Persistent chemosensory dysfunction (PCD) is a common symptom of long-COVID. Chemosensory dysfunction (CD) as well as SARS-CoV-2-specific antibody levels and CD8⁺ T-cell immunity were investigated in a cohort of 44 healthcare workers up to a median of 721 days after a positive PCR test. CD was assessed using questionnaires and psychophysical screening tests. After 721 days, 11 of 44 (25%) participants reported PCD, with five describing an impaired quality of life. One participant reported hyperosmia (increased sense of smell). The risk of PCD at 721 days was higher for participants reporting qualitative changes (parosmia (altered smell), dysgeusia (altered taste), or phantosmia (hallucination of smell)) during initial infection than in those with isolated quantitative losses during the first COVID-19 infection (62.5% vs. 7.1%). The main recovery rate occurred within the first 100 days and did not continue until follow-up at 2 years. No correlation was found between antibody levels and CD, but we observed a trend of a higher percentage of T-cell responders in participants with CD. In conclusion, a significant proportion of patients suffer from PCD and impaired quality of life 2 years after initial infection. Qualitative changes in smell or taste during COVID-19 pose a higher risk for PCD. Full article

This investigation was conducted to demonstrate the potential impacts of different doses of Bisphenol A (BPA) or Nonylphenol (NP) and their mixtures on some biological activities in male albino rats. Seventy male albino rats were allocated to the control group (GI) and were given 1 mL of ethanol. G II and G III were given 100 mg/kg of each of BPA and NP, G IV and G V were given 25 mg/kg of each of BPA and NP, G VI was given a high dose of BPA and NP, and G VII was given a low dose of BPA and NP. All animals were treated orally for 60 days. Serum biomarkers of oxidative stress, antioxidants, immune-inflammatory mediators, and apoptotic markers were determined, as well as a histopathological examination of the testis at the end of the experimental period. The results obtained showed a pronounced increase in malondialdehyde (MDA), protein carbonyl (PC), and 4-hydroxynonenol (4-HNE), concomitant with a significant reduction in serum Superoxide dismutase (SOD), catalase enzyme (CAT), and total antioxidant capacity (TAC) in all treated groups. A significant elevation in TNF Alpha, TNF Beta, and Caspase 3 serum was recorded individually and in the groups treated with high doses. The disturbance is represented by histological damage in the testis in the germinal epithelium and a decrease in spermatozoa inside the lumen of seminiferous tubules. The effects on testis tissues were dose-dependent, pronounced in mixture doses, and remarkable in higher doses. In conclusion, exposure to BPA and NP strongly impacts antioxidants, immune-inflammatory mediators, and testis tissue architecture. Furthermore, the data from this investigation support the idea that exposure to BPA and NP in daily life has multiple damages. Full article

The treatment of hypertension is of major importance to reduce the risk of cardiovascular disease, the leading cause of death worldwide. Angiotensin-converting enzyme (ACE) inhibitors are anti-hypertensive drugs associated with several side effects. Natural products, namely bioactive peptides from brewing by-products, brewers’ spent grain (BSG), and yeast (BSY), are promising alternatives since they can inhibit ACE in vitro. However, the oral intake of these peptides may modify their expected inhibitory effect owing to possible changes in active peptides’ bioavailability, which have not been assessed so far. The goal of this study was to simulate oral administration to evaluate BSG/BSY peptides’ effectiveness by submitting protein hydrolysates sequentially to simulated gastrointestinal digestion, intestinal absorption (Caco-2 cells), and liver metabolism (HepG2 cells). MTT assay was used to assess BSG/BSY protein hydrolysates safeness. The ACE-inhibitory potential of initial and final protein hydrolysates (BSY, BSG, and a new product, MIX) were tested using a fluorometric assay and compared with captopril (1 µM, an ACE-inhibitory drug). Simulation of oral administration greatly increased BSY and MIX protein hydrolysates’ ACE-inhibitory capacity, though final MIX and BSG revealed greater ACE-inhibitory potential than captopril. Notwithstanding, all final protein hydrolysates presented ACE-inhibitory capacity, thus being promising compounds to manage hypertension. Full article

Herbal extracts are part of the solution to the increased demand for organic health care products. Traditionally, the different extracts prepared from Haplophyllum tuberculatum (Forsskal) A. Juss (H. tuberculatum) have been widely used to treat a wide range of illnesses. The aim of this study is to evaluate the antioxidant, analgesic, anti-inflammatory, and wound healing potential of the aqueous (HTAE) and ethanolic (HTEE) extracts of this plant as well as identify its major phytochemical components using LC-MS. Phytochemical analysis of both extracts revealed a rich composition and especially high amounts of glycosylic flavonols, 65.37% and 68.77% for the HTEE and HTAE, respectively. The antioxidant assays performed (DPPH, FRAP and TAC) indicated the excellent activity of the ethanolic extract while the in vivo activities (analgesic, anti-inflammatory, and healing potential) indicated the excellent activity of the aqueous extract. These findings support the therapeutic use of this plant by preventing pain and inflammation and promoting wound healing. To uncover, identify, and isolate compounds of potential medicinal and therapeutic significance, more studies on this species are required. Full article

Angiogenesis, a hallmark of cancer, plays a fundamental role in colorectal cancer (CRC). Anti-angiogenic drugs and chemotherapy represent a standard of care for treating metastatic disease. Immune checkpoint inhibitors (ICIs) have changed the therapeutic algorithm of many solid tumors. However, the efficacy of ICIs is limited to mCRC patients carrying microsatellite instability (MSI-H), which represent approximately 3–5% of mCRC. Emerging evidence suggests that anti-angiogenic drugs could exhibit immunomodulatory properties. Thus, there is a strong rationale for combining anti-angiogenics and ICIs to improve efficacy in the metastatic setting. Our review summarizes the pre-clinical and clinical evidence regarding the combination of anti-angiogenics and ICIs in mCRC to deepen the possible application in daily clinical practice. Full article

It is widely accepted that brain death (BD) is a diagnosis based on clinical examination. However, false-positive and false-negative evaluation results may be serious limitations. Ancillary tests are used when there is uncertainty about the reliability of the neurologic examination. Computed tomography angiography (CTA) is an ancillary test that tends to have the lowest false-positive rates. However, there are various influencing factors that can have an unfavorable effect on the validity of the examination method. There are inconsistent protocols regarding the evaluation criteria such as scoring systems. Among the most widely used different scoring systems the 4-point CTA-scoring system has been accepted as the most reliable method. Appropriate timing and/or Doppler pre-testing could reduce the number of possible premature examinations and increase the sensitivity of CTA in diagnosing cerebral circulatory arrest (CCA). In some cases of inconclusive CTA, the whole brain computed tomography perfusion (CTP) could be a crucial adjunct. Due to the increasing significance of CTA/CTP in determining BD, the methodology (including benefits and limitations) should also be conveyed via innovative electronic training tools, such as the BRAINDEXweb teaching tool based on an expert system. Full article

The Berlin Heart^® EXCOR is a paracorporeal, pulsatile ventricular assist device used in patients of all age groups. However, adolescent and adult patients on EXCOR support are scarcely explored. Herein, we present a detailed description of infectious complications in this patient cohort. From 2006 to 2020, 58 patients received a biventricular assist device (BiVAD) at our institution and were included in this study. Postoperative infections were assessed after BiVAD implantation and subsequent heart transplantation (HTx). A Berlin Heart^® EXCOR BiVAD was implanted as a bridge to transplantation in 58 patients (12–64 years). Most patients were INTERMACS I, and their median age was 49 years. Wound infections (WI) specific to the ventricular assist device (VAD) occurred in 31 (53.4%) patients with a mean time of 113 ± 155 days after BiVAD implantation. HTx was performed in 30 (51.7%) patients and thereof 10 (33.3%) patients developed at least one WI post-HTx. The mean time of WI after HTx was 17 ± 14 days. In four cases, WIs were caused by the same pathogen as before HTx. According to our institutional BiVAD wound classification, the mean wound score was 3. The VAD-specific wound infections were manageable and did not increase mortality nor precluded HTx in Berlin Heart^® EXCOR patients. No specific risk factors for VAD-specific wound infections could be identified. Full article

Anthrax is a zoonotic infection caused by the bacterium Bacillus anthracis (BA). Specific identification of this pathogen often relies on targeting genes located on two extrachromosomal plasmids, which represent the major pathogenicity factors of BA. However, more recent findings show that these plasmids have also been found in other closely related Bacillus species. In this study, we investigated the possibility of identifying species-specific and universally applicable marker peptides for BA. For this purpose, we applied a high-resolution mass spectrometry-based approach for 42 BA isolates. Along with the genomic sequencing data and by developing a bioinformatics data evaluation pipeline, which uses a database containing most of the publicly available protein sequences worldwide (UniParc), we were able to identify eleven universal marker peptides unique to BA. These markers are located on the chromosome and therefore, might overcome known problems, such as observable loss of plasmids in environmental species, plasmid loss during cultivation in the lab, and the fact that the virulence plasmids are not necessarily a unique feature of BA. The identified chromosomally encoded markers in this study could extend the small panel of already existing chromosomal targets and along with targets for the virulence plasmids, may pave the way to an even more reliable identification of BA using genomics- as well as proteomics-based techniques. Full article

Abiotic and biotic stress factors negatively influence the growth, yield, and nutritional value of economically important food and feed crops. These climate-change-induced stress factors, together with the ever-growing human population, compromise sustainable food security for all consumers across the world. Agrochemicals are widely used to increase crop yield by improving plant growth and enhancing their tolerance to stress factors; however, there has been a shift towards natural compounds in recent years due to the detrimental effect associated with these agrochemicals on crops and the ecosystem. In view of these, the use of phenolic biostimulants as opposed to artificial fertilizers has gained significant momentum in crop production. Seaweeds are marine organisms and excellent sources of natural phenolic compounds that are useful for downstream agricultural applications such as promoting plant growth and improving resilience against various stress conditions. In this review, we highlight the different phenolic compounds present in seaweed, compare their extraction methods, and describe their downstream applications in agriculture. Full article

The COVID-19 pandemic has led to the confrontation of the health system with the need to identify solutions for providing medical care to a very large number of patients. The main objective of our study was to describe the measures taken to provide optimal medical care to patients who presented themselves in one of the large emergency hospitals of Romania in the fourth wave of the COVID-19 pandemic. Material and Methods: We conducted a retrospective, observational study on a group of 1417 patients. The statistical analysis was performed using R. Results: The average length of stay of patients in the emergency departments was approximately 2.6 h, increasing to up to 15 days in some more severe cases. For rapid antigen tests, the highest positivity rate for SARS-CoV-2 was identified in patients aged >75 years (53%). Among the identified risk factors associated with the need for mechanical ventilation were advanced age (α < 0.001) and lack of vaccination against SARS-CoV-2 (α < 0.001). Discussion and conclusions: A method of saving the Romanian health system in full hospital bed occupancy conditions in the wards proved to be the provision of medical care in emergency departments. Full article

Due to climate change, the attainment of global food security is facing serious challenges in meeting the growing food demand. Abiotic stresses are the foremost limiting factors for agricultural productivity. However, not much information is available on the effect of multiple abiotic stresses on the morphological and biochemical aspects of kale and mustard. Therefore, an experiment was designed to study the effects of UV-B radiation, CO₂ concentration, and high temperature on the growth, yield, and biochemistry of two Brassica species, namely B. oleracea L. var. acephala Winterbor F1 (hybrid kale) and B. juncea var. Green wave O.G. (mustard greens), which were grown under optimal nutrients and soil moisture conditions in soil–plant–atmosphere–research (SPAR) units. Two levels of UV-B radiation (0 and 10 kJ m⁻² d⁻¹), two concentrations of CO₂ (420 and 720 ppm), and two different temperature treatments (25/17 °C and 35/27 °C) were imposed 12 days after sowing (DAS). Several morphological and biochemical parameters were measured at harvest (40 DAS) in both species. All the traits declined considerably under individual and multi-stress conditions in both species except under elevated CO₂ levels, which had a positive impact. Marketable fresh weight decreased by 64% and 58% in kale and mustard plants, respectively, growing under UV-B treatment. A slight increase in the chlorophyll content was observed in both species under the UV-B treatment alone and in combination with high temperature and elevated CO₂. Understanding the impacts of high temperature, CO₂, and UV-B radiation treatments on leafy vegetables, such as kale and mustard, can help to improve existing varieties to enhance resilience towards environmental stresses while simultaneously improving yield, morphology, and biochemistry in plants. Full article

Introduction: This study primarily sought to evaluate the risk factors for toxic megacolon development and treatment outcomes in Clostridium difficile-positive COVID-19 patients, secondarily to determining predictors of survival. Methods: During the second COVID-19 wave (May 2020 to May 2021), we identified 645 patients with confirmed COVID-19 infection, including 160 patients with a severe course in the intensive care unit. We selected patients with Clostridium difficile infection (CDI) (31 patients) and patients with toxic megacolon (9 patients) and analyzed possible risk factors. Results: Patients who developed toxic megacolon had a higher incidence (without statistical significance, due to small sample size) of cancer and chronic obstructive pulmonary disease, a higher proportion of them required antibiotic treatment using cephalosporins or penicillins, and there was a higher rate of extracorporeal circulation usage. C-reactive protein (CRP) and interleukin-6 values showed significant differences between the groups (CRP [median 126 mg/L in the non-toxic megacolon cohort and 237 mg/L in the toxic megacolon cohort; p = 0.037] and interleukin-6 [median 252 ng/L in the group without toxic megacolon and 1127 ng/L in those with toxic megacolon; p = 0.016]). As possible predictors of survival, age, presence of chronic venous insufficiency, cardiac disease, mechanical ventilation, and infection with Candida species were significant for increasing the risk of death, while corticosteroid and cephalosporin treatment and current Klebsiella infection decreased this risk. Conclusions: More than ever, the COVID-19 pandemic required strong up-to-date treatment recommendations to decrease the rate of serious in-hospital complications. Further studies are required to evaluate the interplay between COVID-19 and CDI/toxic megacolon. Full article

Idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), asthma and sleep disorders are chronic respiratory diseases that affect the airways, compromising lung function over time. These diseases affect hundreds of millions of people around the world and their frequency seems to be increasing every year. Extracellular vesicles (EVs) are small-sized vesicles released by every cell in the body. They are present in most body fluids and contain various biomolecules including proteins, lipids, mRNA and non-coding RNA (micro-RNA). The EVs can release their cargo, specifically micro-RNAs (miRNAs), to both neighboring and/or distal cells, playing a fundamental role in cell–cell communication. Recent studies have shown their possible role in the pathogenesis of various chronic respiratory diseases. The expression of miRNAs and, in particular, of miRNAs contained within the extracellular vesicles seems to be a good starting point in order to identify new potential biomarkers of disease, allowing a non-invasive clinical diagnosis. In this review we summarize some studies, present in the literature, about the functions of extracellular vesicles and miRNAs contained in extracellular vesicles in chronic respiratory diseases and we discuss the potential clinical applications of EVs and EVs-miRNAs for their possible use such as future biomarkers. Full article

This study aimed to analyse the thickness of the adipose tissue (AT) around the upper airways with anthropometric parameters in the prediction and pathogenesis of OSA and obstruction of the upper airways using artificial intelligence. One hundred patients were enrolled in this prospective investigation, who were divided into control (non-OSA) and mild, moderately severe, and severe OSA according to polysomnography. All participants underwent drug-induced sleep endoscopy, anthropometric measurements, and neck MRI. The statistical analyses were based on artificial intelligence. The midsagittal SAT, the parapharyngeal fat, and the midsagittal tongue fat were significantly correlated with BMI; however, no correlation with AHI was observed. Upper-airway obstruction was correctly categorised in 80% in the case of the soft palate, including parapharyngeal AT, sex, and neck circumference parameters. Oropharyngeal obstruction was correctly predicted in 77% using BMI, parapharyngeal AT, and abdominal circumferences, while tongue-based obstruction was correctly predicted in 79% using BMI. OSA could be predicted with 99% precision using anthropometric parameters and AT values from the MRI. Age, neck circumference, midsagittal and parapharyngeal tongue fat values, and BMI were the most vital parameters in the prediction. Basic anthropometric parameters and AT values based on MRI are helpful in predicting OSA and obstruction location using artificial intelligence. Full article

While previous research has demonstrated that multiplex polymerase chain reaction (PCR) can be a cost-effective approach to detect various genes in crops, the availability of multiplex assays to simultaneously screen both grain quality and biotic stress resistance traits in rice (Oryza sativa) is limited. In this work, we report six novel multiplex assays that use a universal protocol to detect major rice grain quality (amylose content and fragrance) and biotic stress (blast, sheath blight, and bacterial leaf blight) traits with amplified products consisting of up to four primer pairs that can be analyzed using a standard agarose-based gel electrophoresis system. Recent studies have suggested that weedy rice has novel sources of disease resistance. However, an intensive screening of weedy biotypes has not been reported in Malaysia. Accordingly, we employed one of the developed multiplex assays to screen reported genes or quantitative trait loci (QTLs) associated with blast, sheath blight, and bacterial leaf blight diseases in 100 weedy rice biotypes collected from five local fields, with phenotyping performed to validate the genotyping results. In conclusion, our universal multiplex protocol is effective for the large-scale genotyping of rice genetic resources, and it can be employed in routine molecular laboratories with limited resources. Full article