Point-of-care testing: a disposable label-free electrochemical CA125 and HE4 immunosensors for early detection of ovarian cancer.

Cancer antigen 125 (CA125) and human epididymal secretory protein 4 (HE4) are critical biomarkers for ovarian cancer diagnosis and progression monitoring; therefore, sensitive determination of their levels in body fluids is crucial. In recent study, label-free CA125 and HE4 immunosensors were prepared using disposable screen-printed carbon electrodes modified with reduced graphene oxide, polythionine, and gold nanoparticles for the sensitive, fast, and practical determination of CA125 and HE4. Differential pulse voltammetry, square wave voltammetry, and electrochemical impedance spectroscopy methods were used for the electrochemical determination of antigens in four different linear ranges (1-100 pg mL- 1, 0.01-10 ng mL- 1, 10-50 ng mL- 1, and 50-500 ng mL- 1). High sensitivity, low limit of detection, and limit of quantification were obtained for each linear range with a correlation coefficient above 0.99. The application stability of CA125 and HE4 immunosensors was determined as 60 days, and the storage stability was determined as 16 weeks. Immunosensors showed high selectivity in nine different antigen mixtures. The reusability of the immunosensors has been tested up to 9 cycles. The Risk of Ovarian Malignancy Algorithm score% values were calculated using the concentration of CA125 and HE4 in the blood serum and evaluated in terms of ovarian cancer risk. For the point-of-care testing, CA125 and HE4 levels at pg mL- 1 concentration were measured in blood serum samples using the developed immunosensors and a hand-held electrochemical reader in approximately 20-30 s, and high recoveries were obtained. These disposable label-free immunosensors are user-friendly and can be used in point-of-care tests for rapid and practical detection of CA125 and HE4 with high selectivity, sensitivity, and repeatability.

A label-free dual immunosensor for the simultaneous electrochemical determination of CA125 and HE4 biomarkers for the early diagnosis of ovarian cancer.

The blood levels of cancer antigen 125 (CA125) and human epididymal secretory protein 4 (HE4) are measured in the diagnosis and progression monitoring of ovarian cancer (OC), and the Risk of Ovarian Malignancy Algorithm (ROMA) score% values are calculated for cancer risk assessment. For the first time, disposable dual screen-printed carbon electrodes modified with reduced graphene oxide, polythionine, and gold nanoparticles were used to fabricate label-free electrochemical dual CA125-HE4 immunosensors for the sensitive, fast, and practical simultaneous determination of CA125 and HE4. DPV and SWV methods were used to simultaneously determine antigens in two different linear ranges (1-100 pg mL-1 and 1-50 ng mL-1). High sensitivity, low LOD, and LOQ were obtained for two linear ranges with a correlation coefficient above 0.99. The application stability of the dual CA125-HE4 immunosensors was determined as 60 days, and the storage stability was determined as 16 weeks. The dual immunosensors exhibited high selectivity in eight different antigen mixtures. The reusability of the dual immunosensors has been tested up to 9 cycles. ROMA score% values for pre-menopausal and post-menopausal status were calculated using the concentration of CA125 and HE4 in the blood serum and assessing OC risk. The disposable dual immunosensors can be used in point-of-care tests for rapid and practical simultaneous determination of CA125 and HE4 with high selectivity, sensitivity, and repeatability.

Lessons learnt from a measles outbreak in Madang Province, Papua New Guinea, June 2014 - March 2015.

OBJECTIVE: This study examined measles vaccine wastage during an outbreak response in Madang Province of Papua New Guinea from June 2014 to March 2015. METHODS: Vaccine wastage was defined as the number of doses received by a health centre minus the total number of doses administered during and returned following the outbreak vaccination campaign. Vaccine data were collected from the Provincial Health Information Office, the Provincial Vaccine Store register and clinic and health centre immunization registers for calculating the vaccine wastage. Interviews were conducted with all 48 health centres involved in the outbreak response using a structured questionnaire to explore the reasons for vaccine wastage. RESULTS: Of the 154 110 doses issued by Madang Province during the outbreak, a total of 85 236 (55%) doses were wasted. The wastage varied by district from 31% to 90%. The total cost of the vaccine wastage was estimated to be 589 810 Kina (US$ 196 604). None of the health centres maintained vaccine stock registers. Most health centres indicated multiple failures in cold chain logistics. Almost 40% of health centres reported incorrectly diluting vaccines. The same percentage of health centres reported using incorrect injection techniques. DISCUSSION: Regular audits of cold chain logistics, staff training and improved processes for recording vaccine administration and wastage will decrease vaccine wastage during vaccine-preventable disease outbreaks and also benefit routine immunization activities.

Evaluation of the effects of intra-arterial sugammadex and dexmedetomidine: an experimental study / Avaliação dos efeitos de sugamadex e dexmedetomidina intra-arterial: estudo experimental

Abstract Background: Intra-arterial injection of medications may cause acute and severe ischemia and result in morbidity and mortality. There is no information in the literature evaluating the arterial endothelial effects of sugammadex and dexmedetomidine. The hypothesis of our study is that sugammadex and dexmedetomidine will cause histological changes in arterial endothelial structure when administered intra-arterially. Methods: Rabbits were randomly divided into 4 groups. Group Control (n = 7); no intervention performed. Group Catheter (n = 7); a cannula inserted in the central artery of the ear, no medication was administered. Group Sugammadex (n = 7); rabbits were given 4 mg/kg sugammadex into the central artery of the ear, and Group Dexmedetomidine (n = 7); rabbits were given 1 µg/kg dexmedetomidine into the central artery of the ear. After 72 h, the ears were amputated and histologically investigated. Results: There was no significant difference found between the control and catheter groups in histological scores. The endothelial damage, elastic membrane and elastic fiber damage, smooth muscle hypertrophy and connective tissue increase scores in the dexmedetomidine and sugammadex groups were significantly higher than both the control and the catheter groups (p < 0.05). There was no significant difference found between the dexmedetomidine and sugammadex groups in histological scores. Conclusion: Administration of sugammadex and dexmedetomidine to rabbits by intra-arterial routes caused histological arterial damage. To understand the histological changes caused by sugammadex and dexmedetomidine more clearly, more experimental research is needed.

Resumo Justificativa: A injeção intra-arterial de medicamentos pode causar isquemia aguda e grave e resultar em morbidade e mortalidade. Não há informações na literatura que avaliem os efeitos endoteliais arteriais de sugamadex e dexmedetomidina. A hipótese de nosso estudo foi que dexmedetomidina e sugamadex causariam alterações histológicas na estrutura endotelial arterial quando administrados por via intra-arterial. Método: Os coelhos foram randomicamente divididos em quatro grupos: grupo controle (n = 7), sem intervenção; grupo cateter (n = 7), uma cânula foi inserida na artéria central da orelha e medicamentos não foram administrados; grupo sugamadex (n = 7), receberam 4 mg/kg de sugamadex na artéria central da orelha; grupo dexmedetomidina (n = 7), receberam 1 µg/kg de dexmedetomidina na artéria central da orelha. Após 72 horas, as orelhas foram amputadas e histologicamente examinadas. Resultados: Não houve diferença significativa entre os grupos controle e cateter referente aos escores histológicos. Os escores do dano causado ao endotélio e à membrana e fibra elásticas, da hipertrofia do músculo liso e do aumento do tecido conjuntivo foram significativamente maiores nos grupos dexmedetomidina e sugamadex do que nos grupos controle e cateter (p < 0,05). Não houve diferença significativa entre os grupos dexmedetomidina e sugamadex nos escores histológicos. Conclusão: A administração de sugamadex e dexmedetomidina a coelhos por via intra-arterial causou danos arteriais histológicos. Para entender as alterações histológicas causadas por sugamadex e dexmedetomidina com mais clareza, estudos experimentais adicionais são necessários.

DNA polymerase gamma of rabbit intestinal epithelial cells.

1. DNA-directed DNA polymerase gamma was isolated from epithelial cells of the rabbit small intestine, and characterized. 2. The molecular weight of the enzyme, determined by Sephadex G-200 filtration was 105 000 +/- 15%. 3. The enzyme showed preference for poly(A) replication on poly(A)-poly(dT) or poly(A)-oligo(dT) 12-18 templates, as compared with activated DNA. Poly(C)-oligo(dG)12-18 replication was not observed. 4. The Michaelis constants for dTTP in replication of activated DNA and poly(A)-oligo(dT)12-18 were 3.3 and 2.0 micron, respectively.

The antitumor activity of certain substituted nucleosides.

Tests were made of the antitumor activity against lymphoid leukemic L 5178 Y cells in vitro, as exhibited by the following compounds: 2'-O-methyl-araC, 5'-0-methyl-araC, N4,2'-O-dimethyl-araC, N4-methyl-araC, 2,2'-anhydro-5'-O-methyl-araC, N4-methyl-2,2'-anhydro-araC, 4-thio-2,2'-anhydro-araU and 5-amino-araU being a new analogue or araC. The synthesis of the latter compound is described. The activity of 5-amino-araU was tested also in vivo against L 1210 mouse leukemia. O'-Alkylation, N4-exo-alkylation and the change in the amino group position from 4 to 5 abolishes the susceptibility of the above analogues to cytidine deaminase but at the same time it substantially reduces their cytotoxic activity. It was shown that 5-ethyl-2'-deoxyuridine inhibits 14 and 26% in vitro the growth of L 5178 Y cells at concentrations 10(-6) and 10(-5) M, respectively. The possible biological significance of the latter compound is discussed.