Evaluation of the HIV-1 Polymerase Gene Sequence Diversity for Prediction of Recent HIV-1 Infections Using Shannon Entropy Analysis

HIV-1 incidence is an important parameter for assessing the impact of HIV-1 interventions. The aim of this study was to evaluate HIV-1 polymerase (pol) gene sequence diversity for the prediction of recent HIV-1 infections. Complete pol Sanger sequences obtained from 45 participants confirmed to have recent or chronic HIV-1 infection were used. Shannon entropy was calculated for amino acid (aa) sequences for the entire pol and for sliding windows consisting of 50 aa each. Entropy scores for the complete HIV-1 pol were significantly higher in chronic compared to recent HIV-1 infections (p < 0.0001) and the same pattern was observed for some sliding windows (p-values ranging from 0.011 to <0.001), leading to the identification of some aa mutations that could discriminate between recent and chronic infection. Different aa mutation groups were assessed for predicting recent infection and their performance ranged from 64.3% to 100% but had a high false recency rate (FRR), which was decreased to 19.4% when another amino acid mutation (M456) was included in the analysis. The pol-based molecular method identified in this study would not be ideal for use on its own due to high FRR; however, this method could be considered for complementing existing serological assays to further reduce FRR.     

一侧大脑中动脉高密度征对脑梗塞早期诊断价值的探讨

目的提高对一侧大脑中动脉高密度征的认识,探讨其在早期脑梗死诊断中的价值.方法9例患者均做了发病早期(1～6 h)CT扫描及发病后24小时CT扫描,其中男性7例,女性2例,年龄46～68岁,平均58岁,所有病例均经临床诊断.结果9例一侧大脑中动脉梗死患者回顾性CT资料分析,发现发病早期(1～6 h)CT检查均见一侧大脑中动脉高密度征,发病后24 h复查,该侧大脑中动脉血供区均呈大片状低密度灶.结论一侧大脑中动脉高密度征,结合典型的临床表现,在早期脑动脉梗死诊断中具有重要意义.     

CT与MRI对成人型环状胰腺诊断的对比分析

目的：探讨成人型环状胰腺的计算机体层成像（computed tomography,CT）及磁共振成像（magnetic resonance imaging,MRI）表现,以提高对该病的认识。方法：回顾性分析我院6例成人型环状胰腺病例,其中3例行CT腹部平扫及增强扫描;另外3例行MRI腹部平扫及增强扫描,1例结合磁共振胰胆管成像（magnetic resonance cholangiopancreatography,MRCP）检查。详细分析每例影像学图像表现,最终诊断由2位高年资医师盲法观察,得出共同结果。结果：CT及MRI能显示环状胰腺直接征象和间接征象,6例均能显示直接征象,即胰头增大,呈环形包绕十二指肠,2例能清楚显示环状部胰管走行。间接征象包括肝内胆管扩张（2例）、胆总管扩张（3例）、胰管扩张（4例）、胰腺炎（1例）、胆囊炎（1例）。结论：CT平扫及增强检查显示成人型环状胰腺图像清晰。     

胰岛素瘤动态三期增强CT和18F-FDG PET/CT影像分析

目的 探讨胰岛素瘤MSCT动态三期增强及¹⁸F-FDG PET/CT显像的影像学特点。方法 回顾性分析我院6例经手术病理证实的胰岛素瘤的临床资料和¹⁸F-FDG PET/CT及同机MSCT动态三期增强影像资料。结果 6例患者均有不同程度低血糖发作病史和典型的惠普尔三联征,其中2例以精神症状首诊。全部病例空腹或发作时血糖均<2.8 mmol/L,胰岛素释放指数均>0.3。6例胰岛素瘤均为单发,1例位于胰尾,2例位于胰体,3例位于胰头,肿瘤直径0.8 cm×0.9 cm~3.0 cm×3.8 cm,平均1.6 cm×1.6 cm。CT平扫肿瘤呈均匀等或稍低密度,边界不清;增强扫描动脉期呈明显均匀强化,静脉期及延迟期强化程度逐渐减低,动脉期强化最为显著。6例患者中,5例肿瘤局部¹⁸F-FDG摄取未见增高,1例多发性内分泌肿瘤1型(MEN 1)相关胰岛素瘤局部¹⁸F-FDG摄取增高,SUV_max＝4.8。结论 MSCT动态三期增强扫描可清晰显示肿瘤的形态和位置,¹⁸F-FDG PET/CT对本病诊断价值有限。     

Real-time forecasting of COVID-19 bed occupancy in wards and Intensive Care Units

Health Care Management Science - This paper presents a mathematical model that provides a real-time forecast of the number of COVID-19 patients admitted to the ward and the Intensive Care Unit...     

Dysregulated production of interleukin-8 in individuals infected with human immunodeficiency virus type 1 and Mycobacterium tuberculosis

Interleukin-8 (IL-8) production in vivo was monitored in four study groups: normal blood donors, patients with pulmonary tuberculosis (TB), patients with human immunodeficiency virus type 1 (HIV-1) infection, and dually infected (HIV/TB) patients. We show that whereas there was evidence of detectable levels of cell-associated IL-8 (mRNA and protein) in peripheral cells of healthy individuals, this was largely lost in the disease states studied. Coupled with this finding was significantly increased circulating levels of IL-8 in HIV-1-infected individuals with or without concomitant pulmonary TB (P < 0.001). On the other hand, the capacity of peripheral mononuclear cells to produce IL-8 spontaneously ex vivo was enhanced in HIV-1 and TB patients (P < 0.05) and many of the HIV/TB group, but their corresponding capacities to respond to various stimuli, in particular phytohemagglutinin, were significantly diminished compared to those of normal donors (P < 0.05). Circulating levels of IL-8 in a group of HIV/TB patients were significantly positively correlated with the percentage of polymorphonuclear leukocytes (PMN) in the peripheral circulation (r = 0.65; P = 0.01), the proportions of IL-8 receptor A (IL-8RA)-expressing (r = 0.86; P < 0.01) and IL-8RB-expressing (r = 0.77; P < 0.01) PMN, and the capacity of PMN to migrate in response to IL-8 as chemoattractant (r = 0.68; P < 0. 01). IL-8RB fluorescence intensity, however, was negatively correlated with plasma IL-8 levels (r = -0.73; P < 0.01). Our results suggest that altered regulation of IL-8 in HIV-1 may have important implications for antimicrobial defenses and for normal immune processes.     

Subfertile men with constitutive chromosome abnormalities do not necessarily refrain from intracytoplasmic sperm injection treatment: a follow-up study on 75 Dutch patients

A follow-up study was performed to investigate the impact of the detection of a chromosome abnormality in infertile men who are candidates for intracytoplasmic sperm injection (ICSI) treatment. In this collaborative study between clinical genetics centres and fertility clinics in the Netherlands, 75 ICSI couples of which the male partners had a chromosome abnormality were included. All couples were extensively counselled on the risk of having a chromosomally unbalanced child. Forty-two out of 75 couples chose to proceed with the ICSI treatment. So far, treatment has resulted in a pregnancy in 11 cases. Four of them opted to have invasive prenatal diagnosis. Despite the genetic risks related to a chromosome abnormality in infertile men, a small majority (56%) of the couples did not refrain from the ICSI treatment.     

Cow's milk-specific T-cell reactivity of children with and without persistent cow's milk allergy: key role for IL-10

BACKGROUND: The role of antigen-specific T cells in the mechanism of food allergy or maintenance of tolerance toward an innocuous antigen, such as cow's milk, is not yet fully understood. OBJECTIVE: The cow's milk-specific T-cell response of donors with various allergic backgrounds was investigated. METHODS: Cow's milk-specific T-cell clones (TCCs) were generated from the blood of children with persistent cow's milk allergy (CMA) and the blood of cow's milk-tolerant allergic and nonallergic control subjects. The TCCs were characterized by their antigen-specific proliferation, cytokine production, and activation status. RESULTS: Cow's milk-specific TCCs of children with persistent CMA were T(H)2 skewed, and the production of IL-4 and IL-13 was significantly correlated with the expression of the activation marker CD25. TCCs of the allergic control subjects were characterized by a high production of IL-10, which was positively correlated with the production of IL-4 and IFN-gamma and with the expression of CD25. TCCs derived from nonallergic control subjects had an attenuated response toward cow's milk in that they did not produce high levels of cytokines nor did they express high levels of surface markers. As in the allergic control subjects, in the nonallergic control subjects IL-10 production was positively correlated with the expression of CD25. CONCLUSION: The activation status of T cells derived from persistent donors with CMA was associated with the production of IL-4 and IL-13, whereas activated TCCs of cow's milk-tolerant control subjects were characterized by the production of IL-10 and, to a lesser extent, IFN-gamma. These findings suggest that activated CD4(+) T cells (characterized by a high CD25 expression) might contribute to the tolerogenic immune response toward an antigen, such as cow's milk, through the production of IL-10.     

Reduced HIV-stimulated T-helper cell reactivity in cord blood with short-course antiretroviral treatment for prevention of maternal-infant transmission

T-helper cell responses to HIV have been associated with protection against maternal-infant HIV transmission in the absence of antiretroviral treatment, but the effects of antiretroviral treatment, now widely used for prevention, on development of these cell-mediated responses is unknown. We tested whether development of T-helper cell responses to HIV and other antigens would be affected by exposure to short-course regimens of zidovudine-lamivudine (ZDV-3TC) given to prevent maternal-infant HIV transmission. Cord blood samples were collected from 41 infants of HIV-infected mothers enrolled in a clinical trial in which they were treated with regimens of ZDV-3TC and from 29 infants whose HIV-infected mothers were not treated with any antiretroviral drugs. T-helper cell reactivity to HIV envelope peptides and other antigens was measured in vitro using a sensitive culture supernatant titration assay based on IL-2-dependent proliferation. Infants in the clinical trial were followed to 18 months to determine their HIV infection status, and venous blood samples were re-tested at 4.5 and 9 months for T-cell reactivity to HIV. HIV-stimulated T-helper cell reactivity in cord blood was detected 10-fold less frequently among those exposed to antiretroviral prophylaxis (2.4%) than among those unexposed (24.1%) (P = 0.007). Reductions in HIV-stimulated responses in cord blood occurred despite detectable HIV RNA (mean 3.38 standard deviation 0.76 log(10) copies per ml) at delivery among treated women and occurred independent of treatment duration. Our results suggest that short-course antiretroviral treatment given to prevent maternal-infant HIV transmission may attenuate HIV-stimulated T-cell memory responses in the neonate.     

Modulation of monocyte/macrophage function by human CD4+CD25+ regulatory T cells

The suppressive effects of CD4+CD25+ regulatory T cells (Tregs) on T cells have been well documented. Here we investigated whether human CD4+CD25+ Tregs can inhibit the proinflammatory properties of monocytes/macrophages. Monocytes and T cells were isolated from peripheral blood of healthy volunteers by magnetic cell separation and cocultured for 40 h. Monocytes were analyzed directly for cytokine production and phenotypic changes or repurified and used in T-cell stimulation and lipopolysaccharide challenge assays. Coculture with CD4+CD25+ Tregs induced minimal cytokine production in monocytes, whereas coculture with CD4+CD25- T cells resulted in large amounts of proinflammatory (tumor necrosis factor-alpha, interferon-gamma, interleukin-6) and regulatory (interleukin-10) cytokines. Importantly, when these CD4+CD25+ Treg-treated monocytes were repurified after coculture and challenged with lipopolysaccharide, they were severely inhibited in their capacity to produce tumor necrosis factor-alpha and interleukin-6 compared with control-treated monocytes. In addition, monocytes that were precultured with CD4+CD25+ Tregs displayed limited upregulation of human leukocyte antigen class II, CD40 and CD80, and downregulation of CD86 compared with control-treated monocytes. This altered phenotype had functional consequences, as shown by the reduction in T cell-stimulatory capacity of Treg-treated monocytes. Together, these data demonstrate that CD4+CD25+ Tregs can exert direct suppressive effects on monocytes/macrophages, thereby affecting subsequent innate and adaptive immune responses.