Corrigendum to 'Single domain antibodies derived from ancient animals as broadly neutralizing agents for SARS-CoV-2 and other coronaviruses': Biomedical Engineering Advances 4 (2022) 100054.

[This corrects the article DOI: 10.1016/j.bea.2022.100054.].

Single domain antibodies derived from ancient animals as broadly neutralizing agents for SARS-CoV-2 and other coronaviruses.

With severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an emergent human virus since December 2019, the world population is susceptible to coronavirus disease 2019 (COVID-19). SARS-CoV-2 has higher transmissibility than the previous coronaviruses, associated by the ribonucleic acid (RNA) virus nature with high mutation rate, caused SARS-CoV-2 variants to arise while circulating worldwide. Neutralizing antibodies are identified as immediate and direct-acting therapeutic against COVID-19. Single-domain antibodies (sdAbs), as small biomolecules with non-complex structure and intrinsic stability, can acquire antigen-binding capabilities comparable to conventional antibodies, which serve as an attractive neutralizing solution. SARS-CoV-2 spike protein attaches to human angiotensin-converting enzyme 2 (ACE2) receptor on lung epithelial cells to initiate viral infection, serves as potential therapeutic target. sdAbs have shown broad neutralization towards SARS-CoV-2 with various mutations, effectively stop and prevent infection while efficiently block mutational escape. In addition, sdAbs can be developed into multivalent antibodies or inhaled biotherapeutics against COVID-19.

Determining Haemodynamic Wall Shear Stress in the Rabbit Aorta In Vivo Using Contrast-Enhanced Ultrasound Image Velocimetry.

Abnormal blood flow and wall shear stress (WSS) can cause and be caused by cardiovascular disease. To date, however, no standard method has been established for mapping WSS in vivo. Here we demonstrate wide-field assessment of WSS in the rabbit abdominal aorta using contrast-enhanced ultrasound image velocimetry (UIV). Flow and WSS measurements were made independent of beam angle, curvature or branching. Measurements were validated in an in silico model of the rabbit thoracic aorta with moving walls and pulsatile flow. Mean errors over a cardiac cycle for velocity and WSS were 0.34 and 1.69%, respectively. In vivo time average WSS in a straight segment of the suprarenal aorta correlated highly with simulations (PC = 0.99) with a mean deviation of 0.29 Pa or 5.16%. To assess fundamental plausibility of the measurement, UIV WSS was compared to an analytic approximation derived from the Poiseuille equation; the discrepancy was 17%. Mapping of WSS was also demonstrated in regions of arterial branching. High time average WSS (TAWSSxz = 3.4 Pa) and oscillatory flow (OSIxz = 0.3) were observed near the origin of conduit arteries. In conclusion, we have demonstrated that contrast-enhanced UIV is capable of measuring spatiotemporal variation in flow velocity, arterial wall location and hence WSS in vivo with high accuracy over a large field of view.

Plasmodium falciparum protein kinase as a potential therapeutic target for antimalarial drugs development.

Malaria is one of the most dangerous infectious diseases due to its high infection and mortality rates, especially in the tropical belt. Plasmodium falciparum (P. falciparum), the most virulent malaria parasite in humans, was recently reported to develop resistance against the final efficient antimalarial drug, artemisinin. Little is known about the resistance mechanisms, which further complicates the problem as a proper counteraction is unable to be taken. Hence, the understanding of drug mode of action and its molecular target is valuable knowledge that needs to be considered to develop the next generation of antimalarial drugs. P. falciparum protein kinase (Pf PK) is an attractive target for antimalarial chemotherapy due to its vital roles in all P. falciparum life stages. Moreover, overall structural differences and the presence of unique Pf PKs that are absent in human kinome, suggesting specific inhibition of Pf PK without affecting human cells is achievable. To date, at least 86 eukaryotic protein kinases have been identified in P. falciparum kinome, by which less than 40 were validated as potential targets at the erythrocytes stage. In this review, recent progress of the furthest validated Pf PKs; Pf Nek-1, Pf CDPK1, Pf CDPK4, Pf PKG, and Pf CLK-3 will be briefly discussed.

Plasmodium falciparum protein kinase as a potential therapeutic target for antimalarial drugs development

@#Malaria is one of the most dangerous infectious diseases due to its high infection and mortality rates, especially in the tropical belt. Plasmodium falciparum (P. falciparum), the most virulent malaria parasite in humans, was recently reported to develop resistance against the final efficient antimalarial drug, artemisinin. Little is known about the resistance mechanisms, which further complicates the problem as a proper counteraction is unable to be taken. Hence, the understanding of drug mode of action and its molecular target is valuable knowledge that needs to be considered to develop the next generation of antimalarial drugs. P. falciparum protein kinase (Pf PK) is an attractive target for antimalarial chemotherapy due to its vital roles in all P. falciparum life stages. Moreover, overall structural differences and the presence of unique Pf PKs that are absent in human kinome, suggesting specific inhibition of Pf PK without affecting human cells is achievable. To date, at least 86 eukaryotic protein kinases have been identified in P. falciparum kinome, by which less than 40 were validated as potential targets at the erythrocytes stage. In this review, recent progress of the furthest validated Pf PKs; Pf Nek-1, Pf CDPK1, Pf CDPK4, Pf PKG, and Pf CLK-3 will be briefly discussed.

A hypothetical oxidative stress regulatory role of alpha giardins in the protozoan parasite Giardia intestinalis.

Giardiasis is an intestinal infection caused by the protozoan parasite Giardia intestinalis, affecting hundreds of millions of people worldwide. This microaerophilic protozoan is capable of surviving in the host intestine in the presence of both oxygen and reactive oxygen species (ROS), despite the lack of conventional ROS-scavenging enzymes. The understanding of how G. intestinalis tolerates free radicals could help to identify essential biological processes that protect themselves against oxidative stress within the human gut. This review outlines the antioxidant mechanisms that are utilized by G. intestinalis, with an emphasis on the potential novel role of alpha giardins. The comprehensive understanding of the processes involved in oxidative stress management may provide new insights into improved treatments for giardiasis, and other medically important protozoan parasitic diseases.

Tracheobronchial stenting is safe and effective in relieving upper airway obstruction.

Many studies have shown that tracheobronchial stenting is effective in relieving respiratory distress secondary to major airway obstruction due to lung or oesophageal cancer. A retrospective review on the benefits and complications of self-expandable metallic stent (SEMS) insertion through flexible bronchoscopy for the palliative treatment of upper airway obstruction in University Malaya Medical Centre was performed. Ten patients underwent this procedure. Relief of dyspnoea was immediate following stent insertion in all patients. Stent migration occurred in one patient and three patients had restenosis of the central airway. We conclude that tracheobronchial stenting via flexible bronchoscopy is feasible and safe.

Practice patterns of some gynaecologists in Malaysia with regards to prophylactic oophorectomy and hormone replacement therapy.

This study aimed to look at the prevailing practice patterns of gynaecologists with regards to prophylactic oophorectomy and usage of hormone replacement therapy. Questionnaires were sent to the first 200 gynaecologists listed in the membership list of the Obstetrical and Gynaecological Society of Malaysia. The response rate was 30%. The results showed that most gynaecologists would perform prophylactic oophorectomy after the age of 49 years. The result was equivocal for the ages between 45 to 49 years. Of those who retained the ovaries at the age of 45 to the menopause, 55% did so because the ovaries were still functional. Almost all gynaecologists would prescribe hormone replacement therapy (HRT) after oophorectomy and the most commonly prescribed form was the oral type. Thirty-five per cent of gynaecologists claimed that more than 80% of their patients were compliant to HRT. The reasons perceived for the poor compliance were mainly poor knowledge and misconception.