​Faecal Consistency: A Measure of Gastrointestinal Parasitic Infections in Goats

Background: Gastrointestinal (GI) parasitism in goats is a serious and widely distributed problem. Diarrhoea, moderate or severe, though a result of various factors involving feed, fodder, seasons and state of gut physiology of digestion, is a common symptom in goats infested with GI parasites, the nematodes and coccidia. Intensity of diarrhoea corresponds to quantum and type of parasitism. Methods: In the present study, 1451 faecal samples collected from goats of different ages ( less than 3 M, greater than 3-6 M, greater than 6-12 M and greater than 12 M) were categorized as normal, lumpy and diarrheic based on their consistency and were processed for parasitic infections. The GI parasitic load was quantified by faecal eggs/oocysts counting (FEC and FOC) per gram of faeces through the modified Mac-master technique. Identification of parasites was based on the morphology of third-stage larvae procured by coproculture of randomly selected positive samples. FEC/FOC data (strongyle and coccidian), being skewed and uneven, were log-transformed to normalize. The transformed data [loge (100+n)] was analyzed statistically and results were interpreted. Result: Means of FEC and FOC in three type of faecal samples viz. normal, lumpy and diarrheic, were significantly different. Similarly, the effect of age on FEC and FOC was significant. The interaction between animals age × faecal sample type was significant in coccidian and non-significant in strongyle infection. The results were discussed to support the hypothesis that faecal consistency was a measure of coccidian and strongyle worm load in goats and can be a basis of targeted selective treatment.

The MEK1/2-inhibitor ATR-002 efficiently blocks SARS-CoV-2 propagation and alleviates pro-inflammatory cytokine/chemokine responses

Coronavirus disease 2019 (COVID-19), the illness caused by a novel coronavirus now called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to more than 260 million confirmed infections and 5 million deaths to date. While vaccination is a powerful tool to control pandemic spread, medication to relieve COVID-19-associated symptoms and alleviate disease progression especially in high-risk patients is still lacking. In this study, we explore the suitability of the rapid accelerated fibrosarcoma/mitogen-activated protein kinase/extracellular signal-regulated kinase (Raf/MEK/ERK) pathway as a druggable target in the treatment of SARS-CoV-2 infections. We find that SARS-CoV-2 transiently activates Raf/MEK/ERK signaling in the very early infection phase and that ERK1/2 knockdown limits virus replication in cell culture models. We demonstrate that ATR-002, a specific inhibitor of the upstream MEK1/2 kinases which is currently evaluated in clinical trials as an anti-influenza drug, displays strong anti-SARS-CoV-2 activity in cell lines as well as in primary air–liquid-interphase epithelial cell (ALI) cultures, with a safe and selective treatment window. We also observe that ATR-002 treatment impairs the SARS-CoV-2-induced expression of pro-inflammatory cytokines, and thus might prevent COVID-19-associated hyperinflammation, a key player in COVID-19 progression. Thus, our data suggest that the Raf/MEK/ERK signaling cascade may represent a target for therapeutic intervention strategies against SARS-CoV-2 infections and that ATR-002 is a promising candidate for further drug evaluation.

Assessment and Modeling of Plasmonic Photothermal Therapy Delivered via a Fiberoptic Microneedle Device Ex Vivo

Plasmonic photothermal therapy (PPTT) has potential as a superior treatment method for pancreatic cancer, a disease with high mortality partially attributable to the currently non-selective treatment options. PPTT utilizes gold nanoparticles infused into a targeted tissue volume and exposed to a specific light wavelength to induce selective hyperthermia. The current study focuses on developing this approach within an ex vivo porcine pancreas model via an innovative fiberoptic microneedle device (FMD) for co-delivering light and gold nanoparticles. The effects of laser wavelengths (808 vs. 1064 nm), irradiances (20–50 mW·mm−2), and gold nanorod (GNR) concentrations (0.1–3 nM) on tissue temperature profiles were evaluated to assess and control hyperthermic generation. The GNRs had a peak absorbance at ~800 nm. Results showed that, at 808 nm, photon absorption and subsequent heat generation within tissue without GNRs was 65% less than 1064 nm. The combination of GNRs and 808 nm resulted in a 200% higher temperature rise than the 1064 nm under similar conditions. A computational model was developed to predict the temperature shift and was validated against experimental results with a deviation of <5%. These results show promise for both a predictive model and spatially selective, tunable treatment modality for pancreatic cancer.

Enhanced Productivity in Horizontal Open Hole Completion Using Integrated Dynamic Diversion Acid Squeeze Technique in Highly Depleted Well: Successful Application in West Kuwait Field

The Minagish field in West Kuwait is a high potential field which poses several challenges in terms of hydrocarbon flow assurance through highly depleted tight carbonate intervals with uneven reservoir quality and curtailed mobility. These conditions have shifted the field development from vertical to horizontal wellbore completions. Achieving complete wellbore coverage is a challenge for any Matrix Acid treatment performed in a long openhole lateral with disparities in reservoir characteristics. The fluid will flow into the path of least resistance leaving large portions of the formation untreated. As a result, economic Acid treatment options dwindle significantly, thus reservoir stimulation results are not always optimum. A multistage acid stimulation technique using Integrated Dynamic Diversion (IDD) has been performed in a West Kuwait field well. The process uses active fluid energy to divert flow into a specific sweet point (high pressure point) in the lateral, which can pinpoint and precisely place acid treatment at the desired location. The process uses two self-directed fluid streams: one inside the pipe and one in the annulus. The process mixes the two fluids downhole with high energy to form a consistent controllable mixture. The technique includes pinpoint fluid jetting at the point of interest, followed by customized foamed HCL acid systems employed for improving individual stage targets in depleted reservoir. The IDD diversion shifts the acid treatment to unstimulated areas to create complex wormholes which increase reservoir contact volume and improve overall conductivity in the lateral. The kinetics and chemical diversion of the IDD methodology are highly critical to control fluid loss in depleted intervals and results in enhanced stimulation. The application of the IDD methodology is a fit-for-purpose solution to address the unique challenges of openhole operations, formation technical difficulties, high-stakes economics, and untapped high potential from intermittent reservoirs. By utilizing this application in one continuous operation, the use of chemical diverters, straddle packers and mechanical plugs for selective treatment in open hole is eliminated, making this multistage completion technology economical for these depleted wells. The paper presents results obtained after stimulating multiple zones along the lateral and describes the lessons learned in the implementation of this methodology. Going forward, the methods described, which can be considered a best practice for application to similar challenges in other fields. Proper candidate selection, optimum completion tools, and the fluid combination of in-situ gel-based diverter used to temporary plug the acid stimulated zone and foamed acid created an increase in the oil production of 430 BOPD.

On-farm culture and pathogen identification: risks and benefits

Selective treatment of clinical mastitis cases based on the results of on-farm culture (OFC) has been suggested by several international experts. It is based on the theory that mastitis cases caused by Gram-negative species has high resolution rates, and those that do not resolve respond poorly to therapy. Several peer-reviewed studies have evaluated the accuracy of different OFC test kits, which are between 60–85% accurate at identifying Gram-positive pathogens. Implementation studies consistently show a reduction in antimicrobial use, although further research across larger populations is needed to assess the impact on mastitis cure. Any OFC protocol should be regularly reviewed with the herd veterinarian. Herds with a high bulk cell count, a high prevalence of Gram-positive pathogens (e.g. Streptococcus uberis), or with a high prevalence of Klebsiella spp. should carefully consider the impact of deferred or withholding treatment on mastitis cure.

Progress of Phototherapy Applications in the Treatment of Bone Cancer

Bone cancer including primary bone cancer and metastatic bone cancer, remains a challenge claiming millions of lives and affecting the life quality of survivors. Conventional treatments of bone cancer include wide surgical resection, radiotherapy, and chemotherapy. However, some bone cancer cells may remain or recur in the local area after resection, some are highly resistant to chemotherapy, and some are insensitive to radiotherapy. Phototherapy (PT) including photodynamic therapy (PDT) and photothermal therapy (PTT), is a clinically approved, minimally invasive, and highly selective treatment, and has been widely reported for cancer therapy. Under the irradiation of light of a specific wavelength, the photosensitizer (PS) in PDT can cause the increase of intracellular ROS and the photothermal agent (PTA) in PTT can induce photothermal conversion, leading to the tumoricidal effects. In this review, the progress of PT applications in the treatment of bone cancer has been outlined and summarized, and some envisioned challenges and future perspectives have been mentioned. This review provides the current state of the art regarding PDT and PTT in bone cancer and inspiration for future studies on PT.

Looking the Gift Horse in the Mouth

This introductory chapter begins with a case study of a prominent donation by Amazon founder Jeff Bezos. Reactions to this announcement represent a common trend in criticism of philanthropy that overlooks the value of democracy. The chapter offers a formal definition of philanthropy as a social practice constituted by impersonal gratuitous transfers of private property. It reports recent statistics about the practice’s development. It argues that philanthropy raises distinctive political questions. It summarizes recent work on philanthropy in moral and political philosophy, noting its limited appreciation of democratic concerns. The chapter closes with a preview of the subsequent chapters and a disclaimer about the selective treatment of topics.

Preliminary Assessment of Body Condition Score as a Possible Marker for the Targeted Selective Treatment of Dairy Sheep Against Gastrointestinal Nematodes

Purpose In the fight against anthelmintic resistance, targeted selective treatments (TSTs), where only a small percentage of a flock receives treatment, have become increasingly popular. Overall, implementation of such treatments can be based on various parameters including Body condition score (BCS). As infection with non-bloodsucking nematodes, frequently encountered on sheep farms in the central Mediterranean basin, commonly causes bodyweight reduction, the aim of this research is to evaluate the effectiveness of BCS as a parameter for the implementation of TSTs in lactating dairy sheep with subclinical gastrointestinal nematode (GIN) infections from the island of Sardinia, Italy. Methods Faecal samples from 1012 ewes divided into 2 groups (third and fifth month of lactation) were collected and their BCS recorded. Faecal egg counts and coprocultures were performed for the assessment of the GIN burden and identification of present species. Results An overall GIN prevalence of 85.4% with a mean eggs per gram (EPG) of faeces of 210.1 ± 347.3 was found. Teladorsagia spp. and Trichostrongylus spp. were the GIN genera most identified. Overall, animals with the lowest BCS had the highest EPG values and a negative correlation (r = − 0.163) between the EPG values and BCS of the studied animals was found, which was most significant for older sheep. Conclusion This research confirmed BCSs and EPG values for GIN in sheep to be negatively correlated, particularly in older ewes. Application of TSTs for lactating sheep with a BCS < 2.25, especially to older ewes, could be beneficial in case of subclinical GIN infections, although further studies are needed to work out precise recommendation.