Cortical acetylcholine dynamics are predicted by cholinergic axon activity and behavior state.

Even under spontaneous conditions and in the absence of changing environmental demands, awake animals alternate between increased or decreased periods of alertness. These changes in brain state can occur rapidly, on a timescale of seconds, and neuromodulators such as acetylcholine (ACh) are thought to play an important role in driving these spontaneous state transitions. Here, we perform the first simultaneous imaging of ACh sensors and GCaMP-expressing axons in vivo, to examine the spatiotemporal properties of cortical ACh activity and release during spontaneous changes in behavioral state. We observed a high correlation between simultaneously recorded basal forebrain axon activity and neuromodulator sensor fluorescence around periods of locomotion and pupil dilation. Consistent with volume transmission of ACh, increases in axon activity were accompanied by increases in local ACh levels that fell off with the distance from the nearest axon. GRAB-ACh fluorescence could be accurately predicted from axonal activity alone, providing the first validation that neuromodulator axon activity is a reliable proxy for nearby neuromodulator levels. Deconvolution of fluorescence traces allowed us to account for the kinetics of the GRAB-ACh sensor and emphasized the rapid clearance of ACh for smaller transients outside of running periods. Finally, we trained a predictive model of ACh fluctuations from the combination of pupil size and running speed; this model performed better than using either variable alone, and generalized well to unseen data. Overall, these results contribute to a growing understanding of the precise timing and spatial characteristics of cortical ACh during fast brain state transitions.

SERS determination of sodium saccharin content on the tipping paper of cigarettes using AgNP substrates prepared with a USB-power supply device.

A novel magnetic agitating heater powered by a USB port has been developed and applied to synthesize silver colloid substrate for surface-enhanced Raman scattering (SERS) detection of sodium saccharin content on the tipping paper of cigarettes. The heater device allows the convenient synthesis of the Ag colloid, and the reaction can be completed on-site in 15 min under mild conditions. The on-site synthesis of SERS substrate effectively avoided the need for storage and concerns regarding the poor stability and short lifespan of colloid substrates. The results demonstrated that the substrate obtained with the device could achieve SERS detection of Rhodamine 6G (R6G) at as low as 10-9 mol L-1 while maintaining a stable intensity with a relative standard deviation (RSD) of 5.52% (n = 5). Using the prepared substrate at the optimal conditions, the limit of detection of sodium saccharin (SS) was 1 mg L-1. By introducing an internal standard KSCN, a linear relationship was observed between the relative intensity at 708 cm-1 and the concentration of the SS in a range of 20-100 mg L-1 (R2 = 0.98). With the developed method, SS was directly extracted from the cigarette paper by immersing it in water, and the extracted solution was subsequently detected. The quantitative spike-recoveries were in the range of 95.5-116.7%, with RSD between 2.3-12.6%. The whole detection procedure including the on-site substrate preparation, took only about 30 min. This work opens new avenues for colloidal synthesis, and the detection method of SS on the cigarette paper also holds great promise in food safety applications.

Pharmacodynamics of Piperacillin-Tazobactam/Amikacin Combination versus Meropenem against Extended-Spectrum ß-Lactamase-Producing Escherichia coli in a Hollow Fiber Infection Model.

Carbapenems are recommended for the treatment of urosepsis caused by extended-spectrum ß-lactamase (ESBL)-producing, multidrug-resistant Escherichia coli; however, due to selection of carbapenem resistance, there is an increasing interest in alternative treatment regimens including the use of ß-lactam-aminoglycoside combinations. We compared the pharmacodynamic activity of piperacillin-tazobactam and amikacin as mono and combination therapy versus meropenem monotherapy against extended-spectrum ß-lactamase (ESBL)-producing, piperacillin-tazobactam resistant E. coli using a dynamic hollow fiber infection model (HFIM) over 7 days. Broth-microdilution was performed to determine the MIC of E. coli isolates. Whole genome sequencing was conducted. Four E. coli isolates were tested in HFIM with an initial inoculum of ~107 CFU/mL. Dosing regimens tested were piperacillin-tazobactam 4.5 g, 6-hourly, plus amikacin 30 mg/kg, 24-hourly, as combination therapy, and piperacillin-tazobactam 4.5 g, 6-hourly, amikacin 30 mg/kg, 24-hourly, and meropenem 1 g, 8-hourly, each as monotherapy. We observed that piperacillin-tazobactam and amikacin monotherapy demonstrated initial rapid bacterial killing but then led to amplification of resistant subpopulations. The piperacillin-tazobactam/amikacin combination and meropenem experiments both attained a rapid bacterial killing (~4-5 log10) within 24 h and did not result in any emergence of resistant subpopulations. Genome sequencing demonstrated that all ESBL-producing E. coli clinical isolates carried multiple antibiotic resistance genes including blaCTX-M-15, blaOXA-1, blaEC, blaTEM-1, and aac(6')-Ib-cr. These results suggest that the combination of piperacillin-tazobactam/amikacin may have a potential role as a carbapenem-sparing regimen, which should be tested in future urosepsis clinical trials.

Human health implications of trace metal contamination in topsoils and brinjal fruits harvested from a famous brinjal-producing area in Bangladesh.

A study was undertaken to determine the contents of trace metals in 60 topsoils and 80 brinjal fruits samples from a famous brinjal-producing area of Bangladesh using atomic absorption spectrophotometer. The study also looked at soil pollution levels, dietary intake of nutritionally important trace elements, and human health risks from toxic metals induced by dermal soil exposure and consumption of brinjal. The content of Pb, Ni, Cd, Cu, Fe, Mn, and Zn in brinjal fruits harvested from farmer's fields ranged from 0.204-0.729, 0.031-0.212, < 0.010-0.061, 1.819-2.668, 3.267-5.910, < 0.010-0.866 and 2.160-3.846 µg g-1, respectively, while the amount of Cr was negligible. The calculated enrichment factors showed that 70, 50, and 25% of soil sampling sites had values in the 2.00-5.00 range for Pb, Zn, and Cd, respectively, while 30% of sites had values > 5.00 for Cd, indicating moderate to significant enrichment of these metals in the soil. The study also revealed that brinjal consumption provides a tiny amount of nutritionally important trace elements required for an adult human. Regarding the computed incremental lifetime cancer risks (ILCR), the study revealed that the values for Pb and Ni in all samples and Cd in 40% of samples were several hundred times higher for males and females than the USEPA threshold level due to oral ingestion of brinjal fruits. In contrast, dermal exposures to soil trace elements were within an acceptable range. The PCA results revealed that the contents of Cd, Pb, Ni, and Cu in soils showed strong positive correlations with those elements present in brinjal. The current study suggests future traceability research, focusing on pinpointing potential entry routes for toxic elements into the vegetable food chain.

Pharmacodynamic evaluation of piperacillin/tazobactam against extended-spectrum ß-lactamase (ESBL)-producing versus non-ESBL-producing Escherichia coli in a hollow-fibre infection model.

Extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli are a global public-health concern. We evaluated the pharmacodynamic activity of piperacillin/tazobactam (TZP) dosing regimens against ESBL-producing versus non-ESBL-producing E. coli. Five E. coli clinical isolates were obtained from Bangladesh. Broth microdilution and whole-genome sequencing (WGS) were performed on the five studied isolates. Three TZP-susceptible ESBL-producing and two non-ESBL-producing E. coli were exposed to TZP regimens of 4.5 g every 6 h (q6h) and every 8 h (q8h) as a 30-min infusion in a dynamic hollow-fibre infection model over 7 days. The extent of bacterial killing was ∼4-5 log10 CFU/mL against ESBL-producing and non-ESBL-producing E. coli with TZP q6h and q8h regimens over the first 8 h. Bacterial killing was similar between two of three ESBL-producing (CTAP#168 and CTAP#169) and two non-ESBL-producing (CTAP#179 and CTAP#180) E. coli clinical isolates over the course of the experiment. ESBL-producing CTAP#173 E. coli was poorly killed (∼1 log) compared with two non-ESBL-producing E. coli over 168 h. WGS revealed that ESBL-producing E. coli isolates co-harboured multiple antimicrobial resistance genes such as blaCTX-M-15, blaEC, blaOXA-1, blaTEM-1 and aac(6')-Ib-cr5. Overall, TZP q6h and q8h dosing regimens attained >3 log bacterial kill against all ESBL-producing or non-ESBL-producing E. coli within 24 h and maintained and prevented the emergence of resistance through the end of the experiment. In conclusion, TZP standard regimens resulted in similar bacterial killing and prevented the emergence of resistance against CTX-M-15-type ESBL-producing and non-ESBL-producing E. coli clinical isolates.

Pharmacodynamic evaluation of piperacillin/tazobactam versus meropenem against extended-spectrum ß-lactamase-producing and non-producing Escherichia coli clinical isolates in a hollow-fibre infection model.

BACKGROUND: Urosepsis caused by extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli is increasing worldwide. Carbapenems are commonly recommended for the treatment of ESBL infections; however, to minimize the emergence of carbapenem resistance, interest in alternative treatments has heightened. OBJECTIVES: This study compared pharmacodynamics of piperacillin/tazobactam versus meropenem against ESBL-producing and non-producing E. coli clinical isolates. METHODS: E. coli isolates, obtained from national reference laboratory in Bangladesh, were characterized by phenotypic tests, WGS, susceptibility tests and mutant frequency analysis. Three ESBL-producing and two non-producing E. coli were exposed to piperacillin/tazobactam (4.5 g, every 6 h and every 8 h, 30 min infusion) and meropenem (1 g, every 8 h, 30 min infusion) in a hollow-fibre infection model over 7 days. RESULTS: Piperacillin/tazobactam regimens attained ∼4-5 log10 cfu/mL bacterial killing within 24 h and prevented resistance emergence over the experiment against ESBL-producing and non-producing E. coli. However, compared with 8 hourly meropenem, the 6 hourly piperacillin/tazobactam attained ∼1 log10 lower bacterial kill against one of three ESBL-producing E. coli (CTAP#173) but comparable killing for the other two ESBL-producing (CTAP#168 and CTAP#169) and two non-producing E. coli (CTAP#179 and CTAP#180). The 6 hourly piperacillin/tazobactam regimen attained ∼1 log10 greater bacterial kill compared with the 8 hourly regimen against CTAP#168 and CTAP#179 at 24 h. CONCLUSIONS: Our study suggests piperacillin/tazobactam may be a potential alternative to carbapenems to treat urosepsis caused by ESBL-producing E. coli, although clinical trials with robust design are needed to confirm non-inferiority of outcome.

Human health exposure and risks of arsenic from contaminated soils and brinjal fruits collected from different producers and retailers levels.

A quantitative assessment was attempted to determine concentrations of total arsenic (As) in farmer's field soils and fruits of brinjal collected from two famous brinjals producing Upazila's, namely Melandaha and Islampur of Jamalpur district, Bangladesh. The study also evaluated cancer and non-cancer health risks for both males and females caused by dermal exposure of soils and dietary intake of brinjal grown in farmers' fields and sold at different markets of four country districts. The study findings revealed that 75% of soil sampling locations had enrichment factor (EFc) values > 1.5, indicating the anthropogenic sources of As, and 50% of the sites possessed EFc values within the range of 2.0-5.0 indicated moderate enrichment of As. The mean concentrations of As in brinjal grown in farmers' fields and retailers of different markets of four districts were 0.18 and 0.39 µg g-1, respectively. The soils of the study area exhibited negligible risk in terms of the calculated hazard quotient, hazard index and incremental lifetiame cancer risk (ILCR) values for As due to dermal and ingestion exposures. In contrast, the same values for As due to the dietary intake of brinjal were thousands of times greater than the threshold level in 40% of farmers' field and all retailers' levels samples. Compared to the producer/farmers' field samples, the calculated average non-carcinogenic and carcinogenic health risks were more than twice in samples collected from different retailers. The present study suggests further pinpoint investigation of potential entry routes of As in the supply chain through future traceability studies.

Outcomes of the Novel Supreme Drug-Eluting Stent in Complex Coronary Lesions: A PIONEER III Substudy.

Background: The Supreme healing-targeted drug-eluting stent (DES) is designed to promote endothelial healing to reduce stent-related adverse events. This may be particularly relevant among complex lesions that have a higher rate of adverse events. We sought to compare 1-year outcomes of percutaneous coronary intervention in complex lesions between the Supreme DES and contemporary durable-polymer, everolimus-eluting stents (DP-EES). Methods: PIONEER III was a multicenter, prospective, single-blind clinical trial, randomizing 1629 patients with either an acute or chronic coronary syndrome in a 2:1 ratio to the Supreme DES or DP-EES. Complex lesions (American College of Cardiology/American Heart Association type B2/C) were found in 1137 patients. Outcomes were also compared for specific parameters of lesion complexity: severe calcification, long length (>20 â€‹mm), and severe tortuosity. The primary end point was target lesion failure at 1 â€‹year. Results: At 1 â€‹year, there was no difference in target lesion failure between the Supreme DES and DP-EES: (5.7% vs 5.6%; hazard ratio 1.00, 95% confidence interval 0.59-1.68, P = .99). Similarly, there were no differences in the secondary end points of lesion success (99.7% vs 99.4%, P = .41), device success (97.0% vs 98.5%, P = .14), target vessel failure (6.5% vs 7.4%, P = .50), major adverse cardiac events (7.8% vs 8.5%, P = .64), or stent thrombosis (0.7% vs 1.1%, P = .48). A trend was observed toward a higher rate of target lesion revascularization with the Supreme DES (2.5% vs 0.9%, P = .06). Conclusions: This study suggests that the Supreme DES is as effective and safe at 1 â€‹year compared with the standard DP-EES across a broad spectrum of lesion complexity.

The incidence of medial end clavicle fractures is higher than had previously been considered.

BACKGROUND: Previous X-ray epidemiological studies have estimated the incidence of medial end clavicle fractures to account for 2-3% of all clavicle fractures. MATERIALS AND METHODS: At our institution X-rays of every patient attending the Emergency Department are reviewed at a Virtual Fracture Clinic by a Consultant Orthopaedic Surgeon. Patients with a fracture are referred to the Shoulder and Elbow Fracture Clinic. Patients without a fracture are contacted and, if there are on-going concerns, are referred to the Shoulder and Elbow Fracture Clinic. Over an 18-month period we identified every patient that attended our Emergency Department that had sustained a clavicle fracture. RESULTS: In total 558 clavicle fractures were identified (139 (24.9%) - lateral, 360 (64.5%) - middle, 59 (10.6%) - medial). Of the 59 medial end fractures, 31 (52.5%) were identified on presentation at the Emergency Department, 13 (22%) at the Virtual Fracture Clinic, 6 (10.2%) on computed tomography scan at the Shoulder and Elbow Fracture Clinic and 9 (15.3%) were admitted directly to the trauma unit. CONCLUSION: The results of this study suggest that the incidence of medial end clavicle fractures in the general population is higher than had previously been considered. LEVEL OF EVIDENCE: IV.

Epidemiological, clinical, and public health response characteristics of a large outbreak of diphtheria among the Rohingya population in Cox's Bazar, Bangladesh, 2017 to 2019: A retrospective study.

BACKGROUND: Unrest in Myanmar in August 2017 resulted in the movement of over 700,000 Rohingya refugees to overcrowded camps in Cox's Bazar, Bangladesh. A large outbreak of diphtheria subsequently began in this population. METHODS AND FINDINGS: Data were collected during mass vaccination campaigns (MVCs), contact tracing activities, and from 9 Diphtheria Treatment Centers (DTCs) operated by national and international organizations. These data were used to describe the epidemiological and clinical features and the control measures to prevent transmission, during the first 2 years of the outbreak. Between November 10, 2017 and November 9, 2019, 7,064 cases were reported: 285 (4.0%) laboratory-confirmed, 3,610 (51.1%) probable, and 3,169 (44.9%) suspected cases. The crude attack rate was 51.5 cases per 10,000 person-years, and epidemic doubling time was 4.4 days (95% confidence interval [CI] 4.2-4.7) during the exponential growth phase. The median age was 10 years (range 0-85), and 3,126 (44.3%) were male. The typical symptoms were sore throat (93.5%), fever (86.0%), pseudomembrane (34.7%), and gross cervical lymphadenopathy (GCL; 30.6%). Diphtheria antitoxin (DAT) was administered to 1,062 (89.0%) out of 1,193 eligible patients, with adverse reactions following among 229 (21.6%). There were 45 deaths (case fatality ratio [CFR] 0.6%). Household contacts for 5,702 (80.7%) of 7,064 cases were successfully traced. A total of 41,452 contacts were identified, of whom 40,364 (97.4%) consented to begin chemoprophylaxis; adherence was 55.0% (N = 22,218) at 3-day follow-up. Unvaccinated household contacts were vaccinated with 3 doses (with 4-week interval), while a booster dose was administered if the primary vaccination schedule had been completed. The proportion of contacts vaccinated was 64.7% overall. Three MVC rounds were conducted, with administrative coverage varying between 88.5% and 110.4%. Pentavalent vaccine was administered to those aged 6 weeks to 6 years, while tetanus and diphtheria (Td) vaccine was administered to those aged 7 years and older. Lack of adequate diagnostic capacity to confirm cases was the main limitation, with a majority of cases unconfirmed and the proportion of true diphtheria cases unknown. CONCLUSIONS: To our knowledge, this is the largest reported diphtheria outbreak in refugee settings. We observed that high population density, poor living conditions, and fast growth rate were associated with explosive expansion of the outbreak during the initial exponential growth phase. Three rounds of mass vaccinations targeting those aged 6 weeks to 14 years were associated with only modestly reduced transmission, and additional public health measures were necessary to end the outbreak. This outbreak has a long-lasting tail, with Rt oscillating at around 1 for an extended period. An adequate global DAT stockpile needs to be maintained. All populations must have access to health services and routine vaccination, and this access must be maintained during humanitarian crises.

Outcome of lymph node tuberculosis management with conventional treatment with and without prednisolone.

The outcome of lymph node tuberculosis (LNTB) management with conventional anti-tubercular treatment alone is unsatisfactory. We conducted a randomised open-label controlled clinical trial in the Department of Respiratory Medicine in Government Institute of Dhaka, Bangladesh from April 2017 to March 2019. Compared with controls, 54 patients of LNTB received category 1 anti-tubercular treatment with additional prednisolone after randomisation. Complete resolution in 21/54 (75%) and 7 (26.9%), symptomatic improvement in 26 (92.9%) and 22 (84.6%) and complications in 11 (39.28%) and 16 (61.53%) were observed in the treatment and control group, respectively. Thus, we recommend the use of steroids in this setting.

The role of iliocapsularis in hip pathology: a scoping review.

The iliocapsularis is a relatively unheard-of muscle, located deep in the hip covering the anteromedial capsule of the hip joint. Little is known about this constant muscle despite its clinical relevance. The aims of this scoping review are to collate the various research studies reporting on the detailed anatomy and function of iliocapsularis and to demonstrate how inter-individual differences in iliocapsularis can be used as a clinical adjunct in guiding diagnosis and treatment of certain hip joint pathologies. A computer-assisted literature search was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Our review found 13 studies including 384 cases meeting our inclusion criteria. About 53.8% of the studies involved human cadavers. The current scoping review indicates the relevant anatomy of the iliocapsularis, being a small muscle which arises from the inferior border of the anterior inferior iliac spine and anteromedial capsule of the hip joint, inserting distal to the lesser trochanter. Therefore, based upon these anatomical attachments, iliocapsularis acts as a dynamic stabilizer by tightening the anterior capsule of the hip joint. Implications of this association may be that the muscle is hypertrophied in dysplastic or unstable hips. Determining the size of the iliocapsularis could be of conceivable use in patients with hip symptoms featuring signs of both borderline hip dysplasia and subtle cam-type deformities. Although future research is warranted, this study will aid physicians to understand the clinical importance of the iliocapsularis.

Investigation of a Large Diphtheria Outbreak and Cocirculation of Corynebacterium pseudodiphtheriticum Among Forcibly Displaced Myanmar Nationals, 2017-2019.

BACKGROUND: Diphtheria, a life-threatening respiratory disease, is caused mainly by toxin-producing strains of Corynebacterium diphtheriae, while nontoxigenic corynebacteria (eg, Corynebacterium pseudodiphtheriticum) rarely causes diphtheria-like illness. Recently, global diphtheria outbreaks have resulted from breakdown of health care infrastructures, particularly in countries experiencing political conflict. This report summarizes a laboratory and epidemiological investigation of a diphtheria outbreak among forcibly displaced Myanmar nationals in Bangladesh. METHODS: Specimens and clinical information were collected from patients presenting at diphtheria treatment centers. Swabs were tested for toxin gene (tox)-bearing C. diphtheriae by real-time polymerase chain reaction (RT-PCR) and culture. The isolation of another Corynebacterium species prompted further laboratory investigation. RESULTS: Among 382 patients, 153 (40%) tested tox positive for C. diphtheriae by RT-PCR; 31 (20%) PCR-positive swabs were culture confirmed. RT-PCR revealed 78% (298/382) of patients tested positive for C. pseudodiphtheriticum. Of patients positive for only C. diphtheriae, 63% (17/27) had severe disease compared to 55% (69/126) positive for both Corynebacterium species, and 38% (66/172) for only C. pseudodiphtheriticum. CONCLUSIONS: We report confirmation of a diphtheria outbreak and identification of a cocirculating Corynebacterium species. The high proportion of C. pseudodiphtheriticum codetection may explain why many suspected patients testing negative for C. diphtheriae presented with diphtheria-like symptoms.

Association of Estimated GFR (By MDRD) with the Carotid Intima Media Thickness (CIMT) in Different Stages of CKD among Patients with Type 2 Diabetes Mellitus.

Most of the mortalities among Diabetic Nephropathy patients are cardiovascular, if we identify the risk factor, measures can be taken to prevent it. Hence an objective was set to evaluate the association between carotid artery intima media thickness (CIMT) with eGFR in patients of CKD stage III, IV and V among patients with type 2 diabetes mellitus; also, correlation with age, BMI, lipid profile. This cross-sectional, observational study was performed in 70 patients in different stages of CKD in Diabetic Patients selected by Inclusion Criteria (Diabetic nephropathy patients with stages III, IV, V and exclusion Criteria (Acute kidney injury, History of carotid surgery, Patients of MI and stroke). This study was performed in Department of Nephrology, Dhaka Medical College in collaboration with the Department of Radiology and Imaging, laboratory of Department of Biochemistry and Department of Microbiology at Dhaka Medical College Hospital (By standard method in laboratory) from 1st January 2016 to 31st December 2016. eGFR was measured by MDRD formula and the CIMT was measured using an ultrasonographic examination. The mean CIMT was 0.9±0.21mm, and 62.9% of the subjects showed IMT thickening (≥1mm). The carotid IMT elevated significantly with the stage progression of CKD (Overall eGFR mean 28.8±14.5mL/min/1.73m² in CIMT<1mm with range from 6 to 54 and 9.1±9.0mL/min/1.73m² in CIMT ≥1mm with range from 3 to 32 (p=0.001). The eGFR was significantly lower in the patients with CIMT thickening than those without CIMT thickening. eGFR was also significantly associated with CKD stages (p=0.001), serum creatinine (p=0.001), BMI (r = -0.330, p=0.005), and negatively associated with age group, duration of hypertension, smoking. However, the CIMT was not significantly different among the patients at different stages of diabetic nephropathy (r = -0.172, p=156) and age group. It has been concluded that the mean CIMT was markedly high in patients with CKD compared to normal expected value. This study showed a relationship between the CIMT and the renal parameters as eGFR and the stages of diabetic nephropathy with a confirm association between the CIMT and diabetic macroangiopathy.

Lumbar Ligament Sprain-degeneration and Prolapsed Lumbar Intervertebral Disc: A Frequent Missed Combination.

Low back pain (LBP) is a frequent complaint in the working milieu of pain physicians. Common LBP generators are the lumbar spine, soft tissues around the spine, and intra-abdominal viscera; however, in recent times, lumbar spine ligament (LL) degeneration is increasingly getting more coverage as an important LBP source. Among various LLs, interspinous and supraspinatus ligaments' sprain-degeneration can perpetuate localized central LBP as described in the present case study. Localized LL sprain-degeneration in association with radiating LBP from prolapsed lumbar intervertebral disc (PLID) compressing adjacent nerve roots might further impair a patient's quality of life. In the present report, we describe both LL sprain-degeneration and PLID (a dual source of LBP) in a 26-year-old Bangladeshi woman; physicians often fail to notice this combination in their regular clinical practice.

Americium and plutonium separation by extraction chromatography for determination by accelerator mass spectrometry.

A simple method was developed to separate Pu and Am using single column extraction chromatography employing N,N,N',N'-tetra-n-octyldiglycolamide (DGA) resin. Isotope dilution measurements of Am and Pu were performed using accelerator mass spectrometry (AMS) and alpha spectrometry. For maximum adsorption Pu was stabilized in the tetra valent oxidation state in 8M HNO3 with 0.05 M NaNO2 before loading the sample onto the resin. Am(III) was adsorbed also onto the resin from concentrated HNO3, and desorbed with 0.1 M HCl while keeping the Pu adsorbed. The on-column reduction of Pu(IV) to Pu(III) with 0.02 M TiCl3 facilitated the complete desorption of Pu. Interferences (e.g. Ca(2+), Fe(3+)) were washed off from the resin bed with excess HNO3. Using NdF3, micro-precipitates of the separated isotopes were prepared for analysis by both AMS and alpha spectrometry. The recovery was 97.7±5.3% and 95.5±4.6% for (241)Am and (242)Pu respectively in reagents without a matrix. The recoveries of the same isotopes were 99.1±6.0 and 96.8±5.3% respectively in garden soil. The robustness of the method was validated using certified reference materials (IAEA 384 and IAEA 385). The measurements agree with the certified values over a range of about 1-100 Bq kg(-1). The single column separation of Pu and Am saves reagents, separation time, and cost.

Sources, spatial variation, and speciation of heavy metals in sediments of the Tamagawa River in Central Japan.

Sediments of the Tamagawa River in central Japan were studied to explain the spatial variation, to identify the sources of heavy metals, and to evaluate the anthropogenic influence on these pollutants in the river. Sediment samples were collected from 20 sites along the river (five upstream, four midstream, and 11 downstream). Heavy metal concentrations, viz. chromium, nickel, copper, zinc, lead, cadmium, and molybdenum, in the samples were measured using inductively coupled plasma-mass spectroscopy. The chemical speciations of heavy metals in the sediments were identified by the widely used five-step Hall method. Lead isotopes were analyzed to identify what portion is contributed by anthropogenic sources. The total heavy metal concentrations were compared with global averages for continental crust (shale) and average values for Japanese river sediments. The mean heavy metal concentrations were higher in downstream sediments than in upstream and midstream samples, and the concentrations in the silt samples were higher than those in the sand samples. Speciation results demonstrate that, for chromium and nickel, the residual fractions were dominant. These findings imply that the influence of anthropogenic chromium and nickel contamination is negligible, while copper, zinc, and lead were mostly extracted in the non-residual fraction (metals in adsorbed/exchangeable/carbonate forms or bound to amorphous Fe oxyhydroxides, crystalline Fe oxides, or organic matter), indicating that these elements have high chemical mobility. The proportion of lead (Pb) isotopes in the downstream silt samples indicates that Pb accumulation is primarily derived from anthropogenic sources.

Menaquinone-4 enhances testosterone production in rats and testis-derived tumor cells.

BACKGROUND: Vitamin K is essential for the posttranslational modification of various Gla proteins. Although it is widespread in several organs, including the testis, the function of vitamin K in these organs is not well characterized. In this study, we investigated the function of vitamin K in the testis and analyzed its role in steroidogenesis. METHODS: Eight-week-old male Wistar rats were fed a diet supplemented with menaquinone-4 (MK-4, 75 mg/kg diet), one of the predominant K2 vitamins present in the testis, for 5 weeks. In vivo testosterone levels of the rats' plasma and testes were measured by enzyme-linked immunosorbent assay, and in vitro testosterone levels of testis-derived tumor cells (I-10 cells) maintained in Ham's F-10 medium with 10% fetal bovine serum were measured following treatment with MK-4 (0 to 100 µM) at several time points. Testosterone and cellular protein levels were analyzed with respect to their effects on steroidogenesis. RESULTS: Testosterone levels in the plasma and testes of MK-4-fed rats were significantly increased compared to those of control rats, with no obvious differences in plasma luteinizing hormone levels. Secreted testosterone levels from I-10 cells were elevated by MK-4, but not by vitamin K1, in a dose-dependent manner independent of cAMP treatment. Western blot analysis revealed that expression of CYP11A, the rate-limiting enzyme in steroidogenesis, and phosphorylation levels of protein kinase A (PKA) and the cAMP response element-binding protein were all stimulated by the presence of MK-4. Enhancement of testosterone production was inhibited by H89, a specific inhibitor of PKA, but not by warfarin, an inhibitor of γ-glutamylcarboxylation. CONCLUSIONS: MK-4 stimulates testosterone production in rats and testis-derived tumor cells via activation of PKA. MK-4 may be involved in steroidogenesis in the testis, and its supplementation could reverse the downregulation of testosterone production in elders.

Targeted imaging of the spatial and temporal variation of matrix metalloproteinase activity in a porcine model of postinfarct remodeling: relationship to myocardial dysfunction.

BACKGROUND: Matrix metalloproteinases (MMPs) are known to modulate left ventricular (LV) remodeling after a myocardial infarction (MI). However, the temporal and spatial variation of MMP activation and their relationship to mechanical dysfunction after MI remain undefined. METHODS AND RESULTS: MI was surgically induced in pigs (n = 23) and cine magnetic resonance (MR) and dual-isotope hybrid single-photon emission CT (SPECT)/CT imaging obtained using thallium-201 and a technetium-99m-labeled MMP targeted tracer ((99m)Tc-RP805) at 1, 2, and 4 weeks post-MI along with controls (n = 5). Regional myocardial strain was computed from MR images and related to MMP zymography and ex vivo myocardial (99m)Tc-RP805 retention. MMP activation as assessed by in vivo and ex vivo (99m)Tc-RP805 imaging and retention studies was increased nearly 4-fold within the infarct region at 1 week post-MI and remained elevated up to 1 month post-MI. The post-MI change in LV end-diastolic volumes was correlated with MMP activity (y = 31.34e(0.48x), P = 0.04). MMP activity was increased within the border and remote regions early post-MI, but declined over 1 month. There was a high concordance between regional (99m)Tc-RP805 uptake and ex vivo MMP-2 activity. CONCLUSIONS: A novel, multimodality, noninvasive hybrid SPECT/CT imaging approach was validated and applied for in vivo evaluation of MMP activation in combination with cine MR analysis of LV deformation. Increased (99m)Tc-RP805 retention was seen throughout the heart early post-MI and was not purely a reciprocal of thallium-201 perfusion. The (99m)Tc-RP805 SPECT/CT imaging may provide unique information regarding regional myocardial MMP activation and predict late post-MI LV remodeling.

Assessment of impact on health of children working in the garbage dumping site in Dhaka, Bangladesh.

Waste dumping is one of the major causes of environment pollution in Bangladesh. This study was designed to assess the impact on health of children working in one of the garbage dumping sites in Dhaka. Blood samples were collected from exposed (n = 20, aged: 8-15 years, exposed to dumped garbage from 6 months to 6 years) and control subjects (n = 15, age matched and never worked in the garbage dumping site). Oxidative stress markers like lipid hydroperoxides, thiobarbituric acid reactive substances and protein carbonyl content were measured. Alkaline comet assay was performed to assess the possible damage in DNA. To check the consequences of possible toxic exposure, we performed liver function tests of the study subjects. Oxidative stress-mediated damage of macromolecules was found to be significantly increased in the exposed children. Liver function tests were found normal. Thus, the children working in garbage dumping site are in severe health risk.