Multi-Functional Boron-Delivery Agents for Boron Neutron Capture Therapy of Cancers.

Boron neutron capture therapy (BNCT) is a binary cancer treatment that involves the irradiation of 10B-containing tumors with low-energy neutrons (thermal or epithermal). The alpha particles and recoiling Li nuclei that are produced in the 10B-capture nuclear reaction are high-linear-energy transfer particles that destroy boron-loaded tumor cells; therefore, BNCT has the potential to be a localized therapeutic modality. Two boron-delivery agents have been used in clinical trials of BNCT in patients with malignant brain tumors, cutaneous melanoma, or recurrent tumors of the head and neck region, demonstrating the potential of BNCT in the treatment of difficult cancers. A variety of potentially highly effective boron-delivery agents have been synthesized in the past four decades and tested in cells and animal models. These include boron-containing nucleosides, peptides, proteins, polyamines, porphyrins, liposomes, monoclonal antibodies, and nanoparticles of various types. The most promising agents are multi-functional boronated molecules and nanoparticles functionalized with tumor cell-targeting moieties that increase their tumor selectivity and contain a radiolabel or fluorophore to allow quantification of 10B-biodistribution and treatment planning. This review discusses multi-functional boron agents reported in the last decade, but their full potential can only be ascertained after their evaluation in BNCT clinical trials.

Amino Acid Derivatives of Chlorin-e6-A Review.

Details of the structural elucidation of the clinically useful photodynamic therapy sensitizer NPe6 (15) are presented. NPe6, also designated as Laserphyrin, Talaporfin, and LS-11, is a second-generation photosensitizer derived from chlorophyll-a, currently used in Japan for the treatment of human lung, esophageal, and brain cancers. After the initial misidentification of the structure of this chlorin-e6 aspartic acid conjugate as (13), NMR and other synthetic procedures described herein arrived at the correct structure (15), confirmed using single crystal X-ray crystallography. Interesting new features of chlorin-e6 chemistry (including the intramolecular formation of an anhydride (24)) are reported, allowing chemists to regioselectively conjugate amino acids to each available carboxylic acid on positions 131 (formic), 152 (acetic), and 173 (propionic) of chlorin e6 (14). Cellular investigations of several amino acid conjugates of chlorin-e6 revealed that the 131-aspartylchlorin-e6 derivative is more phototoxic than its 152- and 173-regioisomers, in part due to its nearly linear molecular conformation.

Early results of displaced femoral neck fragility fractures treated with supercapsular percutaneous-assisted total hip arthroplasty.

BACKGROUND: Total hip arthroplasty (THA) is the preferred treatment for displaced femoral neck fractures in select patients, although dislocation remains a concern. In some studies, the supercapsular percutaneously assisted (SuperPATH) approach has demonstrated early mobilization, short hospital stay, and low dislocation rates in primary THA, but there are little data on its use for fractures. This study describes the perioperative outcomes and early dislocation rate of SuperPATH THA for displaced femoral neck fragility fractures. METHODS: A retrospective review was performed of previous ambulatory patients with a displaced femoral neck fragility fracture treated with THA using the SuperPATH approach. Demographic data, time to ambulation, length of stay, and in-hospital complications during the hospital stay and follow-up period were recorded. Phone interviews were conducted to check for dislocations 1 year after surgery. RESULTS: Thirty-seven consecutive patients were included with an average age of 75.0 years. Hospital stay averaged 5.5 days, and patients were discharged on average postoperative day 3.6. About 83.8% of patients were ambulatory by postoperative day 1, and 94.6% ambulatory before discharge. Twenty-seven percent of patients were discharged home, 46% to inpatient rehabilitation, 24% to skilled nursing facility, and 1 patient to hospice. At follow-up, there was no symptomatic heterotopic ossification and no infections. Thirty-two patients were available for telephone interviews at 1 year, with no dislocations reported. CONCLUSIONS: In this small cohort, the SuperPATH approach for THA appears to be safe and effective for use in femoral neck fragility fractures, resulting in early ambulation and a low dislocation rate.

Single-stage revision anterior cruciate ligament reconstruction using bone grafting for posterior or widening tibial tunnels restores stability of the knee and improves clinical outcomes.

PURPOSE: Revision ACL surgery may be complicated by tunnel malposition and/or tunnel widening and often requires a staged treatment approach that includes bone grafting, a period of several months to allow bone graft incorporation and then definitive revision ACL reconstruction. The purpose of this study was to evaluate the results of a single-staged ACL revision reconstruction technique using a cylindrical dowel bone graft for patients who have existing posteriorly placed and/or widened tibial tunnels in the tibia at a minimum of 2 years follow-up. METHODS: Between 2010 and 2014, patients undergoing single-stage revision ACL reconstruction with the described technique were prospectively enrolled and evaluated. At a minimum of 24 months, patients were evaluated by physical examination, multiple clinical outcome instruments including KOOS, Tegner and Lysholm, and preoperative and postoperative MRIs. RESULTS: At a mean of 35.1 months, 18 consecutive patients had no revision surgery and no subjective knee instability. There were statistically significant improvements in the Tegner (median 2, interquartile range 2.25; p < 0.01), Lysholm (20.0 ± 15.0; p < 0.01), KOOS symptoms scale (12.9 ± 11.8; p < 0.01), KOOS pain scale (15.4 ± 18.7; p < 0.01), KOOS ADL scale (13.5 ± 19.0; p < 0.01), KOOS sports scale (32.8 ± 26.4; p < 0.01), and KOOS QoL scale (18.1 ± 16.9; p < 0.01). Postoperative MRI demonstrated statistically significant anteriorization of the tibial tunnel and a statistically significant decrease in tunnel widening. CONCLUSION: Revision ACL reconstruction utilizing a single-staged tibial tunnel grafting technique resulted in improved knee pain, function, and stability at a minimum of 24-month follow-up. LEVEL OF EVIDENCE: IV.

Comparison of MRI, CT, Dunn 45° and Dunn 90° alpha angle measurements in femoroacetabular impingement.

PURPOSE: To determine if a significant difference existed among alpha angle measurements between 4 imaging techniques, axial oblique CT and MRI, Dunn 45° and Dunn 90° plain radiographs, in patients with symptomatic cam femoroacetabular impingement (FAI) and labral tear. METHODS: A single-surgeon prospective radiographic analysis of consecutive non-arthritic and non-dysplastic -patients with symptomatic FAI and labral tears who underwent surgery was performed. Alpha angle was measured using standard techniques as described by Nötzli. Cam morphology was defined via alpha angle measurement of >50.5 degrees. Group comparisons were made using ANOVA and chi-squared test. Sample size calculation was performed prior to study enrollment. RESULTS: 31 subjects (16 female; 33.5 ± 10.5 years mean age) were included. There was a significant difference in alpha angle measurements between all 4 imaging techniques (F [3,120] = 8.144; p<0.001), with the Dunn 45° view (66.3 ± 11.4°) significantly greater than all 3 other techniques (Dunn 90° [57.5 ± 10.7°; p = 0.015], MRI [53.3 ± 11.5°; p<0.001], and CT (54.9 ± 11.6°; p = 0.001). There was no significant difference in alpha angle between Dunn 90°, MRI, and CT. There was a significant difference in the observed number of hips with cam morphology between imaging techniques (χ2 9.4; p = 0.025). CONCLUSIONS: The Dunn 45° radiograph yielded a significantly higher alpha angle than Dunn 90°, axial oblique MRI, and CT imaging modalities. Use of the Dunn 90° or axial oblique MRI or CT as the threshold for cam osteoplasty may result in untreated symptomatic cam FAI. The authors recommend the Dunn 45° radiograph as the most sensitive evaluation of cam morphology.

Syntheses and PDT activity of new mono- and di-conjugated derivatives of chlorin e6.

Syntheses of three new chlorin e6 conjugates for PDT of tumors are reported. One of the new compounds 17 is conjugated with lysine at the 131-position, but the others are mono-conjugated 14 or diconjugated 15 with the non-amino acid species ethanolamine. Cellular experiments with the three new compounds and previously synthesized non-amino acid 152-conjugates (7-10), 131-monoconjugates 14, 16, and a 131,152-diconjugate 12 are reported. In vitro cytotoxicity experiments show that the 131-conjugates are more toxic than the 152-conjugates, and the most toxic derivative (dark- and photo-toxicity) is the 131-ethylenediamine conjugate 11. The most useful PDT photosentitizers appear to be the ethanolamine derivatives, conjugated at the 152- and the 131,152-positions; these show high phototoxicity but relatively low dark toxicity compared with 11, and also the highest dark/photo cytotoxicity ratios.

Do Skin Lacerations Imply Tissue Transfer From Surgeon to Patient During Arthroscopic Knot Tying?

PURPOSE: To use simulated arthroscopic knot tying to assess (1) whether epithelial cells from the surgeon's hands were transmitted to the suture and (2) whether the number of knots tied or the presence of glove tears would correlate with the number of cells transmitted. METHODS: Knots were tied in a simulated arthroscopic environment using a nonabsorbable No. 2 suture over a metal hook. The surgeon was double gloved for each knot tied. For each "anchor," a surgeon's knot was tied, followed by 3 reversed half-hitches on alternating posts. Multiple skin lacerations were sustained by the surgeon during each knot-tying session. Gloves were collected after tying 2, 4, or 6 anchors. Gloves were tested for perforation by (1) electroconductivity and (2) saline solution load testing. Cytopathologic ThinPrep analysis was applied and allowed for the number of epithelial cells found on each suture (within 10 high-powered fields) to be counted. Statistical analysis included analysis of variance and logistic regression. RESULTS: There was no significant difference in the number of epithelial cells identified in any of the groups compared with the negative control groups (P > .05) or with each other (P > .05). Glove tears were present in 3.3% of gloves (50% in inner and 50% in outer gloves) and 1.7% of gloves (50% in inner and 50% in outer gloves) by electroconductivity and saline solution load testing, respectively. There was no significant association between glove tears and the number of epithelial cells found on the suture (P > .05). CONCLUSIONS: Epithelial cells were transmitted to the suture during simulated arthroscopic knot tying. However, despite multiple skin lacerations produced during knot-tying sessions, the number of cells transmitted was not significantly different when compared with the negative controls. The number of cells transmitted did not correlate with the number of knots tied and/or the presence of glove tears. CLINICAL RELEVANCE: Skin lacerations on the surgeon's fingers are often noted after arthroscopic knot tying. However, despite these skin lacerations, no skin tissue is transferred across the surgical gloves to the suture itself.

Fluoroscopy Learning Curve in Hip Arthroscopy-A Single Surgeon's Experience.

PURPOSE: To determine if (1) absorbed radiation dose and (2) fluoroscopy time decreased with experience over the first 100 cases of a single surgeon's hip arthroscopy practice. METHODS: Subjects who underwent hip arthroscopy for symptomatic femoroacetabular impingement and labral injury were eligible for analysis. Inclusion criteria included the first 100 subjects who underwent hip arthroscopy by a single surgeon (December 2013 to December 2014). Subject demographics, procedure details, fluoroscopy absorbed dose (milligray [mGy]), and time were recorded. Subjects were categorized by date of surgery to one of 4 possible groups (25 per group). One-way analysis of variance was used to determine if a significant difference in dose (mGy) or time was present between groups. Simple linear regression analysis was performed to determine the relation between case number and both radiation dose and fluoroscopy time. RESULTS: Subjects underwent labral repair (n = 93), cam osteoplasty (n = 90), and pincer acetabuloplasty (n = 65). There was a significant (P < .001 for both) linear regression between case number and both radiation dose and fluoroscopy time. A significant difference in mGy was observed between groups, group 1 the highest and group 4 the lowest amounts of radiation (P = .003). Comparing individual groups, group 4 was found to have a significantly lower amount of radiation than group 1 (P = .002), though it was not significantly lower than that of group 2 (P = .09) or group 3 (P = .08). A significant difference in fluoroscopy time was observed between groups, group 1 the highest and group 4 the lowest times (P = .05). Comparing individual groups, group 4 was found to have a significantly lower fluoroscopy time than group 1 (P = .039). Correction for weight, height, and body mass index all revealed the same findings: significant (P < .05) differences in both dose and time across groups. CONCLUSIONS: The absorbed dose of radiation and fluoroscopy time decreased significantly over the first 100 cases of a single surgeon's hip arthroscopy practice learning curve. LEVEL OF EVIDENCE: Level IV, therapeutic, retrospective, noncomparative case series.

Radiographic and clinical comparison of pegged and keeled glenoid components using modern cementing techniques: midterm results of a prospective randomized study.

BACKGROUND: Glenoid component loosening remains a significant issue after anatomic shoulder arthroplasty. Pegged glenoid components have shown better lucency rates than keeled components in the short term; however, midterm to long-term results have not fully been determined. We previously reported early outcomes of the current randomized controlled group of patients, with higher glenoid lucency rates in those with a keeled glenoid. The purpose of this study was to evaluate the radiographic and clinical outcomes of these components at minimum 5-year follow-up. METHODS: Fifty-nine total shoulder arthroplasties were performed in patients with primary glenohumeral osteoarthritis. Patients were randomized to receive either a pegged or keeled glenoid component. Three raters graded radiographic glenoid lucencies. Clinical outcome scores and active mobility outcomes were collected preoperatively and at yearly postoperative appointments. RESULTS: Of the 46 shoulders meeting the inclusion criteria, 38 (82.6%) were available for minimum 5-year radiographic follow-up. After an average of 7.9 years, radiographic lucency was present in 100% of pegged and 91% of keeled components (P = .617). Grade 4 or 5 lucency was present in 44% of pegged and 36% of keeled components (P = .743). There were no differences in clinical outcome scores or active mobility outcomes between shoulders with pegged and keeled components at last follow-up. Within the initial cohort, 20% of the keeled shoulders (6 of 30) and 7% of the pegged shoulders (2 of 29) underwent revision surgery (P = .263). Kaplan-Meier analysis showed no significant difference in survival rates between groups (P = .560). CONCLUSION: At an average 7.9-year follow-up, non-ingrowth, all-polyethylene pegged glenoid implants are equivalent to keeled implants with respect to radiolucency, clinical outcomes, and need for revision surgery.

Synthesis and Spectroscopic and Cellular Properties of Near-IR [a]Phenanthrene-Fused 4,4-Difluoro-4-bora-3a,4a-diaza-s-indacenes.

A new synthetic method to build aryl-fused 4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes (BODIPYs) is reported. The intramolecular cyclization step was completed in a short time (1-2 h) and in high yields (>90%), due to the intrinsic rigid structural conformation of the precursor BODIPY and the high reactivity of its 1,7-bromo groups. The [a]phenanthrene-fused BODIPYs 4a-c were characterized by NMR spectroscopy, HRMS, DFT calculations, and, in the case of 4a, by X-ray crystallography. Spectroscopic studies show that 4a-c strongly absorb and emit in the NIR spectral region, in the range 642-701 nm. In addition, BODIPYs 4b and 4c exhibit no toxicity in the light or dark in HEp2 cells and accumulate intracellularly in a time-dependent manner, mainly in the cell endoplasmic reticulum. These results suggest the potential use of [a]phenanthrene-fused BODIPYs as NIR bioimaging probes.

Arthroscopic hip preservation surgery practice patterns: an international survey.

To design and conduct a survey analyzing pre-, intra- and post- hip arthroscopy practice patterns among hip arthroscopists worldwide. A 21-question, IRB-exempt, HIPAA-compliant, cross-sectional survey was conducted via email using SurveyMonkey to examine pre-operative evaluation, intra-operative techniques and post-operative management. The survey was administered internationally to 151 hip arthroscopists identified from publicly available sources. Seventy-five respondents completed the survey (151 ± 116 hip arthroscopy procedures per year; 8.6 ± 7.1 years hip arthroscopy experience). Standing AP pelvis, false profile and Dunn 45 were the most common radiographs utilized. CT scans were utilized by 54% of surgeons at least some of the time. Only 56% of participants recommended an arthrogram with MRI. Nearly all surgeons either never (40%) or infrequently (58%) performed arthroscopy in Tönnis grade-2 or grade-3 osteoarthritis. Surgeons rarely performed hip arthroscopy on patients with dysplasia (51% never; 44% infrequently). Only 25% of participants perform a routine 'T' capsulotomy and 41% close the capsule if the patient is at risk for post-operative instability. Post-operatively, 52% never use a brace, 39% never use a continuous passive motion, 11% never recommended heterotopic ossification prophylaxis and 30% never recommended formal thromboembolic disease prophylaxis. Among a large number of high-volume experienced hip arthroscopists worldwide, pre-, intra- and post- hip arthroscopy practice patterns have been established and reported. Within this cohort of respondents, several areas of patient evaluation and management remain discordant and controversial without universal agreement. Future research should move beyond expert opinion level V evidence towards high-quality appropriately designed and conducted investigations.

Stemmed tibial revision component alignment: Does an anatomic conflict exist?

INTRODUCTION: Obtaining satisfactory coronal plane alignment is important for success in revision total knee arthroplasty (TKA). The study objective was to determine tibial coronal plane alignment after TKA when a tibial stem was used and assess if there was an anatomic conflict in tibial stemmed component alignment. MATERIALS AND METHODS: A radiographic review of 88 revision TKA cases was performed. Full length leg radiographs were examined for varus/valgus alignment, defined as greater than or equal to three degrees from neutral 180 degrees, canal or non-canal filling tibial stems, and any native tibial bow. RESULTS: In tibias with a native valgus alignment of three or more degrees, a canal-filling stem allowed little flexibility to improve final positioning of the tibial stem and resulted in a valgus alignment of the tibial stem in 87.5% of cases, where a canal filling stem was utilized. A non-canal filling stem utilized in native valgus tibias allowed on average a two-degree improvement in tibial alignment and 64.7% of cases resulted in a neutral placement of the tibial stem. CONCLUSION: Implanting the tibial component in a desired position is limited by type of stem and the native angulation of the tibia. When anatomic conflict exists between tibial mechanical axis and the intramedullary canal, canal filling stems may compromise coronal alignment.

Assessment of a Cultural Competency Program in Podiatric Medical Education.

BACKGROUND: Des Moines University College of Podiatric Medicine and Surgery (CPMS) is implementing a cultural competency program for third-year podiatric medical students. This study assessed the effectiveness of the new educational program on cultural competency at CPMS by comparing pretest and posttest scores of students from the CPMS graduating classes of 2013 and 2014. METHODS: Students from the class of 2013 completed a 10-week online course on cultural competency, and the class of 2014 students did not. A pretest and posttest survey was used to assess cultural competency. The questions were categorized to assess either knowledge acquisition or attitudinal change. The 2013 students completed the pretest before the course and a posttest after completing the course. Without taking the course, 2014 students completed the same pretest and posttest separated by 10 weeks. A repeated-measures analysis of variance was used to compare the knowledge acquisition scores and attitudinal change scores. RESULTS: The repeated-measures analysis of variance revealed a significant interaction effect of taking the attitudinal change course (F(1,77) = 15.2; P < .001). The course did not show a significant interaction on knowledge acquisition (F(1,77) = 0.72; P > .05). CONCLUSIONS: The analysis showed a statistically significant improvement in attitudinal change scores. The study suggests that there needs to be a greater knowledge acquisition component to the cultural competency course at CPMS.

Syntheses and cellular investigations of di-aspartate and aspartate-lysine chlorin e(6) conjugates.

Chlorin e6 is a tricarboxylic acid degradation product of chlorophyll a. Four chlorin e6 bis(amino acid) conjugates were regioselectively synthesized bearing two aspartate conjugates in the 13(1),17(3)- and 15(2),17(3)-positions, or at the 13(1),15(2)via an ethylene diamine linker. One additional conjugate bearing two different amino acids, lysine at 13(1)via an ethylene diamine linker and an aspartate at 15(2)via a ß-alanine linker was also synthesized. The cytotoxicity and uptake of four di(amino acid) chlorin e6 conjugates were investigated in human HEp2 cells, and compared with chlorin e6. The most cytotoxic and most taken up conjugates were the zwitterionic 13(1),15(2)-disubstituted conjugates 28 and 33; these also localized in multiple organelles. In contrast, the anionic 13(1),17(3)- and 15(2),17(3)-di-aspartyl chlorin e6 conjugates 12 and 13 showed low dark cytoxicity and lower phototoxicity compared with chlorin e6.

Impact of substituents and nonplanarity on nickel and copper porphyrin electrochemistry: first observation of a Cu(II)/Cu(III) reaction in nonaqueous media.

Electrochemical studies of the oxidation of dodecasubstituted and highly nonplanar nickel porphyrins in a noncoordinating solvent have previously revealed the first nickel(III) porphyrin dication. Herein, we investigate if these nonplanar porphyrins can also be used to detect the so far unobserved copper(III) porphyrin dication. Electrochemical studies of the oxidation of (DPP)Cu and (OETPP)Cu show three processes, the first two of which are macrocycle-centered to give the porphyrin dication followed by a Cu(II)/Cu(III) process at more positive potential. Support for the assignment of the Cu(II)/Cu(III) process comes from the linear relationships observed between E1/2 and the third ionization potential of the central metal ions for iron, cobalt, nickel, and copper complexes of (DPP)M and (OETPP)M. In addition, the oxidation behavior of additional nonplanar nickel porphyrins is investigated in a noncoordinating solvent, with nickel meso-tetraalkylporphyrins also being found to form nickel(III) porphyrin dications. Finally, examination of the nickel meso-tetraalkylporphyrins in a coordinating solvent (pyridine) reveals that the first oxidation becomes metal-centered under these conditions, as was previously noted for a range of nominally planar porphyrins.

Phenyl derivative of iron 5,10,15-tritolylcorrole.

The phenyl-iron complex of 5,10,15-tritolylcorrole was prepared by reaction of the starting chloro-iron complex with phenylmagnesium bromide in dichloromethane. The organometallic complex was fully characterized by a combination of spectroscopic methods, X-ray crystallography, and density functional theory (DFT) calculations. All of these techniques support the description of the electronic structure of this phenyl-iron derivative as a low-spin iron(IV) coordinated to a closed-shell corrolate trianion and to a phenyl monoanion. Complete assignments of the (1)H and (13)C NMR spectra of the phenyl-iron derivative and the starting chloro-iron complex were performed on the basis of the NMR spectra of the regioselectively ß-substituted bromo derivatives and the DFT calculations.

Early corrosion-related failure of the rejuvenate modular total hip replacement.

BACKGROUND: The Rejuvenate modular-neck stem implant (Stryker Orthopaedics, Mahwah, New Jersey) was recently recalled due to corrosion at the femoral neck-stem junction. The purpose of this study was to investigate the rate of corrosion-related failure and survivorship of this implant and analyze the correlation of implant and patient factors with serum metal ion levels and revisions. METHODS: From June 2009 to July 2012, 123 Rejuvenate total hip arthroplasty stems (ninety-seven modular and twenty-six non-modular) were implanted in 104 patients by a single surgeon. Serum cobalt (Co) and chromium (Cr) levels (micrograms per liter [µg/L]) were measured postoperatively for all patients. Patients with persistent hip pain or elevated metal ion levels underwent magnetic resonance imaging for assessment of osteolysis or adverse local tissue reactions. Correlation of implant factors (stem size, head size, head length, and femoral head-neck offset) and patient factors (age, sex, and body mass index) with serum metal ion levels and revisions were analyzed with use of logistic regression models. RESULTS: The mean duration of follow-up (and standard deviation) was 2.7 ± 0.6 years. The mean Co and Cr levels were 5.4 ± 5.7 µg/L (range, 0.2 to 31 µg/L) and 2.1 ± 1.5 µg/L (range, 0.1 to 4.3 µg/L), respectively. The differences in Co and Cr levels between the two groups (modular and non-modular) were significant: 48% of the total hip arthroplasties in the modular group resulted in elevated metal ion levels (Co >4.0 µg/L and Cr >2.0 µg/L; p < 0.05). The metal ion levels in the non-modular group were normal. In the modular group, higher metal ion levels were significantly correlated with younger age and a higher femoral head-neck offset (p = 0.04). Pain and high Co serum levels were significant predictors of revision surgery (p = 0.006). The rate of revision at the time of this study was 28% in the modular group, with the majority of the revisions performed in the second year after surgery; the Kaplan-Meier survivorship was 40% at four years. CONCLUSIONS: The short-term high rate of corrosion-related revision with Rejuvenate modular-neck stems is striking.

Synthesis, spectroscopic, and cellular properties of α-pegylated cis-A2B2- and A3B-types ZnPcs.

A series of pegylated cis-A2B2- or A3B-type ZnPcs, substituted on the α-positions with tri(ethylene glycol) and hydroxyl groups, were synthesized from a new bis-phthalonitrile. A clamshell-type bis-phthalocyanine was also obtained as a byproduct. The hydroxyl group of one ZnPc was alkylated with 3-dimethylaminopropyl chloride to afford a pegylated ZnPc functionalized with an amine group. All mononuclear ZnPcs were soluble in polar organic solvents, showed intense Q absorptions in DMF, and had fluorescence quantum yields in the range 0.10-0.23. The clamshell-type bis-phthalocyanine adopts mainly open shell conformations in DMF, and closed clamshell conformations in chloroform. All ZnPcs were highly phototoxic to human carcinoma HEp2 cells, particularly the amino-ZnPc mainly protonated under physiological conditions, which showed the highest phototoxicity (IC50 = 0.5 µM at 1.5 J/cm2) and dark cytotoxicity (IC50 = 22 µM), in part due to its high cellular uptake. The ZnPcs localized in multiple organelles, including mitochondria, lysosomes, Golgi and ER.

Differences in microbial signatures between rectal mucosal biopsies and rectal swabs.

There is growing evidence the microbiota of the large bowel may influence the risk of developing colorectal cancer as well as other diseases including type-1 diabetes, inflammatory bowel diseases and irritable bowel syndrome. Current sampling methods to obtain microbial specimens, such as feces and mucosal biopsies, are inconvenient and unappealing to patients. Obtaining samples through rectal swabs could prove to be a quicker and relatively easier method, but it is unclear if swabs are an adequate substitute. We compared bacterial diversity and composition from rectal swabs and rectal mucosal biopsies in order to examine the viability of rectal swabs as an alternative to biopsies. Paired rectal swabs and mucosal biopsy samples were collected in un-prepped participants (n = 11) and microbial diversity was characterized by Terminal Restriction Fragment Length polymorphism (T-RFLP) analysis and quantitative polymerase chain reaction (qPCR) of the 16S rRNA gene. Microbial community composition from swab samples was different from rectal mucosal biopsies (p = 0.001). Overall the bacterial diversity was higher in swab samples than in biopsies as assessed by diversity indexes such as: richness (p = 0.01), evenness (p = 0.06) and Shannon's diversity (p = 0.04). Analysis of specific bacterial groups by qPCR showed higher copy number of Lactobacillus (p < 0.0001) and Eubacteria (p = 0.0003) in swab samples compared with biopsies. Our findings suggest that rectal swabs and rectal mucosal samples provide different views of the microbiota in the large intestine.