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Competing Interests: Conflicts of interest None declared.

Objective: The COVID-19 pandemic emphasized the value of geospatial visual analytics for both epidemiologists and the general public. However, systems struggled to encode temporal and geospatial trends of multiple, potentially interacting variables, such as active cases, deaths, and vaccinations. We sought to ask (1) how epidemiologists interact with visual analytics tools, (2) how multiple, time-varying, geospatial variables can be conveyed in a unified view, and (3) how complex spatiotemporal encodings affect utility for both experts and non-experts., Materials and Methods: We propose encoding variables with animated, concentric, hollow circles, allowing multiple variables via color encoding and avoiding occlusion problems, and we implement this method in a browser-based tool called CoronaViz. We conduct task-based evaluations with non-experts, as well as in-depth interviews and observational sessions with epidemiologists, covering a range of tools and encodings., Results: Sessions with epidemiologists confirmed the importance of multivariate, spatiotemporal queries and the utility of CoronaViz for answering them, while providing direction for future development. Non-experts tasked with performing spatiotemporal queries unanimously preferred animation to multi-view dashboards., Discussion: We find that conveying complex, multivariate data necessarily involves trade-offs. Yet, our studies suggest the importance of complementary visualization strategies, with our animated multivariate spatiotemporal encoding filling important needs for exploration and presentation., Conclusion: CoronaViz's unique ability to convey multiple, time-varying, geospatial variables makes it both a valuable addition to interactive COVID-19 dashboards and a platform for empowering experts and the public during future disease outbreaks. CoronaViz is open-source and a live instance is freely hosted at http://coronaviz.umiacs.io., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Tacrolimus (TAC) has a narrow therapeutic index and shows interindividual variabilities in its blood concentration. Although guidelines recommend a genetic variant (rs776746) to determine the optimized TAC dose, discrepancies in accuracy have been noted. Therefore, studying other variants of CYP3A5 may improve the accuracy of the TAC dose. Clinical exome sequencing (CES) was performed in 219 renal transplant patients. The SNPs of CYP3A5 covered by CES were recorded. The TAC blood trough concentration/dose ( C 0 / D ) was calculated on day 7 and months 1, 3, 6, and 12 of post-transplantation, and association with CYP3A5 genotypes was studied. Further, biopsy-proven rejection and pathological events were analyzed for their association with CYP3A5 genotypes. Out of 35 variants of CYP3A5 covered in CES, rs776746, rs15524, rs4646449, and rs464645 were significantly associated with the TAC C 0 / D on day 7 and months 1, 3, and 6. Further analysis showed that the slow-metabolizing genotypes of all four SNPs synergistically associated with the TAC C 0 / D on day 7 and months 1, 3, 6, and 12. The "CC" genotype of rs776746 showed a significant association (RR = 1.613; p = 0.035) with allograft rejection. In addition, cox regression analysis showed that the presence of the "CA" genotype of rs4646453 increased (HR = 7.258; 95% CI = 1.354-38.904) the risk of development of pathological events, respectively. Four variants of CYP3A5 were synergistically associated with the TAC dose determination. In addition, rs776746 and rs4646453 may be associated with allograft rejection and pathological events, respectively., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

HIV-1 transcript function is controlled in part by twinned transcriptional start site usage, where 5' capped RNAs beginning with a single guanosine (1G) are preferentially packaged into progeny virions as genomic RNA (gRNA) whereas those beginning with three sequential guanosines (3G) are retained in cells as mRNAs. In 3G transcripts, one of the additional guanosines base pairs with a cytosine located within a conserved 5' polyA element, resulting in formation of an extended 5' polyA structure as opposed to the hairpin structure formed in 1G RNAs. To understand how this remodeling influences overall transcript function, we applied in vitro biophysical studies with in-cell genome packaging and competitive translation assays to native and 5' polyA mutant transcripts generated with promoters that differentially produce 1G or 3G RNAs. We identified mutations that stabilize the 5' polyA hairpin structure in 3G RNAs, which promote RNA dimerization and Gag binding without sequestering the 5' cap. None of these 3G transcripts were competitively packaged, confirming that cap exposure is a dominant negative determinant of viral genome packaging. For all RNAs examined, conformations that favored 5' cap exposure were both poorly packaged and more efficiently translated than those that favored 5' cap sequestration. We propose that structural plasticity of 5' polyA and other conserved RNA elements place the 5' leader on a thermodynamic tipping point for low-energetic (~3 kcal/mol) control of global transcript structure and function., Competing Interests: Competing interests statement:The authors declare no competing interest.

To perform first-in-human single-dose escalation trial of ZYKR1, which is a potent, selective, and peripherally-restricted kappa opioid receptor agonist, is the purpose of this study. This randomized, double-blind, placebo-controlled single ascending dose study conducted at Zydus Research Centre, Ahmedabad, India included healthy male participants aged 18-55 years and weighing > 50 kg. The primary objective was to evaluate the safety and tolerability of ZYKR1. The secondary objective was to evaluate the pharmacokinetics and pharmacodynamics (PD) of ZYKR1. Participants received ZYKR1 (0.5 - 6 mcg/kg) or placebo infused intravenously in 15 ± 1 min. Of total five dose groups (0.5 - 6 mcg/kg), each group included eight participants with six and two randomized to ZYKR1 and placebo, respectively. Three participants experienced six treatment-emergent adverse events (TEAEs); two were gastrointestinal disorders (nausea and vomiting at 2 mcg/kg); and four were related to the nervous system (headache (at 2 mcg/kg) and facial tingling, facial numbness and paresthesia (at 6 mcg/kg)); all TEAEs were mild and resolved without sequelae. The C max of ZYKR1 was achieved after 15 - 20 min of start of infusion. The mean exposures (C max and AUC 0 - t ) increased in a dose-proportional manner. The mean t 1/2 ranged from 2.20 to 2.98 h across the dose range. Increase in the mean prolactin level was significantly higher in treatment groups compared with that in the placebo group. Intravenous ZYKR1 at doses up to 6 mcg/kg showed acceptable safety and tolerability and demonstrated a short half-life with principal route of excretion as renal. ZYKR1 displayed a potent PD effect reflected by increased prolactin levels, supporting further study in patients. Trial registration Clinical Trial Registry of India: CTRI/2018/07/014927. Date of registration: 18/07/2018., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Tributyltin (TBT), an organotin endocrine-disrupting substance, is recognized as one of the important toxic environmental pollutants. The present study was carried out to investigate the toxic effects of TBT on behavior and the ovary of adult zebrafish with a focus on oxidative stress markers and oocyte maturation. Adult zebrafish were exposed to three different concentrations (125, 250, and 500 ng/L of water) of TBT for 28 days. TBT exposure produced a concentration-dependent negative effect on the body weight and behavior (anxiety-like symptoms) of adult zebrafish. Alterations in the activity of superoxide dismutase (SOD) and catalase (CAT), the total antioxidant capacity of ovarian tissue by the highest exposure level of TBT resulted in lipid peroxidation as indicated by increased malondialdehyde (MDA) level. The numbers of early-vitellogenic oocytes were significantly increased in zebrafish exposed to TBT as low as 125 ng/L. However, the numbers and size of fully-grown (mature) oocytes were significantly reduced in the highest exposure group only. Correlation between the MDA level and pre-vitellogenic oocytes in the 500 ng/L group indicated that lipid peroxidation prevented the maturation of pre-vitellogenic oocytes. TBT exposure produced significant histological changes in the ovary as evidenced by disturbed maturation of oocytes. In conclusion, TBT adversely affected the maturation of oocytes in zebrafish ovary through oxidative stress-mediated mechanisms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest the authors declare no conflicts of interest.

Objective: Patients with dural venous sinus thrombosis (DVST) in select populations following traumatic brain injury (TBI), including those with blunt mechanism or depressed skull fractures, have been shown to have an increased risk of mortality. The purpose of this study was to assess these findings in a mixed population of head trauma patients., Methods: The authors performed a case-control study using propensity score matching by reviewing 17 years (2004-2021) of data from their institutional trauma registry. Patients with imaging-confirmed DVST were matched to a control group of TBI patients without identified DVST based on age, sex, postresuscitation Glasgow Coma Scale (GCS) score, and Injury Severity Score. All age groups and injury mechanisms were included with a head Abbreviated Injury Scale score ≥ 3. Data on demographics, injury and radiographic characteristics, and patient outcomes were collected. Multivariable logistic regression was performed to identify predictors of inpatient mortality. An additional subgroup analysis of patients with concurrent DVST and blunt cerebrovascular injury (BCVI) was planned a priori., Results: The authors identified 9875 patients who presented to their institution over the study period with TBIs, with a 1.64% incidence of DVST. Concurrent BCVI was diagnosed in 23.5% of patients with a DVST. Following matching, the presence of DVST itself was not significantly associated with inpatient mortality (OR 0.68, 95% CI 0.24-1.88). On regression analysis, penetrating injuries (8.19, 95% CI 1.21-80.0) and lower postresuscitation GCS scores (0.69, 95% CI 0.53-0.84) were independently associated with inpatient mortality for patients with traumatic DVST. Significantly worse functional outcomes were observed in those with DVST at 3 months, with no significant difference at 6 months., Conclusions: The authors observed a prevalence of traumatic DVST of 1.64% in a mixed population of head-injured patients, with 23.5% of patients with DVST having concurrent BCVI. Traumatic DVST alone was not associated with a significantly increased risk of inpatient mortality.

Nonylphenol and its derivatives use as plasticizer or additives in manufacturing industries. Effluents originated from industrial areas are being added to soil, ground water, river and marine water intentionally or unintentionally. Complex mixture of these contaminants enter the food chain and produce sub-lethal deleterious effects mainly on nervous and reproductive systems of aquatic animals and human beings. The information pertaining to oxidative stress-mediated alterations in brain of zebrafish would be helpful to understand the toxicity potential of such compounds in aquatic animals. The aim of the present study was to evaluate the behavioural changes, status of oxidative stress markers; sod, cat, and NF-E2-related factor 2 (nrf2) mRNA gene expression profile; and histopathological changes in the brain of adult zebrafish exposed to 4-nonylphenol (4NP) at concentration of 100 and 200 μg/L of water for 21 days. Zebrafish were divided into four groups viz; control (C1), vehicle (C2, ethanol 10 μg/L of water), treatment 1 (T1, 4-NP, 100 μg/L) and treatment 2 (T2, 4-NP, 200 μg/L). Both exposure levels of 4-NP adversely affected the exploratory behaviour of zebrafish and produced anxiety-like symptom. Concentration-dependent reduction in activity of superoxide dismutase and catalase; and glutathione level, with increased level of malondialdehyde recorded in the brain of exposed zebrafish. Gene expression analysis showed down regulation of sod, cat, nrf2 genes in brain of zebrafish from toxicity groups indicating 4-NP induced oxidative stress in brain. However, noticeable histological alterations were not observed in 4-NP exposed brain of zebrafish., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: The clinical application of the diode laser seems to have beneficial effects in surgery. The laser provides precise and rapid tissue dissection, excellent haemostasis and lessens post-operative inflammation. This study was done to assess the clinical effectiveness of diode laser in the management of different varieties of intraoral soft-tissue lesions., Materials and Methods: After applying exclusion criteria, a total of 50 samples were selected with benign intraoral soft-tissue lesions treated with a diode laser under local anaesthesia between September 2017 and September 2020. Each patient was followed up on the 3 rd , 7 th and 15 th post-operative days for healing, pain, infection and swelling., Results: From all patients, a total of 50 were evaluated in the study; out of all, 60% of patients had no pain on the 2 nd follow-up. As per the Landry Index of Healing, 54% of patients had excellent healing. None of the cases had post-operative bleeding, infection was present in 4% at the 1 st -2 nd follow-up, and in 2% of cases, post-operative swelling was present. The efficacy of diode lasers was tested using the Chi-square test and P < 0.01, which was statistically significant., Discussion: Diode laser seems to be superior over conventional treatment modalities as it provides a bloodless dry field and increases patient comfort during surgery. It also lessens the post-operative pain and swelling. Diode laser can safely and effectively be used as a treatment modality for benign soft-tissue lesions, without any complication and without compromising the health and function of patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Annals of Maxillofacial Surgery.)

Parkinson's disease (PD) is a complex neurodegenerative disease with etiology rooted in genetic vulnerability and environmental factors. Here we combine quantitative epidemiologic study of pesticide exposures and PD with toxicity screening in dopaminergic neurons derived from PD patient induced pluripotent stem cells (iPSCs) to identify Parkinson's-relevant pesticides. Agricultural records enable investigation of 288 specific pesticides and PD risk in a comprehensive, pesticide-wide association study. We associate long-term exposure to 53 pesticides with PD and identify co-exposure profiles. We then employ a live-cell imaging screening paradigm exposing dopaminergic neurons to 39 PD-associated pesticides. We find that 10 pesticides are directly toxic to these neurons. Further, we analyze pesticides typically used in combinations in cotton farming, demonstrating that co-exposures result in greater toxicity than any single pesticide. We find trifluralin is a driver of toxicity to dopaminergic neurons and leads to mitochondrial dysfunction. Our paradigm may prove useful to mechanistically dissect pesticide exposures implicated in PD risk and guide agricultural policy., (© 2023. The Author(s).)

BackgroundAntiretroviral therapy (ART) halts HIV-1 replication, decreasing viremia to below the detection limit of clinical assays. However, some individuals experience persistent nonsuppressible viremia (NSV) originating from CD4+ T cell clones carrying infectious proviruses. Defective proviruses represent over 90% of all proviruses persisting during ART and can express viral genes, but whether they can cause NSV and complicate ART management is unknown.MethodsWe undertook an in-depth characterization of proviruses causing NSV in 4 study participants with optimal adherence and no drug resistance. We investigated the impact of the observed defects on 5'-leader RNA properties, virus infectivity, and gene expression. Integration-site specific assays were used to track these proviruses over time and among cell subsets.ResultsClones carrying proviruses with 5'-leader defects can cause persistent NSV up to approximately 103 copies/mL. These proviruses had small, often identical deletions or point mutations involving the major splicing donor (MSD) site and showed partially reduced RNA dimerization and nucleocapsid binding. Nevertheless, they were inducible and produced noninfectious virions containing viral RNA, but lacking envelope.ConclusionThese findings show that proviruses with 5'-leader defects in CD4+ T cell clones can give rise to NSV, affecting clinical care. Sequencing of the 5'-leader can help in understanding failure to completely suppress viremia.FundingOffice of the NIH Director and National Institute of Dental and Craniofacial Research, NIH; Howard Hughes Medical Institute; Johns Hopkins University Center for AIDS Research; National Institute for Allergy and Infectious Diseases (NIAID), NIH, to the PAVE, BEAT-HIV, and DARE Martin Delaney collaboratories.

In the present work, 224 adult female zebrafish (56 fish in each group) were randomly divided into four groups (two control groups and two toxicity groups) as per duration of exposure (7 and 21 days). All fish of the two toxicity groups were exposed to 0.610 mM acrylamide (ACR) concentration for 7 and 21 days. The effects of ACR exposure on behavior, oxidative stress biomarkers, molecular expression of antioxidant genes (sod, cat, and nrf2), and histopathological examination of the brain and eye were examined. Our result shows that ACR exposure for 7 days produced an anxiety-like behavior in zebrafish. Short-term exposure of ACR resulted in alterations of oxidative stress markers (SOD and CAT activity, and the level of GSH and MDA) in the brain and eye of zebrafish. However, the antioxidant defense system of adult female zebrafish could be able to counteract the free radicals generated in long-term ACR exposure as indicated by non-significant difference in oxidative insult following short-term and long-term exposure. ACR exposure downregulated the mRNA expression of the sod, cat, and nrf2 (nuclear factor erythroid 2-related factor 2) genes in the brain and eye without significant difference between the two toxicity groups. Mild histological changes in the dorsal telencephalic area, tectum opticum, medulla, and hypothalamus area of the brain of zebrafish have been observed following short-term and long-term ACR exposure. In the eye, marked histological changes in the retinal pigmented epithelium layer (RPE), structural changes of the photoreceptor layer (PRL) with disorganized layer of rods and cones, and reduction of the relative thickness of the RPE, PRL, outer nuclear layer (ONL), and inner nuclear layer (INL) have been noted following ACR exposure for 21 days as compared to 7 days. ACR produced neurobehavioral aberrations and oxidative stress within 7 days of exposure, while various histological changes in the brain and eyes have been observed following long-term exposure (21 days) to ACR., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

ZYIL1 is a nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome inhibitor, which prevents NLRP3-induced apoptosis-associated speck-like protein containing a caspase activation and recruitment domain oligomerization, thus inhibiting NLRP3 inflammasome pathway. We investigated the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of ZYIL1 after single and multiple doses in healthy subjects. The subjects aged 18-55 years were enrolled in 2 different studies: single and multiple ascending dose. Blood/urine samples were collected at designated time points for pharmacokinetic and pharmacodynamic analysis. In the single-ascending-dose study, 30 subjects were enrolled (6 subjects each in 5 dose groups). One adverse event was reported during the study. ZYIL1 was well absorbed with median time to maximum plasma concentration at 1-1.5 hours. The exposures were dose proportional across the dose ranges. ZYIL1 is excreted as an unchanged form via the renal route. The mean elimination half-life was 6-7 hours. In the multiple-ascending-dose study, 18 subjects were enrolled (6 subjects each in 3 dose groups). Eleven adverse events were reported by 6 subjects during the study. The accumulation index at steady state for area under the plasma concentration-time curve indicated that ZYIL1 has a marginal accumulation upon repeated dosing. Dose-proportional exposure was observed across the dose ranges. All subjects showed >90% interleukin (IL)-1β inhibition in all dose groups for both studies. Inhibition in IL-1β and IL-18 was observed throughout the 14 days of treatment in the multiple-dose study. The safety profile, rapid absorption, marginal accumulation, and significant inhibition of IL-1β and IL-18 level support its development for the management of inflammatory disorders., (© 2022 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Background: New antimalarials with novel mechanisms of action are needed to combat the emergence of drug resistance. Triaminopyrimidines comprise a novel antimalarial class identified in a high-throughput screen against asexual blood-stage Plasmodium falciparum. This first-in-human study aimed to characterise the safety, pharmacokinetics, and antimalarial activity of the triaminopyrimidine ZY-19489 in healthy volunteers., Methods: A three-part clinical trial was conducted in healthy adults (aged 18-55 years) in Brisbane, QLD, Australia. Part one was a double-blind, randomised, placebo-controlled, single ascending dose study in which participants enrolled into one of six dose groups (25, 75, 150, 450, 900, or 1500 mg) were randomly assigned (3:1) to ZY-19489 or placebo. Part two was an open-label, randomised, two-period cross-over, pilot food-effect study in which participants were randomly assigned (1:1) to a fasted-fed or a fed-fasted sequence. Part three was an open-label, randomised, volunteer infection study using the P falciparum induced blood-stage malaria model in which participants were enrolled into one of two cohorts, with participants in cohort one all receiving the same dose of ZY-19489 and participants in cohort two randomly assigned to receive one of two doses. The primary outcome for all three parts was the incidence, severity, and relationship to ZY-19489 of adverse events. Secondary outcomes were estimation of ZY-19489 pharmacokinetic parameters for all parts; how these parameters were affected by the fed state for part two only; and the parasite reduction ratio, parasite clearance half-life, recrudescent parasitaemia, and pharmacokinetic-pharmacodynamic modelling parameters for part three only. This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12619000127101, ACTRN12619001466134, and ACTRN12619001215112)., Findings: 48 participants were enrolled in part one (eight per cohort for 25-1500 mg cohorts), eight in part two (four in each group, all dosed with 300 mg), and 15 in part three (five dosed with 200 mg, eight with 300 mg, and two with 900 mg). In part one, the incidence of drug-related adverse events was higher in the 1500 mg dose group (occurring in all six participants) than in lower-dose groups and the placebo group (occurring in one of six in the 25 mg group, two of six in the 75 mg group, three of six in the 150 mg group, two of six in the 450 mg group, four of six in the 900 mg group, and four of 12 in the placebo group), due to the occurrence of mild gastrointestinal symptoms. Maximum plasma concentrations occurred 5-9 h post-dosing, and the elimination half-life was 50-97 h across the dose range. In part two, three of seven participants had a treatment-related adverse event in the fed state and four of eight in the fasted state. Dosing in the fed state delayed absorption (maximum plasma concentration occurred a median of 12·0 h [range 7·5-16·0] after dosing in the fed state vs 6·0 h [4·5-9·1] in the fasted state) but had no effect on overall exposure (difference in area under the concentration-time curve from time 0 [dosing] extrapolated to infinity between fed and fasted states was -0·013 [90% CI -0·11 to 0·08]). In part three, drug-related adverse events occurred in four of five participants in the 200 mg group, seven of eight in the 300 mg group, and both participants in the 900 mg group. Rapid initial parasite clearance occurred in all participants following dosing (clearance half-life 6·6 h [95% CI 6·2-6·9] for 200 mg, 6·8 h [95% CI 6·5-7·1] for 300 mg, and 7·1 h [95% CI 6·6-7·6] for 900 mg). Recrudescence occurred in four of five participants in the 200 mg group, five of eight in the 300 mg group, and neither of the two participants in the 900 mg group. Simulations done using a pharmacokinetic-pharmacodynamic model predicted that a single dose of 1100 mg would clear baseline parasitaemia by a factor of 10 9 ., Interpretation: The safety, pharmacokinetic profile, and antimalarial activity of ZY-19489 in humans support the further development of the compound as a novel antimalarial therapy., Funding: Cadila Healthcare and Medicines for Malaria Venture., Competing Interests: Declaration of interests HBP, HP, SS, DP, MJ, AG, and KK are employed by Cadila Healthcare. SC, JJM, CB, and IDR are employed by Medicines for Malaria Venture (MMV). BEB and JSM received funding from Cadila Healthcare and MMV to perform the study. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The toxicity of the binary mixture of cadmium (Cd) and mercury (Hg) on the ovary of adult zebrafish was evaluated in the present study. Adult female zebrafish were exposed to cadmium chloride (1 mg/L), mercury chloride (30 µg/L), and a binary mixture of both metals for 21 days. The toxic effects of both metals on the ovary were investigated by evaluating the oxidative stress markers and related gene expression in ovarian tissue along with the histopathological examination. The significantly decreased level of GSH and increased level of MDA in ovarian tissue of adult female zebrafish exposed to Cd + Hg indicated that the exposure of binary mixture of Cd and Hg caused more lipid peroxidation in the ovary. The significant changes in expression of mRNA of catalase (CAT) and nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) were not observed in the ovary of zebrafish exposed to the binary mixture. Upon histological evaluation, a decreased number of full-growth (mature) oocytes along with degenerative changes due to Cd exposure were noticed, while ovary of zebrafish of the Hg-exposed group had shown a decreased number of pre-and early vitellogenic oocytes along with atretic previtellogenic oocytes compared to the control group. The ovary of zebrafish of the Cd + Hg-exposed group had shown a decreased number of previtellogenic oocytes with marked pathological changes in mature oocytes. Present findings elucidate that simultaneous long-term exposure of Cd and Hg compared to individual exposure significantly damaged the various stages of oocytes of an ovary of adult zebrafish., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Electrocardiography (ECG)-derived machine learning models can predict echocardiography (echo)-derived indices of systolic or diastolic function. However, systolic and diastolic dysfunction frequently coexists, which necessitates an integrated assessment for optimal risk-stratification. We explored an ECG-derived model that emulates an echo-derived model that combines multiple parameters for identifying patient phenogroups at risk for major adverse cardiac events (MACE)., Methods: In this substudy of a prospective, multicenter study, patients from 3 institutions (n=727) formed an internal cohort, and the fourth institution was reserved as an external test set (n=518). A previously validated patient similarity analysis model was used for labeling the patients as low-/high-risk phenogroups. These labels were utilized for training an ECG-derived deep neural network model to predict MACE risk per phenogroup. After 5-fold cross-validation training, the model was tested on the reserved external dataset., Results: Our ECG-derived model showed robust classification of patients, with area under the receiver operating characteristic curve of 0.86 (95% CI: 0.79-0.91) and 0.84 (95% CI: 0.80-0.87), sensitivity of 80% and 76%, and specificity of 88% and 75% for the internal and external test sets, respectively. The ECG-derived model demonstrated an increased probability for MACE in high-risk vs low-risk patients (21% vs 3%; P<0.001), which was similar to the echo-trained model (21% vs 5%; P<0.001), suggesting comparable utility., Conclusions: This novel ECG-derived machine learning model provides a cost-effective strategy for predicting patient subgroups in whom an integrated milieu of systolic and diastolic dysfunction is associated with a high risk of MACE., Competing Interests: Conflicts of Interest Partho Sengupta is a consultant for Kencor Health, Ultromics, and RCE technologies. All other authors have no conflicts of interest to disclose., (© 2022 Aurora Health Care, Inc.)

Introduction: In older adults, excess weight is associated with a higher prevalence of cardiovascular disease, metabolic disease, several important cancers, and numerous other medical conditions. Several indices such as body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) are used to classify general. Some studies also reported that WC and WHR is a better indicator of cardiovascular disease (CVD) risk than BMI and WHR., Aims and Objective: 1. To estimate the prevalence of obesity among the elderly using three scale viz. BMI, WHR, and WHtR 2. To compare the results of these three-scale used for assessment of obesity 3. To determine the presence of association between obesity and hypertension if any., Material and Methods: For selection of the area, in both the urban and rural areas, the sampling units were enumerated and samples were collected from them. The estimated geriatric population combined in both Urban and Rural areas amounted to 12,220 (7% of geriatric population as per Census 2001), out of which 5% was selected as sample. This came out to be 611 elderly subjects which were selected equally from both urban and rural areas. For assessment of obesity BMI, WHR, and WHtR were measured. Assessment of hypertension was as per JNC classification., Result: Prevalence of obesity as per BMI in the urban area was found to be 40%, whereas that in rural areas was found to be 47.4%. WHR and WHtR showed higher prevalence in rural areas (70%) and also in urban areas (60%). BMI and WHR were significantly associated with hypertensive status of elderly., Conclusion: Anthropometric assessments of obesity like WHR and WHTR are more sensitive indicators of obesity among the elderly. BMI is found to be significantly associated with hypertension as well in the present study. Logistic regression showed that the association of BMI with hypertension was higher than other obesity assessments., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

Osteoporosis is a growing epidemic that leads to significant morbidity and mortality among the elderly population due to associated fractures that lead to disabilities and reduced quality of life. Bisphosphonates are well-established as a first-line and cost-effective treatment for osteoporosis. Unfortunately, clinicians are often uncertain as to how to select treatments when bisphosphonates are ineffective as initial treatment or contraindicated. Romosozumab and abaloparatide are 2 alternative agents that have been recently FDA approved for the treatment of osteoporosis in postmenopausal women at high risk for fracture or patients who have failed or are intolerant to other osteoporosis therapies. Currently, the National Osteoporosis Foundation (NOF) has no formal recommendations in regard to these 2 novel agents. The purpose of this review is to help guide pharmacists on how to ensure appropriate utilization of these 2 novel bone-forming agents as potential alternatives to bisphosphonate therapy by providing evidence-based recommendations according to the current literature and key counseling points.

Aim: ZY-19489 is a new antimalarial drug candidate and selective LC-MS/MS method was established for estimation of ZY-19489 and its metabolite in human plasma. Materials & methods: LLE was employed for extraction, mass spectrometric quantification performed using positive ionization mode and DCP-IMP was used as an internal standard. The chromatographic separation was achieved using mobile phase 5 mM ammonium formate in water and 0.1% v/v ammonia solution in methanol:acetonitrile (90:10% v/v) and column Agilent Zorbex Extended C18, 3.5 μm, 100 × 4.6 mm with a 6-min run time. Results: The calibration curve of ZY-19489 was linear over range 1-500 ng/ml and 2-200 ng/ml for metabolite. Assay was reproducible, selective and devoid of matrix effect. Conclusion: The validated assay was implemented for clinical sample analysis derived from healthy human subjects and parasitemia-induced subjects.

Background: Depression is one of the most frequent illnesses found among the elderly. ICD-10 scale and Geriatric Depression Scale (GDS) are used commonly for screening and hence it is important to identify the scale which can be used more effectively in community settings., Objectives: (1) To analyze the factors responsible for the elderly depression and (2) to compare two scales used for the screening (ICD-10 and GDS)., Materials and Methods: A cross-sectional house-to-house survey was carried in Sayla taluka of Surendranagar district by directly questioning the subjects after oral and written consent. The selection of taluka was done using simple random sampling and sample size was calculated on the basis of estimated geriatric population. 306 subjects were interviewed using a predesigned, pretested, and validated questionnaire., Results: GDS showed the prevalence of 16% whereas ICD-10 showed 22%. The factors associated with depression were physical health, poor economical situation, and avoidance by family members. The agreement between the 2 scales using Cohen's kappa statistic showed excellent agreement., Conclusion: Community-based multiphasic screening programs is needed for early diagnosis of geriatric depression. ICD-10 having lesser number of questions can be used in the 1 st phase of screening and those found positive can then be tested by GDS., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Indian Journal of Community Medicine.)

Objectives: This study sought to explore the spectrum of cardiac abnormalities in student athletes who returned to university campus in July 2020 with uncomplicated coronavirus disease 2019 (COVID-19)., Background: There is limited information on cardiovascular involvement in young individuals with mild or asymptomatic COVID-19., Methods: Screening echocardiograms were performed in 54 consecutive student athletes (mean age 19 years; 85% male) who had positive results of reverse transcription polymerase chain reaction nasal swab testing of the upper respiratory tract or immunoglobulin G antibodies against severe acute respiratory syndrome coronavirus type 2. Sequential cardiac magnetic resonance imaging was performed in 48 (89%) subjects., Results: A total of 16 (30%) athletes were asymptomatic, whereas 36 (66%) and 2 (4%) athletes reported mild and moderate COVID-19 related symptoms, respectively. For the 48 athletes completing both imaging studies, abnormal findings were identified in 27 (56.3%) individuals. This included 19 (39.5%) athletes with pericardial late enhancements with associated pericardial effusion. Of the individuals with pericardial enhancements, 6 (12.5%) had reduced global longitudinal strain and/or an increased native T 1 . One patient showed myocardial enhancement, and reduced left ventricular ejection fraction or reduced global longitudinal strain with or without increased native T 1 values was also identified in an additional 7 (14.6%) individuals. Native T 2 findings were normal in all subjects, and no specific imaging features of myocardial inflammation were identified. Hierarchical clustering of left ventricular regional strain identified 3 unique myopericardial phenotypes that showed significant association with the cardiac magnetic resonance findings (p = 0.03)., Conclusions: More than 1 in 3 previously healthy college athletes recovering from COVID-19 infection showed imaging features of a resolving pericardial inflammation. Although subtle changes in myocardial structure and function were identified, no athlete showed specific imaging features to suggest an ongoing myocarditis. Further studies are needed to understand the clinical implications and long-term evolution of these abnormalities in uncomplicated COVID-19., Competing Interests: Funding Support and Author Disclosures This work is supported in part by funds from the National Science Foundation (NSF: # 1920920) National Institute of General Medical Sciences of the National Institutes of Health (NIH: #5U54GM104942-04). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the National Science Foundation. Dr. Sengupta has received consulting for HeartSciences, Kencor Health, and Ultromics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: Bovine-derived collagen membrane is usually and regularly used as a temporary cover or dressing for extraoral wounds and burns. It has wide applications because of its usefulness and biocompatibility. This has provoked us to do a study with the use of collagen membrane even for minor intraoral surgical defects. The aim of this evaluative study was to evaluate the clinical efficacy of collagen membrane in intraoral wounds created by removal of various soft tissue lesions., Materials and Methods: A total of 25 healthy patients (16 males and 9 females) were taken for this study. This study was confined to secondary defects of the oral mucosa, which occur after excision of premalignant lesions and other conditions, such as benign lesions, reactive proliferations, and incisional biopsy wounds. Only those lesions that were sufficiently large and could not be closed primarily were included in the study., Results: The results were evaluated on the day of surgery and in the postoperative period. The usefulness of collagen membrane as an intraoral temporary wound dressing material to promote haemostasis, relieve pain, induce granulation, and assist in rapid epithelialization at the wound site and prevent infection, contracture, scarring, and donor-site morbidity was evaluated, and finally, the efficacy of collagen membrane was tested by the use of Chi-square test and P < 0.001, which is a statistically and clinically significant value., Discussion: Collagen membrane was observed as both biological dressing material and drug carrier. It was found to be a suitable alternative to other graft materials mentioned for the repair of defects in the mucous membrane created by surgical excision of lesions. Therefore, when used judiciously in a controlled clinical situation, collagen membrane is biologically acceptable in nature. It is an alternative to autologous grafts rather than a replacement of other grafts used in the oral cavity., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Annals of Maxillofacial Surgery.)

Introduction: The treatment of subcondylar mandible fractures is a topic of debate and can be variable even though these fractures are commonly seen. The present study aimed at evaluation of various treatment modalities for unilateral condylar fracture in adults., Materials and Methods: Thirty patients with unilateral condylar fractures between the age of 18 and 60 years were evaluated. Treatment protocol included closed reduction for 15 patients and open reduction for 15 patients., Results: Assessment was done functionally for maximum interincisal mouth opening, deviation on maximum interincisal mouth opening, occlusion and facial nerve function, and radiologically for ramus height shortening. In general, there were no statistically significant differences between closed and open methods., Discussion: Both the treatment options for condylar fractures of the mandible yielded acceptable results. Closed treatment appears to be a safe and appropriate modality for most unilateral condylar fractures. Although the open group, in general, showed similar outcomes, this treatment should be reserved for limited indications. The present study has confirmed that both treatment options can yield acceptable results. On clinical examination, there was no significant difference in mouth opening measures, the incidence of occlusal disturbances or in the degree of pain perception., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Annals of Maxillofacial Surgery.)

Aims: Coronary artery calcium (CAC) scoring is an established tool for cardiovascular risk stratification. However, the lack of widespread availability and concerns about radiation exposure have limited the universal clinical utilization of CAC. In this study, we sought to explore whether machine learning (ML) approaches can aid cardiovascular risk stratification by predicting guideline recommended CAC score categories from clinical features and surface electrocardiograms., Methods and Results: In this substudy of a prospective, multicentre trial, a total of 534 subjects referred for CAC scores and electrocardiographic data were split into 80% training and 20% testing sets. Two binary outcome ML logistic regression models were developed for prediction of CAC scores equal to 0 and ≥400. Both CAC = 0 and CAC ≥400 models yielded values for the area under the curve, sensitivity, specificity, and accuracy of 84%, 92%, 70%, and 75%, and 87%, 91%, 75%, and 81%, respectively. We further tested the CAC ≥400 model to risk stratify a cohort of 87 subjects referred for invasive coronary angiography. Using an intermediate or higher pretest probability (≥15%) to predict CAC ≥400, the model predicted the presence of significant coronary artery stenosis ( P  = 0.025), the need for revascularization ( P  < 0.001), notably bypass surgery ( P  = 0.021), and major adverse cardiovascular events ( P  = 0.023) during a median follow-up period of 2 years., Conclusion: ML techniques can extract information from electrocardiographic data and clinical variables to predict CAC score categories and similarly risk-stratify patients with suspected coronary artery disease., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

After oral route of administration, drug absorption is unpredictable and is governed by various factors such as multi drug resistance-1 (MDR1) an efflux transporter and drug metabolizing enzymes (like CYP3A4, CYP3A37, CYP2D6) at intestine and liver. Naturally available phyto chemicals like piperine and quercetin as well as some floroquinolones are known to inhibit MDR1 and CYP3A37 activity and increases bioavailability of co-administered drugs. This study was carried out to investigate the effect of piperine and quercetin alone or in combination with marbofloxacin on CYP3A37 and MDR1 mRNA expression levels in liver and intestine of broiler chicken. After oral administration of piperine and quercetin for 3 consecutive days followed by with or without oral administration of marbofloxacin for 5 days, CYP3A37 and MDR1 mRNA expression levels were determined using quantitative real-time PCR. Total of 36 broiler chickens in seven individual groups were treated with different regimen and the mRNA expression levels at duodenum and liver were analyzed with apt statistical tools. After piperine and quercetin combined treatment with marbofloxacin, CYP3A37 mRNA expression levels were significantly down regulated by 20.57 (p = .034) and 25.95 (p = .003) folds; and MDR1 mRNA expression levels were also significantly down regulated by 11.33 (p = .012) and 33.59 (p = .006) folds in liver and duodenum, respectively. Down regulation of CYP3A37 and MDR1 mRNA in liver and duodenum indicate the combined pretreatment of piperine and quercetin may be useful for improving the pharmacokinetics of orally administered drugs which are substrates for CYP3A37 and MDR1., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To review the efficacy of cefepime for use in infections caused by extended-spectrum beta-lactamase (ESBL)-producing organisms., Data Sources: A PubMed literature search (May 2000 to June 2017) was performed using the keyword cefepime and the MeSH terms beta-lactamases, cephalosporinases, and Enterobacteriaceae infections., Study Selection and Data Extraction: All human, English language studies evaluating cefepime use for the treatment of ESBL-producing Escherichia coli and Klebsiella pneumoniae infections were included., Data Synthesis: Studies assessing the use of cefepime for ESBL infections are few, and clinical studies are limited by design and sample size. The largest pharmacokinetic/pharmacodynamic study, a Monte Carlo simulation using data from the U.S. SENTRY antimicrobial surveillance program, evaluating cefepime use for infections due to ESBL-producing organisms found a 95% to 100% probability of target attainment with traditional cefepime dosing regimens. Most clinical studies found that patients treated with cefepime empirically and definitively had higher rates of mortality than those treated with carbapenems. However, in concordance with other studies reporting minimum inhibitory concentration (MIC) data, lower MICs were associated with lower mortality., Conclusions: Cefepime should be avoided for empiric treatment of suspected ESBL infections and should only be considered for definitive treatment if the MIC ≤1 µg/mL. However, the site and severity of infection, local resistance patterns, and patient-specific risk factors should also help guide antimicrobial selection.

Background: Urinary tract infections (UTIs) remain one of the most common infections in community and susceptibility of uropathogens to commonly used antimicrobials has declined over years. It is important to periodically study susceptibility patterns of uropathogens, so that empiric treatment can be determined using recent data, helping improve patient outcomes., Methods: Urine samples received by the laboratory for culture and susceptibility testing over a period of 3 months were analyzed and included in this study. Antimicrobial susceptibility testing was done on cultured isolates., Results: Of total 3,151 urine samples received, 3,066 were processed, and organisms were isolated from 1,401 (45.69%) samples. Isolation rate from male and female urine samples was 45.29% and 46.32%, respectively. The most commonly isolated organism was Escherichia coli (36.11%), followed by Candida spp. (18.56%), and Klebsiella spp. (18.06%). E. coli was most susceptible to meropenem (91.89%) and imipenem (91.69%). Klebsiella spp. was most susceptible to imipenem(75.89%) and meropenem(75.49%). Susceptibility of E. coli and Klebsiella spp. to nitrofurantoin, cotrimoxazole, and ciprofloxacin was 72.33%, 32.02%, and 18.97%, and 51.77%, 27.27%, and 22.13%, respectively. Candida spp. was most susceptible to amphotericin B (97.30%)., Conclusion: Treatment for UTIs should be determined based on current local antimicrobial susceptibility patterns of uropathogens to minimise therapeutic failures and prevent antibiotic misuse., Competing Interests: There are no conflicts of interest.

Objective: This phase I study of ZYAN1 was conducted to evaluate the safety, tolerability, and pharmacokinetics following oral administration in healthy volunteers., Methods: The study was a randomized, double-blind, placebo-controlled phase I study carried out in two parts in addition to a third part involving an open-label study to evaluate the food/sex effect. A total of 100 subjects were enrolled into the study as follows: part I-single-dose study with ZYAN1 10, 25, 50, 100, 150, 200, and 300 mg (n = 56); part II-multiple-dose study with every other day dosing of ZYAN1 100, 150, 200, and 300 mg (n = 32); and part III-sex and food effect study with ZYAN1 150 mg (n = 12; open-label)., Results: ZYAN1 was well-tolerated after single and multiple oral ascending doses. No drug-related serious adverse events were reported. Following a single ascending dose of ZYAN1, the maximum concentration (C max ) ranged from 566.47 ± 163.03 to 17,858.33 ± 2899.19 ng/mL and the median time to C max (t max ) was approximately 2.5 h for the studied 30-fold oral doses of ZYAN1. Regardless of single or multiple doses, mean C max and area under the concentration-time curve from time zero to time t (AUC t ) values generally showed a dose-proportional increase. The mean elimination half-life (t ½ ) of ZYAN1 ranged from 6.9 to 13 h with negligible accumulation. Following a single dose of ZYAN1, the mean serum erythropoietin (EPO) C max values showed dose response (i.e., 6.6 and 79.9 mIU/L for 10 and 300 mg ZYAN1 doses, respectively), while the time to mean maximal serum EPO concentrations ranged from 10 to 72 h., Conclusion: Oral single (10-300 mg) and multiple dosing (100-300 mg) of ZYAN1 in healthy subjects was found to be safe and well-tolerated. With increasing ZYAN1 dose, there was almost a proportional increase in mean C max and AUC t . The mean serum EPO concentrations showed a trend of dose response. Based on the t ½ , pharmacodynamic activity, and lack of drug accumulation, a once every 2 days dosing regimen of ZYAN1 was appropriate for phase II study., Trial Registration: Australian New Zealand Clinical Trials Registry trial ID ACTRN12614001240639.

Background and Objective: Peroxisome proliferator-activated receptors (PPARs) have recently become a focus of interest for their important roles in glucose and lipid metabolism. In humans, PPAR α activation causes a decrease in plasma triglyceride (TG) levels, enhancement of high-density lipoprotein cholesterol (HDL-C) and simultaneous enhancement of very-low-density lipoprotein (VLDL) lipolysis, whereas PPARγ agonists act as insulin sensitizers and improve insulin resistance, which is very useful in patients with type 2 diabetes mellitus (T2DM). Saroglitazar magnesium is a dual PPAR agonist with potent predominant PPAR α and moderate PPAR γ activity and the first glitazar to be granted marketing authorization in India. This study was conducted to evaluate the oral bioavailability and safety and tolerability of a Lipaglyn™ (saroglitazar magnesium) 4-mg tablet in healthy, adult human subjects under fed relative to fasting conditions., Methods: This was a single-dose, open-label, randomized, single-treatment, two-period, two-conditions (fed vs. fasting), two-sequence, crossover study planned in 54 healthy subjects. Food effect (high-calorie and high-fat breakfast) was examined by comparing pharmacokinetic data of saroglitazar and its metabolite saroglitazar sulfoxide in plasma samples collected pre-dose and serially up to 72 h post-dose. Pharmacokinetic data were analyzed using the standard non-compartmental approach., Results: A total of 54 subjects were enrolled in the study, out of them 50 subjects had completed the study and were analyzed. The presence of food had a minor impact on the disposition of saroglitazar. While food reduced C max (maximum concentration) of saroglitazar by 30%, the extent of absorption as measured by AUC ∞ (area under the concentration time curve from time zero to infinity) was not influenced. This was further supported by the bioequivalence data between fasted and fed conditions for saroglitazar, where 90% CIs (confidence intervals) of the adjusted geometric mean of the fed relative to the fasted condition ranged from 101.37% to 108.07% for AUC ∞ and from 63.45% to 74.68% for C max . Other parameters such as T max (time of maximum concentration) and T 1/2 (elimination half-life) were not influenced by the food intake. Saroglitazar was well tolerated in the study, and the reported adverse events were mild in nature., Conclusion: For the single-dose study, the absorption rate is affected by food as the 90% CI of C max is outside 80.00-125.00%. However, there is no impact of food on the extent of absorption of saroglitazar. The observed lower C max of saroglitazar with food has no clinical relevance since the therapeutic efficacy of saroglitazar was achieved after multiple-dose administration, suggesting the importance of total exposure.

Background: Considering the biological concerns of calcium hydroxide (CH) as a pulpotomy agent, an alternative silicate based dentin substitute i.e. Biodentine (Ca 3 SiO 5 ) was evaluated clinically and radiographically., Aims: To evaluate the effectiveness of dentin substitute (Biodentine) in regenerative pulpotomy of vital primary teeth that would giv a biological base to its use in forming reactive dentin bridge and overcoming the drawbacks of calcium hydroxide., Material and Methods: Randomised clinical trial on 40 bilateral carious primary molars in 20 participant children (aged 5-10 years) was carried out by same operator using Ca 3 SiO 5 (group-1) and CH (group-2) as vital pulpotomy agents. Blinded clinical and radiographic outcomes were observed at 3, 6 and 12 months interval., Results: Clinical outcomes of both protocols were analysed using Pearson's chi-square test applied at P < 0.05. Descriptive statistics were expressed as mean increase in dentin bridge formation in mms from two reference points in standardized radiographs using paired ' t '- test at baseline and 12 months and found to be statistically significant ( P < 0.05) in group-1 when compared with group-2., Conclusion: Group-1 revealed statistically favourable regenerative potential along with clinical success compared to group 2 thereby sharing both indications and mode of action with CH, but without its drawbacks of physical and clinical properties., Competing Interests: There are no conflicts of interest.

Novel concepts and understanding of receptors lead to discoveries and optimization of many small molecules and antibodies as anti-cancerous drugs. Receptor tyrosine kinases (RTKs) are such a promising class of receptors under the investigation in past three decades. RTKs are one of the essential mediators of cell signaling mechanism for various cellular processes. Transformations such as overexpression, dysregulation, or mutations of RTKs may result into malignancy, and thus are an important target for anticancer therapy. Numerous subfamilies of RTKs, such as epidermal growth factor receptor, vascular endothelial growth factor receptor, fibroblast growth factor receptors, insulin-like growth factor receptor, and hepatocyte growth factor receptor, have been being investigated in recent years as target for anticancer therapy. The present review focuses several small molecules drugs as well as monoclonal antibodies targeting aforesaid subfamilies either approved or under investigation to treat the various cancers.

Soft tissue aneurysmal bone cyst is a rare entity, with about 20 cases reported in literature, only 3 of which are in patients over 40 years of age. We present a case of a 41 year old Latin American female who presented for evaluation of atraumatic chest pain with radiation to the left shoulder. Her initial workup was negative, including radiographic imaging of the chest and left shoulder. 4 months later, she presented to her orthopedic surgeon with a palpable mass and mild left shoulder pain. Radiographs acquired at that time demonstrated a 7.0 × 5.5 × 6.7 cm mass with rim calcification in the region of the upper triceps muscle. Subsequent CT imaging showed central areas of hypodensity and thin septations, a few of which were calcified. MR evaluation showed hemorrhagic cystic spaces with multiple fluid-fluid levels and enhancing septations. Surgical biopsy was performed and pathology was preliminarily interpreted as cystic myositis ossificans, however on final review the diagnosis of soft tissue aneurysmal bone cyst was made. The lesion was then surgically excised and no evidence of recurrence was seen on a 3 year post-op radiograph. Following description of our case, we conduct a literature review of the imaging characteristics, diagnosis, and treatment of soft tissue aneurysmal bone cyst.

The present study was carried out to evaluate the effects of exposure at different doses of acephate on hematology, blood biochemistry, oxidative stress and immune system of Wistar rats. The experiment was carried out on 40 Wistar rats, which were divided in four groups. Animals of the three treatment groups were given with different sublethal doses (1/40th, 1/20th, 1/10th of lethal dose 50 value) of acephate by oral gavage. The hematology, blood biochemistry, oxidative stress marker, humoral immune response and cell-mediated immunity were evaluated following acephate exposure. Significant alteration in hematological parameters was not observed following different doses of acephate; however, significant alteration in alkaline phosphatase, gamma glutamyl transferase, acetyl cholinesterase, lipid peroxidase and superoxide dismutase was observed in medium- and high-dose group animals. Nonsignificant decrease in antibody titer in animals exposed to high dose has been observed compared with animals of control group. However, significant alteration in cell-mediated immunity was not observed in animals treated with acephate at different doses., (© The Author(s) 2012.)

Prolonged inappropriate inflammatory responses contribute to the pathogenesis of rheumatoid arthritis (RA) and to aspects of osteoarthritis (OA). The orphan nuclear receptor, NR4A2, is a key regulator and potential biomarker for inflammation and represents a potentially valuable therapeutic target. Both salmon calcitonin (sCT) and hyaluronic acid (HA) attenuated activated mRNA expression of NR4A1, NR4A2, NR4A3, and matrix metalloproteinases (MMPs) 1, 3 and 13 in three human cell lines: SW1353 chondrocytes, U937 and THP-1 monocytes. Ad-mixtures of sCT and HA further down-regulated expression of NR4A2 compared to either agent alone at specific concentrations, hence the rationale for their formulation in nanocomplexes (NPs) using chitosan. The sCT released from NP stimulated cAMP production in human T47D breast cancer cells expressing sCT receptors. When NP were injected by the intra-articular (I.A.) route to the mouse knee during on-going inflammatory arthritis of the K/BxN serum transfer model, joint inflammation was reduced together with NR4A2 expression, and local bone architecture was preserved. These data highlight remarkable anti-inflammatory effects of sCT and HA at the level of reducing NR4A2 mRNA expression in vitro. Combining them in NP elicits anti-arthritic effects in vivo following I.A. delivery., (Copyright © 2013 Elsevier B.V. All rights reserved.)