The Effects of Propofol, Sodium Pentobarbital, and Ketamine Hydrochloride on \u3ci\u3eIn Vitro\u3c/i\u3e Mouse Embryonic Development

Every year more than 75,000 pregnant women are exposed to teratogenic medications or general anesthesia during non-obstetric surgery in the US,1-4 and embryonic effects of general anesthesia are of particular interest in laboratory research and veterinary medicine. The mouse system is used to screen potential toxic effects of anesthetics used in egg retrieval for in vitro fertilization (IVF), or those of pharmacologic agents which may come in contact with the egg or early embryo. Mouse preimplantation 2-cell embryos were exposed in vitro to incremental concentrations of common general anesthetics within and exceeding the normal clinical dosage range for mice (propofol 50-200mg/kg, sodium pentobarbital 50mg/kg, and ketamine hydrochloride 50-100mg/kg) for 72h to determine the effects of each anesthetic on subsequent cleavage and development during prolonged exposure. The anesthetic dosage ranges were as follows: propofol 0-25.0μg/mL, sodium pentobarbital 0-300µg/mL, and ketamine hydrochloride 0-5000µg/mL, embryonic development was evaluated every 24h during the 72h mouse embryo assay culture period. Results found propofol (≥2.01μg/mL), sodium pentobarbital (≥30μg/mL), and ketamine hydrochloride (≥40μg/mL) to exert inhibitory effects to the in vitro development of preimplantation mouse embryos. The percentage of 2-cell embryos developing to more advanced stages was decreased by exposure to higher concentrations of all three compounds. By the 72h endpoint, blastomeres of delayed and arrested embryos began to degenerate, displaying lysis and/or fragmentation; embryos exposed to lower concentrations of each anesthetic demonstrated a significant ability to continue cleavage and differentiation towards blastocyst formation. Conclusion: Embryotoxic effects to preimplantation embryos were observed in a dose-dependent manner after 72h of in vitro culture with propofol, sodium pentobarbital. and ketamine hydrochloride

Ixodid ticks of traditionally managed cattle in central Nigeria: where Rhipicephalus (Boophilus) microplus does not dare (yet?)

BACKGROUND: Ticks and tick-borne diseases (TBDs) undermine cattle fitness and productivity in the whole of sub-Saharan Africa, including Nigeria. The aim of this study was to document the composition of tick species, assessing the burden of infestation, in traditionally managed cattle in an area of central Nigeria where acaricides have not been used historically. METHODS: The study was carried out in September 2010 in 9 villages belonging to three neighbouring local government areas in Plateau State, Nigeria. In each village all visible adult ticks were collected from at least 15 cattle (mean number = 25). Collected ticks were preserved in 70% ethanol to be counted and morphologically identified to the species level. RESULTS: A total of 5011 ixodid ticks (1935 males and 3076 females) were collected from 228 cattle, comprising 14 calves, 33 juveniles, and 181 adults. Three tick genera (i.e., Amblyomma, Hyalomma, and Rhipicephalus, including the Boophilus sub-genus) and 11 species were identified. The most prevalent species was Rhipicephalus (Boophilus) decoloratus (41.4%), followed by Rhipicephalus (Boophilus) annulatus (15.4%), Rhipicephalus guilhoni (12.0%), Rhipicephalus (Boophilus) geigyi (7.6%), Hyalomma truncatum (7.4%), Amblyomma variegatum (6.3%), Rhipicephalus simus Group (4.0%), Rhipicephalus turanicus (1.2%), Rhipicephalus sanguineus (0.3%), Hyalomma rufipes (0.2%), and Rhipicephalus lunulatus (n = 1). Mean tick loads recorded were relatively high (22 ± 1.4), in spite of the practice of hand removal of ticks traditionally undertaken by the Fulani pastoralists in the area. Calves bore a significantly lower tick burden than adults (p = 0.004). Rhipicephalus (Boophilus) microplus was not found in the area, suggesting that the eastbound expansion of this tick species in West Africa, has not yet reached central Nigeria. CONCLUSIONS: This study ascertained the presence of a broad variety of cattle tick species, most of which are of veterinary importance. The presence of each tick species is correlated with the potential occurrence of tick-borne pathogens and suggestions for tick control in the area are considered. Results should assist the diagnosis of related TBDs in cattle as well as the strategic planning of cost-effective tick control

Neurosurgeons and the fight with COVID-19: a position statement from the EANS Individual Membership Committee

Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

Resuming Work After Cancer: A Prospective Study of Occupational Register Data

Introduction Long-term employment rates have been studied in cancer survivors, but little is known about the return to work of cancer patients. This study investigated return to work (RTW) within 2 years after the diagnosis of different types of cancer. Methods This prospective study investigated the associations of demographics (age, gender, socioeconomic status, and residential region) and occupational factors (occupation, duration of employment, and company size) of employees absent from work due to cancer with the time to partial RTW, defined as working at least 50% of the earnings before sickness absence. Likewise, the associations of demographics and occupational factors with full RTW at equal earnings as before sickness absence were investigated. Results The cohort included 5,234 employees who had been absent from work due to cancer between January 2004 and December 2006. The time to partial RTW was shortest among employees with skin cancer (median 55 days) and longest among employees with lung cancer (median 377 days). There were no significant associations between RTW and demographics. With regard to the occupational factors, employees in high occupational classes started working earlier than those in low occupational classes, but the time to full RTW did not differ significantly across occupational classes. Employees working in large companies returned to work earlier than those working in small companies. Conclusion RTW after different types of cancer depended on occupational factors rather than demographics

Clinical pharmacogenomic testing of KRAS, BRAF and EGFR mutations by high resolution melting analysis and ultra-deep pyrosequencing

BACKGROUND: Epidermal growth factor receptor (EGFR) and its downstream factors KRAS and BRAF are mutated in several types of cancer, affecting the clinical response to EGFR inhibitors. Mutations in the EGFR kinase domain predict sensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in lung adenocarcinoma, while activating point mutations in KRAS and BRAF confer resistance to the anti-EGFR monoclonal antibody cetuximab in colorectal cancer. The development of new generation methods for systematic mutation screening of these genes will allow more appropriate therapeutic choices. METHODS: We describe a high resolution melting (HRM) assay for mutation detection in EGFR exons 19-21, KRAS codon 12/13 and BRAF V600 using formalin-fixed paraffin-embedded samples. Somatic variation of KRAS exon 2 was also analysed by massively parallel pyrosequencing of amplicons with the GS Junior 454 platform. RESULTS: We tested 120 routine diagnostic specimens from patients with colorectal or lung cancer. Mutations in KRAS, BRAF and EGFR were observed in 41.9%, 13.0% and 11.1% of the overall samples, respectively, being mutually exclusive. For KRAS, six types of substitutions were detected (17 G12D, 9 G13D, 7 G12C, 2 G12A, 2 G12V, 2 G12S), while V600E accounted for all the BRAF activating mutations. Regarding EGFR, two cases showed exon 19 deletions (delE746-A750 and delE746-T751insA) and another two substitutions in exon 21 (one showed L858R with the resistance mutation T590M in exon 20, and the other had P848L mutation). Consistent with earlier reports, our results show that KRAS and BRAF mutation frequencies in colorectal cancer were 44.3% and 13.0%, respectively, while EGFR mutations were detected in 11.1% of the lung cancer specimens. Ultra-deep amplicon pyrosequencing successfully validated the HRM results and allowed detection and quantitation of KRAS somatic mutations. CONCLUSIONS: HRM is a rapid and sensitive method for moderate-throughput cost-effective screening of oncogene mutations in clinical samples. Rather than Sanger sequence validation, next-generation sequencing technology results in more accurate quantitative results in somatic variation and can be achieved at a higher throughput scale.This work was supported by grants from Spanish Health Ministry (FIS) network RIRAAF (RD 07/0064).Ye

Breast Cancer, Sickness Absence, Income and Marital Status. A Study on Life Situation 1 Year Prior Diagnosis Compared to 3 and 5 Years after Diagnosis

Background: Improved cancer survival poses important questions about future life conditions of the survivor. We examined the possible influence of a breast cancer diagnosis on subsequent working and marital status, sickness absence and income. Materials: We conducted a matched cohort study including 4,761 women 40–59 years of age and registered with primary breast cancer in a Swedish population-based clinical register during 1993–2003, and 2,3805 women without breast cancer. Information on socioeconomic standing was obtained from a social database 1 year prior and 3 and 5 years following the diagnosis. In Conditional Poisson Regression models, risk ratios (RRs) and 95 % confidence intervals (CIs) were estimated to assess the impact of a breast cancer diagnosis. Findings: Three years after diagnosis, women who had had breast cancer more often had received sickness benefits (RR = 1.49, 95 % CI 1.40–1.58) or disability pension (RR = 1.47, 95 % CI 1.37–1.58) than had women without breast cancer. W

Enhanced Motor Function by Training in Spinal Cord Contused Rats Following Radiation Therapy

Weight-bearing stepping, without supraspinal re-connectivity, can be attained by treadmill training in an animal whose spinal cord has been completely transected at the lower thoracic level. Repair of damaged tissue and of supraspinal connectivity/circuitry following spinal cord injury in rat can be achieved by specific cell elimination with radiation therapy of the lesion site delivered within a critical time window, 2-3 weeks postinjury. Here we examined the effects of training in the repaired spinal cord following clinical radiation therapy. Studies were performed in a severe rat spinal cord contusion injury model, one similar to fracture/crush injuries in humans; the injury was at the lower thoracic level and the training was a combined hindlimb standing and stepping protocol. Radiotherapy, in a similar manner to that reported previously, resulted in a significant level of tissue repair/preservation at the lesion site. Training in the irradiated group, as determined by limb kinematics tests, resulted in functional improvements that were significant for standing and stepping capacity, and yielded a significant direct correlation between standing and stepping performance. In contrast, the training in the unirradiated group resulted in no apparent beneficial effects, and yielded an inverse correlation between standing and stepping performance, e.g., subject with good standing showed poor stepping capacity. Further, without any training, a differential functional change was observed in the irradiated group; standing capacity was significantly inhibited while stepping showed a slight trend of improvement compared with the unirradiated group. These data suggest that following repair by radiation therapy the spinal circuitries which control posture and locomotor were modified, and that the beneficial functional modulation of these circuitries is use dependent. Further, for restoring beneficial motor function following radiotherapy, training seems to be crucial