Assessment of Airway Distribution of Transnasal Solutions in Mice by PET/CT Imaging

Purpose

Transnasal administration is one of the most common routes for allergen challenge in mouse models of airway diseases. Although this technique is widely used, neither the amount of allergen that reaches the lung nor its airway distribution has been well established. We used positron emission tomography (PET) and computed tomography (CT) to examine the anatomical distribution of a solution containing a tracer immediately after transnasal delivery and to determine the possible influence of age and administered volume.

Procedures

Forty-six female BALB/c mice were divided into three groups according to instillation volume and age: (A) 15 μl, 8–10 weeks old (N?=?10), (B) 30 μl, 8–10 weeks old (N?=?20), and (C) 30 μl, 32 weeks old (N?=?16). Anesthetized animals underwent a dynamic scan in a dedicated small-animal PET scanner immediately after transnasal administration of a solution containing ¹⁸FDG. Regions of interest were used to obtain quantitative data. Animals were also imaged with a small-animal CT scanner to obtain complementary anatomical information.

Results

Mean?±?SD (5.69?±?4.51%) of the solution administered reached the lungs in group A, 41.84?±?8.03% in group B, and 36.65?±?16.15% in group C. A comparable percentage was delivered to the left and right lungs in all the groups. Analysis of variance revealed a significant difference between the groups in the proportion of the solution that reached the lungs depending on the injection volume (P?Conclusions In this first report on quantitative imaging by PET and CT in small animals, we confirmed the suitability of the transnasal route with an instilled volume of 30 μl delivering fluids into the lower airways, although only about 40% of the dose reaches the lungs.     

输尿管镜气压弹道碎石术治疗输尿管结石560例

1临床资料输尿管结石560(男324,女236)例,年龄16～68(平均38)岁.其中左侧输尿管246例,右侧输尿管268例,双侧输尿管46例,合并肾功能减退者28例,合并妊娠12例,孤肾合并输尿管结石5例,上段输尿管139例,中段输尿管154例,下段输尿管267例,合并输尿管狭窄68例,合并输尿管息肉156例,合并输尿管扩张及不同程度肾积水286例,36例有肾或输尿管切开取石史,196例行体外震波碎石效果不佳,其中16例形成石街.本组经X线诊断的阳性结石388例,经B超或静脉肾盂造影诊断的阴性结石148例,未发现结石经输尿管镜诊断的结石24例.     

Characterization of hepatitis B virus X gene quasispecies complexity in mono-infection and hepatitis delta virus superinfection

Hepatitis delta virus(HDV) seems to strongly suppress hepatitis B virus(HBV)replication, although little is known about the mechanism of this interaction. Both these viruses show a dynamic distribution of mutants, resulting in viral quasispecies. Next-generation sequencing is a viable approach for analyzing the composition of these mutant spectra. As the regulatory hepatitis B X protein(HBx) is essential for HBV replication, determination of HBV X gene(HBX)quasispecies complexity in HBV/HDV infection compared to HBV monoinfection may provide information on the interactions between these two viruses.AIM To compare HBV quasispecies complexity in the HBX 5' region between chronic hepatitis delta(CHD) and chronic HBV mono-infected patients.METHODS Twenty-four untreated patients were included: 7/24(29.2%) with HBeAgnegative chronic HBV infection(CI, previously termed inactive carriers), 8/24(33.3%) with HBeAg-negative chronic hepatitis B(CHB) and 9/24(37.5%) with CHD. A serum sample from each patient was first tested for HBV DNA levels.The HBX 5' region [nucleotides(nt) 1255-1611] was then PCR-amplified for subsequent next-generation sequencing(MiSeq, Illumina, United States). HBV quasispecies complexity in the region analyzed was evaluated using incidencebased indices(number of haplotypes and number of mutations), abundancebased indices(Hill numbers of order 1 and 2), and functional indices(mutation frequency and nucleotide diversity). We also evaluated the pattern of nucleotide changes to investigate which of them could be the cause of the quasispecies complexity.RESULTS CHB patients showed higher median HBV-DNA levels [5.4 logIU/mL,interquartile range(IQR) 3.5-7.9] than CHD(3.4 logIU/mL, IQR 3-7.6)(P = n.s.)or CI(3.2 logIU/mL, IQR 2.3-3.5)(P < 0.01) patients. The incidence and abundance indices indicated that HBV quasispecies complexity was significantly greater in CI than CHB. A similar trend was observed in CHD patients, although only Hill numbers of order 2 showed statistically significant differences(CHB2.81, IQR 1.11-4.57 vs CHD 8.87, 6.56-11.18, P = 0.038). There were no significant differences in the functional indices, but CI and CHD patients also showed a trend towards greater complexity than CHB. No differences were found for any HBV quasispecies complexity indices between CHD and CI patients. G-to-A and C-to-T nucleotide changes, characteristic of APOBEC3 G, were higher in CHD and CI than in CHB in genotype A haplotypes, but not in genotype D. The proportion of nt G-to-A vs A-to-G changes and C-to-T vs T-to-C changes in genotype A and D haplotypes in CHD patients showed no significant differences. In CHB and CI the results of these comparisons were dependent on HBV genotype.CONCLUSION The lower-replication CHD and CI groups show a trend to higher quasispecies complexity than the higher-replication CHB group. The mechanisms associated with this greater complexity require elucidation.     

Neuronal adaptation to simulated and optically-induced astigmatic defocus

Purpose

It is well established that spatial adaptation can improve visual acuity over time in the presence of spherical defocus. It is less well known how far adaptation to astigmatic defocus can enhance visual acuity. We adapted subjects to “simulated” and optically-induced “real” astigmatic defocus, and studied how much they adapt and how selective adaptation was for the axis of astigmatism.

Methods

Ten subjects with a mean age of 26.7 ± 2.4 years (range 23-30) were enrolled in the study, three of them myopic (average spherical equivalent (SE) ± SD: −3.08 ± 1.42D) and seven emmetropic (average SE ± SD: −0.11 ± 0.18D). All had a corrected minimum visual acuity (VA) of log VA 0.0. For adaptation, subjects watched a movie at 4 m distance for 10 min that was convolved frame-by-frame with an astigmatic point spread function, equivalent to +3D defocus, or they watched an unfiltered movie but with spectacle frames with a 0/+3D astigmatic trial lenses. Subsequently, visual acuity was determined at the same distance, using high contrast letter acuity charts. Four experiments were performed. In experiment (1), simulated astigmatic defocus was presented both for adaptation and testing, in experiment (2) optically-induced astigmatic defocus was presented both for adaptation and testing of visual acuity. In all these cases, the +3D power meridian was at 0°. In experiments (3) and (4), the +3D power meridian was at 0° during adaptation but rotated to 90° during testing. Astigmatic defocus was simulated in experiment (3) but optically-induced in experiment (4).

Results

Experiments 1 and 2: adaptation to either simulated or real astigmatic defocus increased visual acuity in both test paradigms, simulated (change in VA 0.086 ± 0.069 log units; p < 0.01) and lens-induced astigmatic defocus (change in VA 0.068 ± 0.031 log units; p < 0.001). Experiments 3 and 4: when the axis was rotated, the improvement in visual acuity failed to reach significance, both for simulated (change in VA 0.042 ± 0.079 log units; p = 0.13) and lens-induced astigmatic defocus (change in VA 0.038 ± 0.086 log units; p = 0.19).

Conclusions

Adaptation to astigmatic defocus occurs for both simulated and real defocus, and the effects of adaptation seem to be selective for the axis of astigmatism. These observations suggest that adaptation involves a re-adjustment of the spatial filters selectively for astigmatic meridians, although the underlying mechanism must be more complicated than just changes in shapes of the receptive fields of retinal or cortical neurons.     

Consensus on the treatment of pancreatic cancer in Spain

Pancreatic cancer (PC) represents one of the greatest oncological challenges of our century, due to its high mortality and incidence. A group of Spanish experts in PC treatment reviewed data available on different therapeutic combinations and established consensus on what would be the best strategy in PC management, depending on the stage of the disease. Surgery with complete resection may produce 5-year survival rates of 18–24%, but definitive control is still precarious. In the absence of consensus, the best evidence suggests that adjuvant chemotherapy with gemcitabine for 6 months using the CONKO-001 regime is the treatment of choice after resection of PC for patients with acceptable functional status. This group recommends chemoradiotherapy (CT-RT) in patients with factors for poor loco-regional prognosis. However, chemotherapy is an option for the treatment of locally advanced PC in patients with good general status and in the absence of metastatic disease the recommended treatment is CT-RT followed by gemcitabine-based chemotherapy. A period of chemotherapy followed by consolidation CT-RT may be appropriate, as it allows selection of patients with locally advanced disease who may benefit most from combined treatment. Erlotinib combined with gemcitabine shows significant survival improvement in PC and must be considered an option in the first-line treatment of advanced and metastatic PC. The gemcitabine-erlotinib combination is proposed as the standard treatment for metastatic PC in patients with PS≥2. In patients with PS<2, gemcitabine-erlotinib is recommended as the first-line treatment option, supported by a maximum degree of evidence, without ruling out other options, such as gemcitabine-oxaliplatin, gemcitabine-capecitabine or gemcitabine alone.     

Orthostatic intolerance in adolescent chronic fatigue syndrome

OBJECTIVES: To demonstrate the association between orthostatic intolerance and the chronic fatigue syndrome (CFS) in adolescents and to delineate the form that orthostatic intolerance takes in these children. STUDY DESIGN: We investigated the heart rate and blood pressure (BP) responses to head-up tilt (HUT) in 26 adolescents aged 11 to 19 years with CFS compared with responses in adolescents referred for the evaluation of simple faint and to responses in 13 normal healthy control children of similar age. RESULTS: A total of 4/13 of the controls and 18/26 simple faint patients experienced typical faints with an abrupt decrease in BP and heart rate associated with loss of consciousness. One CFS patient had a normal HUT. A total of 25/26 CFS patients experienced severe orthostatic symptoms associated with syncope in 7/25, orthostatic tachycardia with hypotension in 15/25, and orthostatic tachycardia without significant hypotension in 3/25. Acrocyanosis, cool extremities, and edema indicated venous pooling in 18/25. None of the control or simple faint patients experienced comparable acral or tachycardic findings. CONCLUSIONS: We conclude that chronic fatigue syndrome is highly related to orthostatic intolerance in adolescents. The orthostatic intolerance of CFS often has heart rate and BP responses similar to responses in the syndrome of orthostatic tachycardia suggesting that a partial autonomic defect may contribute to symptomatology in these patients.     

腰椎间盘突出伴侧隐窝狭窄症的微创治疗破

0引言 腰椎间盘突出症伴侧隐窝狭窄症目前最有效的方法依然是椎间盘突出髓核摘除及神经根通道减压清理术. 如何减少创伤,保持脊柱稳定,尽快康复,以最少的并发症和最低的经济负担,获得优良的中远期疗效一直是脊柱外科的目标[1-3]. 2000-09/2004-03我院开展显微内窥镜椎间盘切除(MED)手术375例,其中120例有椎间盘突出伴侧隐窝狭窄,进行椎间盘摘除及神经根通道清理术. 现将随访到的98例作一短中期疗效的总结报道.     

COVID-19 vaccine effectiveness against SARS-CoV-2 infection during the Delta period,a nationwide study adjusting for chance of exposure,the Netherlands,July to December 2021

BackgroundDifferential SARS-CoV-2 exposure between vaccinated and unvaccinated individuals may confound vaccine effectiveness (VE) estimates.AimWe conducted a test-negative case–control study to determine VE against SARS-CoV-2 infection and the presence of confounding by SARS-CoV-2 exposure.MethodsWe included adults tested for SARS-CoV-2 at community facilities between 4 July and 8 December 2021 (circulation period of the Delta variant). The VE against SARS-CoV-2 infection after primary vaccination with an mRNA (Comirnaty or Spikevax) or vector-based vaccine (Vaxzevria or Janssen) was calculated using logistic regression adjusting for age, sex and calendar week (Model 1). We additionally adjusted for comorbidity and education level (Model 2) and SARS-CoV-2 exposure (number of close contacts, visiting busy locations, household size, face mask wearing, contact with SARS-CoV-2 case; Model 3). We stratified by age, vaccine type and time since vaccination.ResultsVE against infection (Model 3) was 64% (95% CI: 50–73), only slightly lower than in Models 1 (68%; 95% CI: 58–76) and 2 (67%; 95% CI: 56–75). Estimates stratified by age group, vaccine and time since vaccination remained similar: mRNA VE (Model 3) among people ≥ 50 years decreased significantly (p = 0.01) from 81% (95% CI: 66–91) at < 120 days to 61% (95% CI: 22–80) at ≥ 120 days after vaccination. It decreased from 83% to 59% in Model 1 and from 81% to 56% in Model 2.ConclusionSARS-CoV-2 exposure did not majorly confound the estimated COVID-19 VE against infection, suggesting that VE can be estimated accurately using routinely collected data without exposure information.