Chronic inhalation exposure to mainstream cigarette smoke increases lung and nasal tumor incidence in rats.

An animal model of lung carcinogenicity induced by chronic inhalation of mainstream cigarette smoke would be useful for research on carcinogenic mechanisms, smoke composition-response relationships, co-carcinogenicity, and chemoprevention. A study was conducted to determine if chronic whole-body exposures of rats would significantly increase lung tumor incidence. Male and female F344 rats (n = 81 to 178/gender) were exposed whole-body 6 h/day, 5 days/week for up to 30 months to smoke from 1R3 research cigarettes diluted to 100 (LS) or 250 (HS) mg total particulate matter/m(3), or sham-exposed to clean air (C). Gross respiratory tract lesions and standard lung and nasal sections were evaluated by light microscopy. A slight reduction of survival suggested that the HS level was at the maximum tolerated dose as commonly defined. Cigarette smoke exposure significantly increased the incidences of non-neoplastic and neoplastic proliferative lung lesions in females, while nonsignificant increases were observed in males. The combined incidence of bronchioloalveolar adenomas and carcinomas in females were: HS = 14%; LS = 6%; and C = 0%. These incidences represented minima because only standard lung sections and gross lesions were evaluated. Mutations in codon 12 of the K-ras gene occurred in 4 of 23 (17%) tumors. Three mutations were G to A transitions and one was a G to T transversion. The incidence of neoplasia of the nasal cavity was significantly increased at the HS, but not the LS level in both males and females (HS = 6%, LS = 0.3%, C = 0.4% for combined genders). These results demonstrate that chronic whole-body exposure of rats to cigarette smoke can induce lung cancer.     

Mutation analysis of NANOS3 in 80 Chinese and 88 Caucasian women with premature ovarian failure

NANOS3 encodes an RNA-binding protein and has a conserved function in germ cell development. Our objective was to investigate whether mutations in NANOS3 were present in Chinese and Caucasian women with premature ovarian failure. A known synonymous single-nucleotide polymorphism (rs 2016163) in exon 1 was identified through sequencing 80 Chinese and 88 Caucasian women with premature ovarian failure. No additional single-nucleotide polymorphisms or mutations were found in exons encoding for NANOS3. Our findings suggest that mutations in NANOS3 exons are rare in both Chinese and Caucasian women with premature ovarian failure.     

Substandard application of preimplantation genetic screening may interfere with its clinical success

The intent of this study was to evaluate a recent randomized clinical trial evaluating the effect of preimplantation genetic screening (PGS) that reports a negative effect on pregnancy outcome. This article reviews appropriate PGS techniques and how they differ from the trial in question. A closer look at the clinical trial in question reveals significant lack of expertise in biopsy, cell fixation, genetic analysis, and patient selection. At most, this trial demonstrates that in inexperienced hands, PGS can be detrimental. No other conclusions concerning the effect of PGS on pregnancy results can be drawn from the trial.     

Characterization of benign and metastatic vertebral compression fractures with quantitative diffusion MR imaging

BACKGROUND AND PURPOSE: Conventional imaging techniques cannot be used to unambiguously and reliably differentiate malignant from benign vertebral compression fractures. Our hypothesis is that these malignant and benign vertebral lesions can be better distinguished on the basis of tissue apparent diffusion coefficients (ADCs). The purpose of this study was to test this hypothesis by using a quantitative diffusion imaging technique. METHODS: Twenty-seven patients with known cancer and suspected metastatic vertebral lesions underwent 1.5-T conventional T1-weighted, T2-weighted, and contrast-enhanced T1-weighted imaging to identify the lesions. Diffusion-weighted images of the areas of interest were acquired by using a fast spin-echo diffusion pulse sequence with b values of 0-250 s/mm(2). The abnormal regions on the diffusion-weighted images were outlined by using the conventional images as guides, and the ADC values were calculated. On the basis of pathologic results and clinical findings, the cases were divided into two categories: benign compression fractures and metastatic lesions. The ADC values for each category were combined and plotted as histograms; this procedure was followed by statistical analysis. RESULTS: The patient group had 12 benign fractures and 15 metastases. The mean ADC values, as obtained from the histograms, were (1.9 +/- 0.3) x 10(-4) mm(2)/s and (3.2 +/- 0.5) x 10(-4) mm(2)/s for metastases and benign fractures, respectively. CONCLUSION: Our results indicate that quantitative ADC mapping, instead of qualitative diffusion-weighted imaging, can provide valuable information in differentiating benign vertebral fractures from metastatic lesions.     

Previously undescribed palpebral branch from the infraorbital canal: Application to surgery of the eyelid and treatment of orbital floor fractures

The sensory innervation of the inferior eyelid is mainly derived from the inferior palpebral branch (IPb) of the infraorbital nerve (ION). This study aimed to investigate another, to our knowledge, previously unknown branch, and elucidate its location and distribution. Twelve sides from seven fresh frozen cadaveric Caucasian heads were used in this study. The specimens were derived from two male and four female adult cadavers age. The diameter of the IPb of the ION (D1) and branch arising from the upper wall of the infraorbital canal (D2), and distance between the branching points of this branch and the anterior border of the orbit floor (L1) was measured. A branch to the lower eyelid was found arising from the infraorbital canal on the majority of sides. D1 ranged from 0.4 to 1.1 mm. The branch arising from the upper wall of the infraorbital canal was found 10 sides (83%). D2 ranged 0.6 to 1.0 mm. L1 ranged from 10.2 to 19.8 mm. All of the branches arising from the upper wall of the infraorbital canal (10 sides) primarily innervated to the inferior eyelid. We suggest this branch should be named the “posterior IPb” of the ION. Knowledge of this branch might decrease sensory loss following invasive procedures of the lower orbit. Clin. Anat. 30:835–838, 2017. © 2017Wiley Periodicals, Inc.     

Optimized Adenovirus-Antibody Complexes Stimulate Strong Cellular and Humoral Immune Responses against an Encoded Antigen in Na?ve Mice and Those with Preexisting Immunity

The immune response to recombinant adenoviruses is the most significant impediment to their clinical use for immunization. We test the hypothesis that specific virus-antibody combinations dictate the type of immune response generated against the adenovirus and its transgene cassette under certain physiological conditions while minimizing vector-induced toxicity. In vitro and in vivo assays were used to characterize the transduction efficiency, the T and B cell responses to the encoded transgene, and the toxicity of 1 × 10¹¹ adenovirus particles mixed with different concentrations of neutralizing antibodies. Complexes formed at concentrations of 500 to 0.05 times the 50% neutralizing dose (ND₅₀) elicited strong virus- and transgene-specific T cell responses. The 0.05-ND₅₀ formulation elicited measurable anti-transgene antibodies that were similar to those of virus alone (P = 0.07). This preparation also elicited very strong transgene-specific memory T cell responses (28.6 ± 5.2% proliferation versus 7.7 ± 1.4% for virus alone). Preexisting immunity significantly reduced all responses elicited by these formulations. Although lower concentrations (0.005 and 0.0005 ND₅₀) of antibody did not improve cellular and humoral responses in naïve animals, they did promote strong cellular (0.005 ND₅₀) and humoral (0.0005 ND₅₀) responses in mice with preexisting immunity. Some virus-antibody complexes may improve the potency of adenovirus-based vaccines in naïve individuals, while others can sway the immune response in those with preexisting immunity. Additional studies with these and other virus-antibody ratios may be useful to predict and model the type of immune responses generated against a transgene in those with different levels of exposure to adenovirus.     

A 10-year follow up of a paging service for people with memory and planning problems within a healthcare system: How do recent users differ from the original users?

In 2003 Wilson, Scott, Evans, and Emslie published a report of a new healthcare resource; a paging system designed to reduce the everyday problems of people with neurological deficits who experience memory and/or planning problems. The system was established following several research studies carried out to evaluate its effectiveness. Information was collected on the first 40 clients recruited to the service. The purpose of the present study is to determine how the service might have changed over a 10-year period. The most recent users of the service (N?=?40) have been compared with the original cohort of 40 clients. In addition, in 2007 clients were given the opportunity to use their mobile telephones to receive messages; 17 chose to do so. There was no difference in age between the telephone users compared to the pager users, but those using a pager were less likely to have sustained a traumatic brain injury (TBI) and were more likely to be longer post-insult. There were no significant differences in the gender or ages of the people using the pager compared with those using the telephone service. However, the mean overall time since injury for the last 40 referrals was 9.48 years compared to 4.56 years for the original cohort. Both cohorts comprised several diagnostic groups; clients with TBI formed the largest subgroup, followed by those with stroke. This is typical of patients seen for rehabilitation, with other diagnostic groups forming a smaller percentage. We wanted to determine whether the range of diagnoses was similar over the 10-year period. Despite slight differences, we found a similar range of patients referred. In both cohorts the most frequent messages sent each week related to medication (27.9% in the first compared to 28.6% in the second). More messages were sent regarding mood management in the second cohort. No such messages were sent to the first 40 clients, whereas over 27 per week were sent to the last 40. Fewer health authorities (N?=?21) were referring after 10 years in comparison with 26 referrers for the first cohort.