Radiochemical quality control of the radiopharmaceutical, 89SrCl2 produced in FBTR.

89SrCl2 radiopharmaceuticals is mainly used for bone pain palliation in the cancer patients, is being produced in FBTR via 89Y(n, p)89Sr using yttria target. The irradiated yttria target is chemically processed in high pure quartz distilled nitric acid medium in hot cell facility, to avoid the corrosion of components of hotcell due to chloride ions while using HCl medium. Being ionic species, the purified 89Sr(II) cation in aqueous solution containing bulk nitrate and other trace anions, exists as SrXn species where X: F-, Cl-, Br-, NO3-, PO43- and SO42-, n: stoichiometric anion content. The aim of the manuscript is to standardise an efficient ultra-low level anion purification method (ppb range) for the conversion of SrXn to SrCl2 and estimate the residual anionic impurities as recommended by the appropriate source specifications for its medical application. Various methods were standardised for the removal of anions in the SrCl2 source produced by the above process which include evaporation, calcination, anion exchange column, cation exchange column as well as its combination with pre-concentration column of ion chromatography (IC) technique using 89Sr tracers as well as FBTR produced 89Sr solution. Assay of 89Sr and other anions including nitrate for the above study were accomplished using Cerenkov counting and ion chromatography respectively. Thus evaporation-calcination-column chromatography mode was finalised to obtain pure SrCl2 source free from nitrate and other anionic impurities. This is the first ever systematic study for the Radiochemical quality control of nca 89SrCl2 radiopharmaceutical produced in a fast reactor. This study also finds its application to any analytical lab as well as industry where there is a requirement of anion purification in the ppb level.

Associations Between Eight Earth Observation-Derived Climate Variables and Enteropathogen Infection: An Independent Participant Data Meta-Analysis of Surveillance Studies With Broad Spectrum Nucleic Acid Diagnostics.

Diarrheal disease, still a major cause of childhood illness, is caused by numerous, diverse infectious microorganisms, which are differentially sensitive to environmental conditions. Enteropathogen-specific impacts of climate remain underexplored. Results from 15 studies that diagnosed enteropathogens in 64,788 stool samples from 20,760 children in 19 countries were combined. Infection status for 10 common enteropathogens-adenovirus, astrovirus, norovirus, rotavirus, sapovirus, Campylobacter, ETEC, Shigella, Cryptosporidium and Giardia-was matched by date with hydrometeorological variables from a global Earth observation dataset-precipitation and runoff volume, humidity, soil moisture, solar radiation, air pressure, temperature, and wind speed. Models were fitted for each pathogen, accounting for lags, nonlinearity, confounders, and threshold effects. Different variables showed complex, non-linear associations with infection risk varying in magnitude and direction depending on pathogen species. Rotavirus infection decreased markedly following increasing 7-day average temperatures-a relative risk of 0.76 (95% confidence interval: 0.69-0.85) above 28°C-while ETEC risk increased by almost half, 1.43 (1.36-1.50), in the 20-35°C range. Risk for all pathogens was highest following soil moistures in the upper range. Humidity was associated with increases in bacterial infections and decreases in most viral infections. Several virus species' risk increased following lower-than-average rainfall, while rotavirus and ETEC increased with heavier runoff. Temperature, soil moisture, and humidity are particularly influential parameters across all enteropathogens, likely impacting pathogen survival outside the host. Precipitation and runoff have divergent associations with different enteric viruses. These effects may engender shifts in the relative burden of diarrhea-causing agents as the global climate changes.

Interaction of a bovine serum albumin (BSA) protein with mixed anionic-cationic surfactants and the resultant structure.

The interaction of a bovine serum albumin (BSA) protein with the mixture of anionic sodium dodecyl sulfate (SDS) and cationic dodecyltrimethylammonium bromide (DTAB) has been investigated by small-angle neutron scattering (SANS) and dynamic light scattering (DLS). Both SDS and DTAB as individuals interact electrostatically as well as hydrophobically with BSA and form connected protein-decorated micelle like complexes in the aqueous solution, in which the well-defined surfactant micelles are organized along the randomly distributed unfolded polypeptide chain of the protein. The protein-surfactant interaction has been tuned by adding different molar mixtures of SDS and DTAB in BSA aqueous solution. It is found that a lower molar fraction of either surfactant in the protein-mixed surfactant complexes results in the formation of a connected protein-decorated micelle structure similar to those of pure surfactants. As the molar fraction of one of the surfactants in the mixture approaches the equimolar fraction, the structure formed by the protein-mixed surfactant is very different from the connected protein-decorated micelle like structure. Different microstructures of BSA-mixed surfactant complexes are formed, mostly governed by the structure of mixed surfactants arising from the strong electrostatic interaction of oppositely charged components. In this case, unfolded proteins wrap the structures of mixed surfactants around their surface. Along with the connected protein-decorated micelle like structure, rod-like and bilayer vesicles of protein-surfactant complexes are formed at different molar fractions of mixed surfactants.

Use of quantitative molecular diagnostic methods to identify causes of diarrhoea in children: a reanalysis of the GEMS case-control study.

BACKGROUND: Diarrhoea is the second leading cause of mortality in children worldwide, but establishing the cause can be complicated by diverse diagnostic approaches and varying test characteristics. We used quantitative molecular diagnostic methods to reassess causes of diarrhoea in the Global Enteric Multicenter Study (GEMS). METHODS: GEMS was a study of moderate to severe diarrhoea in children younger than 5 years in Africa and Asia. We used quantitative real-time PCR (qPCR) to test for 32 enteropathogens in stool samples from cases and matched asymptomatic controls from GEMS, and compared pathogen-specific attributable incidences with those found with the original GEMS microbiological methods, including culture, EIA, and reverse-transcriptase PCR. We calculated revised pathogen-specific burdens of disease and assessed causes in individual children. FINDINGS: We analysed 5304 sample pairs. For most pathogens, incidence was greater with qPCR than with the original methods, particularly for adenovirus 40/41 (around five times), Shigella spp or enteroinvasive Escherichia coli (EIEC) and Campylobactor jejuni o C coli (around two times), and heat-stable enterotoxin-producing E coli ([ST-ETEC] around 1·5 times). The six most attributable pathogens became, in descending order, Shigella spp, rotavirus, adenovirus 40/41, ST-ETEC, Cryptosporidium spp, and Campylobacter spp. Pathogen-attributable diarrhoeal burden was 89·3% (95% CI 83·2-96·0) at the population level, compared with 51·5% (48·0-55·0) in the original GEMS analysis. The top six pathogens accounted for 77·8% (74·6-80·9) of all attributable diarrhoea. With use of model-derived quantitative cutoffs to assess individual diarrhoeal cases, 2254 (42·5%) of 5304 cases had one diarrhoea-associated pathogen detected and 2063 (38·9%) had two or more, with Shigella spp and rotavirus being the pathogens most strongly associated with diarrhoea in children with mixed infections. INTERPRETATION: A quantitative molecular diagnostic approach improved population-level and case-level characterisation of the causes of diarrhoea and indicated a high burden of disease associated with six pathogens, for which targeted treatment should be prioritised. FUNDING: Bill & Melinda Gates Foundation.

The role of solvent swelling in the self-assembly of squalene based nanomedicines.

Squalene based nanoparticles obtained via nanoprecipitation are promising candidates as efficient anti-cancer drugs. In order to highlight their preparation process and to facilitate further clinical translation, the present study enlightens the paramount role of the solvent in the formation of these nanomedicines. Three different squalene-based nanoparticles, i.e. squalenic acid, deoxycytidine squalene and gemcitabine squalene, have been investigated before and after organic solvent evaporation. Size and structural analysis by Small Angle Neutron Scattering revealed that droplets' size was uniquely controlled by the solvent composition (ethanol-water), which evolved during their gradual formation. The particles were preferably swollen by water and the swelling increased when less ethanol was present. Either coalescence or fragmentation was observed depending on the increase or decrease of the ethanol content, supporting an equilibrium control of the size. Moreover, a high water swelling was observed for the three local organization of the nanodroplets (hexagonal for gemcitabine squalene, cubic for deoxycytidine and not structured for squalenic acid) and could be the source of the previously reported efficiency of related anti-cancer squalene based nanomedicines.

Discovery of STL polyomavirus, a polyomavirus of ancestral recombinant origin that encodes a unique T antigen by alternative splicing.

The family Polyomaviridae is comprised of circular double-stranded DNA viruses, several of which are associated with diseases, including cancer, in immunocompromised patients. Here we describe a novel polyomavirus recovered from the fecal microbiota of a child in Malawi, provisionally named STL polyomavirus (STLPyV). We detected STLPyV in clinical stool specimens from USA and The Gambia at up to 1% frequency. Complete genome comparisons of two STLPyV strains demonstrated 5.2% nucleotide divergence. Alternative splicing of the STLPyV early region yielded a unique form of T antigen, which we named 229T, in addition to the expected large and small T antigens. STLPyV has a mosaic genome and shares an ancestral recombinant origin with MWPyV. The discovery of STLPyV highlights a novel alternative splicing strategy and advances our understanding of the complex evolutionary history of polyomaviruses.

Structural characterization and spectroelectrochemical, anion sensing and solvent dependence photophysical studies of a bimetallic Ru(II) complex derived from 1,3-di(1H-imidazo[4,5-f][1,10]phenanthroline-2-yl)benzene.

The X-ray crystal structure of a mixed-ligand bimetallic ruthenium(II) complex of composition [(bipy)(2)Ru(H(2)Impib)Ru(bipy)(2)](ClO(4))(4) (1), where H(2)Impib = 1,3-di(1H-imidazo[4,5-f][1,10]phenanthroline-2-yl)benzene and bipy = 2,2'-bipyridine, has been determined and showed that the compound crystallized in monoclinic form with the space group P2(1)/c. The absorption, steady state and time-resolved luminescence spectral properties of the complex were thoroughly investigated in different solvents. The compound displays strong luminescence at room temperature with lifetimes in the range of 140-470 ns, depending upon the nature of the solvent. Solvent-induced lifetime tuning makes the complex a suitable solvatochromic probe. The complex is found to undergo one simultaneous two-electron reversible oxidation in the positive potential window (0 to +1.6 V) and four quasi-reversible reductions in the negative potential window (0 to -2.2 V). Spectroelectrochemical studies have also been carried out for the bimetallic compound in the range of 300-1600 nm. With stepwise oxidation of the Ru(ii) centers replacement of MLCT bands by LMCT bands occur with the development of a broad band at λ(max) = 1260 nm, which is ascribed to inter-valence charge-transfer (IVCT) transition for the mixed-valence Ru(II)Ru(III) species. The anion sensing properties of the receptor were thoroughly investigated in acetonitrile solution using absorption, steady state and time-resolved emission spectroscopic studies. The anion sensing studies revealed that the receptor acts as sensor for F(-), AcO(-) and H(2)PO(4)(-). It is evident that in the presence of excess F(-) and AcO(-) ions, deprotonation of the imidazole N-H fragments of the receptor occurs, an event which is signaled by the change of color from yellow to orange visible to the naked eye. From the absorption and emission titration studies the binding/equilibrium constants of the receptor with the anions have also been determined. Anion-induced lifetime quenching by F(-) and AcO(-) and enhancement by H(2)PO(4)(-) makes the receptor a suitable lifetime-based sensor for selective anions. Cyclic voltammetry (CV) measurements of the compound carried out in acetonitrile have provided evidence in favor of anion-dependent electrochemical responses with F(-) and AcO(-) ions.

A prospective randomised, controlled clinical trial comparing medial and lateral entry pinning with lateral entry pinning for percutaneous fixation of displaced extension type supracondylar fractures of the humerus in children.

OBJECTIVE: To compare the efficacy of medial and lateral entry pinning with lateral entry pinning for percutaneous fixation of displaced (Gartland type II and type III) extension type supracondylar fractures of the humerus in children. METHODS: The study was a single center, prospective, randomized controlled clinical trial. Between October 2007 and September 2010, 160 patients who satisfy the inclusion and exclusion criterias were enrolled in the study, with 80 patients in each group. All the percutaneous pinning was done according to a uniform standardized technique. The patients were re-evaluated as outpatients at three weeks, six weeks and three months after the surgery. At three months follow-up visit, following informations were recorded as outcome measures: (i) Carrying angle (deg) (ii) passive range of elbow motion (deg) (iii) Flynn's criteria for grading, based on the loss of carrying angle and loss of total range of elbow motion. (iv) Baumann angle (deg) (v) Change in Baumann angle (deg) between the Intraoperative radiographs after the surgery and radiographs at three months follow-up visit (vi) loss of reduction grading, based on the change in the Baumann angle. RESULTS: There were no significant differences between the two groups with regard to base-line characteristics, withdrawals and complication rate. At three months follow-up visit, patients were evaluated by recording the various outcome measures. There were no significant differences between the two groups with regard to the various outcome measures such as carrying angle, passive range of elbow motion, Flynn grading, Baumann angle, change in the Baumann angle and loss of reduction grading. CONCLUSIONS: If a uniform standardized operative technique is followed in each method, then the result of both the percutaneous fixation methods will be same in terms of safety and efficacy.

Monitoring the introduction of pneumococcal conjugate vaccines into West Africa: design and implementation of a population-based surveillance system.

Routine use of pneumococcal conjugate vaccines (PCVs) in developing countries is expected to lead to a significant reduction in childhood deaths. However, PCVs have been associated with replacement disease with non-vaccine serotypes. We established a population-based surveillance system to document the direct and indirect impact of PCVs on the incidence of invasive pneumococcal disease (IPD) and radiological pneumonia in those aged 2 months and older in The Gambia, and to monitor changes in serotype-specific IPD. Here we describe how this surveillance system was set up and is being operated as a partnership between the Medical Research Council Unit and the Gambian Government. This surveillance system is expected to provide crucial information for immunisation policy and serves as a potential model for those introducing routine PCV vaccination in diverse settings.

Clonidine as an adjuvant in axillary brachial plexus block for below elbow orthopedic surgeries: A comparison between local and systemic administration.

BACKGROUND: Axillary brachial plexus block for below elbow orthopedic surgery provides a safe and low-cost technique with the advantage of prolonged postoperative analgesia. Clonidine, with selective partial agonist activity on α2 adrenergic receptors, has significantly demonstrated its role in this regard as an adjuvant to local anesthetics. The current study compares the locally administered clonidine with systemically administered control group in terms of onset and duration of sensory block, motor block, and analgesia; hemodynamic variability; sedation; and other side effect profile. MATERIALS AND METHODS: Seventy patients (ASA I or II) scheduled for below elbow orthopedic surgeries were randomly allocated in equal numbers to receive either 30 ml of 0.5% plain bupivacaine with 150 µg (1 ml) of inj. clonidine locally in the axillary sheath and 1 ml of normal saline (NS) subcutaneously (Group L) or 30 ml of 0.5% plain bupivacaine with 1 ml of NS locally and 150 µg (1 ml) of inj. clonidine subcutaneously (Group S). Standard monitoring of vital parameters was done. Duration of sensory and motor block, analgesia, hemodynamic changes, and any adverse effects were observed and recorded for different duration up to 24 h. RESULTS: Duration of sensory block (625 ± 35 min), motor block (690 ± 38 min), and analgesia (930 ± 45 min) was significantly longer in Group L than in Group S [sensory block (480 ± 30 min), motor block (535 ± 25 min), and analgesia (720 ± 30 min)] (P < 0.05). Significant alteration of heart rate, systolic blood pressure and diastolic blood pressure, and mean arterial pressure in Group S was observed compared to Group L (P < 0.05). Side effects like nausea and vomiting were comparable, but highly significant sedation score (χ(2) = 47.75 and 49.51 at 120 and 240 min, respectively; P < 0.01) was observed between the two groups. CONCLUSION: Compared to systemic administration, local clonidine as an adjuvant in axillary block resulted in significant prolongation of duration of sensory and motor blockade, and analgesia without any hemodynamic alteration, probably by locally mediated mechanism of action.