Background: Vasoactive Intestinal Peptide (VIP) is known to bind to and protect the Alveolar Type II cell by blocking replication of the SARS-CoV-2 virus, upregulating surfactant production, blocking apoptosis, and blocking cytokine effects. RLF-100 (Aviptadil), a synthetic form of Vasoactive Intestinal Peptide (VIP) has been granted Fast Track Designation and is currently in phase 2/3 placebo-controlled trials. FDA has granted Emergency Use IND and Expanded Access Protocol approval for the use of RLF-100 in patients whose comorbidities render them ineligible for inclusion in the ongoing pivotal trial. Methods: This report describes the first 6 patients with Acute Respiratory Failure in Critical COVID-19, enrolled under Emergency Use IND were treated with three successive 12-hour infusions of intravenous Aviptadil at 50/100/150 pmol/kg/hr, while continuing to receive maximal ICU care. Results: Median patient follow-up time is 14 days. So far, all treated patients have survived. Improved radiographic appearance of typical “ground glass” COVID-19 features to varying degrees is seen in all patients within 72 hours. Improvement in blood oxygenation is seen in all patients, with complete remission from respiratory failure in 4 of 6 patients. An average 56% reduction in inflammatory markers was seen, together with a median 4 point reduction in the NIAID Ordinal Scale. 2/6 patients were discharged from the hospital and 1 patient was downgraded to the general medicine floor. Comment: The short term survival of 6/6 patients with respiratory failure in the setting of COVID-19 and major comorbidity is the most dramatic response ever seen with an antiviral agent. Improvement in radiographic appearance, oxygenation requirement, and inflammatory markers is consistent with in vitro evidence of direct anti-viral effect.

RLF-100 (Aviptadil), a synthetic form of Vasoactive Intestinal Peptide (VIP) is shown to block replication of the SARS-CoV-2 virus and has been granted Fast Track Designation by the US FDA for the treatment of Critical COVID-19 with Respiratory Failure. We describe the clinical course of the first patient treated with this investigational medication in an open label manner -- a 54 year old patient suffering antibody-mediated rejection of his double lung transplant who contracted COVID-19 with respiratory failure refractory to all currently available therapies. He received three infusions of RLF-100 under an FDA-approved emergency use IND. Within 24 hours of the third infusion, substantial improvement in oxygen saturation and radiographic improvement in characteristic COVID-19 pneumonitis was noted. He was discharged from intensive care at that point and scheduled for discharge to home at 1 week on room air. Despite an intervening hospitalization for trauma, he remains alive and free of respiratory failure at 28 days post treatment.

Studies in animal models have suggested that the ketogenic diet may be effective in the treatment of cancer. However, human cohort studies on the ketogenic diet have, thus far, failed to show benefits in cancer survival or in any other hard clinical endpoints of the disease. This paper presents a case report of a patient with glioblastoma multiforme. The patient had initially been treated with standard oncotherapy including surgery, radiotherapy and chemotherapy. Despite standard treatment, the patient experienced a recurrence of the glioblastoma seven months later. Subsequently, the patient refused radiotherapy and chemotherapy and opted to use the paleolithic ketogenic diet (PKD) as a stand-alone therapy. Following the adoption of the PKD, progression of the disease has been completely halted. At the time of writing, the patient has remained in remission for 48 months, is without side-effects and experiences an excellent quality of life without the use of any drugs.

Recent technical advances in the stem cell field have enabled the in vitro generation of complex structures resembling whole organs termed organoids. Most of these approaches employ culture systems that allow stem cell-derived or tissue progenitor cells to self-organize into three-dimensional (3D)-structures. Since organoids can be grown from various species, organs and from patient-derived induced pluripotent stem cells, they create significant prospects for modelling development and diseases, for toxicology and drug discovery studies, and in the field of regenerative medicine. Here, we report on intestinal stem cells, organoid culture, organoid disease modeling, transplantation, current and future uses of this exciting new insight model to veterinary medicine field.

Recent interest in intestinal hormones has risen with the idea that they modulate glucose tolerance and food intake through a variety of mechanisms, and such hormones like peptide YY (PYY), ghrelin, glucagon-like peptide (GLP)-1 and 2, and cholecystokinin (CKK) are therefore excellent therapeutic candidates for the treatment of diabetes and obesity. Furthermore, in the recent years, multiple studies suggest that the microbiota is critically important for normal host functions, while impaired host microbiota interactions contribute to the pathogenesis of numerous common metabolic disorders. In this study, we considered the nutraceutical effects of β-glucans added to pasta at the concentration of 6g\100g. Ten participants have been recruited and hematochemical analyses and intestinal hormones tests have been performed before and after 30 days of pasta intake. Stool specimens have been studied for Lactobacillus Fermentum, Lactobacillus acidophilus, Lactobacillus salivarius, Bifidobacterium longum, and Enterococcus faecium presence before and after 30 days of nutritional intervention. After 30 days of regular intake of pasta enriched by β-glucans results have been evaluated. In conclusion, pasta prepared from barley flour enriched with β-glucans at 6% exhibit promising responses on glucose metabolism, on intestinal hormones responses and on microbiota modification.

β-glucan is a generic term for insoluble dietary fibers exerting various effects on the immune system. As a group, β-glucans are non-cellulose polysaccharides composed of a glucopyranose as the main constituent sugar with β configuration, having a β- (1,3)-linked glucopyranose main chain as a common feature. β-glucans are absorbed through the intestine. Since the 1980s, there have been many studies reporting various effects of β-glucans on the immune system, including reports on receptors, that have slowly clarified their recognition system and action mechanisms. However, these studies focused mostly on treatments of infectious diseases and tumors; thus, the effects of β-glucans ingested in food as dietary fiber and their mechanisms of action remain largely unknown. The uptake of β-glucan into the body may be resemble that of proteins, which are soluble polymers, and insoluble material such as dietary fiber. Dietary fibers have varied structures, with wide-ranging solubility and physiological effects. Understanding whether these substances are actually taken up, how they exert their effects, and their metabolism after being taken up are important issues when considering the functionality and safety of dietary fibers.

Human intestinal flora refers to a large and diverse microbial population present in the digestive tract of the human body, which plays a significant role in the establishment of human immune homeostasis and the normal function of the immune system. Myasthenia Gravis is an autoimmune disease of the neuromuscular junction, mainly involved in the anti-acetylcholine receptor antibody, cellular immune dependence, and complement¹. At present, studies have found that the intestinal flora of Myasthenia Gravis is different from that of healthy people. Probiotic therapy has been shown effective in the experimental autoimmune Myasthenia Gravis animal models. This article reviews the relationship between intestinal flora and Myasthenia Gravis, to provide new ideas for further study of the pathogenesis and clinical treatment of Myasthenia Gravis.

Increased sugar intake is implicated in Type-2 diabetes and fatty liver disease. Mechanisms by which glucose and fructose components promote these conditions are unclear. We hypothesize that alterations in intestinal metabolite and microbiota profiles specific to each monosaccharide are involved. Two groups of six adult C57BL/6 mice were fed for 10-weeks with a diet where either glucose or fructose was the sole carbohydrate component (G and F, respectively). A third group was fed with normal chow (N). Fecal metabolites were profiled every 2-weeks by ¹H NMR and microbial composition was analysed by real-time PCR (qPCR). Glucose tolerance was also periodically assessed. N, G and F mice had similar weight gains and glucose tolerance. Multivariate analysis of NMR profiles indicated that F mice were separated from both N and G, with decreased butyrate and glutamate and increased fructose, succinate, taurine, tyrosine and xylose. Compared to N and G, F mice showed a shift in microbe populations from gram-positive Lactobacillus spp. to gram-negative Enterobacteria species. Substitution of normal chow carbohydrate mixture by either pure glucose or fructose for 10 weeks did not alter adiposity or glucose tolerance. However, F G and N mice generated distinctive fecal metabolite signatures with incomplete fructose absorption as a dominant feature of F mice.

Maintenance of intestinal barrier integrity is crucial for preventing inflammatory bowel diseases (IBDs) onset and exacerbations. In this work we study the effect of a fixed combination of Lactobacillus reuteri and Lactobacillus acidophilus and herbal extracts in an in vitro inflammation experimental model. Caco-2 cell monolayer was exposed to INF-γ+TNF-α or to LPS; Trans Epithelial Electrical Resistance (TEER) and paracellular permeability were investigated. ZO-1 and occludin tight junctions (TJs) were also investigated by mean of immunofluorescence. The pre-treatment with the fixed combination of probiotics and herbal extracts prevented the inflammation-induced TEER decrease, paracellular permeability increase and TJs translocation. In summary the fixed combination of probiotics and herbal extracts investigated in this research was found to be an interesting candidate for targeting the re-establishment of intestinal barrier function in IBDs conditions.

Since there is not a clear consensus about the possibility for COVID-19 to be an airborne disease, exists a controversy regarding the need to use surgical masks to prevent its spread. Here, using the Kepler conjecture for ideal packaging, the number of virions of different sizes that can be accommodated inside droplets was calculated and are proportional to the 3^rd potency of the droplet/virion diameter. The differences between particles of 5 um and 100 μm are around four orders of magnitude, explaining why the airborne spread is much more difficult but still possible. There is no solid evidence yet that the airborne coronaviruses may reach enough concentration to infect, but this may be the case under certain circumstances. The WHO partially recognizes now this fact in a warning to health workers (from my point of view too late, as it was the declaration of a pandemic). Another issue is whether the virus stays infective in aerosols generated from patients. This has not been directly proved yet except with artificial aerosols, but there are no reasons why the virus cannot remain in the air and be infective if the viral charge and time of exposure are enough. We must also consider whether the virus can infect the intestine; there are some signs in this sense. Finally, and most importantly, we need to reduce interactions by using surgical masks to flatten the curve, leave the quarantine and avoid a rebound. For cultural reasons, a social distance of 2 meters (2M) is extremely hard to manage. Surgical masks do reduce the interactions in conditions of proximity and, therefore, help to “flatten the curve”. The WHO and CDC “laissez-faire” on this matter do not help and we are running out of time. Anticipated actions, such as the use of surgical masks for the general population, are critical.

This research was to investigate beneficial impact and molecular mechanism of B. coagulans on piglets intestine. Twenty-four 21 days old weaned piglets were allotted to three treatments: control group (basal diet), B6 group (basal diet + 2×10⁶ CFU/g B. coagulans), B7 group (basal diet + 2×10⁷ CFU/g B. coagulans). The results showed that compared with control group, B6 and B7 group significantly decreased diarrhea rate and the concent of CHOL, GGT and DAO in plasma; decreased villus height and increase crypt depth in jejunum and ileum; increased the activities of SOD and CAT and decreased the concent of MDA and H₂O₂ in intestine. These data suggested that supplementing B. coagulans had beneficial impacts on promoting nutrients metabolism, maintaining intestinal integrity and alleviating oxidative stress and diarrhea. Futher research of molecular mechanisms showed that, these beneficial impacts were regulated by changing expression levels of related proteins (including HSP70, Caspase-3, Bax, Villin and Occludin), and genes (including RPL4, IFN-α, IFN-β, IFN-γ, MX1, MX2, OAS1, IL-1β, IL-4, CXCL-9, CCL-2, AQP3, SGLT-1, LPL, INSR and b^0,+AT), and altering community composition of gut microbiota (particularly family Clostridiaceae, Enterobacteriaceae, and Veillonellaceae and genus Prevotella, Turicibacter, and Lactobacillus).

Obesity and chronic low-grade inflammation are becoming global epidemics. The dysbiosis has a specific role in the metabolism and energy stocks of the host. The discovery that a low-grade of inflammation could be directly connected to the intestinal microbiota metabolic endotoxemia (elevated levels of plasma lipopolysaccharides) has allowed the identification of novel mechanisms involved in the control of the intestinal barrier. In this review, it will analyze the latest news to explain how human symbiotic microorganisms participate in the growth of the fat reserves and promote insulin resistance as a low-grade inflammation. Besides, it will discuss new treatments with probiotics and prebiotics as a promising therapeutic approach to reverse the host's metabolic changes linked to dysbiosis observed in obesity.

The impact of a non-anticholinergic spasmolytic drug (drotaverine hydrochloride) on 23 heart rate (HR), HR variability (HRV) and gastrointestinal tract (GIT) motility in the normal, resting 24 horses was determined. Ten adult riding horses had ECG recordings for 180 minutes after treat-25 ment with drotaverine (180 mg) or saline. Horses from the drotaverine group presented a de-26 creased of GIT contraction for two hours after treatment, but also showed drowsiness. Drotaverine 27 caused a reduction in cardiac vagal modulation of HR at T30 (P=0.050) and T60 (P=0.008) compared 28 to those receiving saline. RMSSD and high frequency (HF) recorded significantly low values after 29 drotaverine treatment by the end of the study, suggesting a decrease in parasympathetic activity. 30 HRV analysis indicated that drotaverine decreased both the low frequency (LF) and Lf/HF ratio 31 reflecting a decrease in sympathetic system. Non linear parameters registered low values after 32 drotaverine administration pointing a diminished in parasympathetic (for SD1) and sympathetic 33 (for SD2) activity. Decreased HRV was suggestive for a pervasive state of sympathetic hypervigi-34 lance of horses. The marked effect of drotaverine on HRV and GIT function in horses should be 35 taken into consideration when evaluating a clinical response to this drug in diseases associated 36 with smooth muscle spasm.

Image processing is a field of which its popularity increases and continues and, that grows dynamically with new technologies. Nowadays, image processing finds itself in use in almost every field. One of these uses is undoubtedly in the field of medicine, where diagnosis and treatment planning are made from images and, which is constantly changing with newly developed techniques. Of course, the most important factor in using this so widely in the medical field is the acquisition of images on every medical field. With the help of these images, the complaints can be seen more easily and the doctor can follow a path in the treatment of the disease. In our study, we used the Region Growing segmentation method to detect the intestinal mass. This study compares the area determined by the specialist with the area obtained with the segmentation process and, it is seen that the created software system can be used as an auxiliary system to specialist doctors.

Inflammatory bowel diseases, which consist of chronic inflammatory conditions of the colon and the small intestine, are considered a global disease of our modern society. Recently, the interest toward the use of herbal therapies for the management of inflammatory bowel diseases has increased because of their effectiveness and favorable safety profile, compared to conventional drugs. Boswellia serrata Roxb. and Curcuma longa L. are amongst the most promising herbal drugs, however, their clinical use in inflammatory bowel diseases is limited and little is known on their mechanism of action. The aim of this work was to investigate the effects of two phytochemically characterized extracts of B. serrata and C. longa in an in vitro model of intestinal inflammation. Their impact on cytokine release and reactive oxygen species production, as well as the maintenance of the intestinal barrier function and on intestinal mucosa immune cells infiltration, has been evaluated. The extracts showed a good protective effect on the intestinal epithelium at 1 µg/ml, with TEER values increasing by approximately 1.5 fold, compared to LPS-stimulated cells. C. longa showed an anti-inflammatory mechanism of action, reducing IL-8, TNF-α and IL-6 production by approximately 30%, 25% and 40%, respectively, compared to the inflammatory stimuli. B. serrata action was linked to its antioxidant effect, with ROS production being reduced by 25%, compared to H₂O₂-stimulated Caco-2 cells. C. longa and B. serrata resulted to be promising agents for the management of inflammatory bowel diseases by modulating in vitro parameters which have been identified in the clinical conditions.

The i-4-1-Health project is a One Health project on the prevalence and spread of antimicrobial resistance in the human and veterinary domain in the Dutch-Belgian cross-border region. This paper describes the main components of the laboratory protocol that was developed to standardise the microbiological methods used for the detection of intestinal carriage of highly-resistant microorganisms.

Hypercholesterolemia accelerates atherosclerosis, and extensive research has been undertaken to ameliorate this abnormality. Plant sterols have been shown to inhibit cholesterol absorption and lower plasma cholesterol level since the 1950s. This ingredient has recently been reappraised as a food additive that can be taken daily in a preclinical period to prevent hypercholesterolemia, considering that cardiovascular-related diseases are the top cause of death globally even with clinical interventions. Intestinal cholesterol handling is still elusive, making it difficult to clarify the mechanism for plant sterol-mediated inhibition. Notably, although the small intestine absorbs cholesterol, it is also the organ that excretes it abundantly, via trans-intestinal cholesterol efflux (TICE). In this review, we show a model where the brush border membrane (BBM) of intestinal epithelial cells stands as the dividing ridge for cholesterol fluxes, making cholesterol absorption and TICE inversely correlated. With this model, we tried to explain the plant sterol-mediated inhibitory mechanism. As well as cholesterol, plant sterols diffuse into the BBM but are effluxed back to the lumen rapidly. We propose that repeated plant sterol shuttling between the BBM and lumen promotes cholesterol efflux, and plant sterol in the BBM may disturb the trafficking machineries that transport cholesterol to the cell interior.

A large body of evidence reports about the positive effects of physical activity in pathophysiological conditions associated with aging. Physical exercise, alone or in combination with other medical therapies, unquestionably causes reduction of symptoms in chronic non-transmissible diseases often leading to significant amelioration or complete healing. The molecular basis of this exciting outcome, however, remain largely obscure. Epigenetics, exploring at the interface between environmental signals and the remodelling of chromatin structure, promises to shed light on this intriguing matter possibly contributing to the identification of novel therapeutic targets. In this review, we shall focalize on the role of sirtuins (Sirts) a class III histone deacetylases (HDACs) which function has been frequently associated, often with a controversial role, to the pathogenesis of aging-associated pathophysiological conditions including cancer, cardiovascular, muscular, neurodegenerative, bones and respiratory diseases. Numerous studies, in fact, demonstrate that Sirt-dependent pathways are activated upon physical and cognitive exercises linking mitochondrial function, DNA structure remodelling and gene expression regulation to designed medical therapies leading to tangible beneficial outcomes. However, in similar conditions, other studies assign to sirtuins a negative pathophysiological role. In spite of this controversial effect, it is doubtless that studying sirtuins in chronic diseases might lead to an unprecedented improvement of life quality in the elderly.

Boron (B) is considered a prebiotic chemical element with a role in both the origin and evolution of life, as well as an essential micronutrient for plants, some bacteria, fungi, and algae. B has beneficial effects on the biological functions of humans and animals, such as reproduction, growth, calcium metabolism, bone formation, energy metabolism, immunity, brain function, and steroid hormones. In the future, naturally organic B (NOB) species may become promising novel prebiotic candidates. We included the most relevant works about NOB species, starting from our 30-year research experience. NOB-containing compounds have been shown essential for the symbiosis between different kingdoms. New insights into the essentiality of NOB species for healthy symbiosis between the human/animal host and the microbiota will determine the use of natural B-based nutraceuticals to target the colon (colonic foods). The mechanism of action (MoA) of NOB species is related to both the B signaling molecule [autoinducer-2–borate (AI-2B)], as well as the fortification of the colonic mucous gel layer with NOB species from the specific prebiotic boron-rich diet. Therefore, both microbiota and the mucous gel layer of the colon become the NOB species’ target. This paper reviews the evidence supporting the essentiality of the NOB species on the symbiosis between the microbiota and the human/animal host with the stated aim of highlighting the MoA and target of these species.

Hepatocellular carcinoma (HCC), one of the leading causes of death worldwide, has a causal nexus with liver injury, inflammation, and regeneration that accumulate over decades. Observations from recent studies have accounted for the involvement of the gut-liver axis in the pathophysiological mechanism responsible for HCC. The human intestine nurtures a diversified colony of microorganisms residing in the host ecosystem. The intestinal barrier is critical for conserving the normal physiology of the gut microbiome. Therefore, a rupture of this barrier or dysbiosis cause the intestinal microbiome to serve as the main source of portal-vein endotoxins such as lipopolysaccharide, in the progression of hepatic diseases. Indeed, increased bacterial translocation is a key sign of HCC. Considering the limited number of clinical studies on HCC with respect to the microbiome, we focus on the clinical as well as animal studies involving the gut microbiota with the current understandings of the mechanism by which the intestinal dysbiosis promotes hepatocarcinogenesis. Future research might offer mechanistic insights into the specific phyla targeting the leaky gut, as well as microbial dysbiosis, and their metabolites, as key pathways that drive HCC-promoting microbiome-mediated liver inflammation and fibrosis, thereby restoring the gut barrier function.

Protozoa and helminths are responsible for several intestinal parasite infections (IPIs). Generally helminth infections are very unsafe but scarcely reported in high-income countries, while protozoa and helminth co-infections are usually reported in children living in inadequate hygienic-sanitary conditions and in rural areas. However, the impact of growing globalization, intense travelling, international adoptions and high levels of immigrants and refugees has significantly incremented the incidence of oro-faecal parasitosis in non endemic areas. Although most IPs clear without treatment when population, even children, emigrate from endemic to different geographical areas, some IPIs such as strongyloidiasis may persist for decades as subclinical infections or as low-grade disease with nonspecific clinical manifestations, unless to reappear under impairment conditions. Herein we report an unusual case of Giardia lamblia and Trichuris spp. chronic asymptomatic co-infection in a healthy adopted Romanian child, living in a Central Italy rural area, and an hidden case of Strongyloides stercoralis in an adopted Burundian child, resident in South Italy, long misdiagnosed as a recurrent undefined dermatitis. Our report suggests the need to review primary care practitioner guidelines and children's hospital procedures for appropriate IPIs screening and follow-up, hence providing new screening and prevention strategies, in agreement with international guidelines.

The Human Gut Microbiome is an important host’s component defining its health. These microorganisms are mutualistic symbionts dependent on factors such as host’s age, subsistence models and sociocultural practices, among others. The conjunction of these factors define the microbial ecosystem dynamics. Using a fecal microbiome approach in children, a comparison of two Mexican communities with contrasting lifestyles: “westernized” (Mexico City) and “non-westernized” (Me’phaa indigenous group) was evaluated. The main differences between these two communities are in bacteria associated with different types of diets (high animal protein and refined sugars vs high fiber food, respectively). In addition, the gut microbiome of Me’phaa children showed higher total diversity and the presence of exclusive phyla, such as Deinococcus-Thermus, Chloroflexi, Elusimicrobia, Acidobacteria and Fibrobacteres. In contrast, Mexico City children had less diversity and the exclusive presence of Saccharibacteria phylum which is associated with the degradation of sugar compounds. This comparison allows further exploration of the selective pressures affecting microbial ecosystemic composition over the course of human evolution and the potential consequences of pathophysiological states correlated with westernization lifestyles.

Submucosal invasion is a critical step in gastric cancer (GC) progression, which greatly enhances metastasis risk. Cancer stem cells are responsible for invasion, metastasis, and tumor growth. To identify stem cell-related markers associated with submucosal invasion in GCs, we investigated the expression of candidate cancer stem cell (CSC) markers (CD133, CD44, and ALDH1A) and intestinal stem cell (ISC) markers (EPHB2, OLFM4, and LGR5) in early GCs with submucosal invasion. Remarkably, expression of all ISC markers and CD133 was frequently confined to the basal area of the lamina propria (basal pattern) in mucosal cancer. The proportion of stem cell marker-positive cells substantially increased during submucosal invasion. Given that ISC markers are restricted to the crypt base of the normal intestinal mucosa, these findings suggest that many early GCs may retain hierarchical characteristics. CD44 expression showed a focal pattern, ALDH1A was predominantly expressed diffusely, and there was no expansion of CD44 or ALDH1A expression in the submucosal cancer cells. RSPO2 from muscularis mucosa seem to be partly responsible for the increased expression of ISC markers in GC cells at the basal areas. We also found that ISC markers were correlated with CDX2 expression in GCs, indicating that ISC markers are involved in the intestinal differentiation in GCs. Interestingly, ISC markers (EPHB2 and OLFM4) and CD133 showed a positive impact on clinical outcomes. In particular, the prognostic value of EPHB2 was significant for intestinal-type GCs in a multivariate analysis. In summary, ISC markers and CD133 showed a basal distribution pattern along with enhanced expression in submucosal invading cells in early GCs. EPHB2 was an independent prognostic marker in intestinal-type GCs.

Using a randomized, double-blinded, placebo-controlled, parallel group design, this investigation determined if the combination of 2-weeks flavonoid supplementation (329 mg/day, quercetin, anthocyanins, flavan-3-ols mixture) and a 45-minute walking bout (62.2±0.9% VO_2max) enhanced the translocation of gut-derived phenolics into circulation in a group of walkers (N = 77). The walkers (flavonoid, placebo groups) were randomized to either sit or walk briskly on treadmills for 45 minutes (thus four groups: placebo-sit, placebo-walk, flavonoid-sit, flavonoid-walk). A comparator group of runners (N = 19) ingested a double flavonoid dose for 2 weeks (658 mg/day) and ran for 2.5 h (69.2±1.2% VO_2max). Four blood samples were collected (pre- and post-supplementation, immediately-post- and 24-h post-exercise/rest). Of the 76 metabolites detected in this targeted analysis, 15 increased after the 2.5-h run, and when grouped were also elevated post-exercise (versus placebo-sit) for the placebo- and flavonoid-walking groups (P < 0.05). A secondary analysis showed that pre-study plasma concentrations of gut-derived phenolics in the runners were 40% higher compared to walkers (P = 0.031). These data indicate that acute exercise bouts (brisk walking, intensive running) are linked to an increased translocation of gut-derived phenolics into circulation, an effect that is amplified when combined with a 2-week period of increased flavonoid intake or chronic training as a runner.

Probiotics are increasingly used by consumers and practitioners to reduce gastrointestinal (GI) distress and improve gut function. Here, we sought to determine whether addition of supplemental bacteriophages (PreforPro) could enhance the effects of a common probiotic, Bifidobacterium animalis subsp. lactis (B. lactis) on GI health. We conducted a 4-week, randomized, parallel-arm, double-blind, placebo-controlled trial where primary outcomes included self-assessments of GI health, a daily stool log, and 16s rRNA analysis of gut microbial populations. We observed within group improvements in GI inflammation (p=0.01) and a trending improvement in colon pain (p=0.08) in individuals consuming B. lactis with PreforPro, but not in the group consuming only the probiotic. There was also a larger increase in Lactobacillus and short chain fatty acid-producing microbial taxa detected in stool of participants taking PreforPro with B. lactis compared to the probiotic alone. Overall, these results suggest the addition of PreforPro as a combination therapy may alter gut ecology to extend the GI benefits of consuming B. lactis or other probiotics.

Gastroenteritis cases associated with non-toxigenic strains of Vibrio parahaemolyticus have been reported in many countries, suggesting the contribution of novel virulence factors. One candidate is zonula occludens toxin (Zot), which increases the intestinal permeability by other bacteria. Recently we identified prophages belonging to the Inoviridae family encoding putative Zot-like toxins in Chilean strains. Based on this information we performed sequence-based analyses of these toxins, followed by phylogenetic and structural analyses using computational tools. Our results showed that Zots found in Chilean V. parahaemolyticus strains are grouped into three different phylogenetic clusters, sharing two conserved motifs (Walker A and B) in their N-terminal region. These motifs are also conserved in Zots from the human pathogens Vibrio cholerae, Neisseria meningitidis and Campylobacter concisus. Although Zots of V. parahaemolyticus do not possess the FCIGRL sequence responsible for the effects produced by V. cholerae, they do possess a conserved secondary structure within their C-terminal region with Zots proteins able to disrupt the intestinal barrier, which is interesting since it has been suggested that the structure and not the Zot sequence would be responsible for the biological effects. This preliminary study provides the basis to study the function of Zots found in V. parahaemolyticus on the intestinal barrier and their possible role as a virulence factor.

Aberrant neutrophil extracellular trap (NET) formation and the loss of barrier integrity in inflamed intestinal tissues have long been associated with inflammatory bowel disease (IBD). However, whether NETs alter intestinal epithelium permeability during colitis remains elusive. Here, we demonstrated that NETs promote the breakdown in intestinal barrier function for the pathogenesis of intestinal inflammation in mouse models of colitis. NETs were abundant in the colon of mice with colitis experimentally induced by dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS). Analysis of the intestinal barrier integrity revealed that NETs impaired gut permeability, enabling the initiation of luminal bacterial translocation and inflammation. Furthermore, NETs induced the apoptosis of epithelial cells and disrupted the integrity of tight junctions and adherens junctions. Intravenous administration of DNase I, an enzyme that dissolves the web-like DNA filaments of NETs, during colitis restored the mucosal barrier integrity which reduced the dissemination of luminal bacteria, and attenuated intestinal inflammation in both DSS and TNBS models. We conclude that NETs serve a detrimental factor in the gut epithelial barrier function leading to the pathogenesis of mucosal inflammation during acute colitis.

This paper studies the influence of three probiotic preparations of various microbiological composition: Bacillus subtilis (O1); Bacillus subtilis + Bacillus amyloliquefaciens (O2); Lactobacil-lus acidophilus (O3) on the growth process and histological structure of the organs of the gastroin-testinal tract of juvenile Oncorhynchus mykiss by morphometric parameters. The effect of the pro-biotic preparations led to the increase in fish growth and influenced different sections of the gastro-intestinal tract. The biggest change was found in the mid intestine and the reliable difference com-pared to the control was obtained at the following parameters: Lamina propria width, intraepithe-lial lymphocytes number of prismatic epithelium and goblet cells area. The changes in the pyloric appendages were less obvious but reported as playing an important functional role. The liver pre-served normal functional structure in all series of the experiment except for the probiotic group Lactobacillus acidophilus, where hepatocyte small-drop vacuolization was observed. That might be connected with the change of the digest activity resulting from a decrease in secretory activity of the intestinal exocrinocytes. The use of all the probiotic preparations led to the similar change in morphometric parameters, in all the groups it was possible to decrease the immune response.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease characterized by profound fatigue, post-exertional malaise (PEM), and neurocognitive dysfunction. Immune dysregulation and gastrointestinal symptoms are commonly observed in ME/CFS patients. Despite affecting approximately 0.89% of the general population, the underlying pathophysiological mechanisms remain poorly understood. This study aimed to elucidate the relationship between immunological characteristics and intestinal barrier function in ME/CFS patients. ME/CFS patients were stratified into two groups based on their immune competence. After documentation of detailed medical records, serum and plasma samples were collected for assessment of inflammatory immune mediators and biomarkers for intestinal barrier integrity by ELISA. We found reduced complement protein C4a levels in immunodeficient ME/CFS patients suggesting a sub-group specific innate immune dysregulation. ME/CFS patients without immunodeficiencies exhibit a mucosal barrier leakage, as indicated by elevated levels of Lipopolysaccharide-binding protein (LBP). Stratifying ME/CFS patients based on immune competence enabled the distinction of two subgroups with different pathophysiological patterns. The study highlights the importance of emphasizing precise patient stratification in ME/CFS, particularly in the context of defining suitable treatment strategies. Given the substantial health and socioeconomic burden associated with ME/CFS, urgent attention and research efforts are needed to define causative treatment approaches.

Necroptosis is a caspases-independent form of programmed cell death exhibiting intermediate features between necrosis and apoptosis. Albeit some physiological roles during embryonic development, tissue homeostasis and innate immune response are documented, necroptosis is mainly considered a pro-inflammatory cell death. Key actors of necroptosis are the receptor-interacting-protein-kinases, RIPK1 and RIPK3, and their target, the mixed-lineage-kinase-domain-like protein, MLKL. The intestinal epithelium has one of the highest rates of cellular turnover in a process that is tightly regulated. Altered necroptosis at the intestinal epithelium leads to uncontrolled microbial translocation and deleterious inflammation. Indeed, necroptosis has been associated to chronic inflammatory diseases and cancer. Drugs that inhibit necroptosis could, therefore, be used therapeutically for the treatment of these diseases, and researches to develop such inhibitors are already underway. In this Review, we outline pathways for necroptosis and its role in chronic inflammation and cancer. We also discuss current and developing therapies that target necroptosis machinery.

Both lactic acid and short chain fatty acid (SCFA) play important roles in maintenance of intestinal epithelial structure and function. Trilactic glyceride (TLG) obtains both excellences of lactic acid and SCFA. This study was to investigate the effects of trilactic glyceride on growth performance, blood parameters, liver function, intestinal morphology and intestine function of piglets. Twelve weaned piglets (21±2 d) were randomly allocated to two treatment groups: 1) control group, piglets fed the basal diet; 2) TLG group, piglets fed the basal diet supplemented with 0.5 % TLG. On day 21 of the trial, D-xylose (0.1 g/kg·BW) was orally administrated to all piglets and blood samples were collected 1 h thereafter. Then, all the piglets were sacrificed to examine intestinal mucosal morphology and collect fatty tissue, liver and intestinal mucosa for further analysis. The results showed that: compared with the control group, TLG group decreased blood ALB and GGT on day 10 and 20, TLG group decreased blood TP and increased blood TG on day 20 of the trail (p < 0.05); TLG group decreased blood D-xylose and LDL, increased blood HDL (p < 0.05). These data suggested that supplementing trilactic glyceride had beneficial impacts on promoting nutrients’ metabolism, maintaining intestinal integrity, and alleviating oxidative stress and diarrhoea. Further research of molecular mechanisms showed changing expression levels of related proteins and genes, suggesting that these could be involved in the regulation of the impact. The community composition of the gut microbiota was also found to be altered in several operational taxonomic units within the genus, Prevotella (order Bacteroidales), and the order, Clostridiales.

The purpose of this study was to see how dietary supplementation with phenylpyruvate affected broiler chicken growth, slaughter performance, gut health microbiota, and immunity. A total of 288 day old broiler chickens were randomly assigned to one of four groups (6 replicates each with 12 chicken). NC (basal diet), PC (basal diet plus antibiotic virginiamycin 15ppm), LCP and HCP (basal diet plus phenylpyruvate 1kg/t and 2kg/t, respectively). Results showed that PC had higher ADFI during the first 21 days, and better FCR than the NC, the LCP and HCP also improved broilers’ FCR 0.001 and 0.037% in relation to NC respectively. HCP has a higher all-eviscerated ratio than NC and less abdominal fat than LCP. HCP has increased villus length and crypt depth in the ileum compared to the NC. Bursa was lower in HCP and thymus was lower in LCP and PC. In contrast HCP have lower pro-inflammatory cytokine IL-1, as well as lower TLR4. The phenylpyruvate improved family Selenomonadaceae, genus Megamonas Bacteroides species that are known for beneficial effects like for maintenance of the cell surface structure, regulating aromatic amino acids and C. jejuni-suppressive treatment respectively. Finally, phenylpyruvate feed supplement can be utilized to improve growth performance and positively modulate gut microbiota, however this is less efficient than antibiotics in improving growth performance, although more efficient in improving productive performance and gut morphology. Moreover, high dose of phenylpyruvate is more effective than low dose

The risk of gastric cancer (GC) declines after Helicobacter pylori (H. pylori) eradication and long-term aspirin use. We evaluated the effects of H. pylori eradication (Cohort 1) and aspirin use (Cohort 2) on the methylation of microRNAs (miRNAs) such as miR-34c, miR-124a-3, miR-129-2, and miR-137 in the gastric mucosa with and without GC, i.e., atrophic mucosa (AM) and intestinal metaplasia (IM). DNA was isolated from AM and IM separately using laser caption microdissection. In Cohort 1, H. pylori eradication was associated with a significant reduction of miR-124a-3 methylation only in AM, but not in IM. miR-129-2 methylation in AM may be a surrogate marker of GC in H. pylori-infected patients. In Cohort 2, aspirin did not reverse miRNA methylation in either AM or IM irrespective of H. pylori infection. miR-129-2 methylation in AM was an independent predictive marker of GC in H. pylori-infected but not -eradicated patients. These results indicate that H. pylori eradication and aspirin use were less effective in improving methylation in IM compared with AM; thus, these interventions are recommended at an early stage prior to the development of IM to prevent GC development.

Recently, Mulroney,et.al., demonstrated that Pfizer’s ModRNA Covid vaccine, but not AstraZeneca Covid vaccine, produce aberrant foreign proteins in vivo due to reading frame shift in ribosomes. This phenomenon could elucidate the notable surge in autoimmune diseases following the administration of ModRNA vaccines compared to Influenza vaccines between 2020 and 2023, as found in the VAERS database. These findings bear significant implications for the future application of mRNA technology, emphasizing the necessity of modifying the design of the mRNA sequence to mitigate these defects. Remarkably, Mulroney and collaborators achieved a reduction in frame shift proteins by introducing additional edits to the mRNA sequences. This adjustment is pivotal for rectifying the flawed design of the ModRNA employed by Pfizer. In light of these findings, many advocate for the immediate recall and further investigation of these products. The notion of a "future mRNA-based therapy" should be postponed indefinitely.

This article discuss the estimation of electrical stresses input that is required to determine lifetime degradation of the HV cables installed within overhead transmission lines (OHTL’s). Abort from lightning effects, these electrical stresses are mainly generated due to repetitive switching operation of the transmission line that produces transient overvoltage (TOV) stress and high frequency stress. The transient overvoltage (TOV) due to switching-off the transmission line at the interface points between the cable and OHTL is estimated using artificial neural network (ANN). PSCAD software is used to build the transmission line model for 749 different case in order to build the required database for ANN training. Two different algorithm input to train ANN with one hidden layer and one output layer using different number of nodes are modeled in MATLAB. The results performance is continuously compared and evaluated till acceptable Regression is achieved to insure the error is less than +/-1.5%. The high frequency due to switching-on the transmission line is also recorded and analyzed. The results show that this new method is efficient, accurate and useful as there is no cable monitoring system is available for each HV cable installed within the transmission line.

Background: Gastrointestinal parasitic infections are one of the global health concerns in developing countries like Bangladesh. Among them, Cryptosporidium spp. plays an essential role in causing diarrhea, malnutrition, and poor cognitive function, especially in children. The study was conducted to identify the frequency of cryptosporidium cases and other parasitic agents. Methods: A Cross-sectional observational study was conducted among 219 hospitalized children with diarrhea. The conventional microscopic technique was applied for parasitic detection. A particular staining procedure was performed to identify oocysts of Cryptosporidium spp. And PCR was conducted to determine the SSU rRNA and gp60 gene of Cryptosporidium. Results: Cyst of Giardia, ova of Ascaris lumbricoides (AL), Trichuris trichiura (TT), AL, and TT were identified in 2.3%, 1.4%, 0.5%, and 0.9% samples by wet mount preparation. The distribution of Cryptosporidium spp. was 1.4% and 4.1%, which was detected by the staining method and nested PCR. Factors independently associated with Cryptosporidium infection are unsafe water, lack of regular hand washing, and insufficiency of exclusive breastfeeding. Conclusions: This is the first report to detect the frequency of Cryptosporidium and other intestinal parasites and associated factors in Chattogram city of Bangladesh.

In the wake of increasing digital fraud, this paper introduces an innovative application of Artificial Intelligence (AI) in detecting fraudulent activities across finance, healthcare, and e-commerce sectors. It presents a detailed analysis of machine learning methodologies, specifically focusing on the advantages of supervised, unsupervised, and deep learning techniques. The paper addresses the challenges such as data imbalance, model interpretability, and ethical implications in AI-based fraud detection. It also discusses the necessity of high-quality datasets and advocates for the integration of traditional and advanced machine learning methods to enhance accuracy and adaptability in fraud identification. However, it acknowledges the limitations including computational demands and overfitting risks. The study underscores the importance of collaborative efforts between AI experts and industry professionals to develop ethical, efficient, and reliable AI solutions for fraud detection.

Eukaryotic enteric pathogens (EEP) are a public health issue in tropical areas. Yet, their interactions with the gut mycobiota remain poorly understood. We conducted a cross-sectional study in Malian children to analyze the impact of EEP on the gut fungal community. EEP were assessed by qPCR and the gut mycobiota was characterized by ITS1-2 metabarcoding in stool samples collected from 296 children. The 100 controls, in whom no EEP was detected, were compared to: a) 196 children with ≥1 EEP; b) 91 with only Blastocystis; c) 35 with only Giardia intestinalis; and d) 12 with another (&lt;1% each) EPP. The gut fungal community structure was homogenous in each children’s group. Linear size-effect discriminant analysis highlighted five relatively more abundant species, including Fusarium longipes and Penicillium caseifulvum, in children with ≥1 EEP, whereas 28, including Aspergillus sydowii and Microdochium colombiense were more abundant in controls. Fusarium, Pyxidiophora, and Stereum abundance was higher in Blastocystis-infected children, whereas Ogataea and Allocryptovalsa were more abundant in controls. Sordariales and Mortierellales abundance was higher in Giardia intestinalis-infected children, whereas Agaricales and Capnodiales abundance was higher in controls. In conclusion, EEP do not significantly alter the gut fungal community structure, and further studies are warranted to confirm our findings that particular taxa are associated with susceptibility or resistance to specific EEP.

AbstractThe escalating impact of artificial intelligence (AI) has birthed the fascinating technology of deepfakes, capable of meticulously crafting hyper-realistic audio-visual manipulations. Within the realm of healthcare, this technology presents a double-edged sword, brimming with potential for revolutionizing various facets of care delivery while simultaneously harboring significant ethical and practical challenges. This research delves into the complex narrative surrounding AI deepfakes in healthcare, meticulously analyzing both the exciting opportunities they offer, and the inherent risks associated with their implementation.Background:Traditional healthcare practices face limitations in patient engagement, accessibility, and training efficacy. Deepfakes, with their ability to simulate real-world scenarios and interactions, emerge as a potential solution, offering personalized patient education, immersive mental health interventions, remote consultations with virtual avatars, and realistic training simulations for medical professionals.Objective:This research aims to comprehensively understand the multifaceted impact of AI deepfakes in healthcare systems. It seeks to: Identify and analyze the potential benefits of deepfakes in specific healthcare applications. Assess the ethical and practical challenges associated with deepfake implementation in healthcare settings. Propose recommendations for safe, responsible, and ethical integration of deepfakes within the healthcare system.Results/Conclusion:The research findings illuminate a landscape replete with opportunities and challenges. Deepfakes offer the potential to enhance patient education, personalize mental health interventions, facilitate remote consultations, and revolutionize medical training. However, concerns regarding misinformation, ethical breaches, data privacy, and technical limitations pose significant challenges.The conclusion emphasizes the need for a balanced approach that capitalizes on the innovative potential of deepfakes while mitigating potential harm. Collaborative efforts involving healthcare professionals, technologists, and policymakers are crucial for establishing ethical frameworks, ensuring responsible development, and harnessing the positive power of deepfakes to build a future where healthcare benefits from cutting-edge technology while prioritizing patient well-being and ethical principles.

We investigated and quantified bacterial accumulation in facemasks used by the general population, using 16S rRNA (Sanger Sequencing), culture and biochemical analysis along with Rose Bengal staining. Additionally, a systematic overview of the literature on face mask contamination was undertaken. We found an average bacterial load of 4.24 × 10⁴ CFU recovered/mask, with a maximum load of 2.85 × 10⁵ CFU. This maximum is 310 times higher than the limit value for contamination of ventilation system outlet surfaces specified by the German standard VDI 6022. Biochemical and molecular identification predominantly found Staphylococcus species (80%), including Staphylococcus aureus, along with endospore-forming Bacillus spp. Literature reports also indicate contamination of masks by bacterial and fungal opportunists of the genera Acinetobacter, Aspergillus, Alternaria, Bacillus, Cadosporium, Candida, Escherichia, Enterobacter, Enterococcus, Klebsiella (including K. pneumoniae), Micrococcus, Microsporum, Mucor, Pseudomonas, Staphylococcus and Streptococcus. Bacterial counts increase linearly with wearing duration, and prolonged use may affect the skin and respiratory microbiomes, promoting consequential eye, skin, oral and airway conditions. These aspects underscore the urgent need for further research and a risk-benefit analysis in respect of mask use, particularly given their unproven efficacy in disrupting the transmission of respiratory viruses and their adverse social consequences.

As Chronic Non-Communicable Diseases (CNCD) increase, preventive approaches become more crucial. In this review, Calorie Restriction (CR) effects on human beings were evaluated, comparing benefits and risks of different CR diets: classic CR vs ketosis-inducing diets, including Intermittent Fasting (IF), Classic Ketogenic Diet (CKD), Fasting Mimicking Diet (FMD), Very-Low-Calorie Ketogenic Diet (VLCKD) and Spanish Ketogenic Mediterranean Diet (SKMD). Special emphasis on Insulin Resistance (IR) was placed, as it mediates Metabolic Syndrome (MS), a risk factor for CNCD, and predicts MS diagnosis. CR is the most robust intervention known to increase lifespan and health span, with high evidence and known biochemical mechanisms. CR improves cardiometabolic risk parameters, boosts exercise insulin sensitivity response, and there may be benefits of implementing moderate CR on healthy young and middle-aged individuals. However, there is insufficient evidence to support long-term CR. CKD is effective for weight and MS management, and may have additional benefits such as prevention of muscle loss and appetite control. SKMD has extreme significance benefits for all the metabolic parameters studied. Studies show inconsistent benefits of IF compared to classic CR. More studies are required to study biochemical parameters, reinforce evidence, identify risks, and seek effective and safe nutritional CR approaches.

Intestinal parasitic infections pose a grave threat to human health, particularly in tropical and subtropical regions. The traditional manual microscopy system of intestinal parasites detection remains the golden standard procedure for the diagnosis of parasites cyst or eggs, but this approach is costly time-consuming (30min/sample), highly tedious, and also required specialist. However, computer vision based on deep learning has made great stride in recent time. Despite the significant advances in deep convolutional neural network-based architectures, little research has been conducted to explore the potential of these techniques in the field of parasitology, specifically for intestinal parasites. Therefore, the goal of this research is to evaluate the performance of proposed state-of-the-art transfer learning architecture for detecting and classifying intestinal parasite eggs from images. We would ensure that patients receive prompt treatment while also relieving experts of extra work if we used such an architecture. Here, in stage first, we applied image pre-processing and augmentation to the dataset, and in stage second, we utilized the YOLOv5 algorithms for detection and classification and then compared their performance based on different parameters. Our algorithms achieved a mean average precision of 97% approximatiely and 8.5 ms detection time per sample for 5,393 intestinal parasite images. Thus, this approach may form a solid theoretical basis for real-time detection and classification in routine clinical examinations while accelerating the process to satisfy increasing demand.

Coastal resources in Lian, Batangas, have undergone significant degradation due to a combination of human activities and natural factors, including sea-level rise, changes in sea-surface temperature, fluctuations in rainfall, increased storm frequency, and sedimentation. This has led to adverse effects on key ecosystems such as corals, mangroves, and seagrasses. To assess the extent of climate change hazards on these coastal resources, a Vulnerability Assessment was conducted in the municipality of Lian, Batangas. The assessment employed a combination of the Coastal Integrity Vulnerability Assessment Toolkit (CIVAT) and Integrated Coastal Sensitivity, Exposure, and Adaptive Capacity to Climate Change (ICSEA-C) guidelines. Additionally, the analysis incorporated detailed mapping using Light Detection and Ranging (LiDAR) data for mangroves and LandSat 8 imagery for corals and seagrasses. The findings at the municipal scale revealed that a staggering 90% of mangroves in Lian, Batangas, were highly vulnerable. This vulnerability was attributed to a high score in intrinsic characteristics and a low adaptive capacity. Similarly, a majority of seagrasses in the area were classified as medium and highly vulnerable at the municipal level. Only 10–20% of seagrasses received low to medium vulnerability scores. Shockingly, almost 100% of the coral reefs in Lian, Batangas, were deemed highly vulnerable, indicating a critical threat to this crucial marine ecosystem.

Understanding the spatially varying effects of demographic factors on the spatio-temporal variation of intestinal parasites infections is important for public health intervention and monitoring. This paper presents a hierarchical Bayesian spatially varying coefficient model to evaluate the effects demographic factors on intestinal parasites morbidities in Ghana. The modeling relied on morbidity data collected by the District Health Information Management Systems. We developed Poisson and Poisson-gamma spatially varying coefficient Models. We used the demographic factors, unsafe drinking water, unsafe toilet and unsafe liquid waste disposal as model covariates. The models were fitted using the Integrated Nested Laplace Approximations (INLA). The overall risk of intestinal parasites infection was estimated to be 10.9 per 100 people with a wide spatial variation in the district-specific posterior risk estimates. Substantial spatial variation of increasing multiplicative effects of unsafe drinking water, unsafe toilet and unsafe liquid waste disposal occurs on the variation of intestinal parasites risk. The structured residual spatial variation widely dominates the unstructured component, suggesting that the unaccounted-for risk factors are spatially continuous in nature. The study concludes that both the spatial distribution of the posterior risk and the associated exceedance probability maps are essential for monitoring and control of intestinal parasites.

Interferon alpha (IFNα) is a protein drug used to treat viral infections and cancer diseases. Due to its poor stability in the gastrointestinal tract, only parenteral administration ensures bioavailability, which is associated with severe side effects. We hypothesized that the nanoencapsulation of IFNα within nanoparticles of the mucoadhesive polysaccharide chitosan would improve the oral bioavailability of this drug. In this work, we produced IFNα-loaded chitosan nanoparticles by the ionotropic gelation method. Their size, size distribution and concentration were characterized by dynamic light scattering and nanoparticle tracking analysis. After confirming their good cell compatibility in Caco-2 and WISH cells, the permeability of unmodified and PEGylated nanoparticles was measured in monoculture (Caco-2) and co-culture (Caco-2/HT29-MTX) cell monolayers. Results indicated that the nanoparticles cross the intestinal epithelium mainly by the paracellular route. Finally, the oral pharmacokinetics in BalbC mice of nanoencapsulated IFNα revealed that it was absorbed reaching an area-under-the-curve of 56.9 pg.h/mL.

In this report we describe the case of a healthy, young, athletic woman who developed acute lymphoblastic leukaemia (ALL)/lymphoblastic lymphoma (LBL) after receiving the second dose of the Pfizer/BioNTech modified mRNA (modRNA) COVID-19 genetic vaccine (marketed as Comirnaty^®). The first dose of the genetic vaccine did not appear to illicit any noticeable side effects, but within 24 hours of the second dose the patient suffered widespread and intensifying bone pain, fever, vomiting, and general malaise. Due to the persistence of the symptoms, the patient underwent a series of tests and examinations including a full laboratory workup, a consult with a clinical immunologist and rheumatologist, a Positron Emission Tomography (PET) imaging, as well as an osteomedullary biopsy. These together led to a definitive diagnosis of ALL. A time interval of 16 weeks from the second vaccination to the diagnosis of cancer was noted. Several similar cases with identical pathology which developed after the modRNA COVID-19 vaccination, are described in case reports in the scientific literature. The massive and indiscriminate use of genetic vaccines to fight COVID-19 is raising serious concerns about their safety and about the technology platform as a whole for this purpose. Growing evidence is accumulating regarding the biodistribution and persistence of the modRNA which can reach, thanks to the lipid nanoparticles, a multitude of tissues and organs of the body, including the bone marrow and other blood-forming organs and tissues. Moreover, there is evidence that the modRNA vaccines display a particular tropism for the bone marrow, influencing the immune system at multiple levels and being able to trigger not only autoimmune-based pathologies, but also neoplastic mechanisms. The aim of this article is to assess, on the basis of the available scientific literature, the risk of developing haematopoietic cancers after modRNA vaccination, and to investigate the potential genetic mechanisms involved in the pathogenesis of disease.

Although working memory (WM) is crucial for intellectual abilities, not much is known about its brain underpinnings, especially the structural connectivity. We used diffusion tensor imaging (DTI) to look across the whole brain for the white matter integrity correlates of the individual differences in the reading span (verbal WM capacity during reading) in healthy adults. Right-handed healthy native Russian speakers (N = 67) underwent DTI on a 3T Philips Ingenia scanner. Verbal WM was assessed with the Daneman-Carpenter reading span test (Russian version). Fractional anisotropy maps from each participant were entered into the group tract-based spatial statistics analysis with the reading span as a covariate; the results were TFCE-corrected. After taking into account effects of age, sex, education and handedness, reading span positively correlated with the white matter integrity in multiple sites: the body, the genu and the splenium of corpus callosum; bilateral corona radiata (anterior, posterior, and superior); bilateral superior longitudinal fasciculus; several tracts in the right hemisphere only, including the internal and external capsule; bilateral superior parietal and frontal white matter. Although the left hemisphere is central for verbal processing, we revealed the important role of the right hemisphere white matter for the verbal WM capacity. Our finding indicates that larger verbal working memory span may originate from additional processing resources of the right hemisphere.

Salmonella spp. contaminates egg and poultry meat leading to foodborne infections in humans. The emergence of antimicrobial-resistant strains limit the use of antimicrobials. We aimed to determine the effects of the food supplement, fermented defatted ‘alperujo’, a modified olive-oil by-product, on Salmonella Typhimurium colonisation in broilers. One hundred and twenty 1-day-old broilers were divided into four experimental groups: 2 control groups and 2 treated groups, and challenged with S. Typhimurium at day 7 or 21. On days 7, 14, 21, 28, 35 and 42 of life, duodenum and caecum tissue samples were collected for histopathological and histomorphometric studies. Additionally, cecum content was collected for Salmonella spp. detection by culture and qPCR, and for metagenomic analysis. Our results showed a significant reduction of Salmonella spp. in the cecum of 42-day-old broilers, suggesting that fermented defatted ‘alperujo’ stimulates Salmonella Typhimurium clearance in that cecum and may contribute to diminishing the risk of carcass contamination at the time of slaughter. Additionally, the improvement of the mucosal integrity suggests that enhancing intestinal health helps to limit Salmonella spp. colonisation in the host, mitigating production losses. These results could provide evidence that FDA would contribute to prophylactic and therapeutic measures to reduce salmonellosis prevalence in poultry farms.

Aptamers have a well-earned place in therapeutic, diagnostic, and sensor applications, and we now show that they provide an excellent foundation for education, as well. Within the context of the Freshman Research Initiative (FRI) at The University of Texas at Austin, students have used aptamer selection and development technologies in a teaching laboratory to build technical and 21st century skills appropriate for research scientists. One of the unique aspects of this course-based undergraduate research experience is that students develop their own projects, and take ownership of their own science in what would otherwise be a traditional teaching lab setting. Of the many successes, this work includes the isolation and characterization of novel calf intestinal alkaline phosphatase (anti-CIAP) RNA aptamers by an undergraduate researcher. Further, preliminary survey data suggest that students who participate in the aptamer research experience express significant gains in their self-efficacy to conduct research, and their perceived ability to communicate scientific results, as well as organize and interpret data. This work will describe the use of aptamers in an educational setting, highlight the positive student outcomes of the aptamer research experience, and more particularly present the research findings relative to the anti-CIAP aptamer.

Cryptosporidiosis is a major human health concern globally. Despite well-established methods, misdiagnosis remains common. Our understanding of the cryptosporidiosis biochemical mechanism remains limited, compounding the difficulty of clinical diagnosis. Here, we used a systems biology approach to investigate the underlying biochemical interactions in C57BL/6J mice infected with Cryptosporidium parvum. Faecal samples were collected daily following infection. Blood, liver tissues and luminal contents were collected 10 days post infection (dpi). High-resolution liquid chromatography and low-resolution gas chromatography coupled with mass spectrometry were used to analyse the proteomes and metabolomes of these samples. Faeces and luminal contents were additionally subjected to 16S rRNA gene sequencing. Univariate and multivariate statistical analysis of the acquired data illustrated altered host and microbial energy pathways during infection. Glycolysis/citrate cycle metabolites were depleted, while short-chain fatty acids and D-amino acids accumulated. An increased abundance of bacteria associated with a stressed gut environment was seen. Host proteins involved in energy pathways and Lactobacillus glyceraldehyde-3-phosphate dehydrogenase were upregulated during cryptosporidiosis. Liver oxalate also increased during infection. Microbiome-parasite relationships were observed to be more influential than the host-parasite association in mediating major biochemical changes in the mouse gut during cryptosporidiosis. Defining this parasite-microbiome interaction is the first step towards building a comprehensive cryptosporidiosis model towards biomarker discovery, and rapid and accurate diagnostics.

The classical propositional calculus (zero-order logic, classical propositional logic), is the most fundamental two-valued logical system. In this paper we present a proof of inconsistency of the classical propositional calculus. Then, we get right away the conclusion that the metatheory of the classical propositional calculus is inconsistent.

Epoxy asphalt (EA) concrete is widely used in constructing long-span steel bridge pavements (SBDPs). This study aims to derive a fatigue damage evolution law, conducting an experimental investigation of SBDP. First, a general theoretical form of the fatigue damage evolution law of materials is established based on the thermal motion of atoms. Then, fatigue experiments demonstrate that this evolution law well represents the known damage–life relationships of SBDP. Taking into account the experimental relationships between damage and fatigue life under symmetrical cyclic loadings with different overload amplitudes and temperature variations, a detailed damage evolution law is deduced. Finally, the role of damage accumulation is discussed on the basis of the proposed damage evolution law for the extreme situation of heavy overload and severe environments. The results show that both heavy loading and falling temperatures increase the fatigue damage of SBDP considerably; therefore, SBDP should avoid heavy loading combined with winter temperatures. EA shows a fatigue life two to three times longer than that of modified matrix asphalt (SMA) or guss asphalt (GA). For the same thickness, EA pavement is demonstrated to be more suitable for an anti-fatigue design of large-span SBDP under high traffic flows and low temperatures.

Background: Continuous subcutaneous apomorphine infusion (CSAI), levodopa-carbidopa intestinal gel infusion (LCIG), and deep brain stimulation of the subthalamic nucleus (STN-DBS) have markedly changed the treatment landscape of advanced Parkinson’s disease (aPD). Despite a similar outcome of all device-aided therapies (DATs), some patients switch or combine DATs. The aim of this retrospective study was to explore the frequency and reasons for switching between or combining DATs in two movement disorders centres in Slovenia and Israel. Methods: We collected and analysed demographic and clinical data from aPD patients who switched between or combined DATs. Motor and non-motor reasons and their frequency for switching/combining were examined, as was the effect of DAT using the Global Improvement subscale of the Clinical Global Impression Scale. Non-parametric tests were used to analyse the data. Results: Of 505 aPD patients treated with DATs at both centres between January 2009 and June 2021, we identified in total 30 patients (6%), who either switched DAT (N=24: 7 LCIG-to-STN-DBS, 1 LCIG-to-CSAI, 5 CSAI-to STN-DBS, 8 CSAI-to-LCIG, 1 STN-DBS-to-LCIG, 1 LCIG-to-CSAI-to-STN-DBS, and 1 STN-DBS-to-CSAI-to-LCIG) or combined DATs (N=6: 5 STN-DBS+LCIG and 1 STN-DBS+CSAI-to-STN-DBS+LCIG). In most of these patients, inadequate control of motor symptoms was the main reason for switching or combining DATs, but non-motor reasons (related to the disease and/or DAT) were also identified. Conclusions: Switching between and combining DATs is uncommon, but in some patients brings substantial clinical improvement and should be considered in those who have either inadequate symptom control on DAT treatment or have developed DAT related complications.

Immune-mediated bowel diseases (IMBD), including Ulcerative colitis and Crohn's disease, represent a significant global health burden with their complex etiology and increasing prevalence. The connection between intestinal parasites and the gut microbiome in immune-mediated bowel disease is a complex and evolving field of research. Several studies have demonstrated that intestinal parasites can modulate the composition and function of the gut microbiome. Parasitic infections can result in alterations in the gut microbial community, including changes in microbial diversity, abundance, and metabolic activity. These changes can influence the immune response and contribute to the development of IMBDs. In contrast, the gut microbiome serves a pivotal function in maintaining intestinal homeostasis and immune regulation. Dysbiosis, characterized by changes in the gut microbial composition, has been associated with the pathogenesis of IMBDs. Imbalances in the gut microbiota can result in increased gut permeability, chronic inflammation, and aberrant immune responses, all of which are hallmarks of IMBDs. The bidirectional interaction between intestinal parasites and the gut microbiome further complicates the understanding of immune-mediated bowel diseases. Certain parasites, such as hookworms and Necator americanus, have been found to downregulate immune responses and may have therapeutic potential in treating celiac disease. On the other hand, infections with parasites like Strongyloides stercoralis and Blastocystis have been shown to mimic the symptoms of IBD, highlighting the intricate relationship between parasites and the pathogenesis of these diseases. Additional investigation is required to comprehensively elucidate the mechanisms that underlie the association between intestinal parasites and the gut microbiome in immune-mediated bowel disease. This knowledge could potentially lead to the development of targeted therapeutic strategies that aim to restore gut microbiota homeostasis and alleviate the symptoms of these debilitating conditions. By understanding and harnessing the complex interplay between parasites, the gut microbiome, and the host immune system, researchers may uncover novel approaches for the management and treatment of immune-mediated bowel diseases.

Transient receptor potential (TRP) channel family proteins are sensors for pain, which sense variety of thermal and noxious chemicals. Sensory neurons innervating the gut abundantly express TRPA1 and TRPV1 channels and are in close proximity of gut microbes. Emerging evidence indicates a bi-directional gut-brain cross-talk in several entero-neuronal pathologies; however, the direct evidence of TRP channels interacting with gut microbial populations is lacking. Herein, we examine whether and how the knockout (KO) of TRPA1 and TRPV1 channels individually or combined TRPA1/V1 double-knockout (dKO) impacts the gut microbiome in mice. We detect distinct microbiome clusters among the three KO mouse models versus wild-type (WT) mice. All three TRP-KO models have reduced microbial diversity, harbor higher abundance of Bacteroidetes, and reduced proportion of Firmicutes. Specifically distinct arrays in the KO models are determined mainly by S24-7, Bacteroidaceae, Clostridiales, Prevotellaceae, Helicobacteriaceae, Rikenellaceae, and Ruminococcaceae. A1KO mice have lower Prevotella, Desulfovibrio, Bacteroides, Helicobacter and higher Rikenellaceae and Tenericutes; V1KO mice demonstrate higher Ruminococcaceae, Lachnospiraceae, Ruminococcus, Desulfovibrio and Mucispirillum; while A1V1dKO mice exhibit higher Bacteroidetes, Bacteroides and S24-7 and lower Firmicutes, Ruminococcaceae, Oscillospira, Lactobacillus and Sutterella abundance. Also, the abundance of taxa involved in biosynthesis of lipids and primary and secondary bile acids is higher while that of fatty acid biosynthesis-associated taxa is lower in all KO groups. To our knowledge, this is the first study demonstrating distinct gut microbiome signatures in TRPA1, V1 and dKO models and should facilitate prospective studies exploring novel diagnostic/ therapeutic modalities regarding the pathophysiology of TRP channel proteins.

Throughout this paper the impact of anxiety on adolescent athlete’s is highlighted through analyzing neurological and psychological aspects involved in sports performance. The neuroanatomy and neuropsychology of the human brain plays a major role in developing athlete’s that has only begun to be analyzed within recent years. Especially in young athletes, there are numerous factors that affect performance on the field that originate from the environment and training the adolescent athlete is involved in. Sports performance is viewed as a major physical factor such as training and lifting weights, however the psychological aspect of sports performance often goes unnoticed. Athletes can begin to develop mental fatigue and anxiety which inevitably can decrease their ability to perform. The athlete’s internal suffering begins to go unnoticed, as the only tangible factor is watching their performance decrease. This causes the athlete to push themselves further in training resulting in greater mental fatigue. This paper emphasizes the numerous factors neurologically that play a role in athletic performance which should be focused on in adolescent athletes as they navigate the challenges and competition that are apparent within athletics. It is critical to understand the processes and hormonal changes the body undergoes with training and playing a sport, this information can change the way adolescent sports are approached and advanced.

The dermatological manifestations of Long Covid (LC) have languished in the shadows of chronic fatigue and brain fog. Yet they are all linked by gut dysbiosis and the cytokine triad of TNF-α, IL-1β, and IL-6. The gut microbiome common not only to LC, psoriasis, AA, and vitiligo but also to neurodegenerative disease has been recently described. This gut microbiome induces an altered tryptophan metabolism linked to autoimmune disease. SARS CoV2 invades enterochromaffin cells rich in ACE2 receptors and curtails absorption of the essential amino acid tryptophan and subsequent synthesis of serotonin and melatonin. This review suggests that an etiologic prebiotic (d-mannose)/probiotic (lactobacilli, bifidobacteria)/postbiotic (butyrate) approach to autoimmune skin disease that improves intestinal barrier integrity and that suppresses the triad of TNF-α, IL-6, and IL-1β may enhance or even eliminate the traditional immunotherapy of targeted monoclonal antibodies, Janus kinase inhibitors, and steroids. Health benefits of this approach extend well beyond suppression of autoimmune skin disease.

Cells execute biological functions to support phenotypes such as growth, migration, and secretion. Complementarily, each function of a cell has resource costs that constrain phenotype. Resource allocation by a cell allows it to manage these costs and optimize their phenotypes. In fact, the management of resource constraints (e.g., nutrient availability, bioenergetic capacity, and macromolecular machinery production) shape activity and ultimately impact phenotype. In mammalian systems, quantification of resource allocation provides important insights into higher-order multicellular functions; it shapes intercellular interactions and relays environmental cues for tissues to coordinate individual cells to overcome resource constraints and achieve population-level behavior. Furthermore, these constraints, objectives, and phenotypes are context-dependent, with cells adapting their behavior according to their microenvironment, resulting in distinct steady-states. This review will highlight the biological insights gained from probing resource allocation in mammalian cells and tissues.

We previously showed that, based on the frequency and distribution of specific cell types, rainbow trout (RT) intestinal mucosa is divided in two regions that form a complex nonlinear 3D pattern and have a different renewal rate. This work had two aims. First, to investigate whether the unusual distribution of cell populations reflects a similar distribution of functional activities. To this end, we determined the protein expression pattern of three well defined enterocytes functional markers: Peptide Transporter 1 (PepT1), Sodium-Glucose/Galactose Transporter 1 (SGLT-1) and fatty acid-binding protein 2 (Fabp2). Second, to characterize the structure of RT intestinal stem cells (ISC) niche and to determine whether the different proliferative rates correlate with a different organization and/or extension of the stem cells population. We studied the expression and localization of well-characterized mammal ISC markers: LGR5, HOPX, SOX9, NOTCH1, DLL1 and WNT3A. Our results indicate that morphological similarity is associated with similar function only between the first portion of the mid-intestine and the apical part of the complex folds in the second portion. Mammal ISC markers are all expressed in RT but their localization is completely different suggesting also substantial functional differences. Finally, higher renewal rates are supported by a more abundant ISC population.

Long Covid has become a blight, its economic consequences overwhelming. But Long Covid (LC) may represent persistent Covid-19 in those with preexisting Candida overgrowth (CO). The features shared by both are striking. LC may be a growing subset of CO. The altered tryptophan metabolism encountered in LC is driven by IFN-γ in reaction to CO. Females are robust producers of IFN-γ, yet estrogen promotes CO.The consequent decline in serotonin and melatonin triggers the mood swings and sleeplessness respectively in LC. The low serotonin, the primary messenger in the gut brain axis, creates autonomic dysfunction. The CO induced gut dysbiosis and leaky gut initiate an autoimmune path. TNFα seen in both LC and this opportunistic yeast is at the center of the cytokine triad that leads to neurodegeneration. The Western diet, high in carbohydrates, alcohol, and glutamate, is exploited by this commensal turned parasite. Residual SARS CoV2 and Candida generate abundant ROS, inducing mitochondrial dysfunction. Alcohol tastes different for many with LC, because acetaldehyde requires functioning hepatic mitochondria. This article delves into the complex physiology and biochemistry that drive the symptoms of this conspicuous connection. Recent research has revealed innovative approaches that might address this global scourge, including D-mannose for the immune dysfunction and butyrate for the gut dysbiosis created by and seen in both LC and intestinal Candidiasis.

Age-related alterations in the gut microbiome composition and its impacts on the host’s health have been well described; however, detailed analyses of the gut microbial structure defining ecological microbe-microbe interactions is limited. One of the ways to determine these interactions is by understanding microbial co-occurrence patterns. We previously showed promising abilities of Lactobacillus acidophilus DDS-1 on the aging gut microbiome and immune system. However, the potential of the DDS-1 strain to modulate microbial co-occurrence patterns is unknown. Hence, we aimed to investigate the ability of L. acidophilus DDS-1 to modulate the fecal, mucosal and cecal-related microbial co-occurrence networks in young and aging C57BL/6J mice. Our Kendall’s tau correlation measures of co-occurrence revealed age-related changes in the gut microbiome, which were characterized by reduced number of nodes and associations across sample types when compared to younger mice. After four-week supplementation, L. acidophilus DDS-1 differentially modulated the overall microbial community structure in fecal and mucosal samples as compared to cecal samples. Beneficial bacteria such as Lactobacillus and Akkermansia acted as connectors in aging networks in response to L. acidophilus DDS-1 supplementation. Our findings provided the first evidence of the DDS-1-induced gut microbial ecological interactions revealing the complex structure of microbial ecosystems with age.

Epithelial–mesenchymal transition (EMT) is defined as a cellular process during which epithelial cells acquire mesenchymal phenotypes and behavior following the downregulation of epithelial features. EMT and its reversed process, the mesenchymal-epithelial transition (MET), and the special form of EMT, the endothelial-mesenchymal transition (EndMT), have been thought as a universal dogma controlling developmental and pathological processes. More than half a century of EMT study has made it a large research field and a mainstream concept. However, discrepancies and disputes over EMT and EMT research have also grown over time. Particularly, neither the epithelial and mesenchymal states/properties nor their regulatory networks nor specific markers have been defined, rendering the EMT, MET and EndMT concepts groundless. Moreover, EMT and MET effects should not be a cause, but rather a consequence of or an accompanying effect during developmental and pathological processes. EMT and MET represented by the change in cell shapes or adhesiveness or symbolized by EMT factors are biased interpretation of the overall change in cellular property and regulatory networks during development and cancer progression. The true meaning of EMT effects in some developmental and pathological processes, such as fibrosis, needs re-evaluation. But the core EMT factors are actually a few components of the regulatory networks of neural stemness, which determines tumorigenicity and pluripotency. The EMT effects in cancer progression and neural crest formation are wrong attribution of the role of neural stemness during cancer progression and the cell-intrinsic property of neural crest cells to the unknown mesenchymal state. It is time to reassess the significance of EMT and its related concepts in scientific research.

A groundbreaking integrated predictive model, termed Cyber Forensics Behavioral Analysis (CFBA), has been developed in an environment characterized by rapidly evolving and increasingly sophisticated cyber threats. This model merges Cyber Behavioral Sciences with Digital Forensics to enhance the prediction accuracy and effectiveness of cyber threats originating from specific Autonomous System Numbers (ASNs). It has been observed that traditional cybersecurity strategies, predominantly focused on technical aspects, must be improved in addressing the complex landscape of cyber threats. Consequently, a novel approach has been proposed in this research, combining technical expertise with insights into the behavior of cybercriminals, thereby addressing a significant gap in existing methodologies. A mixed-methods approach has been employed in the study, integrating quantitative and qualitative research methods. This approach has created a comprehensive framework incorporating digital forensics, cybersecurity, computer science, forensic psychology, and the cyber behavioral sciences which incorporates disciplines scuch as cyberpsychology and forensic cyberpsychology. The study is anchored around four key concepts: (1) Forensic Cyberpsychology, which focuses on understanding psychological aspects of cybercriminal behavior; (2) Digital Forensics, involving the collection and analysis of digital evidence from cyber incidents; (3) Predictive Modeling, which utilizes historical data and patterns to anticipate potential cyber threats; and (4) the Cyber Behavioral Analysis Metric (CBAM) and Cyber Behavioral Score (CBS), tools designed for evaluating and scoring ASNs based on their behavior in terms of cybersecurity threat risks. Challenges encountered in the development of this integration have been significant. Initial setbacks included the misalignment of traditional cyber defense methods with the evolving nature of cyber threats and the absence of a holistic approach in pre-existing models. Through the narrative of these challenges and the subsequent development of the CFBA model, the research highlights the necessity for an interdisciplinary approach to cybersecurity. The outcomes of this study are not merely theoretical but provide practical, actionable tools and frameworks that markedly improve the precision of predicting cyber threats, especially from ASNs. The CFBA model represents a significant shift in cybersecurity strategies, highlighting the importance of integrating behavioral insights with technical knowledge. The study emphasizes the need for ongoing research and collaboration in cybersecurity, advocating for an approach that is as comprehensive and multifaceted as the cyber threats it seeks to mitigate. This research has been conducted to contribute significantly to cybersecurity, offering new perspectives and methodologies in a rapidly changing domain.

The purpose of this paper is to explore the implementation of Retrieval-Augmented Gen- 14 eration (RAG) technology with open-source Large Language Models (LLMs). For this purpose, a 15 web-based application named PaSSER that integrates RAG with three models - Mistral:7b, 16 Llama2:7b: Orca2:7b, is developed. In its development various technologies are used, including 17 Blockchain for managing and storing assessment results of built-in testing modules. PaSSER em- 18 ploys a set of evaluation metrics for LLMs’ performance - METEOR, ROUGE, BLEU, Perplexity, 19 Cosine similarity, Pearson correlation, and F1 score. The specialized knowledge base is in the smart 20 agriculture domain. As an illustration, the paper presents results and analysis of two tests. First one 21 is assessing the performance of LLMs across different hardware configurations, the other is deter- 22 mining the model that delivers most accurate and contextually relevant responses within the RAG. 23 The paper also discusses the integration of blockchain technology with LLMs to manage and store 24 assessment results within a blockchain environment. The tests revealed that Mistral:7b demon- 25 strates the best results across most of the evaluated metrics. The discussion section comments on 26 technical and hardware considerations that affect the performance of LLMs. Future development 27 will focus in leveraging new larger pre-trained open-source LLMs, exploring different finetuning 28 approaches, and further integration with Blockchain and IPFS.

This study investigated the relationship between aluminum adjuvant vaccines and the prevalence of 4 childhood diseases (Autism, Allergies, Asthma, ADD/ADHD) using data from the 2020-2021 National Survey of Children's Health (NSCH) [1] and the Centers for Disease Control National Immunization Survey (CDC NIS) [2]. The study found an association with aluminum adjuvant dosage and the prevalence of each disease studied (Autism, Allergies, Asthma, ADD/ADHD) through a weighted regression analysis of disease prevalence against the summed likelihood of aluminum adjuvant vaccine uptake.

Organ-on-a-chip (OOC) is an emerging technology that simulates an artificial organ within a microfluidic cell culture chip. Current cell biology research focuses on in vitro cell culture due to various limitations of in vivo testing. Unfortunately, in vitro cell culture fails to provide an accurate microenvironment, and in vivo cell culture is expensive and has historically been a source of ethical controversy. OOC aims to overcome these shortcomings and provide the best of both in vivo and in vitro cell culture research. The key component of the OOC design is utilizing microfluidics to ensure a stable concentration gradient, dynamic mechanical stress modeling, and accurate reconstruction of a cellular microenvironment. OOC also has the advantage of complete observation and control of the system, which is impossible to recreate in in vivo research. Multiple throughputs, channels, membranes, and chambers are constructed in a polydimethylsiloxane (PDMS) array to simulate various organs on a chip. Various experiments can be performed utilizing OOC technology, including drug delivery research and toxicology. Current technological expansions involve multiple organ microenvironments on a single chip, allowing for studying inter-tissue interactions. Other developments in the OOC technology include finding a more suitable material as a replacement for PDMS and minimizing artefactual error and non-translatable differences.

Inflammatory diseases are common pathological processes caused by various acute and chronic factors and some of them are autoimmune diseases. Exosomes are fundamental extracellular vesicles secreted by almost all cells, which contain a series of constituents, i.e. cytoskeletal and cytosolic proteins (actin, tubulin, histones), nucleic acids (mRNA, miRNA, DNA), lipids (diacylglycerophosphates, cholesterol, sphingomyelin, ceramide), and other bioactive components (cytokines, signal transduction proteins, enzymes, antigen presentation and membrane transport/fusion molecules, adhesion molecules). This review would be a synopsis of the actual knowledge on the contribution of exosomes from different cell sources as possible therapeutic agents against inflammation, focusing on several inflammatory diseases, neurological diseases, rheumatoid arthritis and osteoarthritis, intestinal bowel disease, asthma, liver and kidney injuries. Current knowledge indicates that the role of exosomes in therapy of inflammation and in inflammatory diseases could be distinctive. Main limitations to their clinical translation are still production, isolation, and storage. Additionally, there is an urgent need to personalize the treatments in terms of selection of exosomes, their dosages and routes of administration, and a deeper knowledge about their biodistribution, type and incidence of adverse events and long-term effects of exosomes. In conclusion, exosomes can very promising next generation therapeutic option, superior to synthetic nanocarriers and cell therapy, and can represent a new strategy of effective, safe, versatile and selective delivery systems in the future.

Intestinal epithelial cell activities during homeostasis and regeneration are well described, but their potential interactions with stromal cells remain unresolved. Exploring the functions of these heterogeneous intestinal mesenchymal stromal cells (iMSCs) remains challenging due to the lack of specific markers for most functionally homogenous subpopulations. In recent years, however, novel clustering techniques such as single-cell RNA sequencing (scRNA-seq), fluorescence-activated cell sorting (FACS), confocal microscope, and computational remodeling of intestinal anatomy have helped identify and characterize some specific iMSC subsets. These methods help researchers learn more about the localization and functions of iMSC populations during intestinal morphogenic and homeostatic conditions. Furthermore, it is imperative to understand their cellular pathways for activation and how they interact with surrounding cellular components, particularly during intestinal epithelial regeneration that follows mucosal injury. This review provides insights into the spatial distribution and functions of some identified iMSC subtypes in intestinal morphogenesis, homeostasis, and regeneration. We reviewed related signaling mechanisms implicated during epithelial and subepithelial stromal cell crosstalk. Future research should focus on elucidating the molecular intermediates of these regulatory pathways to open a new frontier for potential therapeutic targets that can alleviate intestinal mucosa-related injuries.

A paddle wheel aerator is developed in this research, which includes a wireless sensor network for measuring the water quality in the aquaculture of marine shrimp ponds. It can also move to the desired position to fill oxygen and measure water quality. A basic requirement is good standard water quality to prevent shrimp from epidemics and improve production. The water quality paddle wheel aerator applies a microcontroller and sensors to measure eight parameters of water quality. These water quality parameters are observed on the web application via an IoT module. The movement system of the water-quality paddle wheel aerator consists of a LiDAR, GPS, and remote RF signal. Each item of data is recorded immediately on the cloud server while the water-quality paddle wheel moves in the marine shrimp farm. The controlled paddle wheel aerator is harnessed automatically to enhance precisely the spatial monitoring resolution of the measurement system installed, which is needless for a multiple measurement system with high cost of investment. Also, farmers can access real data through the Line application. Hence, they are able to plan and control a good environment for aquaculture, preventing the occurrence of various epidemics and decomposing organic matter in the pond.

Graph databases (GDBs) are becoming increasingly popular across scientific disciplines, being highly suitable to store and connect complex heterogeneous data. In systems biology, they are used as a backend solution for biological data repositories, ontologies, networks, pathways, and knowledge graph (KG) databases. In this review, we analyse all publications using or mentioning graph databases retrieved from PubMed and PubMed Central full-text search, focusing on the top 16 available GDB technologies. Relevant publications are then categorised according to their domain and application. We detail different approaches and highlight advantages of outstanding resources, such as UniProtKB, Disease Ontology, and Reactome, which provide graph-based solutions. We discuss ongoing efforts of the systems biology community to standardise and harmonise KG creation and the maintenance of integrated resources. Outlining prospects, including the use of GDBs as a way of communication between biological data repositories, we conclude that efficient design, querying, and maintenance of GDBs will be key for knowledge generation in systems biology and other research fields with heterogeneous data.

Resistance to therapy and disease progression are the main causes of mortality in most cancers. In particular, the development of resistance is an important limitation affecting the efficacy of therapeutic alternatives for cancer, including chemotherapy, radiotherapy, and immunotherapy. Signaling pathways are largely responsible for the mechanisms of resistance to cancer treatment and progression, and multiple myeloma is no exception. p38 mitogen-activated protein kinase (p38) is downstream of several signaling pathways specific to treatment resistance and progression. Therefore, in recent years, developing therapeutic alternatives directed at p38 MAPK has been of great interest, in order to reverse chemotherapy resistance and prevent progression. In this review, we discuss recent findings on the role of p38, including recent advances in our understanding of its expression and activity as well as its isoforms, and its possible clinical role based on the mechanisms of resistance and progression in multiple myeloma.

The gastrointestinal tract is colonized by trillions of different microorganisms, named the gut microbiota, which is key to degrade undigested food such as dietary fibers. The fermentation of these food components leads to the production of short-chain fatty acids (SCFA) acetate, propionate, and butyrate, which exploit several beneficial roles for the host’s health. Their production and absorption happen in different ways in the human intestine and depend on the type of dietary fiber reaching the gut and the microorganisms involved in the fermentation. The supplementation of SCFAs, mostly butyrate, in treating gastrointestinal, metabolic, cardiovascular, and gut-brain-related diseases has been reported in the medical literature. This review aims to give an overview of the production and absorption dynamics of acetate, propionate, and butyrate in the human gut, with a final focus on the role played by these SCFAs on gastrointestinal and metabolic health and the present therapeutic implications.

Passive marine listening, involving the acoustic monitoring of underwater environments, has become increasingly vital for scientific research, environmental monitoring, and defense applications. However, the success of such applications critically depends on the ability to extract meaningful information from the often noisy and dynamic underwater acoustic environment. In this context, Mel-frequency cepstral coefficients (MFCCs) have emerged as an essential tool for feature extraction, capturing the spectral characteristics of marine sounds and making them ideal for species identification and sound event detection. This research presents an innovative approach to enhance the robustness of MFCC-based passive marine listening through adaptive noise reduction techniques. The proposed approach utilizes dynamic spectral subtraction to counter underwater noise, resulting in enhanced signal-to-noise ratios for desired sounds. This adaptive system adjusts to dynamic underwater noise, allowing it to concentrate on target sounds and suppress interference effectively. The experimentation further validates the effectiveness of the proposed approach, with results reaching 99% on the full dataset of 570 mammals and vessels, demonstrating the effectiveness of SVM and Random Forests in the classification of underwater audio.

Flavin-dependent monooxygenases (FMOs) have made substantial influence as catalysts for monooxygenation reactions, impacting diverse field such as drug metabolism, environmental studies, and natural product synthesis. Their application in biocatalysis boasts several advantages over conventional chemical catalysis, such as heightened selectivity, safety, sustainability, and eco-friendliness. In the realm of biomedicine, FMOs are pivotal in antibiotic research, modulating natural products, antimicrobial agents, and pathways involved in drug synthesis. They're also underscored as potential pharmaceutical targets, pivotal in disease progression and viable for therapeutic intervention. Additionally, FMOs play a substantial role in environmental science, especially in pesticide processing and plant vitality. Their involvement in biosynthesizing compounds like polyethers, tropolones, and ω-hydroxy fatty acids, with remarkable regio- and stereoselectivity, renders them indispensable in drug discovery and development. As our comprehension of FMOs' catalytic mechanisms and structures advances, coupled with cutting-edge biotechnologies like computational design and directed evolution, FMOs are poised to occupy an increasingly significant role in both scientific exploration and industrial applications.

Abstract: Social media has become a vital tool in ensuring productivity among Undergraduates, as studies have shown an increased number of users globally. This study assessed the impact of social media usage on undergraduates’ academic performance and working memory. Participants from three different universities such as the University of Georgia (UG), Eastern European University (EEU), and Batumi State University (BSU) completed this study using online google forms. UG and EEU are in the capital city, and BSU is in Batumi City. The study questionnaires were approved by the institutional review board before the data collection. Descriptive analyses were assessed for all study populations, characteristics, frequencies, percentages, means, and standard deviations using Statistical Package for Social Science (SPSS Inc., Chicago, IL, version 25.0 for Windows) software. 41.3% were male students, as most of the participants were foreign students living and studying in Georgia. Male students had the risk of ‘conflict’ with families and friends because of social media. Female students are at increased risk of using social media as an ‘escape’ from negative feelings. 89.7% of students that perform physical activities, considering their academic workload had the risk of preoccupation complaints. 87.9% felt dissatisfied regularly because they wanted to spend more time on social media. Utilization of social media differed based on the characteristics of the participants such as age, gender, and geography. We observed the increase in prevalence of social media addiction, its effect on academic performance and working memory among undergraduate students.

The brain being arguably the most complex organ in the human body, its detailed functioning is yet to be fully deciphered, let alone accurately modeled. Nonetheless, the medical community has gathered quite a remarkable amount of studies about the consequences of illnesses and injuries on its development and functioning. This bibliographic review aims to cover mostly the findings related to the changes in the physical distribution of neurons and their connections - the connectome -, both structural and functional, as well as their modelling. It does not intend to offer an extensive medical description of all injuries and diseases affecting the brain, rather presenting the most common ones succinctly so the need for accurate brain modelling can be fully understood and pondered, offering propositions to this aim.

The development of plant-based meat analogues has become a significant challenge for the food industry in recent years due to the increasing demand for sustainable and healthier proteins in the context of a global protein transition. Plant-based meat analogues imitate the visual, textural, and chemical properties of traditional meat products and are required to closely resemble meat to appeal to consumers. In addition, consumers demand natural, clean-label, and nutritional and healthy products. To address these challenges, the food industry must develop highly healthy, nutritious, and E-number-free meat analogue products. Understanding the functionality of each ingredient and its role in the food matrix is crucial to being a key player in the innovation of the meat analogues market. This review provides updated information on the primary ingredients utilized for the development of plant-based burger meat alternatives and their functionality. The key components of meat analogue burgers are outlined, including plant proteins, binding agents, fats and oils, flavorings, colorings, preservatives, fortificants, and clean-label considerations.

Migraine is a neurovascular disorder that can be debilitating for individuals and society. Current research focuses on finding effective analgesics and management strategies for migraines by targeting specific receptors and neuropeptides. Nevertheless, the responder rates of recently approved calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and receptor inhibitors remain around 50 percent. To address the need for novel therapeutic targets, researchers are exploring the potential of another secretin family peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), as a ground-breaking treatment avenue for migraine. Preclinical models have revealed how PACAP affects the trigeminal system, which is implicated in headache disorders. Clinical studies have demonstrated the significance of PACAP in migraine pathophysiology; however, a few clinical trials remain inconclusive: the pituitary adenylate cyclase-activating peptide 1 receptor mAb, AMG 301 showed no benefit for migraine prevention, while the PACAP ligand mAb, Lu AG09222 significantly reduced the number of monthly migraine days over placebo in a phase 2 clinical trial. Meanwhile, another secretin family peptide vasoactive intestinal peptide (VIP) is gaining interest as a potential new target. In light of recent advances in PACAP research, we emphasize the potential of PACAP as a promising target for migraine treatment, highlighting the significance of exploring PACAP as a member of the antimigraine armamentarium, especially for patients who do not respond to or contraindicated to anti-CGRP therapies. By updating our knowledge on PACAP and its unique contribution to migraine pathophysiology, we can pave the way for reinforcing PACAP and other secretin peptides, including VIP, as a novel treatment option for migraines.

Astronauts in space are subject to a continuous bombardment of ionizing radiation. The Earth's magnetic field and the ISS shield some biologically damaging particles traveling through. Still, travel beyond low-Earth orbit and extravehicular activities are exceedingly more dangerous and there is a concern for the acute and late-occurring adverse health effects befalling astronauts. So, it is vital to consider the current tools and models used to describe and study the organic consequences of ionizing radiation exposure. It is equally important to see where these models may improve. This article reviews the historical development and current state of knowledge of radiation effects impacting astronauts in orbit. We explain the space radiation environment, cellular microenvironment, and how these may be incorporated in radiobiological models to aid in our understanding of the influence space travel may have on astronaut health. The topics discussed in this paper include a review of DNA damage and repair mechanisms and the numerical models that aim to explain the biological effects resulting from ionizing radiation damage. Historically, radiobiological models focused on how radiation damages nuclear DNA, built upon the hypotheses of Crowther and Lea in the 1940s and 1960s, and neglected other sub-cellular targets outside of nuclear DNA.

The automotive industry has witnessed a significant push towards increased fuel efficiency and reduced carbon emissions. Among many factors influencing overall vehicle efficiency, aerodynamic drag is a critical consideration, accounting for a substantial portion of fuel consumption. Our investigation focused on the drag coefficients of three prominent 2023 passenger car models – the Toyota Corolla, Hyundai Elantra, and Kia Soul. Using ANSYS Fluent to perform computational fluid dynamics, we demonstrated an inverse correlation between drag force and gas mileage, underlining the significance of aerodynamic design in fuel efficiency. Notably, the Hyundai Elantra emerged as the most aerodynamically efficient of the three vehicles, followed closely by the Toyota Corolla. In contrast, the boxier-designed Kia Soul exhibited significantly higher drag coefficients and drag forces, rendering it the least efficient of the trio. These findings emphasize the importance of environmental factors in car design. Shaping aerodynamic profiles directly impacts fuel efficiency, stability, and overall performance.

In the domain of financial trading, where accuracy and swift response to data discrep- ancies are paramount for maintaining clienttrust, our research paper delves into the development of a real-time alert system utilizing SpringBoot, a framework renowned for its robustness and adaptability in enterprise applications. We embark on a comprehensive journey, beginning with addressing thefoundational challenges inherent in monitoring trade inquiries - the necessity for real-time processing, unwavering data accuracy,and ensuring unwavering system reliability. The study then methodically transitions to the architectural design, where we explore howSpringBoot’s capabilities are optimally utilized to meet these challenges. Following this, we delve into the im- -plementationphase, detailing the strategic selection of compatible technologies and methods for effective data management and discrepancydetection. The paper culminates in a thorough evalu- ation of the system, where we assess performance across various operationalscenarios, scrutinize the accuracy of the discrepancy detection mechanisms, and integrate real-world feedback from users in thetrading sector. This holistic approach not only highlights the versatility and efficiency of SpringBoot in creating reliable alert systems in the high-stakes world of financial trading but also serves as a detailed guide for similar endeavors in this field

The last 50 years witnessed the emergence of various so called “hyperpolarization technologies” that allow generating large magnetizations of spin ensembles. This Editorial Essay provides a brief overview of the use of these technologies in various fields, including medicine, chemistry, and quantum sensing. It is concluded that critical questions still need to be addressed to harness benefits of nuclear hyperpolarization in clinical medical imaging while interdisciplinary innovation can unlock potential of novel (yet unexplored) methods. My hope is that this Editorial Essay provides valuable insights into the current state and future directions of spin technologies.

The visual span refers to the number of letters readers can identify in a single fixation without using linguistic skills. Proponents of the visual span hypothesis postulate an influence of early visual processing on reading speed. Given the slowness of reading Arabic texts, the present work aims to study the development of the visual span and its effects on reading speed in the Arabic-speaking context. Thirty-four subjects participated in the study. The trigram task and the rapid serial visual presentation (RSVP) paradigm were used to estimate visual span size and reading speed. In line with our initial assumptions, the results showed a significant effect of grade level on reading speed (F(2,31) = 30.93, p<0.001), visual span size (F(2,31) = 20.57, p<0.001). In good alignment with previous work, our results show that visual span size could explain around 40% of the reading speed variability. Interestingly, our analyses revealed a narrowing of visual span size in our Arabic sample. The results of study 2, suggest that the poor performance in the trigram task is due to poor visual attention capacities in our Arabic readers

“All diseases originate in the gut.” Hippocrates (400 BC) A healthy gut microbiome via the gut-brain-axis (GBA) elevates heart rate variability (HRV), a general measure of health and well-being. A dysbiotic gut microbiome, low in biodiversity and butyrate producers, alters tryptophan metabolism with release of proinflammatory cytokines, predominantly TNF-α, IL-6, and IL-1β. These also characterize chronic inflammation, oxidative stress, and a multitude of diseases, all exhibiting low HRV. Gut dysbiosis upregulates IFN-γ and with it IDO (indoleamine 2,3 dioxygenase). Tryptophan pivots from serotonin synthesis to that of IDO induced kynurenine, increasing the kynurenine to tryptophan ratio (KTR). An elevated KTR is positively linked to neurodegenerative and autoimmune diseases and negatively linked to HRV. Elevated IDO activity is not only enzymatic but also an intracellular signal transducer potentiated by TGF-β. This cytokine is the primary determinant of the TME. Also proposed is the gut-lung dysbiosis concept and consequent degradation of ACE2 (richest in lungs and gut). Leaky gut induced autoantibodies related to G-protein coupled receptors (GPCRs) in combination with increased Ang II further potentiate oxidative stress. Aldosterone and paroxysmal orthostatic tachycardia syndrome (POTS) paradoxes are highlighted in the context of GPCR and gut dysbiosis, and the role of Candida is explored. The triple play of a prebiotic (d-mannose), probiotic (bifidobacteria and lactobacilli), and postbiotic (butyrate) might improve intestinal barrier integrity, oppose entry of GPCR antigens, suppress the inflammatory cytokine triad, balance IFN-γ and TGF-β, suppress oxidative stress, depress KTR, elevate HRV, and extend lifespan and its quality.

Long-span steel structure trusses are widely used in factory buildings, but with the growth of service time and the increase of dynamic load fatigue, a considerable part of the long-span truss with dynamic load appears serious transverse cracks at the bottom of the middle span and oblique deformation of the abdomen in the operation process. The U-shaped cracks at the bottom and belly, as well as the mid-span down deflection of the main truss, reduced the functional function of the factory building truss structure, and had to limit the original crane load, which affected the normal safety and durability of the structure. Therefore, the application principle of the variable axial force cable system in the long-span factory building truss structure and 3D3S software modeling [1] were used. Analyzing and studying the reinforcement method of large-span powerhouse truss can provide practical experience for subsequent similar projects. In view of the above phenomenon, the large-span powerhouse trusses of Hongcheng Powerhouse 1 and No.2 located in Tonglu, Zhejiang Province are used as the research object, and the variable axial force cable method is proposed to strengthen and lift the load. Considering the span of large-span powerhouse truss, the cable system with 22m controlling force of 400kN is proposed to be selected for powerhouse 1, and the cable system with variable axial force of 24m is proposed to be selected for Powerhouse 2. The force model of large-span truss is established by using the finite element method commonly used to analyze the force of truss. Under two working conditions, The influence of reinforcement effect is analyzed and compared from three aspects: stiffness, bearing capacity and stability. And the phenomenon of uneven stress distribution is analyzed. The stress distribution characteristics of each node are understood by simulating the most disadvantageous node plates with the greatest internal force before and after reinforcement.

Modern research applies the Open Science approach that fosters the production and sharing of Open Data according to the FAIR (Findable, Accessible, Interoperable, Reusable) principles. In the geospatial context this is generally achieved through the setup of OGC Web services that implements open standards that satisfies the FAIR requirements. Nevertheless, the requirement of Findability is not fully satisfied by those services since there’s no use of persistent identifiers and no guarantee that the same dataset used for a study can be immutably accessed in a later period: a fact that hinders the replicability of research. This is particularly true in recent years where data-driven research and technological advances have boosted frequent updates of datasets. Here, we review needs and practices, supported by some real case examples, on frequent data or metadata updates in geo-datasets of different data types. Additionally we assess the currently available tools that support data versioning for databases, files and log-structured tables. Finally we discuss challenges and opportunities to enable geospatial web services that are fully FAIR: a fact that would provide, due to the massive use and increasing availability of geospatial data, a great push toward open science compliance with ultimately impacts on the science transparency and credibility.

Barrett’s esophagus (BE) is a premalignant lesion for esophageal adenocarcinoma (EAC). Development of Barrett’s esophagus is caused by biliary reflux that provokes intensive mutagenesis in stem cells of epithelium in distal esophagus and gastro-esophageal junction. Other possible cell origins of Barrett’s esophagus include stem cells of mucosal esophageal glands and their ducts, of stomach, residual embryonic cells and circulating bone marrow stem cells. Classic conception of healing of caustic lesion was replaced by idea of cytokine storm that forms inflammatory microenvironment for phenotypic shift toward intestinal metaplasia of distal esophagus. The review summarizes contemporary concepts of BE and EAC pathogenesis.

Chronological frameworks based on artefact typologies are essential for interpreting the archaeological record, but they inadvertently treat transitions between phases as abrupt events and disregard the temporality of transformation processes within and between individual phases. This study presents an absolute chronological investigation of a dynamic material culture from Early Iron Age urnfields in Denmark. The chronological framework of Early Iron Age in Southern Scandinavia is largely unconstrained by absolute dating, primarily due to it coinciding with the so-called ‘Hallstatt calibration plateau’ (c.750 to 400 cal BC), and it is difficult to correlate it with Central European chronologies due to a lack of imported artefacts. This study applies recent methodological advances in radiocarbon dating and Bayesian chronological modelling, specifically a statistical model for wood-age offsets in cremated bone and presents the first large-scale radiocarbon investigation of regional material culture from Early Iron Age in Southern Jutland, Denmark. Dated material is primarily cremated bone from 111 cremation burials from three urnfields. The study presents absolute date ranges for 16 types of pottery and 15 types of metalwork, which include most of the recognised metalwork types from the period. This provides new insights into gradual change in material culture, when certain artefact types were in production and primary use, how quickly types were taken up and later abandoned, and distinguishing periods of faster and slower change. The study also provides the first absolute chronology for the period, enabling correlation with chronologies from other regions. Urnfields were introduced at the Bronze-Iron Age transformation, which is often assumed to have occurred c.530-500 BC. We demonstrate that this transformation took place in the 7^th century BC, however, which revives the discussion of whether the final Bronze Age period VI should be interpreted as a transitional phase to the Iron Age.

SDG target 12.3 calls for halving food waste at retail, food service, and household by 2030. The food waste index for this purpose includes parts attached to food that are usually removed intentionally ("unavoidable food waste") and allows counting the conversion to animal feed and utilisation as biomaterial as means of reduction. In Japan, the "Food Waste Recycling Law" which has been in effect since 2001, promotes the recycling of food waste generated from businesses, designating feed conversion as top priority. On the other hand, based on the more recent "Food Loss Reduction Promotion Act" of 2019, the government is currently promoting the reduction of avoidable food waste, as to meet the SDG target. Based on statistical sources and interviews with Ministry officers, this paper explains the history and achievements of Japan's 23-year policy based on the Food Recycling Law, as well as the tension between the two legislations.

Among the number of hurdles that the vaccines based in modRNA platforms have been facing, there is now another critical one: immune imprinting which decreases even more the effectiveness of the modRNA Covid vaccines.

The aim of the study was to evaluate the impact of probiotics obtained from agro-industrial substrates fermented with lactic acid bacteria and/or yeasts on the health and changes in the microbiota of the digestive tract of guinea pigs. Eighty male guinea pigs, Kuri breed, 30 days old and 250 g live weight, were randomly selected and divided into four groups of 20 animals each. T0, Control, T1, Lactobacillus acidophilus and L. bulgaricus. T2, Saccharomyces cerevisiae and Kluyveromyces fragilis and T3. L acidophilus, L bulgariccus, S cerevisiae and K. fragilis. T1, T2 and T3 contained molasses-vinasse substrate in their base, the dose administered was 0.75 mL/animal orally. The parameters evaluated were weight gain, occurrence of diarrhea and mortality, blood profile, macroscopic lesions in the digestive tract organs and changes in the microbiota of the stomach, caecum, small and large intestine. Treatments T1, T2 and T3 improved weight gain (p<0.05) and reduced the presence of guinea pigs with diarrhea (p<0.05) and there was no mortality; hematic indices did not vary significantly (p>0.05) between treatments; animals in the control group presented a greater amount (p<0.05) of macroscopic lesions in the digestive tract organs; in the T1, T2 and T3 group there was an improvement in the natural microbiota. It is concluded that the inclusion of microbial additive in young guinea pigs improves intestinal health, consequently, improves weight gain, reduces diarrhea and deaths, and normalizes the natural microbiota of the gastrointestinal tract.

Manipulation of the intestinal microbiome is an emerging area of research, especially in hind-gut fermenters such as the horse. The aim of this study was to determine whether fecal pH can provide a simple and cost-effective tool to document changes in the intestinal metabolome and microbiome following supplementation of feed with an enzyme rich malt extract (ERME). Fecal pH was determined weekly in triplicate using a commercial soil pH meter in 72 Thoroughbred racehorses in training before and during supplementation with ERME (300mls per day divided into two feeds) alongside their regular feeding schedule. No control group was included. Fecal pH increased over the 4 weeks of treatment from 6.20 (6.15-6.24) to 6.40 (6.38-6.44; P&lt;0.0001). Changes were not observed at one-week intervals but were apparent after 2 weeks There was a significant increase in the proportion of horses with a ‘normal’ pH at the end of the study (55%) compared to the start of the study (11%; p&lt;0.001). These data support the further validation of the use of fecal pH in large scale microbiome/metabolome studies in the horse, although comparisons with these outcomes are now warranted.

Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), defines as an idiopathic, chronic, relapsing, inflammatory disease affecting the gastrointestinal tract and leading to chronic damage. Endoscopy with biopsies is considered the gold standard for IBD diagnosis, whereas magnetic resonance (MRI) for CD extension and complication assess-ment. However, the latter are invasive procedures; thus, the need for a reliable, accessible and noninvasive way to perform IBD diagnosis and monitoring in the tight control era, like intestinal ultrasound (IUS) is. Compared to endoscopy and MRI, IUS has shown reliable diagnostic accuracy in assessing CD and UC severity and extension. Performing IUS in a point-of-care setting (POCIUS) can guide the clinician in driving the diagnostic and therapeutic pathway, thus accel-erating clinical decisions. POCIUS performed with pocket devices can represent the future of physical examination in outpatient or inpatient examination. Accordingly, we performed a liter-ature review about the application of IUS in CD and UC diagnosis. Furthermore, we explored the technical aspects of this imaging technique and its application in a point-of-care setting.

Polydatin, a polyphenolic compound sourced from various natural origins, has garnered attention due to its potential anti-tumor properties and low toxicity. This research utilized Molecular Docking methods to investigate the molecular interactions between Polydatin and the Crystal Structure of Human UDP-glucuronic acid decarboxylase (UXS1), aiming to uncover the mechanisms contributing to its anti-tumor effects. The study revealed a substantial binding energy value of approximately -10 kcal/mol for the Polydatin-UXS1 interaction, indicating a robust and favorable binding. This suggests that Polydatin holds significant promise in cancer research, offering insights into its ability to interact with and potentially modulate the activity of UXS1. Moreover, the additional step of predicting toxicity properties using the pKCSM server provides valuable insights into the safety profiles of polydatin ( or piceid). From these results, the parameters for polydatin: —Max. tolerated dose (human),- Oral Rat Acute Toxicity (LD50), and - Oral Rat Chronic Toxicity (LOAEL)—suggest a favorable safety profile.These findings position Polydatin as a compelling candidate for further exploration in cancer research, highlighting both its efficacy and safety considerations.

In the dynamic landscape of the telecommunications industry, understanding and mitigating customer churn is paramount for maintaining competitive advantage and sustaining revenue streams. This comprehensive literature review delves into the intricacies of customer churn prediction, a crucial aspect in fortifying the bond between telecom businesses and their customers. The review methodically analyzes 11 articles published between 2000 and March 2024, spotlighting the strategic role of Customer Relationship Management and the prevalence of high churn rates that necessitate a shift from customer acquisition to retention strategies. Furthermore, the review navigates through the challenges inherent in churn prediction, including the complexities of managing large, imbalanced, and noisy datasets and the intricacies involved in model selection and optimization. Despite these challenges, the paper highlights the superior capability of machine learning techniques in handling complex datasets to provide accurate predictions, albeit acknowledging their practical complexities. The main aim of the study is to provide an overview, serving as a knowledge base for researchers interested in machine learning techniques within the realm of telecommunications.

“Energy” is probably the most important term in science and technology. The reason is energy can be converted while it is overall conserved, and thereby correlates changes of a wide variety. Despite its successful use in many areas over more than a century, an analysis of current literature shows that definitions of what energy is and explanations why it is conserved are inconsistent. With regard to energy forms not even a definition was found, and examples given are often wrong. Looking at two interacting objects in the most simple situations, with energy conservation but without conversion, a consistent understanding of energy and its conservation can be derived. Based on it, the systematic set of energy forms with a clear definition of each is then presented.

Improper lifting measures of long-span spatial steel structures during construction process may delay the construction period and even cause safety accidents. Few studies on long-span spatial steel structures considered time-varying mechanical characteristic during construction process. In order to achieve safe and efficient installation in a long-span spatial steel structure, this research presents a time-varying mechanical analysis of the synchronous and asynchronous integral lifting and a single and interlaced point’s asynchronous integral lifting analysis method of a long-span spatial steel structure. The results showed that in the case of asynchronous lifting of single point, the displacement influence on other members is related to the distance. The closer the distance from the lifting point, the greater the influence. In asynchronous integral lifting, the lifting point with large lifting force is first installed to the specified position, and the lifting point with small lifting force is installed to the specified position.

Background: While the clinical factors of the post-COVID-19 condition (PCC) are becoming clearer, the economic implications remain uncertain, posing a challenge to healthcare professionals in terms of understanding and managing this emerging phenomenon. This article aims to investigate the demographic and clinical characteristics of PCC patients and quantify the economic impact of their healthcare resource utilisation. Methods: A retrospective and case-control observational study was conducted, comparing the case group of PCC population before and after diagnosis with a control group. Demographic and clinical variables were analysed with the objective of describing the population. Economic analysis was performed to evaluate the resource costs in procedures and primary, secondary (both outpatient and inpatient) and emergency care. Findings: PCC patients (N=341) exhibited older age and elevated cardiovascular risk factors compared to controls (N=49,078). There were differences in the socio-economic distribution between male and female patients in the PCC patients. Hypertension and diabetes mellitus type 2 were the most common chronic diseases observed among the case patients. Economic analysis revealed that PCC patients were approximately four times as costly as control patients, with increased utilisation of healthcare resources. However, post-diagnosis PCC patients showed a reduction in costs, primarily driven by decreased primary care visits and hospitalisations. Conclusion: Coordinated care management for PCC patients is associated with reduced costs and improved healthcare resource utilisation. Further research is warranted to investigate long-term health outcomes and establish causal relationships between COVID-19 sequelae and healthcare resource utilisation.

Pathogens such as bacteria, fungi and viruses are important components of soil and aquatic communities, where they can benefit from decaying and living organic matter, and may opportunistically infect human and animal hosts. One-third of human infectious diseases is constituted by sapronotic disease agents that are natural inhabitants of soil or aquatic ecosystems. They are capable of existing and reproducing in the environment outside of the host for extended periods of time. However, as ecological research on sapronosis is infrequent and epidemiological models are even rarer, very little information is currently available. Their importance is overlooked in medical and veterinary research, as well as the relationships between free environmental forms and those that are pathogenic. Here, using dynamical models in realistic aquatic metacommunity systems, we analyze sapronosis transmission, using the human pathogen Mycobacterium ulcerans that is responsible for Buruli ulcer. Our work constitutes the first set of metacommunity models of sapronotic disease transmission, and is highly flexible for adaptation to other types of sapronosis. The importance of sapronotic agents on animal and human disease burden needs better understanding and new models of sapronosis disease ecology to guide the management and prevention of this important group of pathogens.

Despite available global efforts and funding, Tuberculosis (TB) continues to affect a considerable number of patients worldwide. Policy makers and stakeholders set clear goals to reduce TB incidence and mortality, but the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) complicate the reach of these goals. Drug-resistance TB needs to be diagnosed rapidly and accurately to effectively treat patients, prevent the transmission of MDR-TB, minimise mortality, reduce treatment costs and avoid unnecessary hospitalisations. In this narrative review, we provide a comprehensive overview of laboratory methods for detecting drug resistance in MTB, focusing on phenotypic, molecular and other drug susceptibility testing (DST) techniques. We found a large variety of methods used, with the BACTEC MGIT 960 being the most common phenotypic DST and the Xpert MTB/RIF being the most common molecular DST. We emphasise the importance of integrating phenotypic and molecular DST to address issues like resistance to new drugs, heteroresistance, mixed infections and low-level resistance mutations. Notably, most of the analysed studies adhered to the outdated definition of XDR-TB and did not consider the pre-XDR definition, thus posing challenges in aligning diagnostic methods with the current landscape of TB resistance.