of considerable ecological importance, as it determines the ability of animals to find food and mates and to disperse to more favourable environments. Although there have been studies demonstrating that animals can plastically increase their locomotor capacity in response to nutritionally stressful environments, it remains largely unexplored whether and how parental diet can adjust offspring locomotor capacity and its related traits. In this study, we tested the hypothesis that the parental intake of a nutritionally suboptimal diet would induce hyperactivity in the offspring and that this transgenerational effect could lead to improved offspring performance in an insect herbivore, the bean bug (Riptortus pedestris Fabricius) (Hemiptera: Alydidae). We compared the locomotor activity, metabolic phenotype and performance traits of two groups of R. pedestris nymphs born to parents raised on soybeans [Glycine max (L.) Merr, Fabaceae; standard diet] or peanuts (Arachis hypogaea L., Fabaceae; high‐fat diet). Despite being smaller at birth, the offspring of peanut‐fed parents moved faster and more frequently than those of soybean‐fed parents during their early development. The newly hatched offspring born to peanut‐fed parents had higher relative energy reserves in somatic tissues than those born to soybean‐fed parents, indicating that differential parental provisioning could underpin this parental effect on offspring locomotor activity. Possibly through increased foraging activity, the hyperactive offspring of peanut‐fed parents grew faster into heavier adults than the offspring of soybean‐fed parents, implying that parentally induced increase in offspring locomotor activity is adaptive. This study provides experimental evidence for diet‐mediated transgenerational plasticity of locomotor activity in invertebrates and sheds novel insights into the role of parental diet history in shaping offspring phenotype. [ABSTRACT FROM AUTHOR]

Sensory pathways provide complex and multifaceted information to the brain. Recent advances have created new opportunities for applying our understanding of the brain to sensory prothesis development. Yet complex sensor physiology, limited numbers of electrodes, and nonspecific stimulation have proven to be a challenge for many sensory systems. In contrast, the vestibular system is uniquely suited for prosthesis development. Its peripheral anatomy allows site-specific stimulation of 3 separate sensory organs that encode distinct directions of head motion. Accordingly, here, we investigated whether implementing natural encoding strategies improves vestibular prosthesis performance. The eye movements produced by the vestibulo-ocular reflex (VOR), which plays an essential role in maintaining visual stability, were measured to quantify performance. Overall, implementing the natural tuning dynamics of vestibular afferents produced more temporally accurate VOR eye movements. Exploration of the parameter space further revealed that more dynamic tunings were not beneficial due to saturation and unnatural phase advances. Trends were comparable for stimulation encoding virtual versus physical head rotations, with gains enhanced in the latter case. Finally, using computational methods, we found that the same simple model explained the eye movements evoked by sinusoidal and transient stimulation and that a stimulation efficacy substantially less than 100% could account for our results. Taken together, our results establish that prosthesis encodings that incorporate naturalistic afferent dynamics and account for activation efficacy are well suited for restoration of gaze stability. More generally, these results emphasize the benefits of leveraging the brain's endogenous coding strategies in prosthesis development to improve functional outcomes.

Dieser Beitrag bietet einen Überblick über die Aus- und Fortbildung im wissenschaftlichen Bibliothekswesen Österreichs in den Jahren 2020 und 2021.

After a short introduction of the LIS landscape in Austria, the development of LIS education for academic librarians will be discussed. Until 2004 library education in Austria consisted mainly of vocational training to which only university graduates and eventually high-school graduates were admitted. In the nineteen-nineties, with Austria joining the European Union and the creation of universities of applied sciences, LIS education became possible at the university level. For various reasons, the two established LIS programmes were discontinued after a relatively short time period. Major changes in university legislation concerning the legal autonomy of Austrian universities meant, however, that a post-graduate interuniversity library and information studies programme could be launched in 2004. With the fourth revision of the curriculum in 2019, the programme has become even more aligned with international practice in terms of content, didactic methods and flexibility. The increased dynamism in library education has also had an impact on the creation of non-academic training and continuing education programmes.

With determination, zeal, and commitment, American Baptist missionaries arrived in Burma in 1813 and proselytized the ethnic Burman and the ethnic Karen. Whereas their mission efforts among the Burman ended in failure, they converted many Karen to Christianity. This article has explored why they failed among the Burman, but relatively succeeded among the Karen. The thesis of this essay is that American missionaries failed among the Burman, mostly because Buddhism already permeated Burman society for centuries, and that they Christianized many Karen, largely because they still practiced a cosmic religion. [ABSTRACT FROM AUTHOR]

Background: Clustering lifestyle risk behaviors is important for predicting cardiovascular disease risk. However, it is unclear which behavior mediates other ones to influence cardiovascular disease risk. We aimed to assess the causal inference of each lifestyle risk behavior for the atherosclerotic cardiovascular disease (ASCVD) risk of the general population. Methods: We performed a Bayesian network mediation analysis using data from the Korea National Health and Nutrition Examination Survey from 2014 to 2019. The main exposure was a combination of lifestyle risk behaviors including unhealthy weight, heavy alcohol consumption, inadequate sleep, physical inactivity, excessive sodium intake, and current smoking among subjects 40 to 79 years of age. The high risk of ASCVD (≥7.5% for the 10-year risk) was assessed using logistic regression, Bayesian networks, and structural equational models to examine the causal relationships between these six lifestyle risk behaviors. Results: Among all participants, the most prevalent lifestyle risk behavior for those at high risk for ASCVD was excessive sodium intake (95.6%), followed by inadequate sleep (49.9%) and physical inactivity (43.8%). Older age (65–79 years) and male sex were directly associated with a high risk for ASCVD. Physical inactivity, current smoking, excessive sodium intake, and unhealthy weight indirectly mediated the effects of older age (8.2% of the older age) and male sex (39.9% of males) to high ASCVD risk. Physical inactivity, current smoking, excessive sodium intake, and unhealthy weight particularly mediated the high ASCVD risk sequentially. Heavy alcohol consumption and inadequate sleep were not directly associated with high ASCVD risk and did not indirectly mediate the effects of older age and males on the high ASCVD risk. Conclusion: Lifestyle risk behaviors mediated the atherosclerotic cardiovascular disease risk in a different manner. Especially, physical inactivity preceded current smoking, excessive sodium intake, and unhealthy weight in relation to high ASCVD risk, and this causal relationship was different according to age and sex. Therefore, tailored strategies according to specific target populations may be needed to effectively reduce the high ASCVD risk. [ABSTRACT FROM AUTHOR]

Background: Despite the heavy demand for and knowledge of the benefits of diversity, there is a persistent lack of racial, ethnic, and gender diversity in orthopaedic surgery. Since the implementation of diversity initiatives, data have shown that general surgery has been one of the top competitive surgical fields and has demonstrated growth in racial, ethnic, and gender diversity, making general surgery a good point of reference and comparison when analyzing racial and ethnic growth in orthopaedic surgery. Questions/purposes: (1) What were the growth rates for Black and Hispanic orthopaedic residency applicants and residents between 2015 and 2022? (2) How did the growth rates of Black and Hispanic individuals in orthopaedic surgery compare with those of general surgery? (3) How did applicant recruitment and resident acceptance differ between Black and Hispanic people in orthopaedic surgery?. Methods: Applicant data were obtained from historical specialty-specific data from the Association of American Medical Colleges Electronic Residency Application Service Statistics database between 2018 and 2022, and resident data were obtained from the Accreditation Council of Graduate Medical Education Data Resource Book between 2015 and 2021. Between 2018 and 2022, the number of residency applicants totaled 216,677, with 17,912 Black residency applicants and 20,413 Hispanic residency applicants. Between 2015 and 2021, the number of active residents totaled 977,877, with 48,600 Black residents and 62,605 Hispanic residents. Because the applicant and resident data do not overlap throughout all years of observation, a sensitivity analysis of overlapping years (between 2018 and 2021) was conducted to ensure observed trends were consistent and valid throughout the study. All datasets obtained were used to establish the different racial and ethnic proportions of Black and Hispanic residency applicants and residents in four nonsurgical primary care specialties and four surgical subspecialties. A reference slope was created using data from the Association of American Medical Colleges and Accreditation Council of Graduate Medical Education to represent the growth rate for total residency applicants and residents, independently, across all residency specialties reported in each database. This slope was used for comparison among the resident and applicant growth rates for all eight selected specialties. Datapoints were placed into a scatterplot with regression lines, using slope equations to depict rate of growth and R² values to depict linear fit. Applicant growth corresponded to applicant recruitment and resident growth corresponded to resident acceptance. Chi-square tests were used to compare residents and residency applicants for the Black and Hispanic populations, separately. Two-way analysis of variance with a time-by-specialty interaction term (F-test) was conducted to determine differences between growth slopes. Results: There was no difference in the growth rate of Black orthopaedic surgery applicants between 2018 and 2022, and there was no difference in the growth rate of Hispanic orthopaedic surgery applicants (R² = 0.43; p = 0.23 and R² = 0.63; p = 0.11, respectively). However, there was a very slight increase in the growth rate of Black orthopaedic surgery residents between 2015 and 2021, and a very slight increase in the growth rate of Hispanic orthopaedic surgery residents (R² = 0.73; p = 0.02 and R² = 0.79; p = 0.01, respectively). There were no differences in orthopaedic and general surgery rates of growth for Black applicants between 2018 and 2022 (0.004 applicants/year versus -0.001 applicants/year; p = 0.22), and no differences were found in orthopaedic and general surgery rates of growth for Black residents between 2015 and 2021 (0.003 residents/year versus 0.002 residents/year; p = 0.59). Likewise, Hispanic orthopaedic applicant growth rates did not differ between 2018 and 2022 from the rates of general surgery (0.004 applicants/year versus 0.005 applicants/year; p = 0.68), and there were no differences in orthopaedic and general surgery rates of growth for Hispanic residents (0.007 residents/year versus 0.01 residents/year; p = 0.35). Furthermore, growth rate comparisons between Black orthopaedic applicants and residents between 2018 and 2021 showed applicant growth was larger than resident growth, illustrating that the recruitment of Black applicants increased slightly more rapidly than resident acceptance. Growth rate comparisons between Hispanic applicants and residents showed a larger rate of resident growth, illustrating Hispanic resident acceptance increased slightly faster than applicant recruitment during that time. Conclusion: We found low acceptance of Black residents compared with the higher recruitment of Black applicants, as well as overall low proportions of Black and Hispanic applicants and residents. Future studies might explore the factors contributing to the higher acceptances of Hispanic orthopaedic residents than Black orthopaedic residents. Clinical Relevance: We recommend that more emphasis should be placed on increasing Black and Hispanic representation at the department level to ensure cultural considerations remain at the forefront of applicant recruitment. Internal or external reviews of residency selection processes should be considered, and more immersive, longitudinal orthopaedic surgery clerkships and research mentorship experiences should be targeted toward Black and Hispanic students. Holistic reviews of applications and selection processes should be implemented to produce an increased racially and ethnically diverse applicant pool and a diverse residency work force, and implicit bias training should be implemented to address potential biases and diversity barriers that are present in residency programs and leadership. [ABSTRACT FROM AUTHOR]

Dieser Beitrag bietet einen Überblick über die Aus- und Fortbildung im wissenschaftlichen Bibliothekswesen Österreichs in den Jahren 2019 und 2020.