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The development of bacteria‐specific infection radiotracers is of considerable interest to improve diagnostic accuracy and enabling therapy monitoring. The aim of this study was to determine if the previously reported radiolabelled 1,4,7,10‐tetraazacyclododecane‐N,N′,N″,N‴‐tetraacetic acid (DOTA) conjugated peptide [68Ga]Ga‐DOTA‐K‐A9 could detect a staphylococcal infection in vivo and distinguish it from aseptic inflammation. An optimized [68Ga]Ga‐DOTA‐K‐A9 synthesis omitting the use of acetone was developed, yielding 93 ± 0.9% radiochemical purity. The in vivo infection binding specificity of [68Ga]Ga‐DOTA‐K‐A9 was evaluated by micro positron emission tomography/magnetic resonance imaging of 15 mice with either subcutaneous Staphylococcus aureus infection or turpentine‐induced inflammation and compared with 2‐deoxy‐2‐[18F]fluoro‐D‐glucose ([18F]FDG). The scans showed that [68Ga]Ga‐DOTA‐K‐A9 accumulated in all the infected mice at injected doses ≥3.6 MBq. However, the tracer was not found to be selective towards infection, since the [68Ga]Ga‐DOTA‐K‐A9 also accumulated in mice with inflammation. In a concurrent in vitro binding evaluation performed with a 5‐carboxytetramethylrhodamine (TAMRA) fluorescence analogue of the peptide, TAMRA‐K‐A9, the microscopy results suggested that TAMRA‐K‐A9 bound to an intracellular epitope and therefore preferentially targeted dead bacteria. Thus, the [68Ga]Ga‐DOTA‐K‐A9 uptake observed in vivo is presumably a combination of local hyperemia, vascular leakiness and/or binding to an epitope present in dead bacteria. [ABSTRACT FROM AUTHOR]

When determining whether or not remediation of subslab contamination is warranted, it is often important to know if the presence of volatile organic compounds (VOCs) in indoor air is caused primarily by interior sources, or primarily by subslab contamination. With a Building Pressure Control test, the pressure differential across the building envelope and, thereby, also the pressure differential across the slab, can be controlled by a blower. By measuring the indoor air concentrations of VOCs under depressurization (upward pressure gradient over the slab) and under pressurization (downward pressure gradient over the slab), it can be determined if the subslab contamination contributes significantly to the VOC concentrations in indoor air. This technique has been applied at several sites in the Central Denmark Region, and the results show that a Building Pressure Control test is a quick and effective method to examine if VOC contamination in indoor air is caused primarily by interior sources or primarily by subslab sources. With numerous measurement points in the indoor air, at some sites this test method has identified the area where the subslab contamination is located. A pressure differential at -5/+5 Pa across the building envelope was sufficient at all the test sites to control the pressure gradient across the slab to be uniquely upward/downward. [ABSTRACT FROM AUTHOR]

Investigations at former dry cleaning sites in Denmark show that sewer systems often are a major vapor intrusion pathway for chlorinated solvents to indoor air. In more than 20 percent of the contaminated drycleaner sites in Central Denmark Region, sewer systems were determined to be a major vapor intrusion pathway. Sewer systems can be a major intrusion pathway if contaminated groundwater intrudes into the sewer and contamination is transported within the sewer pipe by water flow in either free phase or dissolved states. Additionally, the contamination can volatilize from the water phase or soil gas can intrude the sewer system directly. In the sewer, the gas phase can migrate in any direction by convective transport or diffusion. Indications of the sewer as a major intrusion pathway are: higher concentrations in the upper floors in buildings,, higher concentrations in indoor air than expected from soil gas measurements,, higher concentrations in bathrooms/kitchen than in living rooms,, chlorinated solvents in the sewer system, and, a pressure gradient from the sewer system to indoor air., Measurements to detect whether or not the sewer system is an intrusion pathway are simple. In Central Denmark Region, the concentrations of contaminants are routinely measured in the indoor air at all floors, the outdoor air, behind the water traps in the building, and in the manholes close to the building. The indoor and outdoor air concentration, as well as concentrations in manholes, are measured by passive sampling on sorbent samplers over a 14-day period, and the measurements inside the sewer system are carried out by active sampling using carbon tubes (sorbent samplers). Furthermore, the pressure gradient over the building slab and between the indoor air and the sewer system are also measured. A simple test is depressurization of the sewer system. Using this technique, the pressure gradient between the sewer system and the indoor air is altered toward the sewer system-the contamination cannot enter the indoor air through the sewer system. If the sewer system is a major intrusion pathway, the effect of the test can be observed immediately in the indoor air. Remediation of a sewer transported contamination can be: prevention of the contaminants from intruding into the sewer system or, prevention of the contaminated gas in the sewer system from intruding into the indoor air., Remediation techniques include the following: lining of the sewer piping to prevent the contamination from intruding into the sewer;, sealing the sewer system in the building to prevent the contamination from the sewer system to intrude the indoor air;, venting of manholes; and, depressurizing the sewer system. [ABSTRACT FROM AUTHOR]

Introduction: Systemic chemotherapy is able to convert colorectal liver metastases (CRLM) that are initially unsuitable for local treatment into locally treatable disease. Surgical resection further improves survival in these patients. Our aim was to evaluate disease-free survival (DFS), overall survival, and morbidity for patients with CRLM treated with RFA following effective downstaging by chemotherapy, and to identify factors associated with recurrence and survival. Materials and methods: Included patients had liver-dominant CRLM initially unsuitable for local treatment but eligible for RFA or RFA with resection after downstaging by systemic chemotherapy. Chemotherapeutic regimens consisted predominantly of CapOx, with or without bevacizumab. Follow-up was conducted with PET-CT or thoraco-pelvic CT. Results: Fifty-one patients had a total of 325 CRLM (median = 7). Following chemotherapy, 183 lesions were still visible on CT (median = 3). Twenty-six patients were treated with RFA combined with resection. During surgery, 309 CRLM were retrieved on intraoperative ultrasound (median = 5). Median survival was 49 months and was associated with extrahepatic disease at time of presentation and recurrences after treatment. Estimated cumulative survival at 1, 3 and 4 years was 90, 63 and 45 %, respectively. Median DFS was 6 months. Twelve patients remained free of recurrence after a mean follow-up of 32.6 months. Conclusion: RFA of CRLM after conversion chemotherapy provides potential local control and a good overall survival. To prevent undertreatment, the involvement of a multidisciplinary team in follow-up imaging and assessment of local treatment possibilities after palliative chemotherapy for liver-dominant CRLM should always be considered. [ABSTRACT FROM AUTHOR]

Background: Patients with colorectal liver metastases (CRLM) who are ineligible for curative surgery are potential candidates for radiofrequency ablation (RFA). Although RFA has emerged as a well accepted and documented treatment modality, there are still some reservations because of initially high rates of local site recurrences (LSR). The aim of the present study was to evaluate LSR levels following RFA treatment, with a specific focus on re-treatment and survival. Patients and methods: All patients ineligible for curative resection of CRLM and undergoing RFA alone or in combination with resection were prospectively included from July 2000 to December 2010 and retrospectively analyzed. Patients with untreatable extrahepatic disease were excluded. FDG PET-CT was conducted at 3-6 month intervals after RFA. Patients with LSR were evaluated for re-treatment. Results: A total of 132 patients were treated with RFA, which was combined with resection in 64 patients. A total of 290 lesions were ablated, with a mean number of 2.19 per patient and a mean size of 2.2 cm. Median survival was 41 months, with a 3- and 5-year survival of, respectively, 60 and 30.8 %. Following initial RFA, 39 patients developed an LSR in 40 ablated lesions, and local recurrence was strongly related to lesion size. Re-treatment could be performed in 26/39 patients, of whom eight remained disease-free. Conclusions: Radiofrequency ablation can be applied to CRLM of less than 3 cm with curative intent. In the absence of extensive intrahepatic or extrahepatic disease, renewed treatment of local recurrences should be considered and is often successful. [ABSTRACT FROM AUTHOR]

J. Neurochem. (2012) 121, 373-382. Abstract Several metabolic neuroimaging studies have indicated that bipolar patients with mania exhibit alterations in metabolic activity, suggesting that perturbations in corticolimbic function contribute to the functional deficits associated with the disease. Because pharmacological stimulation of Kv7 channel function has shown anti-manic like efficacy in the D-amphetamine and chlordiazepoxide (AMPH+CDP) induced hyperactivity mouse model of mania, we addressed whether this effect of Kv7 channels could be associated with changes in cerebral [14C]2-deoxyglucose (2-DG) uptake, a surrogate marker of brain metabolic activity. Acute administration of the Kv7 channel modulators, retigabine (pan Kv7.2-Kv7.5 channel opener) and ICA-27243 (Kv7.2/Kv7.3 channel-preferring opener) reduced 2-DG uptake in several mouse forebrain structures with a brain regional signature similar to the mood stabilizers, lithium and valproate. Combined administration of AMPH+CDP enhanced 2-DG uptake in the striatum, cortex and thalamus, and both retigabine and ICA-27243 fully prevented this stimulatory effect of AMPH+CDP. In addition, both Kv7 channel openers dose-dependently increased phospho-serine-9 levels of GSK3β in the prefrontal cortex and hippocampus, a common molecular mechanism shared by anti-manic drugs. In combination, these data emphasize the potential of Kv7 channel openers in the treatment of bipolar disorder, and suggest that heteromeric Kv7.2/Kv7.3 channels may present a novel anti-manic therapeutic target. [ABSTRACT FROM AUTHOR]

Phenylketonuria (PKU) is an inherited metabolic disease characterized by phenylalanine (Phe) accumulation due to defects in the enzyme phenylalanine hydroxylase (PAH). Phe accumulation can lead to cognitive impairment. Some individuals with PKU respond to tetrahydrobiopterin (BH4) treatment, the natural cofactor of PAH, by a reduction in blood Phe concentrations. We tested 12 patients with PKU, 8–29 years of age, all carrying the common Y414C mutation in the PAH gene. Three were homozygous and nine were compound heterozygous, with the second mutation being a putative null mutation. During the study period, genuine protein was increased to approximately 1 g/kg. The patients were treated with 20, 10, and 5 mg BH4/kg/day for 1 week on each dose, starting with 20 mg/kg. A positive response was defined as a decline in blood Phe > 30%. Blood Phe was measured four times a week. Nonresponding children were excluded from the study. Eleven of 12 patients had a positive response with 20 mg/kg, 5/10 responded on 10 mg/kg, and 1/9 on 5 mg/kg. Two were late responders, with a response on 20 mg/kg after >48 h. We could confirm the previously reported inconsistent responsiveness of Y414C in the nine heterozygous patients, whereas the three homozygous patients had early median Phe declines of 73%, 51%, and 27%, respectively, on the three different doses. The varying responses despite uniform trial conditions and genotypes may be due to individual differences in BH4 absorption or metabolism. No side effects were observed. [ABSTRACT FROM AUTHOR]

Objectives: Certain milk factors may help to promote the growth of a host-friendly colonic microflora (e.g. bifidobacteria, lactobacilli) and explain why breast-fed infants experience fewer and milder intestinal infections than those who are formula-fed. The effects of supplementation of formula with two such milk factors was investigated in this study.Materials and Methods: Infant rhesus macaques were breast-fed, fed control formula, or formula supplemented with glycomacropeptide (GMP) or alpha-lactalbumin (alpha-LA) from birth to 5 months of age. Blood was drawn monthly and rectal swabs were collected weekly. At 4.5 months of age, 10(8) colony-forming units of enteropathogenic E.coli O127, strain 2349/68 (EPEC) was given orally and the response to infection assessed. The bacteriology of rectal swabs pre- and post-infection was determined by culture independent fluorescence in situ hybridization.Results: Post-challenge, breast-fed infants and infants fed alpha-LA-supplemented formula had no diarrhea, whilst those infants fed GMP-supplemented formula had intermittent diarrhea. In infants fed control formula the diarrhea was acute.Conclusions: Supplementation of infant formula with appropriate milk proteins may be useful for improving the infant's ability to resist acute infection caused by E.coli. [ABSTRACT FROM AUTHOR]