The Cellular Characterization of SARS-CoV-2 Spike Protein in Virus-Infected Cells Using the Receptor Binding Domain Binding Specific Human Monoclonal Antibodies.

A human monoclonal antibody panel (PD4, PD5, PD7, SC23, and SC29) was isolated from the B cells of convalescent patients and used to examine the S protein in SARS-CoV-2-infected cells. While all five antibodies bound conformational-specific epitopes within SARS-CoV-2 spike (S) protein, only PD5, PD7, and SC23 were able to bind to the receptor binding domain (RBD). Immunofluorescence microscopy was used to examine the S protein RBD in cells infected with the Singapore isolates SARS-CoV-2/0334 and SARS-CoV-2/1302. The RBD-binders exhibited a distinct cytoplasmic staining pattern that was primarily localized within the Golgi complex and was distinct from the diffuse cytoplasmic staining pattern exhibited by the non-RBD-binders (PD4 and SC29). These data indicated that the S protein adopted a conformation in the Golgi complex that enabled the RBD recognition by the RBD-binders. The RBD-binders also recognized the uncleaved S protein, indicating that S protein cleavage was not required for RBD recognition. Electron microscopy indicated high levels of cell-associated virus particles, and multiple cycle virus infection using RBD-binder staining provided evidence for direct cell-to-cell transmission for both isolates. Although similar levels of RBD-binder staining were demonstrated for each isolate, SARS-CoV-2/1302 exhibited slower rates of cell-to-cell transmission. These data suggest that a conformational change in the S protein occurs during its transit through the Golgi complex that enables RBD recognition by the RBD-binders and suggests that these antibodies can be used to monitor S protein RBD formation during the early stages of infection. IMPORTANCE The SARS-CoV-2 spike (S) protein receptor binding domain (RBD) mediates the attachment of SARS-CoV-2 to the host cell. This interaction plays an essential role in initiating virus infection, and the S protein RBD is therefore a focus of therapeutic and vaccine interventions. However, new virus variants have emerged with altered biological properties in the RBD that can potentially negate these interventions. Therefore, an improved understanding of the biological properties of the RBD in virus-infected cells may offer future therapeutic strategies to mitigate SARS- CoV-2 infection. We used physiologically relevant antibodies that were isolated from the B cells of convalescent COVID-19 patients to monitor the RBD in cells infected with SARS-CoV-2 clinical isolates. These immunological reagents specifically recognize the correctly folded RBD and were used to monitor the appearance of the RBD in SARS-CoV-2-infected cells and identified the site where the RBD first appears.

High-affinity five/six-letter DNA aptamers with superior specificity enabling the detection of dengue NS1 protein variants beyond the serotype identification.

Genetic alphabet expansion of DNA by introducing unnatural bases (UBs), as a fifth letter, dramatically augments the affinities of DNA aptamers that bind to target proteins. To determine whether UB-containing DNA (UB-DNA) aptamers obtained by affinity selection could spontaneously achieve high specificity, we have generated a series of UB-DNA aptamers (KD: 27-182 pM) targeting each of four dengue non-structural protein 1 (DEN-NS1) serotypes. The specificity of each aptamer is remarkably high, and the aptamers can recognize the subtle variants of DEN-NS1 with at least 96.9% amino acid sequence identity, beyond the capability of serotype identification (69-80% sequence identities). Our UB-DNA aptamers specifically identified two major variants of dengue serotype 1 with 10-amino acid differences in the DEN-NS1 protein (352 aa) in Singaporeans' clinical samples. These results suggest that the high-affinity UB-DNA aptamers generated by affinity selection also acquire high target specificity. Intriguingly, one of the aptamers contained two different UBs as fifth and sixth letters, which are essential for the tight binding to the target. These two types of unnatural bases with distinct physicochemical properties profoundly expand the potential of DNA aptamers. Detection methods incorporating the UB-DNA aptamers will facilitate precise diagnoses of viral infections and other diseases.

Multiplex targeted mass spectrometry assay for one-shot flavivirus diagnosis.

Targeted proteomic mass spectrometry is emerging as a salient clinical diagnostic tool to track protein biomarkers. However, its strong analytical properties have not been exploited in the diagnosis and typing of flaviviruses. Here, we report the development of a sensitive and specific single-shot robust assay for flavivirus typing and diagnosis using targeted mass spectrometry technology. Our flavivirus parallel reaction monitoring assay (fvPRM) has the ability to track secreted flaviviral nonstructural protein 1 (NS1) over a broad diagnostic and typing window with high sensitivity, specificity, extendibility, and multiplexing capability. These features, pivotal and pertinent to efficient response toward flavivirus outbreaks, including newly emerging flavivirus strains, circumvent the limitations of current diagnostic assays. fvPRM thus carries high potential in positioning itself as a forerunner in delivering early and accurate diagnosis for disease management.

Engineered NS1 for Sensitive, Specific Zika Virus Diagnosis from Patient Serology.

Dengue virus (DENV) and Zika virus (ZIKV) belong to the Flaviviridae family of viruses spread by Aedes aegypti mosquitoes in tropical and subtropical areas. Accurate diagnostic tests to differentiate the 2 infections are necessary for patient management and disease control. Using characterized ZIKV and DENV patient plasma in a blind manner, we validated an ELISA and a rapid immunochromatographic test for ZIKV detection. We engineered the ZIKV nonstructural protein 1 (NS1) for sensitive serologic detection with low cross reactivity against dengue and developed monoclonal antibodies specific for the ZIKV NS1 antigen. As expected, the serologic assays performed better with convalescent than acute plasma samples; the sensitivity ranged from 71% to 88%, depending on the performance of individual tests (IgM/IgG/NS1). Although serologic tests were generally less sensitive with acute samples, our ZIKV NS1 antibodies were able to complement the serologic tests to achieve greater sensitivity for detecting early infections.

Government trust, perceptions of COVID-19 and behaviour change: cohort surveys, Singapore.

OBJECTIVE: To evaluate how public perceptions and trust in government communications affected the adoption of protective behaviour in Singapore during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We launched our community-based cohort to assess public perceptions of infectious disease outbreaks in mid-2019. After the first case of COVID-19 was reported in Singapore on 23 January, we launched a series of seven COVID-19 surveys to both existing and regularly enrolled new participants every 2 weeks. As well as sociodemographic properties of the participants, we recorded changing responses to judge awareness of the situation, trust in various information sources and perceived risk. We used multivariable logistic regression models to evaluate associations with perceptions of risk and self-reported adopted frequencies of protective behaviour. FINDINGS: Our cohort of 633 participants provided 2857 unique responses during the seven COVID-19 surveys. Most agreed or strongly agreed that information from official government sources (99.1%; 528/533) and Singapore-based news agencies (97.9%; 522/533) was trustworthy. Trust in government communication was significantly associated with higher perceived threat (odds ratio, OR: 2.2; 95% confidence interval, CI: 1.6-3.0), but inversely associated with perceived risk of infection (OR: 0.6; 95% CI: 0.4-0.8) or risk of death if infected (OR: 0.6; 95% CI: 0.4-0.9). Trust in government communication was also associated with a greater likelihood of adopting protective behaviour. CONCLUSION: Our findings show that trust is a vital commodity when managing an evolving outbreak. Our repeated surveys provided real-time feedback, allowing an improved understanding of the interplay between perceptions, trust and behaviour.

Outpatient primary and tertiary healthcare utilisation among public rental housing residents in Singapore.

BACKGROUND: Globally, public housing is utilized to provide affordable housing for low-income households. Studies have shown an association between public housing and negative health outcomes. There is paucity of data pertaining to outpatient primary and tertiary healthcare resources utilization among public rental housing residents in Singapore. METHODS: A retrospective cohort study was performed, involving patients under the care of SingHealth Regional Health System (SHRS) in Year 2012. Healthcare utilization outcomes evaluated included number of outpatient primary and specialist care clinic visits, emergency department visits and hospitalization in Year 2011. Multivariate logistical analyses were used to examine the association between public rental housing and healthcare utilization. RESULTS: Of 147,105 patients, 10,400 (7.1%) patients stayed in public rental housing. There were more elderly (54.8 ± 18.0 vs 49.8 ± 17.1, p < 0.001) and male patients [5279 (50.8%) vs 56,892 (41.6%), p < 0.001] residing in public rental housing. Co-morbidities such as hypertension and hyperlipidemia were more prevalent among public rental housing patients. (p < 0.05). After adjustment for covariates, public rental housing was not associated with frequent outpatient primary care clinic or specialist outpatient clinic attendances (p > 0.05). However, it was associated with increased number of emergency department visits (OR: 2.41, 95% CI: 2.12-2.74) and frequent hospitalization (OR: 1.56, 95% CI: 1.33-1.83). CONCLUSION: Residing in public rental housing was not associated with increased utilization of outpatient healthcare resources despite patients' higher disease burden and frequency of emergency department visits and hospitalizations. Further research is required to elucidate their health seeking behaviours.

Longitudinal Study of Cellular and Systemic Cytokine Signatures to Define the Dynamics of a Balanced Immune Environment During Disease Manifestation in Zika Virus-Infected Patients.

Background: Since its unexpected reemergence, Zika virus (ZIKV) has caused numerous outbreaks globally. This study characterized the host immune responses during ZIKV infection. Methods: Patient samples were collected longitudinally during the acute, convalescence and recovery phases of ZIKV infection over 6 months during the Singapore outbreak in late 2016. Plasma immune mediators were profiled via multiplex microbead assay, while changes in blood cell numbers were determined with immunophenotyping. Results: Data showed the involvement of various immune mediators during acute ZIKV infection accompanied by a general reduction in blood cell numbers for all immune subsets except CD14+ monocytes. Importantly, viremic patients experiencing moderate symptoms had significantly higher quantities of interferon γ-induced protein 10, monocyte chemotactic protein 1, interleukin 1 receptor antagonist, interleukin 8, and placental growth factor 1, accompanied by reduced numbers of peripheral CD8+ T cells, CD4+ T cells, and double-negative T cells. Levels of T-cell associated mediators, including interferon γ-induced protein 10, interferon γ, and interleukin 10, were high in recovery phases of ZIKV infection, suggesting a functional role for T cells. The identification of different markers at specific disease phases emphasizes the dynamics of a balanced cytokine environment in disease progression. Conclusions: This is the first comprehensive study that highlights specific cellular changes and immune signatures during ZIKV disease progression, and it provides valuable insights into ZIKV immunopathogenesis.

MRSA Transmission Dynamics Among Interconnected Acute, Intermediate-Term, and Long-Term Healthcare Facilities in Singapore.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is the most common healthcare-associated multidrug-resistant organism. Despite the interconnectedness between acute care hospitals (ACHs) and intermediate- and long-term care facilities (ILTCFs), the transmission dynamics of MRSA between healthcare settings is not well understood. METHODS: We conducted a cross-sectional study in a network comprising an ACH and 5 closely affiliated ILTCFs in Singapore. A total of 1700 inpatients were screened for MRSA over a 6-week period in 2014. MRSA isolates underwent whole-genome sequencing, with a pairwise single-nucleotide polymorphism (Hamming distance) cutoff of 60 core genome single-nucleotide polymorphisms used to define recent transmission clusters (clades) for the 3 major clones. RESULTS: MRSA prevalence was significantly higher in intermediate-term (29.9%) and long-term (20.4%) care facilities than in the ACH (11.8%) (P < .001). The predominant clones were sequence type [ST] 22 (n = 183; 47.8%), ST45 (n = 129; 33.7%), and ST239 (n = 26; 6.8%), with greater diversity of STs in ILTCFs relative to the ACH. A large proportion of the clades in ST22 (14 of 21 clades; 67%) and ST45 (7 of 13; 54%) included inpatients from the ACH and ILTCFs. The most frequent source of the interfacility transmissions was the ACH (n = 28 transmission events; 36.4%). CONCLUSIONS: MRSA transmission dynamics between the ACH and ILTCFs were complex. The greater diversity of STs in ILTCFs suggests that the ecosystem in such settings might be more conducive for intrafacility transmission events. ST22 and ST45 have successfully established themselves in ILTCFs. The importance of interconnected infection prevention and control measures and strategies cannot be overemphasized.

Mu rhythm suppression demonstrates action representation in pianists during passive listening of piano melodies.

Musicians undergo extensive training which enhances established neural links between auditory and motor areas of the brain. Long-term training develops, strengthens and enables flexibility in these connections allowing proficiency in performance. Previous research has indicated that passive listening of trained music results in the recruitment of premotor areas. It has been argued that this sound-action representation may rely on activity in mirror neuron systems and that these systems are heavily dependent on actual sensorimotor experience. Action observation studies using electroencephalography have associated changes in mu rhythm activity with the mirror neuron system in the visuomotor domain. We aimed to investigate similar effects in the audiomotor domain. We utilised a mu suppression method in our action-listening study to detect involuntary motor coactivation when pianists passively listened to piano melodies. Wavelet analysis revealed sensorimotor mu rhythm suppression while pianists listened passively to piano melodies. Thus, we show that this spectral analysis method can also be used to demonstrate that auditory stimuli can activate the human mirror neuron system when sounds are linked to actions. Mu suppression could be a useful index for further research on action representation and training-induced plasticity.

Ethnic disparities in trauma mortality outcomes.

BACKGROUND: Ethnic disparities in trauma mortality outcomes have been demonstrated in the United States according to the US National Trauma Data Bank. The aim of this study was to determine the effect of race/ethnicity on trauma mortality in Singapore. METHODS: This was a retrospective review of patients aged 18-64 years with an injury severity score (ISS) ≥ 9 in the Trauma Registry of Tan Tock Seng Hospital, a 1,300-bed trauma center in Singapore, from 2006 to 2010. Chinese, Malay, and Indian patients were compared with patients of other ethnic groups. Multiple logistic regression analyses determined differences in survival rates after adjusting for demographics, anatomic and physiologic ISS and revised trauma score, mechanism or type of injury. RESULTS: A total of 4,186 patients (66.4 % of the database) met the inclusion criteria. Most patients were male (76.3 %) and young (mean age 40 years). Using Chinese as the reference group, we found no statistically significant differences in unadjusted or adjusted mortality rates among the ethnic groups. Independent predictors of mortality included age [odds ratio (OR) 1.05, 95 % confidence interval (CI) 1.03-1.06, p < 0.0001], presence of severe head injury (OR 1.75, 95 % CI 1.13-2.69, p = 0.012), and increasing ISS (p < 0.0001). CONCLUSIONS: Ethnicity is not an independent predictor of trauma mortality outcomes in the Singapore population. Our findings contrast with those from the United States, where race/ethnicity (Black and Hispanic) remains a strong independent risk factor for trauma mortality. This study attests to the success of the Singapore health care/trauma system in delivering the same quality of care regardless of ethnicity.

International Counseling Values: Recognizing Valued Approaches Identified by International Counseling Professionals Through Qualitative Inquiry.

People may assume that the counseling profession functions with a shared set of values that promote well-being and mental health to individuals, families, and communities across the globe. Common values, such as described in training programs, ethical codes, and other areas, reflect the approach and direction for providing professional counseling services among counseling professionals throughout the world. The researchers designed this qualitative study using a phenomenological approach to explore how counseling values are experienced and implemented across various cultures. The 16 participants of the study include counseling professionals from different countries to increase representation from eight regions of the world. The researchers recognize valued approaches commonly identified among the participants implementing counseling services, including marital and family counseling, child and school counseling, faith integration, indigenous practices, and person-centered safe spaces. While each of these valued approaches is described in detail, final applications of the data offer proposed steps to improve the advancement of counseling on a global scale, including strategies for transcultural counseling training, resource adaptability, and bilateral development in the profession.

Budget Impact Analysis of Adopting a One-Step Nucleic Acid Amplification Testing (NAAT) Alone Diagnostic Pathway for Clostridioides difficile in Japan Compared to a Two-Step Algorithm with Glutamate Dehydrogenase/Toxin Followed by NAAT.

Clostridioides difficile infection (CDI) is a major healthcare-associated infection that leads to a significant health economic burden in Japan. Using a decision tree model, we evaluated the budget impact of adopting a one-step nucleic acid amplification test (NAAT) alone pathway compared to a two-step diagnostic algorithm with glutamate dehydrogenase (GDH) and toxin antigen, followed by NAAT. The analysis was conducted from the government payer's perspective for 100,000 symptomatic, hospitalized adults requiring a CDI diagnostic test. One-way sensitivity analysis was conducted for all data inputs. The NAAT alone strategy costed JPY 225,886,360 (USD 2,424,714) more, but was more effective, resulting in 1749 more patients accurately diagnosed and 91 fewer deaths compared to the two-step algorithm. Additionally, the NAAT alone pathway costed JPY 26,146 (USD 281) less per true positive CDI diagnosed. The total budget impact, and cost per CDI diagnosed was most sensitive to GDH sensitivity in one-way sensitivity analysis, where a lower GDH sensitivity resulted in greater cost savings with the NAAT alone pathway. Findings from this budget impact analysis can guide the adoption of a NAAT alone pathway for CDI diagnosis in Japan.

Impaired categorical perception of lexical tones in Mandarin-speaking congenital amusics.

The degree to which cognitive resources are shared in the processing of musical pitch and lexical tones remains uncertain. Testing Mandarin amusics on their categorical perception of Mandarin lexical tones may provide insight into this issue. In the present study, a group of 15 amusic Mandarin speakers identified and discriminated Mandarin tones presented as continua in separate blocks. The tonal continua employed were from a high-level tone to a mid-rising tone and from a high-level tone to a high-falling tone. The two tonal continua were made in the contexts of natural speech and of nonlinguistic analogues. In contrast to the controls, the participants with amusia showed no improvement for discrimination pairs that crossed the classification boundary for either speech or nonlinguistic analogues, indicating a lack of categorical perception. The lack of categorical perception of Mandarin tones in the amusic group shows that the pitch deficits in amusics may be domain-general, and this suggests that the processing of musical pitch and lexical tones may share certain cognitive resources and/or processes (Patel 2003, 2008, 2012).

The impact of modifying obsessive-compulsive beliefs about perfectionism.

BACKGROUND AND OBJECTIVES: Cognitive-behavioural models of obsessive-compulsive disorder (OCD) suggest that maladaptive beliefs about perfectionism play a key role in the development and maintenance of OCD. Cognitive-bias modification for interpretation bias (CBM-I) is an experimental procedure that can test this proposed causal relation. METHODS: As such, the current study investigated whether multiple CBM-I sessions administered in different contexts can modify perfectionism biases. Undergraduate students high in OCD-related perfectionism beliefs were randomly allocated to either an experimental (n = 44) or control (n = 44) training condition and completed self-report and behavioural measures of perfectionism and OCD symptoms. RESULTS: As predicted, relative to the control condition, participants in the experimental condition exhibited a significant decrease in perfectionism beliefs, from baseline to after one CBM-I training session, which was maintained at one-week follow-up. Contrary to hypotheses, there were no significant differences between conditions on measures of OCD symptoms and perfectionistic behaviour. LIMITATIONS: Issues with the current study's behavioural measures may have precluded any differences between conditions. CONCLUSIONS: Results underscore the need to further refine cognitive-behavioural models of OCD to understand the precise causal relation between beliefs and symptoms.

Competitive ELISA for a serologic test to detect dengue serotype-specific anti-NS1 IgGs using high-affinity UB-DNA aptamers.

Serologic tests to detect specific IgGs to antigens related to viral infections are urgently needed for diagnostics and therapeutics. We present a diagnostic method for serotype-specific IgG identification of dengue infection by a competitive enzyme-linked immunosorbent assay (ELISA), using high-affinity unnatural-base-containing DNA (UB-DNA) aptamers that recognize the four categorized serotypes. Using UB-DNA aptamers specific to each serotype of dengue NS1 proteins (DEN-NS1), we developed our aptamer-antibody sandwich ELISA for dengue diagnostics. Furthermore, IgGs highly specific to DEN-NS1 inhibited the serotype-specific NS1 detection, inspiring us to develop the competitive ELISA format for dengue serotype-specific IgG detection. Blood samples from Singaporean patients with primary or secondary dengue infections confirmed the highly specific IgG detection of this format, and the IgG production initially reflected the serotype of the past infection, rather than the recent infection. Using this dengue competitive ELISA format, cross-reactivity tests of 21 plasma samples from Singaporean Zika virus-infected patients revealed two distinct patterns: 8 lacked cross-reactivity, and 13 were positive with unique dengue serotype specificities, indicating previous dengue infection. This antigen-detection ELISA and antibody-detection competitive ELISA combination using the UB-DNA aptamers identifies both past and current viral infections and will facilitate specific medical care and vaccine development for infectious diseases.

Cross-sectional study of prevalence and risk factors, and a cost-effectiveness evaluation of screening and preventive treatment strategies for latent tuberculosis among migrants in Singapore.

OBJECTIVES: WHO recommends that low burden countries consider systematic screening and treatment of latent tuberculosis infection (LTBI) in migrants from high incidence countries. We aimed to determine LTBI prevalence and risk factors and evaluate cost-effectiveness of screening and treating LTBI in migrants to Singapore from a government payer perspective. DESIGN: Cross-sectional study and cost-effectiveness analysis. SETTING: Migrants in Singapore. PARTICIPANTS: 3618 migrants who were between 20 and 50 years old, have not worked in Singapore previously and stayed in Singapore for less than a year were recruited. PRIMARY AND SECONDARY OUTCOME MEASURES: Costs, quality-adjusted life-years (QALYs), threshold length of stay, incremental cost-effectiveness ratios (ICERs), cost per active TB case averted. RESULTS: Of 3584 migrants surveyed, 20.4% had positive interferon-gamma release assay (IGRA) results, with the highest positivity in Filipinos (33.2%). Higher LTBI prevalence was significantly associated with age, marital status and past TB exposure. The cost-effectiveness model projected an ICER of S$57 116 per QALY and S$12 422 per active TB case averted for screening and treating LTBI with 3 months once weekly isoniazid and rifapentine combination regimen treatment compared with no screening over a 50-year time horizon. ICER was most sensitive to the cohort's length of stay in Singapore, yearly disease progression rates from LTBI to active TB, followed by the cost of IGRA testing. CONCLUSIONS: For LTBI screening and treatment of migrants to be cost-effective, migrants from high burden countries would have to stay in Singapore for ~50 years. Risk-stratified approaches based on projected length of stay and country of origin and/or age group can be considered.

The remodelling index risk stratifies patients with hypertensive left ventricular hypertrophy.

AIMS: Hypertensive left ventricular hypertrophy (LVH) is associated with increased cardiovascular events. We previously developed the remodelling index (RI) that incorporated left ventricular (LV) volume and wall-thickness in a single measure of advanced hypertrophy in hypertensive patients. This study examined the prognostic potential of the RI in reference to contemporary LVH classifications. METHODS AND RESULTS: Cardiovascular magnetic resonance was performed in 400 asymptomatic hypertensive patients. The newly derived RI (EDV3t, where EDV is LV end-diastolic volume and t is the maximal wall thickness across 16 myocardial segments) stratified hypertensive patients: no LVH, LVH with normal RI (LVHNormal-RI), and LVH with low RI (LVHLow-RI). The primary outcome was a composite of all-cause mortality, acute coronary syndromes, strokes, and decompensated heart failure. LVHLow-RI was associated with increased LV mass index, fibrosis burden, impaired myocardial function and elevated biochemical markers of myocardial injury (high-sensitive cardiac troponin I), and wall stress. Over 18.3 ± 7.0 months (601.3 patient-years), 14 adverse events occurred (2.2 events/100 patient-years). Patients with LVHLow-RI had more than a five-fold increase in adverse events compared to those with LVHNormal-RI (11.6 events/100 patient-years vs. 2.0 events/100 patient-years, respectively; log-rank P < 0.001). The RI provided incremental prognostic value over and above a model consisting of clinical variables, LVH and concentricity; and predicted adverse events independent of clinical variables, LVH, and other prognostic markers. Concentric and eccentric LVH were associated with adverse prognosis (log-rank P = 0.62) that was similar to the natural history of hypertensive LVH (5.1 events/100 patient-years). CONCLUSION: The RI provides prognostic value that improves risk stratification of hypertensive LVH.

Immune cell phenotypes associated with disease severity and long-term neutralizing antibody titers after natural dengue virus infection.

Prior immunological exposure to dengue virus can be both protective and disease-enhancing during subsequent infections with different dengue virus serotypes. We provide here a systematic, longitudinal analysis of B cell, T cell, and antibody responses in the same patients. Antibody responses as well as T and B cell activation differentiate primary from secondary responses. Hospitalization is associated with lower frequencies of activated, terminally differentiated T cells and higher percentages of effector memory CD4 T cells. Patients with more severe disease tend to have higher percentages of plasmablasts. This does not translate into long-term antibody titers, since neutralizing titers after 6 months correlate with percentages of specific memory B cells, but not with acute plasmablast activation. Overall, our unbiased analysis reveals associations between cellular profiles and disease severity, opening opportunities to study immunopathology in dengue disease and the potential predictive value of these parameters.

Impaired sensorimotor integration in focal hand dystonia patients in the absence of symptoms.

BACKGROUND: Functional imaging studies of people with focal hand dystonia (FHD) have indicated abnormal activity in sensorimotor brain regions. Few studies however, have examined FHD during movements that do not provoke symptoms of the disorder. It is possible, therefore, that any differences between FHD and controls are confounded by activity due to the occurrence of symptoms. Thus, in order to characterise impairments in patients with FHD during movements that do not induce dystonic symptoms, we investigated the neural correlates of externally paced finger tapping movements. METHODS: Functional MRI (fMRI) was used to compare patients with FHD to controls with respect to activation in networks modulated by task complexity and hand used to perform simple and complex tapping movements. RESULTS: In the 'complexity network,' patients with FHD showed significantly less activity relative to controls in posterior parietal cortex, medial supplementary motor area (SMA), anterior putamen and cerebellum. In the 'hand network,' patients with FHD showed less activation than controls in primary motor (M1) and somatosensory (S1) cortices, SMA and cerebellum. Conjunction analysis revealed that patients with FHD demonstrated reduced activation in the majority of combined network regions (M1, S1 and cerebellum). CONCLUSION: Dysfunction in FHD is widespread in both complexity and hand networks, and impairments are demonstrated even when performing tasks that do not evoke dystonic symptoms. These results suggest that such impairments are inherent to, rather than symptomatic of, the disorder.

Efficacy and Safety of a New Cosmeceutical Regimen Based on the Combination of Snail Secretion Filtrate and Snail Egg Extract to Improve Signs of Skin Aging.

BACKGROUND: Two extracts derived from the gastropod Cryptomphalus aspersa have been shown to have dermal regeneration properties: SCA® (secretion filtrate) with fibroblast growth factor-like activity and IFC®-CAF (cellular activating factor), a snail egg extract with skin stem cell activation activity. OBJECTIVE: The objectives of this study were to evaluate the synergic antiaging activity and tolerability of SCA and IFC-CAF in a combined regimen compared to vehicle as a placebo control. METHODS: A three-month, single-center, double-blinded, randomized, vehicle-controlled trial assessed the effects of a daily skincare routine divided into two treatment phases, as follows: intensive (1 month) and maintenance (2 months). Fifty women, aged 45-65 years, with signs of photoaging were randomized to receive either the active ingredients (n=30) or vehicle (n=20). Clinical evaluations included objective measurements of barrier function and skin hydration, elasticity, and color/brightness. Subjective assessments were conducted according to the Rao-Goldman and Glogau scales for wrinkles, the Patient Global Assessment (PGA) scale and Investigator Global Assessment (IGA) scale. RESULTS: Subjects in the active treatment group experienced reductions in transepidermal water loss and significant improvements in skin roughness, firmness, and elasticity. Both groups showed significant improvements in fine lines and wrinkles. PGA and IGA assessments indicated greater improvement in the active treatment group. CONCLUSION: The active snail extract treatment appears to be effective in improving signs of skin aging in women 45 to 65 years old. Larger randomized, controlled studies are needed to confirm our results.