Preeclampsia causes various presentations by increased endothelial permeability and microvascular damages. Maternal ascites related severe preeclampsia is generally explained by increased capillary permeability due to endothelial cell dysfunction and reduced intravascular oncotic pressure. Here we report a patient with postpartum massive ascites associated with preeclampsia.

Biotechnological application of multiple enzymes in different phases for target compounds synthesis poses a significant challenge for industrial process development. At the same time, a growing demand for natural flavors and fragrances opens up possibilities for novel biotechnological processes to replace current chemical synthesis routes, with additional advantages such as avoiding harsh reaction conditions and toxic chemicals, and less by-products in the system. Within complex biotechnological processes, the key for unfolding their industrial application potential in bioprocess engineering lies in their mathematical modeling. In this contribution, a multi-enzyme cascade reaction in a two-phase system implemented in a miniplant-scale reactor setup is mathematically modeled for the example of the flavoring agent cinnamyl cinnamate. Using our validated model and a mathematical optimization tool based on a genetic algorithm, optimization runs are performed to demonstrate the potential of computer-aided process development for complex biotechnological processes.

Background and Purpose Vancomycin is one of the most common antibiotics administered in the hospital setting, yet acute kidney injury is a major limiting factor. Common combinations of antibiotics with vancomycin have been reported to worsen and improve vancomycin-induced kidney injury. We aimed to study the impact of flucloxacillin and imipenem-cilastatin on kidney injury when combined with vancomycin in our translational rat model. Experimental Approach Male Sprague-Dawley rats received allometrically scaled (1) vancomycin (2) flucloxacillin, (3) vancomycin+flucloxacillin, (4) vancomycin+imipenem-cilastatin, or (5) saline for 4 days. Vancomycin was administered intravenously and flucloxacillin or imipenem-cilastatin were administered intraperitoneally. Kidney injury was evaluated via drug accumulation and urinary biomarkers including urinary output, kidney injury molecule-1 (KIM-1), clusterin, and osteopontin. Relationships between vancomycin accumulation in the kidney and urinary kidney injury biomarkers were explored. Key Results Urinary output increased every study day for vancomycin+flucloxacillin; whereas in the vancomycin group it was elevated after the first dose only. In the vancomycin+flucloxacillin group, urinary KIM-1/24h increased on all days compared to vancomycin. In the vancomycin+imipenem-cilastatin group, urinary KIM-1/24h was decreased on days 1 and 2 compared to vancomycin. Similar trends were observed for clusterin. More vancomycin accumulated in the kidney with vancomycin+flucloxacillin compared to vancomycin and vancomycin+imipenem-cilastatin. The accumulation of vancomycin in the kidney tissue correlated with increasing urinary KIM-1 (4-parameter Hill Slope, R2=0.7985). Conclusion and Implications Vancomycin+flucloxacillin caused more kidney injury compared to vancomycin alone and vancomycin+imipenem-cilastatin in a translational rat model as determined by multiple kidney injury biomarkers. The combination of vancomycin+imipenem-cilastatin was nephroprotective.

Mitochondria continuously undergo morphologically dynamic processes of fusion and fission to maintain their size, shape, amount, and function; yet the precise molecular mechanisms by which mitochondrial dynamics is regulated remain to be fully elucidated. Here, we report a previous unappreciated but critical role of eukaryotic elongation factor 2 (eEF2) in regulating mitochondrial fission. eEF2, a G-protein superfamily member encoded by EEF2 gene in human, has long been appreciated as a promoter of the GTP-dependent translocation of the ribosome during protein synthesis. We found unexpectedly in several types of cells that eEF2 was not only present in the cytosol but also in the mitochondria. Furthermore, we showed that mitochondrial length was significantly increased when the cells were subjected to silencing of eEF2 expression, suggesting a promotive role for eEF2 in the mitochondrial fission. Inversely, overexpression of eEF2 decreased mitochondrial length, suggesting an increase of mitochondrial fission. Inhibition of mitochondrial fission caused by eEF2 depletion was accompanied by alterations of cellular metabolism, as evidenced by a reduction of oxygen consumption and an increase of oxidative stress in the mitochondria. We further demonstrated that eEF2 and Drp1, a key driver of mitochondrial fission, co-localized at the mitochondria, as evidenced by microscopic observation, co-immunoprecipitation, and GST pulldown assay. Deletion of the GTP binding motif of eEF2 decreased its association with Drp1 and abrogated its effect on mitochondria fission. Moreover, we showed that wild-type eEF2 stimulated GTPase activity of Drp1, whereas deletion of the GTP binding site of eEF2 diminished its stimulatory effect on GTPase activity. This work not only reveals a previously unrecognized function of eEF2 (i.e., promoting mitochondrial fission), but also uncovers the interaction of eEF2 with Drp1 as a novel regulatory mechanism of the mitochondrial dynamics. Therefore, eEF2 warrants further exploration for its potential as a therapeutic target for the mitochondria-related diseases.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) enters the host cell by binding to angiotensin-converting enzyme 2 (ACE2). While evolutionarily conserved, ACE2 glycoproteins differ across various species and differential interactions with Spike (S) glycoproteins of SARS-CoV-2 viruses impact species specificity. Reverse zoonoses led to SARS-CoV-2 outbreaks on multiple American mink ( Mustela vison) farms during the pandemic and gave rise to mink-associated S substitutions known for transmissibility between mink and zoonotic transmission to humans. In this study, we used bio-layer interferometry (BLI) to discern the differences in binding affinity between multiple human and mink-derived S glycoproteins of SARS-CoV-2 and their respective ACE2 glycoproteins. Further, we conducted a structural analysis of a mink variant S glycoprotein and American mink ACE2 (mvACE2) using cryo-electron microscopy (cryo-EM), revealing four distinct conformations. We discovered a novel intermediary conformation where the mvACE2 glycoprotein is bound to the receptor-binding domain (RBD) of the S glycoprotein in a “down” position, approximately 34° lower than previously reported “up” RBD. Finally, we compared residue interactions in the S-ACE2 complex interface of S glycoprotein conformations with varying RBD orientations. These findings provide valuable insights into the molecular mechanisms of SARS-CoV-2 entry.

We report first in man implantations of the newly designed Evita-open-NEO hybrid prosthesis (HP) for complex aortic arch disease from 3 different countries in Asia-Pacific including suggestions on how to proceed with optimized perioperative coagulation.

Cryptococcus neoformans infection is a known cause of meningoencephalitis in immunocompromised patients. However, it is less frequent in immunocompetent individuals. Here we report a case of a 60 years old COVID-19 patient with a history of several co-morbidities who received tocilizumab and corticosteroids, which lead to Cryptococcemia.

ABSTRACT Rationale, aims and objectives The primary aim of the study was to understand the mindset of doctors and pharmacists, as they embark upon prescribing in a polypharmacy and multi-morbidity context during routine practice at a hospital acute admissions unit. The study also aimed to evaluate to what extent attitudes, embedded within real-life decision-making scenarios, relate to existing theory and models of prescribing decisions. Methods Anonymised case studies were identified from the medical notes of patients aged 65 and over with conditions likely to be associated with multi-morbidity, medication issues and polypharmacy: namely: fall, urinary tract infection, confusion or lower respiratory tract infection. A total of 39 doctors based on the acute medical admissions unit and 9 pharmacists were recruited to one of three focus groups. Patient case-studies provided the context for discussion from which verbatim transcripts were thematically analysed using an interpretative, qualitative approach. Sub-themes were matched to Murshid and Mohaidin’s proposed model of physician prescribing decisions. Results Seven principal themes were identified that were associated with prescribing decisions on the acute medical unit, namely, ‘patient characteristics’, ‘drug characteristics’, ‘pharmacist factors’, ‘trustworthiness’, ’reliability of medication history, ‘competing pressures and priorities’ and ‘responsibilities of prescribers’. Conclusion Prescribing decisions on the acute medical admissions unit were influenced by a variety of factors, some of which have already been acknowledged within existing theories and models. The findings provisionally offer new insights, which, subject to confirmation by further research, bring to light three attitudinal characteristics that may impact negatively upon the quality of prescribing decisions. These include, first, how perceived poor reliability of medication history may result in information gaps that compromise prescribing decisions; second, how competing pressures and priorities restrict doctors’ aptitude to conduct a review of medication and finally, how doctors may rationalise the assignment of medication review to the GP.

The ongoing explosion of fine-resolution movement data in animal systems provides a unique opportunity to empirically quantify spatial, temporal, and individual variation in transmission risk and improve our ability to forecast disease outbreaks. However, we lack a generalizable framework that can leverage movement data to quantify transmission risk and how it affects pathogen invasion and persistence on heterogeneous landscapes. We developed a flexible framework “Movement-driven modeling of spatio-temporal infection risk” (MoveSTIR) that leverages diverse data on animal movement to derive metrics of direct and indirect contact by decomposing transmission into constituent processes of contact formation and duration and pathogen deposition and acquisition. We use MoveSTIR to demonstrate that ignoring fine-scale animal movements on actual landscapes can mis-characterize transmission risk and epidemiological dynamics. MoveSTIR unifies previous work on epidemiological contact networks and can address applied and theoretical questions at the nexus of movement and disease ecology.

We reflect on the progress in the area of Explainable AI (XAI) Program relative to previous work in the area of intelligent tutoring systems (ITS). A great deal was learned about explanation—and many challenges uncovered—in research that is directly relevant to XAI. We suggest opportunities for future XAI research deriving from ITS methods, as well as the challenges shared by both ITS and XAI in using AI to assist people in solving difficult problems effectively and efficiently.

IntroductionMultiple Sclerosis (MS) is a chronic autoimmune disorder causing nerve sheath demyelination and symptoms such as muscle weakness, mobility decline, and lack of coordination 1,2, generating unique health challenges and an economic burden 3-5. Patients experience reductions in bone and skeletal muscle mass6, muscle strength and function 7,8, and increased fracture risk 9, negatively impacting quality of life 10. Lower limb strength impairments8, poor balance 11 and spasticity12 also contribute to a lower quality of life10. Pharmacological treatments have been the primary option for patients with MS 13.Recent research has explored non-pharmacological treatments such as exercise, nutritional supplementation, and improved sleep quality14-21. Resistance exercise (RE) is particularly beneficial for MS rehabilitation, as it improves muscle strength and function, mobility, quality of life 22,23, and the immune system 24. High-dose vitamin D supplementation raises interleukin-10 (IL-10) levels in MS patients19, who tend to have lower levels of IL-10, which may contribute to the disease’s development 25. However, RE and vitamin D may not always improve physical fitness20,21. This could be due to unsatisfactory energy and protein intake, containing essential amino acids (EAA), which are necessary to stimulate muscle protein synthesis (MPS) and ultimately address sarcopenia 26, a condition prevalent in MS patients 27. EAA-based supplements enriched with L-leucine increase protein intake and optimise MPS in healthy older adults without compromising total energy intake during mealtimes28,29 and plasma EAA concentration is associated with muscle function in older women in the community 30. A higher protein intake, including specific amino acids, may positively impact bone health through mechanisms such as increasing insulin-like growth factor 1 (IGF-1) 31,32. Therefore, addressing dietary protein deficiencies alongside RE may optimise musculoskeletal health and function in female MS patients. This case study evaluated the effects of a 24-week home-based intervention, including EAAs and vitamin D3 supplementation, on muscle, bone, muscle strength, and function in a female patient with MS.

Introduction: A large proportion of patients with infectious mononucleosis (IM) have abnormal liver function tests (LFT) at presentation. There is no guideline regarding the management and follow-up of these patients. Some patients also have abdominal ultrasound due to deranged LFT, the need for this practice is unclear. The aim of this systematic review was to evaluate the evidence base on LFT assessment in IM, time to resolution of derangement, and the role of abdominal ultrasound. Methods: A systematic search of PubMed, EMBASE and the Cochrane library was done. Two authors independently screened records for eligibility using pre-defined criteria. We included both adult and paediatric populations. Quality assessment of included studies was done. Results: A total of 3924 patients were included from 32 studies. A combination of typical clinical features, heterophile antibodies and EBV-specific antibodies were used to ascertain diagnosis. The following proportion of patients had abnormal LFTs: AST (57%); ALT (62%); ALP (65%); Bilirubin (16%); GGT (41%). Reported median (i.q.r.) time to resolution of LFT was 8 (6–12) weeks. Maximum time to resolution was >6 months. Clinical hepatomegaly and splenomegaly were found in 35% and 44% of patients respectively. Enlarged liver and spleen on ultrasound were seen in 16/29 (55%) and 38/38 (100%) of patients respectively. There were no reports of decompensated liver disease. Conclusion: Derangement in LFTs can persist over six months from initial presentation in IM. However, this is self-limiting. The evidence suggests serial liver function assessments and ultrasound abdomen are not required in immunocompetent patients with subclinical derangement in LFTs.

Theory predicts that threatened species living in small populations will experience high levels of inbreeding that will increase their negative genetic load but recent work suggests that the impact of load may be minimized by purging resulting from long term population bottlenecks. Empirical studies that examine this idea using genome-wide estimates of inbreeding and genetic load in threatened species are limited. Here we use genome resequencing data to compare levels of inbreeding, levels of genetic load and population history in threatened Eastern massasauga rattlesnakes (Sistrurus catenatus) which exist in small isolated populations and closely-related yet outbred Western massasauga rattlesnakes (S. tergeminus). In terms of inbreeding, S. catenatus genomes had a greater number of ROHs of varying sizes indicating sustained inbreeding through repeated bottlenecks when compared to S. tergeminus. At the species level, outbred S. tergeminus had higher genome-wide levels of genetic load in the form of greater numbers of derived deleterious mutations compared to S. catenatus presumably due to long-term purging of deleterious mutations in S. catenatus. In contrast, mutations that escaped the “drift sieve” and were polymorphic within S. catenatus populations were more abundant and more often found in homozygote genotypes than in S. tergeminus suggesting a reduced efficiency of purifying selection in smaller S. catenatus populations. Our results support an emerging idea that the historical demography of a threatened species has a significant impact on the type of genetic load present which impacts implementation of conservation actions such as genetic rescue.

Na+,K+ATPase (NKA), a transmembrane protein essential for maintaining the electrochemical gradient across the plasma membrane, acts as a receptor for cardiotonic steroids (CTS) such as ouabain. CTS binding to NKA, triggers signalling pathways or inhibits NKA activity in a concentration-dependent manner, resulting in a modulation of Ca2+ levels, which are essential for homeostasis in neurons. However, most of the pharmacological strategies for avoiding neuronal death do not target NKA activity, due to its complexity and poor comprehension of the mechanisms involved in NKA modulation. The present review aims to discuss two points regarding the interplay between NKA and Ca2+ signalling in the brain: NKA impairment causing illness as well as neuronal death due to Ca2+ signalling and benefits to the brain by modulating NKA activity. These interactions play an essential role in neuronal cell fate determination and are relevant to finding new targets for the treatment of neurodegenerative diseases.

Large scale changes in land use pattern such as deforestation and machine-intensive farming process have increased carbon concentrations in atmosphere which negatively affects agricultural sector. Cross-disciplinary approaches were applied to investigate the land use changes and their impacts on the soil properties over Kanshi watershed. The results revealed that vegetation cover has been declined over the Kanshi catchment area during the last two decades. The deforestation and urbanization are the basic reasons for the fall of water tables in the Kanshi catchment area. Furthermore, the decreasing trend of rainfall and increasing trend of temperature was estimated during the last two decades. While the water discharge was decreased by 44.15 % during the last two decades in the Kanshi watershed. This substantial and significant change resultant due to climate change or increased intercession of anthropogenic activities on the earth surface. The highest stream flow was found in 1992 in the Kanshi catchment due to heavy rainfall. But in 2019, flow was on its peak value. Such variations in flow of stream increase due to fluctuations in rainfall pattern and vegetation cover resulted land degradation. 85% of local community is agreed that extensive agricultural practices, population growth, settlement patterns and brick industry have significant negative impact on vegetative cover and water discharge.

Introduction: Following the Covid-19 pandemic, the face-to-face meetings are delayed to a future date , which is still not clear. However, seminars, meetings, and conferences are necessary for updating our knowledge and skills. The web-based seminars (webinars) are the solutions to this issue. This study aimed to show the participant behavior when webinars present at the Covid-19 pandemic era. Methods: Between December 2017 – July 2020, 58 webinars were broadcasted via the Uropedia, electronic library of SUST. Data of all webinars were collected with the YouTube analytics and application of the Uropedia. Data of streaming webinars included participant behaviors such as content views, engagement time, total unique attendees, average engagement time, and the number of audience to leads. Data were split into two groups; group-1 is webinars before Covid-19 (before March 2020), group-2 is the webinars during Covid-19. Results: Total broadcast time and total page view number were found to be 112.6 hours (6761 min.) and 15919, respectively. The median participant age was 40.1 years. Median content view and median engagement time were found to be 261.0 min., and 12.2 min., respectively. Comparison of two groups revealed a significant increment in the content views (group 1;134.0 range=86.0-87.0 and group 2; 414.0 range=296.0-602.0, p<0.001) and the number of the unique attendees (group 1; 18.0 range=10.0-26.0 and group 2; 57.0 range=27.0-100.0, p<0.001) following Covid-19. However, the median engagement time of the audience did not seem to change with the Covid-19 pandemic (group 1; 11.5 range=10.0-13.3 min. and group 2; 13.2 range=9.4-18.1 min., p=0.12). Conclusion: The webinars are effective ways to share information and have many advantages, including low cost, reaching the high number of audiences. Audience number and page visits seemed to increase following the Covid-19 pandemic. However, The engagement time did not seem to affect a critical attitude of the audience

Objective: The current study aimed to evaluate eye care needs along with ocular findings in patients treated in intensive care units due to Covid-19 infection. Materials and Methods: A total of 93 patients, 58 men and 35 women, who were under follow-up and treatment in intensive care due to COVID-19 infection between 01/01/2021 and 02/15/2021 were included in the study. Detailed eye examinations of the patients were performed with a portable handheld biomicroscope and direct and indirect ophthalmoscope. Cases requiring treatment for eye diseases were identified and treated. Results: The mean patient age was 68.32 ± 9.97 years; 35 patients were followed-up and treated with non-invasive mechanical ventilation and 58 patients with invasive mechanical ventilation support. Mild, moderate, and severe chemosis was observed in 19 patients (20.4%), 10 patients (10.8%), and 4 patients (4.3%), respectively. Conjunctivitis (8.6%) was observed in 8 patients. Corneal abrasion was present in 7 patients (7.5%). Keratitis secondary to exposure keratopathy was observed in one patient. Eye care and medical treatment was initiated for these patients. We noted 8 patients (8.6%) with retinal haemorrhage; however, to the best of our knowledge, these patients may show acute retinal involvement secondary to systemic diseases or have previous retinal findings other than Covid-19 infection or treatments. Conclusion: Findings of ocular involvement due to COVID-19 infection were detected in the present study. Retinal haemorrhages were detected in addition to the common findings in viral infections. Especially in patients supported with mechanical ventilation, the detection and treatment of conditions that require eye care for exposure keratopathy is very important for recovering from the disease and the quality of vision.

Purpose: Successful resuscitation and early defibrillation are critical in survival after in- or out-of-hospital cardiopulmonary arrest. This study aimed to determine the knowledge, skills, and attitudes of the pediatric healthcare professionals about the defibrillator use and to offer solutions if there was room for improvement. Procedures: This was a multicenter survey study. Findings: The study included 716 healthcare professionals with an average age of 30.1 ± 5.8 years; 50% (n=358) were pediatric residents and 41.3% (n=296) had less than three years of professional experience. Self-declared level of knowledge about defibrillation/cardioversion was low-to-medium for 66.5% (n=476); 60.8% (n=435) had never practiced these procedures and 22.2% (n=159) had never received any training about defibrillator use. There was a significant relationship between professional experience and the proportion of participants who correctly responded to the first-shock dose for defibrillation but not for cardioversion. Conclusion: Professional experience is crucial in the correct defibrillator use. However, the defibrillation/cardioversion procedures are prone to errors since they are not commonly applied in day to day practice. An ideal approach to improve the experience of personnel could be to use practical training with case-based simulations and to educate the personnel about the features of the defibrillators available in their clinics.