Pathomechanism and Management of Stroke in COVID-19: Review of Immunopathogenesis,Coagulopathy, Endothelial Dysfunction,and Downregulation of ACE2

Coronavirus disease 2019 (COVID-19) can reportedly manifest as an acute stroke, with most cases presenting as large vessel ischemic stroke in patients with or without comorbidities. The exact pathomechanism of stroke in COVID-19 remains ambiguous. The findings of previous studies indicate that the most likely underlying mechanisms are cerebrovascular pathological conditions following viral infection, inflammation-induced endothelial dysfunction, and hypercoagulability. Acute endothelial damage due to inflammation triggers a coagulation cascade, thrombosis propagation, and destabilization of atherosclerosis plaques, leading to large-vessel occlusion and plaque ulceration with concomitant thromboemboli, and manifests as ischemic stroke. Another possible mechanism is the downregulation of angiotensin-converting enzyme 2 as the target action of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Acute stroke management protocols need to be modified during the COVID-19 pandemic in order to adequately manage stroke patients with COVID-19.     

Novel dermacozine-1-carboxamides as promising anticancer agents with tubulin polymerization inhibitory activity

In the present study, novel dermacozine-1-carboxamides (8a–8n) were synthesized and screened for their in vitro cytotoxic activity against three different cancer cell lines: MCF-7 (breast cancer), A-549 (lung cancer) and DU145 (prostate cancer). All the compounds showed more efficiency against the DU145 cell line than against the MCF-7 and A-549 cell lines. Furthermore, 8a (CTC₅₀: 7.02 μM) and 8l (CTC₅₀: 6.32 μM) have been found to be more effective against the DU145 cells as they arrest the cell cycle at the G2/M phase by interfering with tubulin polymerization; these results indicate that these compounds act as potential anti-cancer agents by inhibiting tubulin polymerization.

In the present study, novel dermacozine-1-carboxamides (8a–8n) were synthesized and screened for their in vitro cytotoxic activity against three different cancer cell lines: MCF-7 (breast cancer), A-549 (lung cancer) and DU145 (prostate cancer).     

On the Microstructure of Laser Beam Powder Bed Fusion Alloy 718 and Its Influence on the Low Cycle Fatigue Behaviour

Additive manufacturing of Alloy 718 has become a popular subject of research in recent years. Understanding the process-microstructure-property relationship of additively manufactured Alloy 718 is crucial for maturing the technology to manufacture critical components. Fatigue behaviour is a key mechanical property that is required in applications such as gas turbines. Therefore, in the present work, low cycle fatigue behaviour of Alloy 718 manufactured by laser beam powder bed fusion process has been investigated. The material was tested in as-built condition as well as after two different thermal post-treatments. Three orientations with respect to the building direction were tested to evaluate the anisotropy. Testing was performed at room temperature under controlled amplitudes of strain. It was found that defects, inclusions, strengthening precipitates, and Young’s modulus influence the fatigue behaviour under strain-controlled conditions. The strengthening precipitates affected the deformation mechanism as well as the cycle-dependent hardening/softening behaviour. The defects and the inclusions had a detrimental effect on fatigue life. The presence of Laves phase in LB-PBF Alloy 718 did not have a detrimental effect on fatigue life. Young’s modulus was anisotropic and it contributed to the anisotropy in strain-life relationship. Pseudo-elastic stress vs. fatigue life approach could be used to handle the modulus-induced anisotropy in the strain-life relationship.     

Clinical evaluation of post-operative analgesia comparing suprascapular nerve block and interscalene brachial plexus block in patients undergoing shoulder arthroscopic surgery

BackgroundShoulder arthroscopic surgeries have a high incidence of severe post-operative pain significant enough to interfere with recovery and rehabilitation. A regional anaesthetic technique combined with general anaesthesia reduces intra-operative requirements of anaesthesia and provides a better post-operative pain relief. As the commonly employed technique of interscalene brachial plexus block (ISB) is associated with potential serious complications, suprascapular nerve block (SSB) can be used as a safer alternative.Methods and materialIn this prospective study, 60 ASA 1 or 2 adult patients undergoing shoulder arthroscopic surgery were randomised into two groups – ISB and SSB. In group ISB, ISB with 20 ml of 0.5% bupivacaine mixed with 75 μg clonidine was given. In the SSB group SSB was given with 15 ml of 0.5% bupivacaine with 75 μg clonidine. Pain was assessed using visual analogue scale and verbal pain scale scores and time to first rescue analgesia was noted. We used Student's t test and Chi-square/Fisher Exact test and used a statistical software to compare data.ResultsIn the present study, the mean duration of analgesia was 2.53 ± 2.26 h in SSB group compared to 7.23 ± 6.83 h in group ISB (p value < 0.05). Overall rescue analgesic requirements were higher in SSB group compared to ISB group (63.3% versus 40.0%) but this was statistically not significant (p value > 0.05).ConclusionBoth interscalene and SSB can be used to provide intra-operative and post-operative analgesia in patients undergoing shoulder arthroscopy.     

A Sociological Analysis and Exploration of Factors Associated with Commercial Preparations of Smokeless Tobacco Use in Sri Lanka

Background: Use and addiction to commercial preparation of Smokeless Tobacco (CPSLT) is creating new socio-cultural issues and health challenges in Sri Lanka.  The objective of this sociological study is to investigate and analyse the socio-cultural factors that influence CPSLT use Sri Lanka to enable development of effective interventions.  Methods: This is a qualitative study for which data was collected through in-depth interviews in selected groups that use CPSLT. Thirty-five interviews were carried out in seven of the 24 districts in the country representing urban, rural, plantation communities and different livelihood and ethnic, gender and age groups in the year 2016. Purposive and snowball sampling techniques were used for selecting interviewees. The data was analysed by using qualitative data analysis techniques and sociological perspectives. Results: This study reveals that the CPSLT use has integrated with the culture of several sociological and livelihood groups. Products such Thool (tobacco powder) and Maawa (dried areca-nut with flaked tobacco and some flavoured chemicals) were identified as the most popular forms of CPSLT.  Use of CPSLT has developed as a silent sub-culture specific to several social and livelihood groups. The informal CPSLT industry operating in the urban and sub-urban areas is influencing the school children and youth engaged in sports. Different groups of users express different reasons and justifications for its use. Conclusion: Use of CPSLT is closely integrated with the day to-day lifestyle and values of people of specific groups. and is an unseen part of life. Therefore, interventions will be urgently required to control the use of CPSLT to prevent its significant health impacts, considering the different contexts, symbolisms and justifications of its among the different groups.     

Synthesis, characterization, and in vitro antimicrobial evaluation of new 5-chloro-8-bromo-3-aryl-1,2,4-triazolo[4,3-c]pyrimidines

A series of new 5-chloro-8-bromo-3-aryl-1,2,4-triazolo[4,3-c]pyrimidines (4a–j) have been accomplished in excellent yields by the oxidative cyclization of pyrimidinylhydrazines (3a–j) of various aryl aldehydes with one equivalents of iodobenzene diacetate in methanol. The chemical structures of the synthesized compounds were confirmed by elemental analyses, FT-IR, ¹H NMR, ¹³C NMR, and mass spectral studies. Ten new compounds (4a–j) were tested in vitro for their antimicrobial activity against clinically isolated strains. Variable and modest activities were observed against the investigated strains of bacteria and fungi. Compounds 4f, 4i, and 4j demonstrated good antimicrobial activity against all the tested microbial strains.     

Ultrasound image-guided therapy enhances antitumor effect of cisplatin

Purpose

The aim of this study was to clarify whether ultrasound image-guided cisplatin delivery with an intratumor microbubble injection enhances the antitumor effect in a xenograft mouse model.

Methods

Canine thyroid adenocarcinoma cells were used for all experiments. Before in vivo experiments, the cisplatin and microbubble concentration and ultrasound exposure time were optimized in vitro. For in vivo experiments, cells were implanted into the back of nude mice. Observed by a diagnostic ultrasound machine, a mixture of cisplatin and ultrasound contrast agent, Sonazoid, microbubbles was injected directly into tumors. The amount of injected cisplatin and microbubbles was 1 μg/tumor and 1.2 × 10⁷ microbubbles/tumor, respectively, with a total injected volume of 20 μl. Using the same diagnostic machine, tumors were exposed to ultrasound for 15 s. The treatment was repeated four times.

Results

The combination of cisplatin, microbubbles, and ultrasound significantly delayed tumor growth as compared with no treatment (after 18 days, 157 ± 55 vs. 398 ± 49 mm³, P = 0.049). Neither cisplatin alone nor the combination of cisplatin and ultrasound delayed tumor growth. The treatment did not decrease the body weight of mice.

Conclusion

Ultrasound image-guided anticancer drug delivery may enhance the antitumor effects of drugs without obvious side effects.     

Internal iliac artery pseudo aneurysm occlusion using amplatzer vascular plug

Pseudoaneurysm of the internal iliac artery is a rare occurrence. Our patient presented with pain over the lower abdomen which also radiated to the back. An Angiogram of the aorta and the iliac arteries showed a pseudoaneurysm of the right internal iliac artery which measured about 8 x 8 cm with a proximal branch of the internal iliac artery distended. Initial efforts of trying to embolize the pseudoaneurysm revealed that there was a connection between the pseudoaneurysm and the interanal iliac vein where foam was getting dislodged into the venous system. Subsequently, we decided to use a vascular plug which has just been recently being introduced. Post procedure there was no more flow into the right internal iliac artery pseudoaneurysm.