Comparative Study of Tumor Targeting and Biodistribution of pH (Low) Insertion Peptides (pHLIP® Peptides) Conjugated with Different Fluorescent Dyes

Purpose Acidification of extracellular space promotes tumor development, progression, and invasiveness. pH (low) insertion peptides (pHLIP® peptides) belong to the class of pH-sensitive membrane peptides, which target acidic tumors and deliver imaging and/or therapeutic agents to cancer cells within tumors. Procedures Ex vivo fluorescent imaging of tissue and organs collected at various time points after administration of different pHLIP® variants conjugated with fluorescent dyes of various polarity was performed. Methods of multivariate statistical analyses were employed to establish classification between fluorescently labeled pHLIP® variants in multidimensional space of spectral parameters. Results The fluorescently labeled pHLIP® variants were classified based on their biodistribution profile and ability of targeting of primary tumors. Also, submillimeter-sized metastatic lesions in lungs were identified by ex vivo imaging after intravenous administration of fluorescent pHLIP® peptide. Conclusions Different cargo molecules conjugated with pHLIP® peptides can alter biodistribution and tumor targeting. The obtained knowledge is essential for the design of novel pHLIP®-based diagnostic and therapeutic agents targeting primary tumors and metastatic lesions

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

Targets of wnt/ß-catenin transcription in penile carcinoma

Penile squamous cell carcinoma (PeCa) is a rare malignancy and little is known regarding the molecular mechanisms involved in carcinogenesis of PeCa. The Wnt signaling pathway, with the transcription activator ß-catenin as a major transducer, is a key cellular pathway during development and in disease, particularly cancer. We have used PeCa tissue arrays and multi-fluorophore labelled, quantitative, immunohistochemistry to interrogate the expression of WNT4, a Wnt ligand, and three targets of Wnt-ß-catenin transcription activation, namely, MMP7, cyclinD1 (CD1) and c-MYC in 141 penile tissue cores from 101 unique samples. The expression of all Wnt signaling proteins tested was increased by 1.6 to 3 fold in PeCa samples compared to control tissue (normal or cancer adjacent) samples (p<0.01). Expression of all proteins, except CD1, showed a significant decrease in grade II compared to grade I tumors. High magnification, deconvolved confocal images were used to measure differences in co-localization between the four proteins. Significant (p<0.04-0.0001) differences were observed for various permutations of the combinations of proteins and state of the tissue (control, tumor grades I and II). Wnt signaling may play an important role in PeCa and proteins of the Wnt signaling network could be useful targets for diagnosis and prognostic stratification of disease

Development of XRMF techniques for measurement of multi-layer film thicknesses on semiconductors for VLSI and ULSI integrated circuits. Final CRADA report for CRADA number Y-1292-0130

A CRADA with Kevex Instruments was carried out to develop improved XRMF instrumentation for the nondestructive analysis of electronic components during manufacture. Experiments conducted at Y-12 proved the feasibility of a new Kevex x-ray tube design. Tests also show that the current commercial supply of straight glass capillaries is unreliable; however, other vendors of tapered single and multiple glass capillaries were identified. The stability of the Y-12 x-ray microprobe was significantly enhanced as a result of this CRADA

DETERMINATION OF FLUORINE IONS PENETRATION DEGREE INTO ENAMEL BY EMPA

Des dents saines ont été traitées de façon exogène par différents produits fluorés. Le fluor a ensuite été analysé par sonde électronique. Les résultats montrent que la meilleure prophylaxie des caries est assurée par des composés fluorés organiques plutôt que minéraux.Exogen application of different preparations was done at completely healthy teeth of children up to 11 years. A month after application of fluorine, the relative teeth were extracted and the same were prepared by stamdard methods for investigation by electron microprobe ARL, type SEMQ. The results obtained showed that the highest degree of fluorine ions migration was stimulated by organic "fluorite" (amin fluoride). Very poor results were obtained by NaF, while the values obtained by "fluor-protector" ranges between these two preparates. All up to date investigations showed that protective characteristics of fluorine against caries formation were reached only in case when enamel surface contained fluorine concentration of 103, µg. Thus, our results undoubtedly proved the fact that the first condition for good prophylaxy is obtained by application of aminofluoride and then by "fluor-protector"

Determination of Fluorine Ions Penetration Degree Into Enamel by Empa.

Exogen of different preparations was applied to completely healthy teeth of children up to 11 years. A month after application of fluorine, teeth were extracted and prepared by standard methods for investigation by electron microprobe ARL, type SEMQ. The results obtained showed that the highest degree of fluorine ions migration was stimulated by organic fluorite' (amin fluoride). Very poor results were obtained by NaF, while the values obtained by 'fluor-protector' ranges between these two preparates. All up to date investigations showed that protective characteristics of fluorine against caries formation were reached only in case when enamel surface contained fluorine concentration of 10**3, mu g. Thus, our results proved that the first condition for good prophylaxy is obtained by application of aminofluoride and then by 'fluor-protector'