Dual induction of the Epo-Egr-TNF-alpha- plasmid in hypoxic human colon adenocarcinoma produces tumor growth delay

Gene therapy is a modality for the treatment of solid tumors that involves the introduction of a suicide gene into the tumor cells. Genetic radiotherapy involves the placement of a radiation-sensitive promoter upstream from a suicide gene. Because of their irregular vasculature some solid tumors are chronically hypoxic and hence are resistant to conventional treatment with chemotherapy and ionizing radiation (IR). The purpose of this study was to demonstrate that regional tumor hypoxia could be exploited to improve local tumor control. The cDNA coding the erythropoietin hypoxia-responsive element (EPO) was placed upstream from the Egr-TNF-alpha construct. WIDR human colon adenocarcinoma cells were injected into the right hind limb of nude mice and treated with Epo-Egr-TNF-alpha plasmid with or without IR. Tumor volumes were measured by calipers and tumor necrosis factor (TNF)-alpha content of the tumor was determined by enzyme-linked immunosorbent assay. Treatment with the combined regimen of Epo-Egr-TNF-alpha plasmid + IR resulted in significant tumor growth delay. Tumor TNF-alpha content was increased by 30 per cent in the combined treatment group compared with each treatment alone. Regional tumor hypoxia can be exploited successfully to induce tumor growth delay, enhance local control, and enhance the therapeutic ratio.     

The Association between Diet Quality and Health Status in Mobile Food Pantry Users in Northeastern Connecticut

Low-income Americans tend to have poor diet quality and disease prevalence overall. Mobile food pantries aim to improve these outcomes, and have rarely been studied. This cross-sectional study aimed to evaluate the association between diet quality and health status in mobile food pantry users. Data were collected from two mobile food pantry sites in Northeastern Connecticut (n = 83). Sociodemographic food security and diet quality data were collected. Overall, diet quality was low among all participants with intakes of fruits, vegetables, and whole grains of concern. Participant adherence to the 2020–2025 US Dietary Guidelines were low, with no participants meeting recommendations for whole grains. Obesity, diabetes, and hypertension prevalence in this population exceeded national averages. After adjusting for covariates, hypertension was associated with higher dairy and added sugar intake, as well as a greater intake of added sugar from sugar-sweetened beverages (p < 0.05). Although results were not statistically significant, participants with obesity, diabetes, and hypertension showed a trend of having lower adherence to the guidelines than those without these chronic diseases. Questions assessing participant interest in changing their diets were also posed, indicating overall high interest in learning about current diet quality and weight improvement.     

Biotransformation of alprazolam by members of the human cytochrome P4503A subfamily

1. To aid in the prediction of drug interactions with alprazolam, the human CYP involved in the 1'- and 4-hydroxylation of alprazolam were characterized using human liver microsomes, expressed enzymes and selective chemical inhibitors. 2. The formation of 4-hydroxyalprazolam and 1-hydroxyalprazolam at an alprazolam concentration of 62.5 μM were reduced by the prototypic CYP3A inhibitor, troleandomycin (50 μM), by 97 and 99% respectively. Only microsomes from B-lymphoblastoid cells expressing CYP3A4 were capable of catalysing the 1'- and 4-hydroxylation of alprazolam. 3. The formation rates of 1'-hydroxyalprazolam and 4-hydroxyalprazolam at an alprazolam concentration of 1 mM were significantly correlated (n=19, r=0.95, p&lt;0.01) indicating that the same enzyme(s) mediated these biotransformations. A significant (p&lt;0.01) correlation was observed between alprazolam 4- and 1'-hydroxylase activity and CYP3A-mediated midazolam 4-hydroxylase, midazolam 1'-hydroxylase, dextromethorphan N-demethylase and erythromycin N-demethylase activities. 4. In conclusion, in adult human liver the CYP3A subfamily members are the principal enzymes involved in the 1'- and 4-hydroxylation of alprazolam. Thus, clinically significant drug-drug interactions between alprazolam and other CYP3A substrates are to be expected.     

Qualitative analysis by interviews and video recordings to establish the components of a skilled low-cavity non-rotational vacuum delivery

Objectives  The objectives of this study were to define the components of a skilled low-cavity non-rotational vacuum delivery (occiput anterior, vertex at station +2 or below and less than 45-degree rotation from midline) and to facilitate the transfer of skills from expert to trainee obstetricians.
Design  Qualitative study using interviews and video recordings.
Setting  Two university teaching hospitals (St Michael's Hospital, Bristol, and Ninewell's Hospital, Dundee).
Participants  Ten obstetricians and eight midwives identified as experts in conducting or supporting operative vaginal deliveries.
Methods  Semi-structured interviews were carried out using routine clinical scenarios. The experts were also video recorded conducting low-cavity vacuum deliveries in a simulation setting. The interviews and video recordings were transcribed verbatim and analysed using thematic coding. The anonymised data were independently coded by three researchers and compared for consistency of interpretation. The experts reviewed the coded interviews and video data for respondent validation and clarification. The themes that emerged following the final coding were used to formulate a list of skills.
Main outcome measures  Key technical skills of a low-cavity non-rotational delivery.
Results  The final list included detailed technical skills required for conducting a low-cavity vacuum delivery. The combination of semi-structured interviews and simulation videos allowed the formulation of a comprehensive skills tool for future evaluation.
Conclusion  This explicitly defined skills list could aid trainees understanding of the technique of low-cavity vacuum delivery. This is an important first step in evaluating clinical competence in intrapartum procedures.     

Intracranial infectious aneurysms: a comprehensive review

Intracranial infectious aneurysms, or mycotic aneurysms, are rare infectious cerebrovascular lesions which arise through microbial infection of the cerebral arterial wall. Due to the rarity of these lesions, the variability in their clinical presentations, and the lack of population-based epidemiological data, there is no widely accepted management methodology. We undertook a comprehensive literature search using the OVID gateway of the MEDLINE database (1950–2009) using the following keywords (singly and in combination): “infectious,” “mycotic,” “cerebral aneurysm,” and “intracranial aneurysm.” We identified 27 published clinical series describing a total of 287 patients in the English literature that presented demographic and clinical data regarding presentation, treatment, and outcome of patients with mycotic aneurysms. We then synthesized the available data into a combined cohort to more closely estimate the true demographic and clinical characteristics of this disease. We follow by presenting a comprehensive review of mycotic aneurysms, highlighting current treatment paradigms. The literature supports the administration of antibiotics in conjunction with surgical or endovascular intervention depending on the character and location of the aneurysm, as well as the clinical status of the patient. Mycotic aneurysms comprise an important subtype of potentially life-threatening cerebrovascular lesions, and further prospective studies are warranted to define outcome following both conservative and surgical or endovascular treatment.     

妊娠糖尿病妇女使用门冬胰岛素或常规人胰岛素在疗效、安全性方面的比较

在一项随机、平行分组的开放试验中，27例妊娠糖尿病妇女（年龄30．7±6．3岁，HbA1c〈7％）随机分为门冬胰岛素治疗组（餐前5分钟注射）和常规人胰岛素治疗组（餐前30分钟注射）。试验时间为从诊断妊娠糖尿病（18～28周）至产后6周。研究期间两组的总体血糖水平均控制良好（试验开始和结束时HbA1c≤6％）。进餐试验时，试验6周时的平均血糖水平（门冬胰岛素组4．2±0．57mmol／L，常规人胰岛素组4．8±0．86mmol／L）略低于试验0周时（门冬胰岛素组4．9±0．59mmol／L，常规人胰岛素组5．1±0．36mmol／L）。     

Epistatic relationship between the cancer susceptibility genes CHEK2 and p27.

We studied the effects of p27 and CHEK2 variants on prostate and colon cancer risk in a case-control study. Modest effects on prostate cancer risk were observed for both CHEK2 missense and truncating variants. However, the excess cancer risk was restricted to the subgroup of men who were homozygous for the VV genotype in codon 109 of the p27 gene. Among men with the VV p27 genotype, the odds ratios associated with truncating and missense CHEK2 mutations were 3.1 (P < 0.0001) and 1.9 (P < 0.0001), respectively. Among men with other p27 genotypes (GG and VG), the odds ratios were 1.5 and 1.2 for truncating and missense CHEK2 mutations, respectively, and were not statistically significant. The interaction between CHEK2 and p27 was confirmed in a group of patients with colon cancer. Thus, it seems that the clinical expression of CHEK2 variant alleles on prostate and colon cancer risk may be restricted to individuals with a specific genotype (VV) of the p27 gene. Two-gene models provide numerous challenges for gene identification and cancer risk assessment.