Introduction: Pulmonary vein isolation is not sufficient for the treatment of non-paroxysmal atrial fibrillation (AF). We aimed to clarify the effects of pulmonary vein isolation and left atrial low-voltage area ablation on acute termination of AF and freedom from AF. Methods: Ninety-five patients with non-paroxysmal AF were prospectively divided into left atrial substrates modification-first (LASM-first, n=47) and pulmonary vein isolation-first (PVI-first, n=48) groups. All patients underwent ablation during AF with acute AF termination as the procedural endpoint. In the former, LASM was performed, and PVI was performed only if AF termination was unsuccessful. In the latter, PVI was performed to observe whether AF was terminated, and if not, LASM was performed. In non-terminating AF, electrical cardioversion was performed. The patients were followed up 3, 6, and 12 months after ablation. Results: More patients reached the procedural endpoint with LASM alone than with PVI alone (45% vs. 15%; P < 0.01). Of the 95 patients, acute termination of AF occurred in 67 patients (70.5％) after PVI combined with LASM. At a median follow-up of 15 months, 69 of 95 patients (72.6％) achieved freedom from AF. More patients with AF termination with LASM alone achieved freedom from AF when compared to those who had undergone PVI alone (86% vs. 43%; P=0.04). Conclusions: LASM terminated non-paroxysmal AF in nearly half of the cases, with a better rate of freedom from AF when compared to cases without AF termination. However, for PVI, AF termination did not lead to better AF freedom rate.

Background: Patients with AF and likelihood of bleeding can undergo left atrial appendage occlusion (LAAO) as an alternative method of stroke prophylaxis. Short-term anti-thrombotic drugs are used post-procedure to offset the risk of device-related thrombus, evidence for this practice is limited. Objectives: To investigate optimal post-implant antithrombotic strategy in high bleeding-risk patients. Methods: Patients with AF and high-risk for both stroke and bleeding undergoing LAAO were advised their peri-operative drug therapy by a multi-disciplinary physician panel. Those deemed to be at higher risk of bleeding from anti-thrombotic drugs were assigned to minimal treatment with no antithrombotics or aspirin-alone. The remaining patients received standard care (STG)with a 12week course of dual-antiplatelets or anticoagulation post-implant. We compared mortality, device-related thrombus, ischemic stroke and bleeding events during the 90 days post-implant and long-term. Event-free survival was assessed using Kaplan-Meier survival analysis, with logrank testing for statistical significance. Results: 75 pts underwent LAAO of whom 63pts(84%) had a prior serious bleeding event. The 42pts on minimal treatment were older(74.3±7.7vs71.2±7.2) with higher HASBLED score (3.6±0.9vs3.3±1.2) than the 33pts having standard care. There were no device-related thrombi or strokes in either group at 90 days post-procedure; STG had more bleeding events (5/33vs0/42,p=0.01) with associated deaths (3/33vs0/42,p=0.05). During long-term follow up (median 2.2yrs), all patients transitioned onto no antithrombotic drugs (43pts(61%)) or a single-antiplatelet (29pts(39%)). There was no evidence of early minimal treatment adversely affecting long-term outcomes. Conclusions: Short-term anti-thrombotic drugs may not be needed after LAAO implant in patients with high bleeding risk and could be harmful. Larger, prospective studies would be warranted to test these findings.

Estimation of changes in abundances and densities is essential for the research, management, and conservation of animal populations. Recently, technological advances have facilitated the surveillance of animal populations through the adoption of passive sensors, such as camera traps (CT). Several methods, including the random encounter model (REM), have been developed for estimating densities of unmarked populations but require additional field work. Hierarchical abundance models, such as the N-mixture model (NMM), can estimate densities without performing additional fieldwork but do not explicitly estimate the area effectively sampled. This obscures the interpretation of its densities and requires its users to focus on relative measures of abundance instead. We compare relative trends in density/ abundance for three species (wild boar, red deer, and fox) based on the REM and NMM. The NMM applied here is adapted to overcome two issues potentially leading to poor abundance estimates: (i) we specify a joint observation model, based on a beta distribution, for all species within a community to strengthen the inference on infrequently detected species, and (ii) we model species-specific counts as a Poisson process, relaxing the assumption that each individual can only be detected once per survey. We reveal that NMM and REM provided density estimates in the same order of magnitude for wild boar, but not for foxes and red deer. Assuming a Poisson detection process in the NMM was important to control for inflation of density estimates for frequently detected species. Both methods correctly identified species ranking of abundance/density but did not always agree on relative ranks of yearly estimates within a single population, nor on its linear population trends. Our results suggest that relative population trends are better preserved between NMM and REM compared to absolute densities. Thus practitioners working with counts-only data should resort to relative abundances, rather than absolute densities.

IntroductionFungal infections, most commonly caused by the dermatophytes species, are one of the most common skin conditions. Historically, these infections have been treated with antifungals such as terbinafine, fluconazole, and itraconazole. Within the past two years, there has been a rise in the incidence of fungal infections resistant to these once effective therapies, particularly emerging in India (1). We now see the spread of the “Indian epidemic” of recalcitrant cases of fungal infections to skin of color in other parts of sub-continental Asia, particularly Pakistan (2). We report a rare case of resistance to oral griseofulvin, terbinafine, and fluconazole in the treatment of tinea corporis.

Topic: Complex Management of Bartter Syndrome in a 2-Month-Old Preterm Infant: A Multidisciplinary Approach for Optimal Outcomes

Vairimorpha (=Nosema) ceranae is a widespread pollinator parasite that commonly infects honeybees and wild pollinators, including bumblebees. Honeybees are highly competent V. ceranae hosts and previous work in experimental flight cages suggests V. ceranae can be transmitted during visitation to shared flowers. However, the relationship between floral visitation in the natural environment and the prevalence of V. ceranae among multiple bee species has not been explored. Here, we analyzed the number and duration of pollinator visits to particular components of squash flowers—including the petals, stamen, and nectary—at six farms in southeastern Michigan, USA. We also determined the prevalence of V. ceranae in honeybees and bumblebees at each site. Our results showed that more honeybee flower contacts and longer duration of contacts with pollen and nectar was linked with greater V. ceranae prevalence in bumblebees. Honeybee visitation patterns appear to have a disproportionately large impact on V. ceranae prevalence in bumblebees even though honeybees are not the most frequent flower visitors. Floral visitation by other pollinators was not linked with V. ceranae prevalence in bumblebees. Further, V. ceranae prevalence in honeybees was unaffected by floral visitation behaviors by any pollinator species. These results suggest that honeybee visitation behaviors on shared floral resources may be an important contributor to increased V. ceranae spillover to bumblebees in the field. Understanding how V. ceranae infection risk is influenced by pollinator behavior in the shared floral landscape is critical for reducing parasite spillover into declining native bee populations.

Resistant starch is a prebiotic fiber that is best known for its ability to increase butyrate production by the gut microbiota. This butyrate then plays an important role modulating the immune system and inflammation. However, the ability to use this resistant starch appears to be a rare trait within the gut microbiota, with only a few species such as Ruminococcus bromii and Bifidobacterium adolescentis having been demonstrated to possess this ability. Furthermore, these bacteria do not directly produce butyrate themselves, rather they rely on cross-feeding interactions with other gut bacteria for its production. Here we demonstrate that the often-used probiotic organism Clostridium butyricum also possesses the ability to utilize resistant starch from a number of sources, with direct production of butyrate. We further explore the enzymes responsible for this trait, demonstrating that they exhibit significant synergy, though with different enzymes exhibiting more or less importance depending on the source of the resistant starch. Thus, the co-administration of Clostridium butyricum may have the ability to improve the beneficial effects of resistant starch.

A new method for the design of event-triggered stabilizing state feedback controllers for nonlinear fractional-order interconnected systems is proposed in this paper. A new condition for the existence of state feedback controllers ensuring the closed-loop system is asymptotically stable is established based on fundamental mathematical transformations and linear matrix inequalities. A numerical example with simulation results is provided to demonstrate the effectiveness of the proposed design method.

Objective: To observe the changes of depression-like behavior in SD rats induced by maternal separation (MS) stress and to explore the effects of probiotics on antidepressant-like behavior and cAMP/CREB signaling pathway. Methods: Newborn SD rats were selected as experimental subjects and divided into MS+NS group, CON+NS group, MS+P group and CON+P group using random number table method, 12 rats in each group. At PND 22-49, the MS+P and CON+P groups were given 1×109 CFU (0.1 ml) of probiotic colonies by gavage daily and the corresponding dose (1 ml/100g) according to the change of body weight, and the MS+NS and CON+NS groups were given the corresponding saline dose (1 ml/100g). Behavioral tests were performed at PND50-56, and rats were executed at PND57 for laboratory tests. Results: FST increased, OPT increased and SPT decreased after probiotic intervention. It was suggested that the MS-induced depression-like behavior was improved to some extent. Compared with the model group, probiotic intervention increased the number of neurons in the CA1 region of the hippocampus, decreased serum-associated inflammatory factors, increased serum 5-HT concentration, and decreased CORT concentration in rats. In addition, the intervention increased the expression levels of cAMP, CREB and BDNF in the hippocampus of MS rats. Conclusion: Probiotics can alleviate anxiety/depression-like behavior in SD rats, which may be related to the activation of cAMP/CREB signaling pathway. The protective effect of probiotics as therapeutic food care in preventing or alleviating MS-induced depression-like behaviors provides an experimental basis for the application of probiotics to alleviate or improve anxiety/depression.

WIN55,212-2(WIN) is a cannabinoid receptor agonist. We previously found that WIN may induce cell cycle arrest and inhibit the proliferation and migration of hepatocellular carcinoma (HCC) BEL7402 cells. Auranofin (AUR) is an FDA-approved drug against rheumatoid arthritis that is currently enrolled in clinical trials as an anti-tumor agent. However, the precise functions of WIN and/or AUR on HCC carcinogenesis remain unexplored. In the present study, we aimed to study the synergistic antitumor effects and the associated underlying mechanisms of AUR/WIN combination therapy on HCC. We showed that WIN/AUR cotreatment synergistically suppressed HepG2 cell proliferation, migration and invasion. Western blot assay found that WIN/AUR cotreatment synergistically downregulated the expression of Bcl-2, cyclin D1, β-catenin, c-myc, and MMP-9 and increased the expression of Bip and ATF4, further activating Caspase3, Caspase 8, Caspase 9 and PARP cleavage. Cotreatment of AUR/WIN also arrested cell cycle at the G1 phase and induced senescence and apoptosis, evidenced by an increase in the number of SA-β-gal + senescent cells and loss of mitochondrial membrane potential (MMP) in AUR/WIN-cotreated cells. Luciferase reporter assay found that the activation of Wnt/β-catenin signaling was significantly suppressed upon WIN/AUR cotreatment in comparison with other groups. Moreover, WIN/AUR cotreatment synergistically inhibited tumor growth in subcutaneous xenograft mice models. In conclusion, our results demonstrated WIN/AUR-mediated apoptosis and suppressive effects on cell growth, migration and invasion were associated with Bcl-2 downregulation, endoplasmic reticulum (ER) stress and caspase activation, leading to downregulation of Wnt/β-catenin signaling. Therefore, WIN/AUR cotreatment may present promising combination therapy for the treatment of HCC.

Disseminated Gonococcal Infection with Dermatitis-Arthritis Syndrome

A document by Manish Kharel. Click on the document to view its contents.

Crosslinking thermosets with hyperbranched polymers confers them superior comprehensive performance. However, it still remains a further understanding of polymer crosslinking from the molecular chains to the role of aggregates. In this study, three hyperbranched polysiloxane structures (HBPSi-R) are synthesized as model macromolecules, each featuring distinct terminal groups (R denotes amino, epoxy, and vinyl groups) while similar molecular backbone (Si-O-C). These structures were subsequently copolymerized with epoxy monomers to construct interpenetrating HBPSi-R/epoxy/anhydride co-polymer systems. The spatial molecular configuration and flexible Si-O-C branches of HBPSi-R endow them with remarkable reinforcement and toughening effects. Notably, an optimum impact strength of 28.9 kJ mol-1 is achieved with a mere 3% loading of HBPSi-V, nearly three times that of the native epoxy (12.9 kJ mol-1). By contrasting the terminal effects, the aggregation states and crosslinking modes were proposed, thus clarifying the supramolecular-dominant aggregation mechanism and covalent-dominant dispersion mechanism, which influences the resulting material properties. This work underscores the significance of aggregate science in comprehending polymer crosslinking and provides theoretical insights for tailoring material properties at a refined molecular level in the field of polymer science.

Intrusion Detection Systems (IDSs) are crucial in protecting IoT networks from unauthorized access and security threats. The ability to detect anomalies and suspicious activities in real-time is vital for preventing cyber-attacks and minimizing the damage caused by them. Traditional IDSs have relied on signature-based approaches, which are limited in their ability to detect novel and unknown attacks. To overcome these limitations, this paper proposes a novel deep learning architecture named as Inverted Funnelized Multilayer Network (IFMN) for detecting intrusions in IoT networks. The proposed approach for intrusion detection employs a feature selection model that uses a Hybrid Yellow saddle goatfish algorithm and Particle Swarm Optimization algorithm for Feature Selection (HYFSPSO) to identify the optimal features. The effectiveness of the selected features is evaluated using a decision tree (DT) classification method, ensuring only the most informative features are used in the deep learning architecture for intrusion detection. For analyzing and proving the effectiveness of our scheme the current research have used three benchmark datasets i.e. KDD-CUP99, NSL-KDD and UNSW-NB15 datasets. The simulations of the proposed architecture are conducted in MATLAB and evaluated using performance matrices. While comparing the outcomes on 3 datasets results revealed that proposed HYSGPSO-DL based IDS approach is more effective on NSL-KDD and UNSW-NB15 datasets with an accuracy of 99.96% and 99.80%, while as it achieved an accuracy of 99.53% on KDD-CUP99 dataset. Additionally, comparative analysis with existing intrusion detection systems shows that our proposed scheme outperforms the state-of-the-art methods.

Type II diabetes mellitus (T2DM) accounts for approximately 90% of all diabetes mellitus cases in the world. Glucagon-like peptide-1 receptor (GLP-1R) agonists have established an increased capability to target directly or indirectly six core defects associated with T2DM, while, the underlying molecular mechanisms of these pharmacological effects are not fully known. This exploratory study was conducted to analyze the effect of treatment with GLP-1R agonists on urinary peptidome of T2DM patients. Urine samples of thirty-two T2DM patients from the PROVALID study (A Prospective Cohort Study in Patients with T2DM for Validation of Biomarkers) collected at pre- and post-treatment with GLP-1R agonist drugs were analyzed by CE-MS. In total, 70 urinary peptides were significantly affected by GLP-1R agonist treatment; generating from 26 different proteins. The downregulation of MMP proteases, based on the concordant downregulation of urinary collagen peptides was highlighted. Treatment also resulted in downregulation of peptides from SERPINA1, APOC3, CD99, CPSF6, CRNN, SERPINA6, HBA2, MB, VGF, PIGR and TTR, many of which were previously found to be associated with increased insulin resistance and inflammation. The findings indicate potential molecular mechanisms of GLP-1R agonists in the context of management of T2DM and prevention or delaying the progression of its associated diseases.

Individuals of a species cope with environmental variability through behavioral adjustments driven by individuals’ responsiveness to environmental stimuli. Three key empirical observations have been made for many animal species: The coexistence of different degrees of responsiveness within one species; the consistency of an individual’s degree of responsiveness across time; and the correlation of an individual’s degree of responsiveness across contexts. Taking up key elements of existing approaches, we provide one unifying explanation for all three observations, by identifying a unique evolutionarily stable strategy of an appropriately defined game within a stochastic environment that has all three features. Coexistence is explained by a form of negative frequency dependence. Consistency and correlation is explained through potentially small, individual, differences of states animals have and the resulting differential advantages they can get from it. Our results allow us to identify a variety of testable implications.

Adipose tissue is not only required for energy storage but is an essential endocrine organ with a central role in the pathology of obesity. The understanding of its role, both in human and equine medicine, is continually evolving. With obesity being an ever-growing problem in the equine population, gaining owner compliance is critical when implementing management plans. The aim of this review is to encourage the inclusion of the concept of adiposity in discussions with horse owners on obesity and metabolic syndrome. In doing this, we hope to improve clients understanding and therefore maximise the impact of diagnostic tests, monitoring tools and management.

Objectives: Previous observational studies have revealed a connection between sarcopenia and COVID-19. To evaluate their causal relationship, we utilized a bidirectional two-sample Mendelian randomization (MR) analysis to study the link of cause and effect between sarcopenia and COVID-19. Methods: Inverse variance weighting (IVW), MR-Egger, weighted, and weighted median were used in this research. Then we used the MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) and MR-Egger regression methods to estimate the pleiotropy of instrumental variables (IVs), while the outliers were excluded by MR-PRESSO. Moreover, we used Cochran’s Q statistic to evaluate the heterogeneity among the IVs. And we used leave-one-out sensitivity analysis to identify the SNPs that significantly affect the outcomes. Finally, the Bonferroni correction was used to correct each result. Results: The IVW results suggested that faster WP decreased the risk of all types of COVID-19 (COVID-19 infection: OR = 0.469, 95% CI: 0.326,0.676, P = 4.82E-05; COVID-19 hospitalization: OR = 0.247, 95% CI: 0.122,0.502, P = 1.11E-04; severe COVID-19: OR = 0.120, 95% CI: 0.046,0.314, P = 1.53E-05). However, there was no causal relationship between ASM, LH or RH and COVID-19, and WP adjusted for BMI had no significant connection with all types of COVID-19. Furthermore, no causal association of COVID-19 on sarcopenia was observed in the results of reverse MR analysis. Conclusion: Our bidirectional two-sample MR study suggests the causal relationship between WP and COVID-19 but it may be caused by the mediating role of BMI, thus there is no causal association between sarcopenia and COVID-19.

The seeds of ethanolic extract Aframomum pruinosum (EE) are popularly used in the management of cardiovascular conditions. This study was undertaken to evaluate the capacity of EE to prevent the development of cardiac hypertrophy in rats. Isoproterenol (0.3 mg/kg/day, sc) was injected to male rats alone or concomitantly with EE (37.5, 75, or 150 mg/kg, per os) or propranolol (20 mg/kg/day, per os) for 7 consecutive days and Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate measurements were performed. Cardiac homogenates were used to assay myeloperoxidase (MPO), superoxide dismutase (SOD), catalase, nitric oxide (NO) and reduced glutathione (GSH). Also, sections of heart tissue were stained with Hematoxylin-Eosin, Masson trichrome, or for immunohistological labelling of atrial natriuretic peptide (ANP). Chemical profiling of EE was done by gas chromatography-mass spectrometry (GC-MS). Isoproterenol administration caused a decline in SBP and DBP (p < 0.001). Heart rate, cardiac mass, cardiomyocyte surface, and MPO levels were significantly (p < 0.001) increased. All these alterations were significantly prevented (p < 0.01 and p < 0.001) by EE. EE inhibited immune cell infiltration and cardiac fibrosis elicited by isoproterenol injection. The overexpression of ANP in the atrium and ventricle induced by the isoproterenol was significantly (p < 0.001) prevented by EE. GC-MS analysis showed that EE possesses many compounds mainly nerolidol 2. EE possesses antihypertrophic effect against isoproterenol-induced cardiac hypertrophy that may result from its antifibrotic, anti-inflammatory properties, as well as its capacity to down regulate the expression of ANP.

Quantitative risk assessments of chemicals are routinely performed in rodents; however, there is growing recognition that non-animal approaches can be human-relevant alternatives. There is an urgent need to build confidence in non-animal alternatives given the international support to reduce the use of animals in toxicity testing where possible. In order for scientists and risk assessors to prepare for this paradigm shift in toxicity assessment, standardization and consensus on in vitro testing strategies and data interpretation will need to be established. To address this issue, an Expert Working Group (EWG) of the 8th International Workshop on Genotoxicity Testing (IWGT) evaluated the utility of quantitative in vitro genotoxicity concentration-response data for risk assessment. The EWG first evaluated available in vitro methodologies and then examined the variability and maximal response of in vitro tests to estimate biologically relevant values for the critical effect sizes considered adverse or unacceptable. Next, the EWG reviewed the approaches and computational models employed to provide human-relevant dose context to in vitro data. Lastly, the EWG evaluated risk assessment applications for which in vitro data are ready for use and applications where further work is required. The EWG concluded that in vitro genotoxicity concentration-response data can be interpreted in a risk assessment context. However, prior to routine use in regulatory settings, further research will be required to address the remaining uncertainties and limitations.

Pregnancy after atypical placental site nodule; a case-report

The use of hyperinsulinemia-euglycemia therapy in the treatment of amlodipine overdose in a dog.Authors: Connor Ellis, DVMa*, Adesola Odunayo, DVM, MS, DACVECCaa Department of Small Animal Clinical Sciences, University of Florida, Gainesville, FL, USA*Corresponding author: dr.connor.ellis@gmail.comCo-author: odunayoa@ufl.eduDeclarations of interest: None.No financial support was provided for the preparation of this manuscript.There are no conflicts of interest to declare for this manuscript.Consent statement:Written informed consent was obtained from the owner of this patient to publish this report in accordance with the journal’s patient consent policy.Manuscript type: case reportKeywords: amlodipine, calcium channel blockers, dog, hyperinsulinemiaKey Clinical Message: Hyperinsulinemia-euglycemia therapy (HIET) can be used for treatment of hypotension as well as other clinical signs associated with calcium channel blocker toxicosis. The use of HIET should be considered for amlodipine toxicosis in dogs.IntroductionAmlodipine is a frequently prescribed drug used to control hypertension in human and small animal patients1. This dihydropyridine calcium-channel blocker (CCB) inhibits the influx of calcium ion into the cell through the L-type calcium channel, causing peripheral vasodilation and afterload reduction1. Amlodipine is metabolized by the liver, widely distributed and highly protein bound, with a long half-life of approximately 30 hours in dogs2. While generally well tolerated, reported adverse reactions of amlodipine have been described at doses within the recommended range of 0.1-0.4 mg/kg PO q243–5.The minimum oral toxic dose of each CCB has not been well established in humans or animals, but signs of toxicity have been reported in CCBs at therapeutic doses6. Toxic doses of CCBs have been associated with significant morbidity and mortality6. Clinical signs in affected animals commonly include bradycardia, bradyarrhythmias, and hypotension, with other recognized adverse effects including pleural effusion, gingival hyperplasia, peripheral edema, gastrointestinal distress, hypothermia, central nervous system depression, and electrolyte abnormalities6. While there are currently no consensus guidelines for the treatment of CCB toxicosis in human or veterinary medicine, several retrospective studies and case series have been published in the offering best practice recommendations6–9. A recent veterinary review on CCB toxicosis highlighted decontamination and cardiovascular optimization using fluids and vasoactive medications as the most important interventions. Therapeutic recommendations also included the use of glucagon or intravenous lipid emulsion as secondary options for refractory toxicoses, and other supportive therapies as needed6.An important therapeutic intervention that has resulted in improved patient outcomes over the last 15 years in human patients is hyperinsulinemic-euglycemic therapy (HIET), with multiple publications outlining its efficacy in the human literature10–12. HIET utilizes supraphysiologic doses of insulin, with human doses ranging from 0.5-2.0 U/kg/hour, and concurrent dextrose supplementation to maintain euglycemia12. In brief, blockade of the L-type calcium channels that result in the antihypertensive effect of CCBs also decreases the release of insulin from pancreatic beta cells and reduces glucose uptake by tissues by decreasing sensitivity to insulin, with concurrent vasodilation and hypoperfusion leading to negative inotropy. Increasing insulin availability encourages glucose utilization by the myocardium and suppresses phosphodiesterase III activity, leading to intracellular calcium influx and a positive inotropic effect6. Treatment with HIET is considered a first-line intervention in CCB toxicity in human patients13. There are limited reports of the use of HIET in CCB toxicity in clinical patients in veterinary medicine. There is one case report of survival after HIET was utilized for diltiazem toxicosis in one dog, and another report of HIET therapy utilized for amlodipine toxicosis in a cat, although HIET was discontinued after 3 hours due to refractory hypoglycemia14,15. There are also two animal model studies outlining efficacy of HIET for CCB toxicosis in anesthetized dogs16,17. To the authors’ knowledge, this is the first report describing a protocol for HIET for the treatment of amlodipine toxicosis in the dog.Case descriptionA 1-year-old spayed female mixed breed dog, weighing 14.8 kg, presented to the emergency service for evaluation of ataxia and lethargy approximately 48 hours after ingestion of at least 10 mg of amlodipine (at least a 0.7 mg/kg dose). The ingestion was not witnessed by the owner, but the dog had access to a bottle containing 8 tablets of 10 mg standard release amlodipine, of which one was missing, and half of another tablet had been chewed, resulting in a maximum exposure dose of ~1 mg/kg. The dog reportedly displayed no adverse clinical signs for 24 hours after the potential ingestion, then developed lethargy, anorexia, vomiting, and ataxia in the next 24 hours. After consultation with a poison control center (Pet Poison Helpline, SafetyCall International, LLC), immediate veterinary care was recommended.At presentation, the dog was hypothermic with a rectal temperature of 37.2°C (98.9°F), bradycardic (80 beats/min), tachypneic (52 breaths/min), and dull. The dog was weakly ambulatory and the physical exam was otherwise normal. Systolic blood pressure using a Doppler ultrasonographic device (Parks Medical Electronics, Inc.) was 65 mm Hg. Venous blood was obtained when the peripheral catheter was placed for a PCV/total solids and blood gas with electrolytes. Pertinent findings included a PCV of 54% and a total solids of 66 g/L, a mixed acid-base status, hypocapnia, hyponatremia, hyperkalemia, ionized hypocalcemia, hyperglycemia, hyperlactatemia, decreased bicarbonate, and azotemia (Table 1).TABLE 1. Serial venous blood gas analysis.

The use or deployment of aerial seeding technology in forestry has shown to be efficient, rapid, and most suitable for restoration of large degraded and inaccessible areas. The technology is relatively cheaper compared to conventional methods of restoration. Although aerial seeding has been widely used globally in forestry, its application is comparatively new in Kenyan forestry. This paper reviews selected experiences from countries that pioneered the use of aerial seeding in restoring large degraded forestlands and highlights key requirements for successful aerial seeding programs. Literature shows that the use of aerial seeding in forestland restoration dates back in 1950s with reports showing moderate to high success rate in USA, Canada, Russia, Australia, New Zealand, China and India. Success of aerial seeding is largely determined by interaction of factors such as seed characteristics, timing of seeding, site conditions or micro-site environment. Competition from surrounding vegetation, and seed predation affect the efficiency of aerial seeding negatively. The paper concludes that aerial seeding technology is efficient, cost effective and therefore suitable for use in the restoration of the expansive degraded forests in Kenya.

Among many operating parameters that control cell culture environment, appropriate mixing and aeration are crucial for cells to meet oxygen demand in aerobic microbial and mammalian production processes. A model-based manufacturing facility fit approach was applied to define agitation and air flow rates during cell culture process scale-up from laboratory to manufacturing, of which computational fluid dynamics (CFD) was the core modeling tool. The realizable k-ε turbulent dispersed Eulerian two-fluid model was used to simulate gas-liquid flow in the bioreactor and predict volumetric oxygen transfer coefficients ( kLa), where the simulation was performed in the basal medium and the resulting kLa was adjusted using modification factors for surfactants such as Pluronic F68 and Antifoam C. The CFD prediction of kLa resulted in adequate agreement with the empirical values in 15,000-L and 25,000-L bioreactors. The model was then applied to define a range of agitation and bottom air flow rates for meeting cellular oxygen demand and mitigating risks of cell damage and safety hazards. The recommended operating conditions led to the completion of five manufacturing runs with a 100% success rate. The model-based approach reduced the required number of at scale development batches and hence enabled seamless scale-up, shortened timelines, and cost savings in cell culture process technology transfer.