不同年龄阿尔茨海默病患者脑核团ADC值与年龄的相关性

目的 探讨不同年龄阿尔茨海默病（AD）患者ADC值与年龄的相关性。方法 选取30例AD患者（AD组）和年龄与之相匹配的30名志愿者（对照组），按年龄段各分为6个亚组[55~59岁（n=3）、60~64岁（n=4）、65~70岁（n=9）、71~74岁（n=5）、75~80岁（n=6）、>80岁（n=3）]，测量双侧海马、红核、尾状核、杏仁体、壳核ADC值，并进行配对t检验、独立样本t检验、单因素方差分析及Pearson相关分析。结果 AD组红核左、右侧ADC值有统计学差异（P=0.022）。AD组不同年龄亚组右侧海马、双侧尾状核、右侧壳核ADC值差异有统计学意义（P均<0.05）；2组不同年龄亚组双侧海马、壳核、尾状核ADC值差异有统计学意义（P均<0.05）。AD组右侧海马（r=0.615，P<0.001）、右侧壳核（r=0.653，P=0.001）及双侧尾状核（左侧：r=0.397，P=0.030；右侧：r=0.429，P=0.020）ADC值与年龄呈正相关。结论 AD患者右侧海马和壳核、双侧尾状核ADC值随年龄增加而增大。ADC值可为临床预测和早期诊断AD脑内右侧海马和壳核、双侧尾状核神经退行性病变提供参考。     

Effectiveness of the 10-valent pneumococcal conjugate vaccine against radiographic pneumonia among children in rural Bangladesh: A case-control study

BackgroundPneumococcal conjugate vaccine (PCV) effectiveness against radiographic pneumonia in South Asia is unknown. Bangladesh introduced PCV10 in 2015 using a three dose primary series (3 + 0). We sought to measure PCV10 effectiveness for two or more vaccine doses on radiographic pneumonia among vaccine-eligible children in rural Bangladesh.MethodsWe conducted a matched case-control study over two years from 2015 to 2017 using clinic and community controls in three subdistricts of Sylhet, Bangladesh. Cases were vaccine eligible 3–35 month olds at Upazila Health Complex outpatient clinics with World Health Organization-defined radiographic primary endpoint pneumonia (radiographic pneumonia). Clinic controls were matched to cases within a one week time window by age, sex, and clinic and had an illness unlikely to be Streptococcus pneumoniae; community controls were healthy and similarly matched within a one week time window by age and sex, and distance from the clinic. We estimated adjusted vaccine effectiveness (aVE) using conditional logistic regression.ResultsWe matched 1262 cases with 2707 clinic and 2461 community controls. Overall, aVE using clinic controls was 21.4% (95% confidence interval, −0.2%, 38.4%) for ≥2 PCV10 doses and among 3–11 month olds was 47.3% (10.5%, 69.0%) for three doses. aVE increased with higher numbers of doses in clinic control sets (p = 0.007). In contrast, aVE using community controls was 7.6% (95% confidence interval, −22.2%, 30.0%) for ≥2 doses. We found vaccine introduction in the study area faster and less variable than expected with 75% coverage on average, which reduced power. Information bias may also have affected community controls.ConclusionsClinic control analyses show PCV10 prevented radiographic pneumonia in Bangladesh, especially among younger children receiving three doses. While both analyses were underpowered, community control enrollment – compared to clinic controls – was more difficult in a complex, pluralistic healthcare system. Future studies in comparable settings may consider alternative study designs.     

Generation and preclinical immunogenicity study of dengue type 2 virus-like particles derived from stably transfected mosquito cells

Recent phase IIb/III trials of a tetravalent live attenuated vaccine candidate revealed a need for improvement in the stimulation of protective immunity against diseases caused by dengue type 2 virus (DENV-2). Our attempts to develop particulate antigens for possibly supplementing live attenuated virus preparation involve generation and purification of recombinant DENV-2 virus-like particles (VLPs) derived from stably (prM+E)-expressing mosquito cells. Two VLP preparations generated with either negligible or enhanced prM cleavage exhibited different proportions of spherical particles and tubular particles of variable lengths. In BALB/c mice, VLPs were moderately immunogenic, requiring adjuvants for the induction of strong virus neutralizing antibody responses. VLPs with enhanced prM cleavage induced higher levels of neutralizing antibody than those without, but the stimulatory activity of both VLPs was similar in the presence of adjuvants. Comparison of EDIII-binding antibodies in mice following two adjuvanted doses of these VLPs revealed subtle differences in the stimulation of anti-EDIII binding antibodies. In cynomolgus macaques, VLPs with enhanced prM cleavage augmented strongly neutralizing antibody and EDIII-binding antibody responses in live attenuated virus-primed recipients, suggesting that these DENV-2 VLPs may be useful as the boosting antigen in prime-boost immunization. As the levels of neutralizing antibody induced in macaques with the prime-boost immunization were comparable to those infected with wild type virus, this virus-prime VLP-boost regimen may provide an immunization platform in which a need for robust neutralizing antibody response in the protection against DENV-2-associated illnesses could be tested.     

Novel vaccination strategies and approaches against human tuberculosis

Tuberculosis (TB) remains one of a major health problem worldwide. Tuberculosis vaccine research has made an extraordinary progress over the past few years. However, there is still no replacement for the Bacillus Calmette‐Guérin vaccine, the only TB vaccine licensed for human use. Therefore, the discovery and development of new TB vaccines remains a priority. This article discusses current strategies used to diversify TB vaccines and includes discussion of the status of efforts to improve protection against Mycobacterium tuberculosis (M tb) infection or TB disease by developing new and safe TB vaccines. This article also highlights the current research efforts in immune‐enhancing approaches to improve vaccination efficacy. The development of more effective TB vaccines might have significant impact on global TB control.     

The magnitude and timing of recalled immunity after breakthrough infection is shaped by SARS-CoV-2 variants

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Depression in a Patient With Alzheimer Disease

This is a case study of a 73-year-old woman recently diagnosed with Alzheimer disease living in an assisted living facility who presented to an outpatient behavioral health clinic with her son for evaluation and treatment of depression. This article highlights the presentation of depression (a diagnosis) versus apathy (a symptom of Alzheimer disease) and the need to assess for co-occurring mood disorders that warrant pharmacologic intervention as well as treatment for cognitive decline in Alzheimer disease.     

Rotavirus,vaccine failure or diagnostic error?

Immunochromatography (ICG) is highly used in clinical settings for rotavirus (RV) diagnosis. The specificity of the tests differs by brand type and is not 100%, therefore its use when the prevalence of the disease is low (i.e. in vaccinated children) may result in a proportion of false positive diagnoses.In some areas, vaccine effectiveness studies or surveillance is done using ICG. Our objective was to estimate the validity of ICG test in vaccinated children, and estimate the number of false positive results in the Valencian Region of Spain, where all RV infections are diagnosed using ICG and are not confirmed by PCR.Population based registries were used to identify all results from the RV antigen tests performed between January 2008 and June 2012 in children under 37 months. Hospitalization and vaccination status of the patients were obtained by linking different databases through a unique identification number. The Positive Predictive Value of the ICG test depending on the vaccination status of the child, hospitalization and the rotavirus season was estimated by a Bayesian model of latent classes.Of the 48,833 tests with valid results, 9429 were done in vaccinated children, and of those 3963 (42%) during the rotavirus season. The prevalence of positive results in vaccinated varied from 2.9 to 21.4% of the tests depending on the hospitalization and seasonality. The estimated PPV also varied from 27.1 to 84.6% when stratified by these two parameters. Globally it is calculated that approximately 267 out of the 520 (51.3%) positives in vaccinated children were false positive tests.The large percentage of false positives, due to an excessive number of tests in vaccinated and out of the RV season, if interpreted as vaccine failures, can cause a loss of confidence in the vaccine and lower the estimates of vaccine effectiveness.