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Abstract Background The most prominent non-occupational source of exposure to methylmercury is the consumption of fish. In this study we examine a fish consuming population to determine the extent of temporal exposure and investigate the extent to which single time estimates of methylmercury exposure based on blood-Hg concentration can provide reliable estimates of longer-term average exposure. Methods Blood-mercury levels were obtained from a portion of the Arsenic Mercury Intake Biometric Study (AMIBS) cohort. Specifically, 56 Japanese women residing in the Puget Sound area of Washington State, US were sampled on three occasions across a one-year period. Results An average of 135 days separated samples, with mean blood-mercury levels for the visits being 5.1, 6.6 and 5.0 μg/l and geometric means being 2.7, 4.5 and 3.1 μg/l. The blood-mercury levels in this group exceed national averages with geometric means for two of the visits being between the 90th and 95th percentiles of nationally observed levels and the lowest geometric mean being between the 75th and 90th percentile. Group means were not significantly different across sampling periods suggesting that exposure of combined subjects remained relatively constant. Comparing intra-individual results over time did not reveal a strong correlation among visits (r = 0.19, 0.50, 0.63 between 1st and 2nd, 2nd and 3rd, and 1st and 3rd sample results, respectively). In comparing blood-mercury levels across two sampling interval combinations (1st and 2nd, 2nd and 3rd, and 1st and 3rd visits, respectively), 58% (n = 34), 53% (n = 31) and 29% (n = 17) of the individuals had at least a 100% difference in blood-Hg levels. Conclusions Point estimates of blood-mercury, when compared with three sample averages, may not reflect temporal variability and individual exposures estimated on the basis of single blood samples should be treated with caution as indicators of long-term exposure. Reliance on single blood samples can make predicting ongoing methylmercury exposure highly speculative due to the large intra-individual variability.

Abstract Background The detection of insulin autoantibodies (IAA) aids in the prediction of autoimmune diabetes development. However, the long-standing, gold standard 125I-insulin radiobinding assay (RBA) has low reproducibility between laboratories, long sample processing times and requires the use of newly synthesized radiolabeled insulin for each set of assays. Therefore, a rapid, non-radioactive, and reproducible assay is highly desirable. Methods We have developed electrochemiluminescence (ECL)-based assays that fulfill these criteria in the measurement of IAA and anti-insulin antibodies (IA) in non-obese diabetic (NOD) mice and in type 1 diabetic individuals, respectively. Using the murine IAA ECL assay, we examined the correlation between IAA, histopathological insulitis, and blood glucose in a cohort of female NOD mice from 4 up to 36 weeks of age. We developed a human IA ECL assay that we compared to conventional RBA and validated using samples from 34 diabetic and 59 non-diabetic individuals in three independent laboratories. Results Our ECL assays were rapid and sensitive with a broad dynamic range and low background. In the NOD mouse model, IAA levels measured by ECL were positively correlated with insulitis severity, and the values measured at 8-10 weeks of age were predictive of diabetes onset. Using human serum and plasma samples, our IA ECL assay yielded reproducible and accurate results with an average sensitivity of 84% at 95% specificity with no statistically significant difference between laboratories. Conclusions These novel, non-radioactive ECL-based assays should facilitate reliable and fast detection of antibodies to insulin and its precursors sera and plasma in a standardized manner between laboratories in both research and clinical settings. Our next step is to evaluate the human IA assay in the detection of IAA in prediabetic subjects or those at risk of type 1 diabetes and to develop similar assays for other autoantibodies that together are predictive for the diagnosis of this common disorder, in order to improve prediction and facilitate future therapeutic trials.

The human ATP-binding cassette (ABC) transporter, ABCG2, is responsible for multidrug resistance in some tumours. Detailed knowledge of its activity is crucial for understanding drug transport and resistance in cancer, and has implications for wider pharmacokinetics. The binding of substrates and inhibitors is a key stage in the transport cycle of ABCG2. Here, we describe a novel binding assay using a high affinity fluorescent inhibitor based on Ko143 and time-resolved Förster resonance energy transfer (TR-FRET) to measure saturation binding to ABCG2. This binding is displaced by Ko143 and other known ABCG2 ligands, and is sensitive to the addition of AMP-PNP, a non-hydrolysable ATP analogue. This assay complements the arsenal of methods for determining drug:ABCG2 interactions and has the possibility of being adaptable for other multidrug pumps., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The Omicron variant of SARS-CoV-2 is more transmissible than prior variants of concern (VOCs). It has caused the largest outbreaks in the pandemic, with increases in mortality and hospitalizations. Early data on the spread of Omicron were captured in countries with relatively low case counts, so it was unclear how the arrival of Omicron would impact the trajectory of the pandemic in countries already experiencing high levels of community transmission of Delta., Objective: The objective of this study is to quantify and explain the impact of Omicron on pandemic trajectories and how they differ between countries that were or were not in a Delta outbreak at the time Omicron occurred., Methods: We used SARS-CoV-2 surveillance and genetic sequence data to classify countries into 2 groups: those that were in a Delta outbreak (defined by at least 10 novel daily transmissions per 100,000 population) when Omicron was first sequenced in the country and those that were not. We used trend analysis, survival curves, and dynamic panel regression models to compare outbreaks in the 2 groups over the period from November 1, 2021, to February 11, 2022. We summarized the outbreaks in terms of their peak rate of SARS-CoV-2 infections and the duration of time the outbreaks took to reach the peak rate., Results: Countries that were already in an outbreak with predominantly Delta lineages when Omicron arrived took longer to reach their peak rate and saw greater than a twofold increase (2.04) in the average apex of the Omicron outbreak compared to countries that were not yet in an outbreak., Conclusions: These results suggest that high community transmission of Delta at the time of the first detection of Omicron was not protective, but rather preluded larger outbreaks in those countries. Outbreak status may reflect a generally susceptible population, due to overlapping factors, including climate, policy, and individual behavior. In the absence of strong mitigation measures, arrival of a new, more transmissible variant in these countries is therefore more likely to lead to larger outbreaks. Alternately, countries with enhanced surveillance programs and incentives may be more likely to both exist in an outbreak status and detect more cases during an outbreak, resulting in a spurious relationship. Either way, these data argue against herd immunity mitigating future outbreaks with variants that have undergone significant antigenic shifts., (©Alexander L Lundberg, Ramon Lorenzo-Redondo, Judd F Hultquist, Claudia A Hawkins, Egon A Ozer, Sarah B Welch, P V Vara Prasad, Chad J Achenbach, Janine I White, James F Oehmke, Robert L Murphy, Robert J Havey, Lori A Post. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 03.06.2022.)

Background: Variants of the SARS-CoV-2 virus carry differential risks to public health. The Omicron (B.1.1.529) variant, first identified in Botswana on November 11, 2021, has spread globally faster than any previous variant of concern. Understanding the transmissibility of Omicron is vital in the development of public health policy., Objective: The aim of this study is to compare SARS-CoV-2 outbreaks driven by Omicron to those driven by prior variants of concern in terms of both the speed and magnitude of an outbreak., Methods: We analyzed trends in outbreaks by variant of concern with validated surveillance metrics in several southern African countries. The region offers an ideal setting for a natural experiment given that most outbreaks thus far have been driven primarily by a single variant at a time. With a daily longitudinal data set of new infections, total vaccinations, and cumulative infections in countries in sub-Saharan Africa, we estimated how the emergence of Omicron has altered the trajectory of SARS-CoV-2 outbreaks. We used the Arellano-Bond method to estimate regression coefficients from a dynamic panel model, in which new infections are a function of infections yesterday and last week. We controlled for vaccinations and prior infections in the population. To test whether Omicron has changed the average trajectory of a SARS-CoV-2 outbreak, we included an interaction between an indicator variable for the emergence of Omicron and lagged infections., Results: The observed Omicron outbreaks in this study reach the outbreak threshold within 5-10 days after first detection, whereas other variants of concern have taken at least 14 days and up to as many as 35 days. The Omicron outbreaks also reach peak rates of new cases that are roughly 1.5-2 times those of prior variants of concern. Dynamic panel regression estimates confirm Omicron has created a statistically significant shift in viral spread., Conclusions: The transmissibility of Omicron is markedly higher than prior variants of concern. At the population level, the Omicron outbreaks occurred more quickly and with larger magnitude, despite substantial increases in vaccinations and prior infections, which should have otherwise reduced susceptibility to new infections. Unless public health policies are substantially altered, Omicron outbreaks in other countries are likely to occur with little warning., (©Alexander L Lundberg, Ramon Lorenzo-Redondo, Egon A Ozer, Claudia A Hawkins, Judd F Hultquist, Sarah B Welch, PV Vara Prasad, James F Oehmke, Chad J Achenbach, Robert L Murphy, Janine I White, Robert J Havey, Lori Ann Post. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 31.01.2022.)

The five members of the mammalian G subfamily of ATP-binding cassette transporters differ greatly in their substrate specificity. Four members of the subfamily are important in lipid transport and the wide substrate specificity of one of the members, ABCG2, is of significance due to its role in multidrug resistance. To explore the origin of substrate selectivity in members 1, 2, 4, 5 and 8 of this subfamily, we have analysed the differences in conservation between members in a multiple sequence alignment of ABCG sequences from mammals. Mapping sets of residues with similar patterns of conservation onto the resolved 3D structure of ABCG2 reveals possible explanations for differences in function, via a connected network of residues from the cytoplasmic to transmembrane domains. In ABCG2, this network of residues may confer extra conformational flexibility, enabling it to transport a wider array of substrates.

Postoperative infections after back operations can produce complex wounds with myonecrosis, deep dead space, and exposed orthopedic hardware, bone, and dura. Three ambulatory patients with complex postoperative back wounds that resulted from infections were treated successfully with antibiotics, debridement, irrigation, and closure of deep dead space with a superior gluteal muscle flap. Several surgical maneuvers can be performed to increase the length of the superior gluteal muscle flap. The inferior portion of the gluteus maximus was left intact to preserve gluteus maximus function. All three patients obtained healed wounds. The exposed A.O. plating system was not removed. There has not been any recurrence of infections. The superior gluteal muscle flap is a reasonable flap to fill deep dead space in the low back and has some advantages over free flaps.

The contoured anterior spinal plate (CASP) was developed for secure fixation of the anterior thoracolumbar spine. This is a report of 38 patients with various spinal pathologies treated with this system. The results were excellent regarding plate fixation and fusion. Comments on surgical technique and indications are provided.

Surgical fusion results are presented from a retrospective study of 126 consecutive multilevel discectomy and vertebrectomy cases for spondylosis to evaluate fusion rates using autograft and allograft fibula strut graft for reconstruction. The nonunion rate was high in both groups: 27% of the autograft group and 41% of the allograft group. The nonunion rate increased with increasing numbers of motion segments fused. Age and sex were not significant factors.

Lipopolysaccharide (LPS) was shown to induce tumoricidal activity in peritoneal macrophages. The optimal concentration was found to be 25 micrograms/mL. Approximately 20-h exposure to LPS was required before maximal tumor cell killing was attained. Optimal tumor killing was obtained with a ratio of tumor cell to macrophages of 1:40 with the macrophages in a confluent layer. Diphenylene iodonium (DPI) reduced the tumor cell killing in a dose dependent manner up to 1 microM. Under similar conditions DPI was shown to inhibit the superoxide production of macrophages and this supports the view that the production of oxygen radicals is important in the killing of tumor cells by macrophages and that the inhibitor DPI can be used to investigate their contribution to cytotoxicity.

Five children, aged 7-15 years, with brachial palsies and flail shoulders, had fusions performed. Four of the five had improved function; however, there was progressive loss of fused abduction position over time.