Neutralizing antibodies are recognized to be one of the essential elements of the adaptive immune response that must be induced by an effective vaccine against HIV. However, only a limited number of antibodies have been identified to neutralize a broad range of primary isolates of HIV-1 and attempts to induce such antibodies by immunization were unsuccessful. The difficulties to generate such antibodies are mainly due to intrinsic properties of HIV-1 envelope spikes, such as high sequence diversity, heavy glycosylation, and inducible and transient nature of certain epitopes. In vitro neutralizing antibodies are identified using "conventional" neutralization assay which uses phytohemagglutinin (PHA)-stimulated human PBMCs as target cells. Thus, in essence the assay evaluates HIV-1 replication in CD4+ T cells. Recently, several laboratories including us demonstrated that some monoclonal antibodies and HIV-1-specific polyclonal IgG purified from patient sera, although they do not have neutralizing activity when tested by the "conventional" neutralization assay, do exhibit potent and broad neutralizing activity in "unconventional" ways. The neutralizing activity of these antibodies and IgG fractions is acquired through post-translational modifications, through opsonization of virus particles into macrophages and immature dendritic cells (iDCs), or through expression of antibodies on the surface of HIV-1-susceptible cells. This review will focus on recent findings of this area and point out their potential applications in the development of preventive strategies against HIV.

PURPOSE: Upward feedback is becoming more widely used in medical training as a means of quality control. Multiple biases exist, thus the accuracy of upward feedback is debatable. This study aims to identify factors that could influence upward feedback, especially in medical training. METHODS: A systematic review using a structured search strategy was performed. Thirty-five databases were searched. Results were reviewed and relevant abstracts were shortlisted. All studies in English, both medical and non-medical literature, were included. A simple pro-forma was used initially to identify the pertinent areas of upward feedback, so that a focused pro-forma could be designed for data extraction. RESULTS: A total of 204 articles were reviewed. Most studies on upward feedback bias were evaluative studies and only covered Kirkpatrick level 1-reaction. Most studies evaluated trainers or training, were used for formative purposes and presented quantitative data. Accountability and confidentiality were the most common overt biases, whereas method of feedback was the most commonly implied bias within articles. CONCLUSION: Although different types of bias do exist, upward feedback does have a role in evaluating medical training. Accountability and confidentiality were the most common biases. Further research is required to evaluate which types of bias are associated with specific survey characteristics and which are potentially modifiable.
Bias (Epidemiology) ; Confidentiality ; Quality Control ; Social Responsibility

Objective:To investigate the associations of major depressive disorder with coronary heart disease (CHD)and stroke in Chinese adults aged 30 -79 years.Methods:In 2004 -2008,China Ka-doorie Biobank was conducted in 1 0 geographically defined regions (5 urban and 5 rural)of China.A to-tal number of 51 2 891 participants aged 30 -79 years were recruited in the baseline survey.A laptop-based electronic questionnaire was administrated face-to-face by trained health workers,collecting the general demographic and socio-economic status,dietary and other lifestyle behaviours (e.g.smoking,al-cohol drinking,physical activity),medical history and family history of common chronic diseases.Major depressive episodes (MDE)in the past 1 2 months were assessed with the World Health Organization composite international diagnostic interview-short form (CIDI-SF).The physical measurements included the heights and weights,which were used to calculate the body mass indexes (BMI).Chi squared and t test were used to compare the differences in participants characteristics according to their major depressive disorder.Logistic models were employed to estimate the odds ratios (OR)and 95% CI of their major de-pressive disorder with prevalent coronary heart disease and stroke.Results:Among the 51 2 891 partici-pants,3 281 (0.6%)showed an MDE in the preceding 1 2 months,1 5 472 (3.0%)reported prevalent CHD,and 8 884 (1 .7%)reported prevalent stroke.Major depressive disorder was significantly associa-ted with an increased risk of CHD and risk of stroke.Age-and gender-adjusted ORs (95% CI)were 1 . 80 (1 .53 -2.1 2)for CHD and 2.53 (2.09 -3.05)for stroke.The associations were significant after further adjustment for potential confounders,such as other socio-demographic status,smoking,alcohol drinking,physical activity,and BMI,prevalent hypertension,diabetes as well as family history of cardio-vascular diseases (OR =1 .83,95% CI =1 .54 -2.1 8 for CHD;OR =2.1 9,95% CI =1 .79 -2.69 for stroke).Moreover,gender significantly interacted with MDE on prevalent stroke (P for multiplicative in-teraction =0.01 3).The men with an MDE in the past 1 2 months had the highest risk of stroke in the joint analyses of gender and depression disorder (OR =5.02,95% CI =3.70 -6.82).Conclusion:The findings from this large cross-sectional study suggest that the presence of MDE is a risk factor for both CHD and stroke in Chinese adults aged 30 -79 years,but further prospective studies are warranted to validate the results.

Correlation between nonlinear subharmonic scattering of ultrasound contrast agent microbubbles and ambient pressure is expected to be used for local brain tissue pressure monitoring. Although high-frequency ultrasound has achieved high-resolution imaging of intracranial microvessels, the research on high-frequency subharmonic scattering characteristics of microbubbles is insufficient at present, which restricts the research progress of estimating local brain tissue pressure based on high-frequency subharmonic scattering of microbubbles. Therefore, under the excitation of 10 MHz high-frequency ultrasound, the effects of different acoustic pressures and ambient pressures on the high-frequency subharmonic scattering characteristics of three different ultrasound contrast agents including SonoVue, Sonazoid and Huashengxian were investigated in this in vitro study. Results showed that the subharmonic scattering amplitudes of the three microbubbles increased with the increase of ambient pressure at the peak negative acoustic pressures of 696, 766 and 817 kPa, and there was a favorable linear correlation between subharmonic amplitude and ambient pressure. Under the above three acoustic pressures, the highest correlation coefficient of SonoVue was 0.948 ( P = 0.03), the highest sensitivity of pressure measurement was 0.248 dB/mm Hg and the minimum root mean square error (RMSE) was 2.64 mm Hg. Sonazoid's highest correlation coefficient was 0.982 ( P < 0.01), the highest sensitivity of pressure measurement was 0.052 dB/mm Hg and the minimum RMSE was 1.51 mm Hg. The highest correlation coefficient of Huashengxian was 0.969 ( P = 0.02), the highest sensitivity of pressure measurement was 0.098 dB/mm Hg and the minimum RMSE was 2.00 mm Hg. The above in vitro experimental results indicate that by selecting ultrasound contrast agent microbubbles and optimizing acoustic pressure, the correlation between high-frequency subharmonic scattering of microbubbles and ambient pressure can be improved, the sensitivity of pressure measurement can be upgraded, and the measurement error can be reduced to meet the clinical demand for local brain tissue pressure measurement, which provided an important experimental basis for subsequent research in vivo.
Contrast Media ; Microbubbles ; Ultrasonography/methods*

OBJECTIVETo examine the socio-demographic patterns on 12-month major depressive episodes (MDE) among Chinese adults aged 30-79 years.

METHODSSocio-demographic variables from half a million Chinese people aged 30-79 years in the China Kadoorie Biobank study during 2004-2008, were collected. For those showing signs of depression, an additional World Health Organization Composite International Diagnostic Interview-Short Form (CIDI-SF) was face to face administrated, to assess the MDE according to Diagnostic and Statistical Manual of Mental Disorder (DSM)- IV criteria. Chi squared and non-parametric tests were used to compare the differences between socio-demographic categories, depressive symptoms and help-seeking behaviors. Associations with MDE for socio-demographic variables were examined by logistic models.

RESULTSA total of 3 281(6.40‰) studied subjects showed an MDE in the preceding 12 months. Gender, marital status, occupation and household income were correlated with MDE. Somatization was common in Chinese MDE patients while symptoms as weight change (99.91%), sleeping disorder (83.60%) and feeling tired (81.59%), stood for the top 3. As for each episode, the proportions and the total number of depressive symptoms appeared higher among females (P < 0.05). One third of the patients did not seek for any social support or psychotherapy with only 8.99% had ever taken antidepressant drugs.

CONCLUSIONRates of depression varied significantly between social groups in Chinese adults aged 30-79. In this study, only 65.19% of the MDE patients ever has sought help or received treatment.

Adult ; Aged ; China ; epidemiology ; Demography ; Depression ; Depressive Disorder, Major ; epidemiology ; psychology ; Diagnostic and Statistical Manual of Mental Disorders ; Female ; Humans ; Logistic Models ; Middle Aged

OBJECTIVE: To design and fabricate edentulous custom trays by chair-side computer-aided design and 3-dimensional printing (CAD/3DP) system of independent research and development and to evaluate their clinical effects based on prosthodontists'satisfaction using the visual analogue scale (VAS). METHODS: Fifteen edentulous patients were randomly recruited by three prosthodontists who passed the unified operating process training. The custom trays for each patient were fabricated using both chair-side CAD/3DP system of independent development and manually conventional method, and the final impressions were made by silicone impression materials (light body). The prosthodontist's satisfaction was surveyed by the three prosthodontists via the questionnaire based on visual analogue scales. RESULTS: In the degree of the prosthodontist's satisfaction of final impressions, the average satisfactions of "try in" (the overall size, shape, convenience, etc.) on the 3DP custom tray made by independent development chair-side system and the manually conventional method were 9.18±0.19 and 8.23±0.22, respectively. The average satisfactions of the border line position (border extensions, frenal notch)were 8.91±0.40 and 7.96±0.23, respectively. The average satisfactions of the stability in border molding were 8.80±0.83 and 8.01±0.81, respectively. The average satisfactions of the quality of final impression (completeness, thickness of impression material, exposure of custom tray, shape of border) were 8.94±0.68 and 7.99±0.42, respectively. The average satisfactions of the difficulty of high quality impression (times of repetition, efficiency) were 9.20±0.37 and 7.88±0.22, respectively. The average satisfactions of the overall satisfaction were 9.11±0.49 and 7.95±0.15, respectively. There was significant difference in the satisfaction of "try in", border line position, stability in border molding, quality of final impression, difficulty of high quality impression, and overall satisfaction between the 3DP custom tray made by chair-side system of independent development and the manually conventional method (P<0.05). CONCLUSION In the degree of the prosthodontist's satisfaction of final impression, the 3DP custom tray made by chair-side system of independent development is higher than that of the conventional custom tray, and it meets the clinical requirements and can be popularized in clinical application.
Computer-Aided Design ; Dental Impression Materials ; Dental Impression Technique ; Humans ; Mouth, Edentulous ; Printing, Three-Dimensional

Oligodontia is the congenital absence of six or more teeth and comprises the more severe forms of tooth agenesis. Many genes have been implicated in the etiology of tooth agenesis, which is highly variable in its clinical presentation. The purpose of this study was to identify associations between genetic mutations and clinical features of oligodontia patients. An online systematic search of papers published from January 1992 to June 2021 identified 381 oligodontia cases meeting the eligibility criteria of causative gene mutation, phenotype description, and radiographic records. Additionally, ten families with oligodontia were recruited and their genetic etiologies were determined by whole-exome sequence analyses. We identified a novel mutation in WNT10A (c.99_105dup) and eight previously reported mutations in WNT10A (c.433 G > A; c.682 T > A; c.318 C > G; c.511.C > T; c.321 C > A), EDAR (c.581 C > T), and LRP6 (c.1003 C > T, c.2747 G > T). Collectively, 20 different causative genes were implicated among those 393 cases with oligodontia. For each causative gene, the mean number of missing teeth per case and the frequency of teeth missing at each position were calculated. Genotype-phenotype correlation analysis indicated that molars agenesis is more likely linked to PAX9 mutations, mandibular first premolar agenesis is least associated with PAX9 mutations. Mandibular incisors and maxillary lateral incisor agenesis are most closely linked to EDA mutations.
Humans ; Phenotype ; Wnt Proteins