Direct comparison of antibody responses to four SARS-CoV-2 vaccines in Mongolia.

Different SARS-CoV-2 vaccines are approved in various countries, but few direct comparisons of the antibody responses they stimulate have been reported. We collected plasma specimens in July 2021 from 196 Mongolian participants fully vaccinated with one of four COVID-19 vaccines: Pfizer/BioNTech, AstraZeneca, Sputnik V, and Sinopharm. Functional antibody testing with a panel of nine SARS-CoV-2 viral variant receptor binding domain (RBD) proteins revealed marked differences in vaccine responses, with low antibody levels and RBD-ACE2 blocking activity stimulated by the Sinopharm and Sputnik V vaccines in comparison to the AstraZeneca or Pfizer/BioNTech vaccines. The Alpha variant caused 97% of infections in Mongolia in June and early July 2021. Individuals who recover from SARS-CoV-2 infection after vaccination achieve high antibody titers in most cases. These data suggest that public health interventions such as vaccine boosting, potentially with more potent vaccine types, may be needed to control COVID-19 in Mongolia and worldwide.

Operculo-insular and anterior cingulate plasticity induced by transcranial magnetic stimulation in the human motor cortex: a dynamic casual modeling study.

The ability to induce neuroplasticity with noninvasive brain stimulation techniques offers a unique opportunity to examine the human brain systems involved in pain modulation. In experimental and clinical settings, the primary motor cortex (M1) is commonly targeted to alleviate pain, but its mechanism of action remains unclear. Using dynamic causal modeling (DCM) and Bayesian model selection (BMS), we tested seven competing hypotheses about how transcranial magnetic stimulation (TMS) modulates the directed influences (or effective connectivity) between M1 and three distinct cortical areas of the medial and lateral pain systems, including the insular cortex (INS), anterior cingulate cortex (ACC), and parietal operculum cortex (PO). The data set included a novel fMRI acquisition collected synchronously with M1 stimulation during rest and while performing a simple hand motor task. DCM and BMS showed a clear preference for the fully connected model in which all cortical areas receive input directly from M1, with facilitation of the connections INS→M1, PO→M1, and ACC→M1, plus increased inhibition of their reciprocal connections. An additional DCM analysis comparing the reduced models only corresponding to networks with a sparser connectivity within the full model showed that M1 input into the INS is the second-best model of plasticity following TMS manipulations. The results reported here provide a starting point for investigating whether pathway-specific targeting involving M1↔INS improves analgesic response beyond conventional targeting. We eagerly await future empirical data and models that tests this hypothesis.NEW & NOTEWORTHY Transcranial magnetic stimulation of the primary motor cortex (M1) is a promising treatment for chronic pain, but its mechanism of action remains unclear. Competing dynamic causal models of effective connectivity between M1 and medial and lateral pain systems suggest direct input into the insular, anterior cingulate cortex, and parietal operculum. This supports the hypothesis that analgesia produced from M1 stimulation most likely acts through the activation of top-down processes associated with intracortical modulation.

Sensitivity and specificity of commercially available rapid diagnostic tests for viral hepatitis B and C screening in serum samples.

Early diagnosis of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is pivotal for optimal disease management. Sensitivity and specificity of 19 rapid diagnostic test (RDT) kits by different manufacturers (ABON, CTK Biotech, Cypress Diagnostics, Green Gross, Human Diagnostic, Humasis, InTec, OraSure, SD Bioline, Wondfo) were assessed on serum samples of 270 Mongolians (90 seropositive for hepatitis B surface antigen (HBsAg), 90 seropositive for hepatitis C antibody (HCV-Ab), 90 healthy subjects). All tested RDTs for detection of HBsAg performed with average sensitivities and specificities of 100% and 99%, respectively. Albeit, overall sensitivity and specificity of RDTs for detection of HCV-Ab was somewhat lower compared to that of HBsAg RDTs (average sensitivity 98.9%, average specificity 96.7%). Specificity of RDTs for detection of HCV-Ab was dramatically lower among HBsAg positive individuals, who were 10.2 times more likely to show false positive test results. The results of our prospective study demonstrate that inexpensive, easy to handle RDTs are a promising tool in effective HBV- and HCV-screening especially in resource-limited settings.

Modulating Brain Networks With Transcranial Magnetic Stimulation Over the Primary Motor Cortex: A Concurrent TMS/fMRI Study.

Stimulating the primary motor cortex (M1) using transcranial magnetic stimulation (TMS) causes unique multisensory experience such as the targeted muscle activity, afferent/reafferent sensory feedback, tactile sensation over the scalp and "click" sound. Although the human M1 has been intensively investigated using TMS, the experience of the M1 stimulation has not been elucidated at the whole brain. Here, using concurrent TMS/fMRI, we investigated the acute effect of the M1 stimulation of functional brain networks during task and at rest. A short train of 1 Hz TMS pulses applied to individuals' hand area in the M1 during motor execution or at rest. Employing the independent component analysis (ICA), we showed the M1 stimulation decreased the motor networks activity when the networks were engaged in the task and increased the deactivation of networks when the networks were not involved in the ongoing task. The M1 stimulation induced the activation in the key networks involved in bodily self-consciousness (BSC) including the insular and rolandic operculum systems regardless of states. The degree of activation in these networks was prominent at rest compared to task conditions, showing the state-dependent TMS effect. Furthermore, we demonstrated that the M1 stimulation modulated other domain-general networks such as the default mode network (DMN) and attention network and the inter-network connectivity between these networks. Our results showed that the M1 stimulation induced the widespread changes in the brain at the targeted system as well as non-motor, remote brain networks, specifically related to the BSC. Our findings shed light on understanding the neural mechanism of the complex and multisensory experience of the M1 stimulation.

Hypertension prevalence and control in Ulaanbaatar, Mongolia.

This study examines the prevalence, awareness, treatment, and control of hypertension in Ulaanbaatar, Mongolia, using both the American Heart Association and conventional thresholds (130/80 and 140/90 mm Hg, respectively). In this randomized cross-sectional study, two-stage cluster sampling was used to obtain a sample of 4515 individuals aged ≥20 years. Hypertension was defined by the use of antihypertensives in the last 2 weeks or a blood pressure at or above the thresholds of 140/90 and 130/80 mm Hg. The mean age of the participants was 41.1 ± 14.0 years and 54.5% were women. Hypertension prevalence was 25.6% (using 140/90 mm Hg) and 46.5% (using 130/80 mm Hg). Prevalence increased with age and below 50 years men were consistently more likely to be hypertensive. Among hypertensive participants, the rates of awareness, treatment, and control were 69.7%, 46.8%, and 24.0% (using 140/90 mm Hg) and 49.1%, 25.8%, and 6.4% (using 130/80 mm Hg, respectively). Men had lower rates of awareness, treatment, and control compared with women, with the most pronounced differences at younger ages. This study shows that awareness, treatment, and control rates in Ulaanbaatar are better than in most low- and middle-income countries but are still suboptimal. The largest "care gap" was in young men where a regulatory requirement for annual workplace blood pressure screening has the potential to enhance care. A major hypertension control program has just been initiated in Ulaanbaatar.

Hypertension knowledge, attitudes, and practices of nurses and physicians in primary care in Ulaanbaatar Mongolia.

Increased blood pressure is a leading risk for death globally, and interventions to enhance hypertension control have become a high priority. An important aspect of clinical interventions is understanding the knowledge, attitudes, and practices (KAP) of differing primary healthcare practitioners. We examined KAP surveys from 803 primary care practitioners in Ulaanbaatar, Mongolia (response rate 80%), using a comprehensive KAP survey developed by the World Hypertension League (WHL). The WHL KAP survey uniquely includes an assessment of key World Health Organization recommended interventions to enhance hypertension control. There were few substantive differences between healthcare professional disciplines. Primary care practitioners mostly had a positive attitude toward hypertension management. However, confidence and practice in performing specific tasks to control hypertension were suboptimal. A low proportion indicated they systematically screened adults for hypertension and many were not aware of the need to or were confident in prescribing more than two antihypertensive medications. It was the practice of a high proportion of doctors to not pharmacologically treat most people with hypertension who were at high cardiovascular risk. There was a reluctance by physicians to task share hypertension diagnosis, drug prescribing and assessing cardiovascular risk to nurses. The minority of health care professions use a hypertension management algorithm, and few have patient registries with performance reporting functions. There were few substantive differences based on the age, gender, and years of clinical practice of the practitioners. The study findings support the need for standardized education and training of primary care practitioners in Ulaanbaatar to enhance hypertension control.

Hypertension, knowledge, attitudes, and practices of primary care physicians in Ulaanbaatar, Mongolia.

We examined the knowledge, attitudes, and practices of primary care doctors in Ulaanbaatar, Mongolia using a recently developed World Hypertension League survey. The survey was administered as part of a quality assurance initiative to enhance hypertension control. A total of 577 surveys were distributed and 467 were completed (81% response rate). The respondents had an average age of 35 years and 90.1% were female. Knowledge of hypertension epidemiology was low (13.5% of questions answered correctly); 31% of clinical practice questions had correct answers and confidence in performing specific tasks to improve hypertension control had 63.2% "desirable/correct" answers. Primary care doctors mostly had a positive attitude toward hypertension management (76.5% desirable/correct answers) and highly prioritized hypertension management activities (85.7% desirable/correct answers). Some important highlights included the majority (> 80%) overestimating hypertension awareness, treatment, and control rates; 78.2% used aneroid blood pressure manometers; 15% systematically screened adults for hypertension in their clinics; 21.8% reported 2 or more drugs were required to control hypertension in most people; and 16.1% reported most people could be controlled by lifestyle changes alone. 55% of respondents were not comfortable prescribing more than 1 or 2 antihypertensive drugs in a patient and the percentage of desirable/correct responses to treating various high-risk patients was low. Most (53%-74%) supported task shifting to nonphysician health care providers except for drug prescribing, which only 13.9% supported. A hypertension clinical education program is currently being designed based on the specific needs identified in the survey.

Where does TMS Stimulate the Motor Cortex? Combining Electrophysiological Measurements and Realistic Field Estimates to Reveal the Affected Cortex Position.

Much of our knowledge on the physiological mechanisms of transcranial magnetic stimulation (TMS) stems from studies which targeted the human motor cortex. However, it is still unclear which part of the motor cortex is predominantly affected by TMS. Considering that the motor cortex consists of functionally and histologically distinct subareas, this also renders the hypotheses on the physiological TMS effects uncertain. We use the finite element method (FEM) and magnetic resonance image-based individual head models to get realistic estimates of the electric field induced by TMS. The field changes in different subparts of the motor cortex are compared with electrophysiological threshold changes of 2 hand muscles when systematically varying the coil orientation in measurements. We demonstrate that TMS stimulates the region around the gyral crown and that the maximal electric field strength in this region is significantly related to the electrophysiological response. Our study is one of the most extensive comparisons between FEM-based field calculations and physiological TMS effects so far, being based on data for 2 hand muscles in 9 subjects. The results help to improve our understanding of the basic mechanisms of TMS. They also pave the way for a systematic exploration of realistic field estimates for dosage control in TMS.

A novel quantitative microarray antibody capture assay identifies an extremely high hepatitis delta virus prevalence among hepatitis B virus-infected mongolians.

Hepatitis delta virus (HDV) causes the most severe form of human viral hepatitis. HDV requires a hepatitis B virus (HBV) coinfection to provide HDV with HBV surface antigen envelope proteins. The net effect of HDV is to make the underlying HBV disease worse, including higher rates of hepatocellular carcinoma. Accurate assessments of current HDV prevalence have been hampered by the lack of readily available and reliable quantitative assays, combined with the absence of a Food and Drug Administration-approved therapy. We sought to develop a convenient assay for accurately screening populations and to use this assay to determine HDV prevalence in a population with abnormally high rates of hepatocellular carcinoma. We developed a high-throughput quantitative microarray antibody capture assay for anti-HDV immunoglobulin G wherein recombinant HDV delta antigen is printed by microarray on slides coated with a noncontinuous, nanostructured plasmonic gold film, enabling quantitative fluorescent detection of anti-HDV antibody in small aliquots of patient serum. This assay was then used to screen all HBV-infected patients identified in a large randomly selected cohort designed to represent the Mongolian population. We identified two quantitative thresholds of captured antibody that were 100% predictive of the sample either being positive on standard western blot or harboring HDV RNA detectable by real-time quantitative PCR. Subsequent screening of the HBV+ cohort revealed that a remarkable 57% were RNA+ and an additional 4% were positive on western blot alone. CONCLUSION: The quantitative microarray antibody capture assay's unique performance characteristics make it ideal for population screening; its application to the Mongolian HBV surface antigen-positive population reveals an apparent ∼60% prevalence of HDV coinfection among these HBV-infected Mongolian subjects, which may help explain the extraordinarily high rate of hepatocellular carcinoma in Mongolia. (Hepatology 2017;66:1739-1749).

Vertex Stimulation as a Control Site for Transcranial Magnetic Stimulation: A Concurrent TMS/fMRI Study.

BACKGROUND: A common control condition for transcranial magnetic stimulation (TMS) studies is to apply stimulation at the vertex. An assumption of vertex stimulation is that it has relatively little influence over on-going brain processes involved in most experimental tasks, however there has been little attempt to measure neural changes linked to vertex TMS. Here we directly test this assumption by using a concurrent TMS/fMRI paradigm in which we investigate fMRI blood-oxygenation-level-dependent (BOLD) signal changes across the whole brain linked to vertex stimulation. METHODS: Thirty-two healthy participants to part in this study. Twenty-one were stimulated at the vertex, at 120% of resting motor threshold (RMT), with short bursts of 1 Hz TMS, while functional magnetic resonance imaging (fMRI) BOLD images were acquired. As a control condition, we delivered TMS pulses over the left primary motor cortex using identical parameters to 11 other participants. RESULTS: Vertex stimulation did not evoke increased BOLD activation at the stimulated site. By contrast we observed widespread BOLD deactivations across the brain, including regions within the default mode network (DMN). To examine the effects of vertex stimulation a functional connectivity analysis was conducted. CONCLUSION: The results demonstrated that stimulating the vertex with suprathreshold TMS reduced neural activity in brain regions related to the DMN but did not influence the functional connectivity of this network. Our findings provide brain imaging evidence in support of the use of vertex simulation as a control condition in TMS but confirm that vertex TMS induces regional widespread decreases in BOLD activation.

Comparative incidence rates of mild adverse effects to transcranial magnetic stimulation.

OBJECTIVES: Past research has largely neglected to investigate mild adverse effects (MAEs) to transcranial magnetic stimulation (TMS), including headache and nausea. Here we explored the relationship between MAEs, participant characteristics (age and gender) and protocol parameters, including mode of application, coil geometry, stimulated brain region, TMS frequency, TMS intensity, and active vs. sham stimulation. METHODS: Data from 1270 standard post-monitoring forms was obtained from 113 healthy participants. Analyses aimed to identify the risk factors associated with MAE reports and specific symptoms. RESULTS: The overall rate of MAEs across TMS sessions was ∼5%, with ∼78% of symptoms occurring post-session. Initial TMS sessions were followed by a higher MAE incidence rate relative to later testing sessions. No associations between participant characteristics, TMS frequency, or intensity were observed. CONCLUSIONS: TMS-related MAEs are relatively common and may be exacerbated by initial expectations or anxieties of participants. A significant proportion of MAEs may reflect reporting of coincidental phenomena that are unrelated to TMS. Recommendations for future safety studies are proposed and monitoring documentation is provided. SIGNIFICANCE: Our findings illustrate the importance of standardized monitoring of MAEs. Such research aids our understanding of how MAEs arise and may lead to interventions for reducing their incidence.

On the importance of specialized radiofrequency filtering for concurrent TMS/MRI.

The concurrent application of TMS and MRI is challenging due to the MR-image artifacts, which are produced by using the two techniques in combination. One such artifact arises from the introduction of radio frequency noise through the lead of the TMS-coil into the scanner. Here we describe four methods used in the literature to integrate TMS into the MR environment and quantify in detail the efficacy of one approach in filtering RF interference. We show that RF filtering has a dramatic effect on the overall signal-to-fluctuation-noise ratio (SfNR) of the acquired echo-planar imaging data. The reduction in SfNR when integrating a TMS system into the MR scanner varies from 20% up to 80% (compared with MR scanner in the absence of TMS system), depending on the configuration used. Using an RF-filter in-line with the TMS-coil eliminates much of this loss in SfNR. However the RF filter also causes a ∼7% decrease in the functional efficacy of TMS. Overall, this study highlights the importance of RF-filtering when designing and installing a concurrent TMS/MRI system.

Reducing image artefacts in concurrent TMS/fMRI by passive shimming.

A significant problem in the concurrent application of transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) is the image artefact caused by the effect of the TMS-coil on the homogeneity of the static magnetic field (B0). The resulting field inhomogeneity can lead to spatial distortions and local signal loss in echo-planar (EP) images. Here we demonstrate that passive shimming using thin patches of austenitic stainless steel can reduce the effect of the TMS-coil on B0 by ~80%, thus essentially eliminating the associated artefact. Initially the effect of the TMS-coil on B0 was measured using the phase of gradient echo images. Consequently the ideal distribution for the steel was simulated using the magnetic properties of the steel and the effects of the TMS-coil. Finally we demonstrate the effect of two different implementations of the passive shim on a spherical phantom and in vivo.