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In the last decade, most of the evidence on the clinical benefits of including cruciferous foods in the diet has been focused on the content of glucosinolates (GSL) and their corresponding isothiocyanates (ITC), and mercapturic acid pathway metabolites, based on their capacity to modulate clinical, biochemical, and molecular parameters. The present systematic review summarizes findings of human studies regarding the metabolism and bioavailability of GSL and ITC, providing a comprehensive analysis that will help guide future research studies and facilitate the consultation of the latest advances in this booming and less profusely researched area of GSL for food and health. The literature search was carried out in Scopus, PubMed and the Web of Science, under the criteria of including publications centered on human subjects and the use of Brassicaceae foods in different formulations (including extracts, beverages, and tablets), as significant sources of bioactive compounds, in different types of subjects, and against certain diseases. Twenty-eight human intervention studies met inclusion criteria, which were classified into three groups depending on the dietary source. This review summarizes recent studies that provided interesting contributions, but also uncovered the many potential venues for future research on the benefits of consuming cruciferous foods in our health and well-being. The research will continue to support the inclusion of GSL-rich foods and products for multiple preventive and active programs in nutrition and well-being. [ABSTRACT FROM AUTHOR]

Obesity and related metabolic health issues are a growing human threat, with many theories regarding its causes. In swine, physiologically alike to humans, considerable knowledge on obesity mechanisms has been accumulated. Calorie counting is the basis for managing swine diets and applied with great accuracy. Epigenetic programing predisposes pigs to insulin insensitivity, but pigs seem to sense this insensitivity and consequently eat less, preventing obesity. Pigs naturally prefer to eat small breakfasts and large dinners. Deviating from this eating pattern or providing diets with a high glycemic burden can trigger obesity; however, pigs will restrict food intake to prevent serious obesity. Interestingly, in practice, problems with obesity are rarely seen, even when pigs are fed poorly timed diets similar to junk food, likely because swine diets are balanced for every nutrient. Indeed, feeding pigs diets deficient in micronutrients does trigger obesity. For humans, several micronutrient requirements have not been set officially, and diets optimized for all micronutrients are rarely provided. In conclusion, various obesity triggers are being debated for humans, which have been proven in swine. Obesity problems in pigs are nevertheless less excessive, likely because pigs recognize unhealthy eating practices and consequently reduce food intake to avoid serious complications. Finally, swine diets are normally balanced for all nutrients, which may be an important practice to prevent obesity, from which human health could greatly benefit. [ABSTRACT FROM AUTHOR]

In the 1970s, Eucommia leaf tea, known as Tochu-cha in Japanese, was developed from roasted Eucommia leaves in Japan and is considered as a healthy tea. The antihypertensive, diuretic, anti-stress, insulin resistance improving, and anti-obesity effects of Eucommia leaf extract have been reported. However, the identification and properties of the active components as well as the underlying mechanism of action are largely unknown. In this review, we summarize studies involving the oral administration of geniposidic acid, a major iridoid component of Eucommia leaf extract which increases plasma atrial natriuretic peptide (ANP) on the atria of spontaneously hypertensive rats (SHR) by activating the glucagon-like peptide-1 receptor (GLP-1R). To achieve the antihypertensive effects of the Eucommia leaf extract through ANP secretion in humans, combining a potent cyclic adenosine monophosphate phosphodiesterase (cAMP-PDE) inhibitor, such as pinoresinol di-β-d-glucoside, with geniposidic acid may be necessary. Changes in the gut microbiota are an important aspect involved in the efficacy of asperuloside, another component of the Eucommia leaf extract, which improves obesity and related sequelae, such as insulin resistance and glucose intolerance. There are species differences of mechanisms associated with the antihypertensive and anti-obesity effects between rodents and humans, and not all animal test results are consistent with that of human studies. This review is focused on the mechanisms in antihypertensive and anti-obesity effects of the Eucommia leaf extract and summarizes the differences of mechanisms in their effects on rodents and humans based on our studies and those of others. [ABSTRACT FROM AUTHOR]

The risk stratification of patients with atrial fibrillation (AF) for subsequent cardiovascular events could help in guiding prevention strategies. In this study, we aimed at investigating circulating microRNAs as prognostic biomarkers for major adverse cardiovascular events (MACE) in AF patients. We conducted a three-stage nested case–control study within the framework of a prospective registry, including 347 AF patients. First, total small RNA-sequencing was performed in 26 patients (13 cases with MACE) and the differential expression of microRNAs was analyzed. Seven candidate microRNAs with promising results in a subgroup analysis on cardiovascular death were selected and measured via using RT-qPCR in 97 patients (42 cases with cardiovascular death). To further validate our findings and investigate broader clinical applicability, we analyzed the same microRNAs in a subsequent nested case–control study of 102 patients (37 cases with early MACE) by using Cox regression. In the microRNA discovery cohort (n = 26), we detected 184 well-expressed microRNAs in circulation without overt differential expression between the cases and controls. A subgroup analysis on cardiovascular death revealed 26 microRNAs that were differentially expressed at a significance level < 0.05 (three of which with an FDR-adjusted p-value <0.05). We, therefore, proceeded with a nested case–control approach (n = 97) focusing on patients with cardiovascular death and selected, in total, seven microRNAs for further RT-qPCR analysis. One microRNA, miR-411-5p, was significantly associated with cardiovascular death (adjusted HR (95% CI): 1.95 (1.04–3.67)). Further validation (n = 102) in patients who developed early MACE showed similar results (adjusted HR (95% CI) 2.35 (1.17–4.73)). In conclusion, circulating miR-411-5p could be a valuable prognostic biomarker for MACE in AF patients. [ABSTRACT FROM AUTHOR]

Recombinant human erythropoietin (rHuEPO) is one of the most effective drugs for the treatment of anemia in patients with chronic kidney disease. However, EPO-resistance is an important contributor to the increased risk of adverse effects. We previously showed that EPO treatment could induce precursor cell depletion, resulting in EPO-resistance. We further found that the combination of EPO with romiplostim, a thrombopoietin receptor agonist that can stimulate the expansion of hematopoietic stem cells, can treat EPO-resistance. In this study, we performed interspecies pharmacodynamic (PD) scaling of this combination therapy for human dose prediction. The pharmacokinetic parameters of both rHuEPO and romiplostim in humans were obtained from previous studies. The PD parameters obtained in rats were scaled to humans using allometric equations. The relationship between PD parameters of the megakaryocyte lineage from rats, monkeys, and humans was in agreement with those from the literature on allometric scaling. The PD response was translated to humans based on allometric scaling and agreed with the observed data. These parameters were used to simulate hemoglobin and platelet response in humans. RHuEPO 50 IU/kg thrice weekly and romiplostim 1 μg/kg once every 4 weeks from the second week is the recommended combination dosing regimen according to the model prediction. Our work successfully scaled the PD of rHuEPO and romiplostim monotherapy from rats to humans. The predicted dosing regimen of each drug in the combination therapy is less intensive than the approved starting dose of each drug, which supports additional evaluations of the combination therapy in humans. [ABSTRACT FROM AUTHOR]

The portal venous system is a network of vessels that carry blood from the capillary beds of the major abdominal organs to the liver. During embryology, the portal venous system can develop aberrantly, leading to vascular connections between the portal and systemic venous circulation known as portosystemic shunts. The purpose of this comparative review with a few short representative case reports was to present the similarities and differences in portosystemic shunts in humans and small animals and their radiologic evaluation. Aberrant vascular connections between the portal and systemic venous circulation enable portal blood to bypass metabolism and detoxification in the liver, leading to significant clinical implications. Portosystemic shunts are very rare in humans, but these connections are much more common in small animals, affecting up to 0.6% of small animals. Portosystemic shunts can be congenital or acquired and are divided into intrahepatic and extrahepatic types. Because of its ability to accurately assess abdominal structures, large vessels, and their flow dynamics without anesthesia, ultrasonography has become the first imaging modality employed for the diagnostic evaluation of portosystemic shunts in both humans and small animals. This is usually followed by contrast-enhanced computed tomographic angiography in order to better define the exact shunt anatomy and to plan treatment. It is important to understand the embryology, anatomy, pathology, and pathophysiology of portosystemic shunts in order to understand the findings of radiologic imaging and to initiate appropriate treatment. [ABSTRACT FROM AUTHOR]

Background: The various mechanisms involved in peripheral nerve regeneration, induced by exercise and electrical nerve stimulation, are still unclear. Objective: The aim of this review was to summarize the influence of physical exercise and/or electrical stimulation on peripheral nerve repair and regeneration and the variation of impact of intervention depending on timing, as well as kind and dosage of the intervention. A literature survey was conducted on PubMed, Scopus, and Web of Science, between February 2021 to July 2021, with an update in September 2022. Methodology: The literature search identified 101,386 articles with the keywords: "peripheral nerve" OR "neuropathy" AND "sprouting" OR "neuroapraxia" OR "axonotmesis" OR "neurotmesis" OR "muscle denervation" OR "denervated muscle" AND "rehabilitation" OR "physical activity" OR "physical exercise" OR "activity" OR "electrical stimulation". A total of 60 publications were included. Eligible studies were focused on evaluating the process of nerve repair (biopsy, electromyographic parameters or biomarker outcomes) after electrical stimulation or physical exercise interventions on humans or animals with peripheral sensory or motor nerve injury. Synthesis: This study shows that the literature, especially regarding preclinical research, is mainly in agreement that an early physical program with active exercise and/or electrical stimulation promotes axonal regenerative responses and prevents maladaptive response. This was evaluated by means of changes in electrophysiological recordings of CMAPs for latency amplitude, and the sciatic functional index (SFI). Furthermore, this type of activity can cause an increase in weight and in muscle fiber diameter. Nevertheless, some detrimental effects of exercising and electrical stimulation too early after nerve repair were recorded. Conclusion: In most preclinical studies, peripheral neuropathy function was associated with improvements after physical exercise and electrical stimulation. For humans, too little research has been conducted on this topic to reach a complete conclusion. This research supports the need for future studies to test the validity of a possible rehabilitation treatment in humans in cases of peripheral neuropathy to help nerve sprouting. [ABSTRACT FROM AUTHOR]

Selenium (Se) is an essential trace element for humans and animals. Its necessity for plants is still under examination. Due to the contradictory nature of Se and its significance, it has received much interest in recent years. Se deficiency can be harmful to humans, yet almost a billion people are deficient. Its deficiency has been associated with cancers, impairment of organs, and a number of other ailments. The biofortification of plants and livestock is a guaranteed practice to increase human selenium consumption. Strategies such as foliar spraying, the direct application of Se in plants and Se feed, and injections in livestock have been employed. Se biofortification has been shown to have additional beneficial effects in plants and livestock. In plants, it has been reported to mitigate different types of stress and increase yield. In animal biofortification, Se has been shown to reduce the detrimental effects of ailments and promote healthy growth. Se biofortification, nevertheless, confronts a number of difficulties. For instance, the bulk of biofortified products must be prepared before consumption, lowering the Se concentration. The objective of this review is to convey the current understanding of the Se biofortification of plants and animals, as well as its difficulties, taking into account both the detrimental consequences of Se deficiency and benefits of Se biofortification. [ABSTRACT FROM AUTHOR]

Background: visceral leishmaniasis (VL) is a critical public health problem in over ninety countries. The control measures adopted in Brazil have been insufficient when it comes to preventing the spread of this overlooked disease. In this context, a precise diagnosis of VL in dogs and humans could help to reduce the number of cases of this disease. Distinct studies for the diagnosis of VL have used single recombinant proteins in serological assays; however, the results have been variable, mainly in relation to the sensitivity of the antigens. In this context, the development of multiepitope-based proteins could be relevant to solving such problem. Methods: a chimeric protein (rMELEISH) was constructed based on amino acid sequences from kinesin 39 (k39), alpha-tubulin, and heat-shock proteins HSP70 and HSP 83.1, and tested in enzyme-linked immunosorbent (ELISA) for the detection of L. infantum infection using canine (n = 140) and human (n = 145) sera samples. Results: in the trials, rMELEISH was able to discriminate between VL cases and cross-reactive diseases and healthy samples, with sensitivity and specificity values of 100%, as compared to the use of a soluble Leishmania antigenic extract (SLA). Conclusions: the preliminary data suggest that rMELEISH has the potential to be tested in future studies against a larger serological panel and in field conditions for the diagnosis of canine and human VL. [ABSTRACT FROM AUTHOR]

We present the case of a 60-year-old man who was diagnosed with a subcutaneous nodule on the upper eyelid of his left eye. The patient reported multiple mosquito bites during numerous work trips to Ukraine. Histopathological examination of the nodule isolated during surgery suggested Dirofilaria repens infestation. The infection was brought to Poland from the territory of Ukraine. Ophthalmologists must be aware of uncommon presentations of parasitic infestations when they consider infections of the ocular adnexa. [ABSTRACT FROM AUTHOR]

Although antibiotic resistance is a major issue for both human and animal health, very few studies have investigated the role of the bacterial host spectrum in its dissemination within natural ecosystems. Here, we assessed the prevalence of methicillin resistance among Staphylococcus aureus (MRSA) isolates from humans, non-human primates (NHPs), micromammals and bats in a primatology center located in southeast Gabon, and evaluated the plausibility of four main predictions regarding the acquisition of antibiotic resistance in this ecosystem. MRSA strain prevalence was much higher in exposed species (i.e., humans and NHPs which receive antibiotic treatment) than in unexposed species (micromammals and bats), and in NHP species living in enclosures than those in captivity—supporting the assumption that antibiotic pressure is a risk factor in the acquisition of MRSA that is reinforced by the irregularity of drug treatment. In the two unexposed groups of species, resistance prevalence was high in the generalist strains that infect humans or NHPs, supporting the hypothesis that MRSA strains diffuse to wild species through interspecific transmission of a generalist strain. Strikingly, the generalist strains that were not found in humans showed a higher proportion of MRSA strains than specialist strains, suggesting that generalist strains present a greater potential for the acquisition of antibiotic resistance than specialist strains. The host spectrum is thus a major component of the issue of antibiotic resistance in ecosystems where humans apply strong antibiotic pressure. [ABSTRACT FROM AUTHOR]

Background: There is a need for long-term evidence of immediate function dental implants inserted in grafted bone. The aim of this retrospective study was to investigate the outcome of full-arch rehabilitations supported by implants in grafted bone. Methods: Thirty-six patients (women: 24; men: 12; average age: 53.5 years) were included (225 implants). Primary outcome measure: to assess implant cumulative success rates evaluated through life tables. Secondary outcome measures: to evaluate implant and prosthetic survival, marginal bone loss, and the incidence of both biological and mechanical complications. Results: Twenty-five implants were unsuccessful giving a dental implant CS rate of 88.1% at 14 years and a 76.8% survival estimation (Kaplan–Meier) using the patient as the unit of analysis. No prosthesis was lost. Average MBL at 10 years was 2.01 mm. The incidence of biological complications was 36%, with smoking affecting it significantly (p < 0.001). The incidence of mechanical complications was 86.1% (45.2% and 54.8% in provisional and definitive prosthesis, respectively. Conclusions: The rehabilitation of atrophic maxillae through dental implants in immediate function inserted in grafted bone is a valid treatment alternative, despite the relevant rate of implant failures and incidence of complications. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of the study was to verify whether the human DR-ELISA for the detection of antibodies against the agent of COVID-19 can be applied in cats, as well as to assess the risk factors that determine the spread of the virus among the cat population in Bulgaria. Therefore, 92 serum samples collected from 68 domestic and 24 stray cats were analyzed and compared with a multi-species ELISA kit. The results showed 83.33% positive results in stray cats and 41.18% in domestic cats, respectively, by both assays. Cats under 7 years had a five times higher risk than those over 7 years. The risk was seven times higher for stray cats than for domestic cats. Additionally, the results indicate the highest risk for cats in villages. This study demonstrates that human DR-ELISA may be helpful in monitoring the circulation of the virus in cats. The aim of this study was to verify whether the human DR-ELISA for the detection of anti-SARS-CoV-2 antibodies can be applied in cats, and to assess the risk factors that determine the spread of the virus among the cat population in Bulgaria. The study included 92 serum samples collected from 68 domestic and 24 stray cats aged from 3 months to 20 years of age in the period of January–June 2021. The samples originated from three regions in Bulgaria and from three places of inhabitance. DR-ELISA based on peroxidase-labeled SARS-CoV-2 N protein was employed to detect IgA, IgG and IgM antibodies in the samples. Subsequently, the results were compared with a commercially available multi-species ELISA kit. There was high seroprevalence (83.33%) in stray cats and 41.18% in domestic cats, confirmed by the human and veterinary ELISA kit. The positive cases in the regional cities were 42.86%, in small towns 50% and in villages 78.26%. Cats under 7 years had a five times higher risk than those over 7 years (p = 0.001). The risk was seven times higher for stray cats than for domestic cats (p = 0.001). In addition, the results indicate that the risk was the highest for cats in villages (p = 0.006) compared to cats in other places of inhabitance. This study demonstrates that human DR-ELISA may be successfully applied to monitor the circulation of SARS-CoV-2 in cats and other susceptible species. Cats might serve as sentinel animals for tracking the virus in nature and in inhabited areas (strays) and to discover asymptomatic cases in humans/owners. [ABSTRACT FROM AUTHOR]

Cystic echinococcosis (CE), or hydatid cyst disease (HCD), is a zoonosis of significant importance caused by the cestode of Echinococcus granulosus sensu lato (s. l.) that affects mainly nomadic populations and has substantial economic consequences. Due to the 76% rural and nomadic population, Baluchistan is a highly endemic region in Pakistan for CE; however, it has not yet been investigated for CE. For this purpose, this study was carried out to investigate the molecular epidemiology of CE in this region. In total, 23 human hydatid cyst samples were collected from tertiary health care units in Baluchistan and processed for DNA extraction, which was then followed by sequencing of the cox1 mitochondrial gene of all 23 collected samples, genotyping, and phylogenetic and haplotype analysis. Most subjects were livestock owners (39.13%) in rural settings (73.91%). Most patients (73.19%) were pet owners (dogs) and used water from open sources for drinking. The liver was the most affected organ (52.17%), followed by the lungs (17.39%). Sequence analysis based on the cox1 gene revealed that EG genotype 1 (G1) was the most prevalent (56.52%), followed by G3 (34.78%), while some samples (8.7%) were identified as the Echinococcus canadensis (G6/7) genotype. A total of five haplotypes were detected with high haplotype diversity (0.80) and low nucleotide diversity (0.033). Phylogenetic analysis revealed two diverse sub-clades, each of G1 and G3 isolates from Baluchistan, that were evolutionarily related to previously reported G1 and G3 isolates from Pakistan and China. On the other hand, the G6/7 isolates of this study were evolutionarily identical to the already reported G6/7 isolates from Pakistan, Turkey, and Kazakhstan. This study concludes that diverse G1 and G3 EG isolates are present in this part of Pakistan, while the G6/G7 genotype was reported for the first time from Baluchistan. [ABSTRACT FROM AUTHOR]

Pathogenic species of Legionella can infect human alveolar macrophages through Legionella-containing aerosols to cause a disease called Legionellosis, which has two forms: a flu-like Pontiac fever and severe pneumonia named Legionnaires' disease (LD). Legionella is an opportunistic pathogen that frequently presents in aquatic environments as a biofilm or protozoa parasite. Long-term interaction and extensive co-evolution with various genera of amoebae render Legionellae pathogenic to infect humans and also generate virulence differentiation and heterogeneity. Conventionally, the proteins involved in initiating replication processes and human macrophage infections have been regarded as virulence factors and linked to pathogenicity. However, because some of the virulence factors are associated with the infection of protozoa and macrophages, it would be more accurate to classify them as survival factors rather than virulence factors. Given that the molecular basis of virulence variations among non-pathogenic, pathogenic, and highly pathogenic Legionella has not yet been elaborated from the perspective of virulence factors, a comprehensive explanation of how Legionella infects its natural hosts, protozoans, and accidental hosts, humans is essential to show a novel concept regarding the virulence factor of Legionella. In this review, we overviewed the pathogenic development of Legionella from protozoa, the function of conventional virulence factors in the infections of protozoa and macrophages, the host's innate immune system, and factors involved in regulating the host immune response, before discussing a probably new definition for the virulence factors of Legionella. [ABSTRACT FROM AUTHOR]

Simple Summary: The assessment of differences between sexes (sexual dimorphism) in tooth formation allows for a better understanding of the developmental processes that contribute to phenotypical variations. Here, we tested for sexual dimorphism in the absence of third molar formation (agenesis) in modern humans with and without agenesis of teeth other than the third molars. No sexual dimorphism was detected in the patterns or the severity of third molar agenesis in any group. When teeth other than the third molars were absent, both sexes showed third molar agenesis and bilateral occurrence more often. There was no sexual dimorphism in the patterns or the severity of third molar agenesis, despite the higher vulnerability compared to other teeth. Moreover, there was no sexual dimorphism in single tooth agenesis with regard to any tooth. This indicates that the third molars are more often and more globally affected by genetic or epigenetic factors involved in tooth agenesis, with no differences between sexes. This is consistent with the evolutionary trend in humans towards a reduced molar number. In preadolescent patients with multiple tooth agenesis, the higher possibility of additional third molar agenesis should be considered during dental treatment planning. Sexual dimorphism in the human dentition is of interest from a developmental, evolutionary, and clinical point of view. Here, we investigated sexual dimorphism in third molar agenesis patterns and severity in non-syndromic white European individuals with (group A: 303 individuals) and without agenesis (group B: 303 individuals) of teeth other than the third molars. There was no sexual dimorphism in the patterns or the severity of third molar agenesis within groups. Both sexes showed a higher number of third molar agenesis per individual in group A than in group B. The most common third molar agenesis pattern was that of no third molars. For both females and males, bilateral third molar agenesis was approximately three times more frequent in group A than in group B (p < 0.001), whereas no difference was detected for unilateral agenesis. These findings indicate a strong genetic control of the developmental process of tooth formation, with any disruptions affecting both sexes in a similar manner. Overall, the higher vulnerability of third molar formation could be associated with the evolutionary trend in humans towards a reduced number of molar teeth, which seems to show no sex-related differences. [ABSTRACT FROM AUTHOR]

Spastic type cerebral palsy (CP) is a complex neuromuscular disorder that involves altered skeletal muscle microanatomy and growth, but little is known about the mechanisms contributing to muscle pathophysiology and dysfunction. Traditional genomic approaches have provided limited insight regarding disease onset and severity, but recent epigenomic studies indicate that DNA methylation patterns can be altered in CP. Here, we examined whether a diagnosis of spastic CP is associated with intrinsic DNA methylation differences in myoblasts and myotubes derived from muscle resident stem cell populations (satellite cells; SCs). Twelve subjects were enrolled (6 CP; 6 control) with informed consent/assent. Skeletal muscle biopsies were obtained during orthopedic surgeries, and SCs were isolated and cultured to establish patient–specific myoblast cell lines capable of proliferation and differentiation in culture. DNA methylation analyses indicated significant differences at 525 individual CpG sites in proliferating SC–derived myoblasts (MB) and 1774 CpG sites in differentiating SC–derived myotubes (MT). Of these, 79 CpG sites were common in both culture types. The distribution of differentially methylated 1 Mbp chromosomal segments indicated distinct regional hypo– and hyper–methylation patterns, and significant enrichment of differentially methylated sites on chromosomes 12, 13, 14, 15, 18, and 20. Average methylation load across 2000 bp regions flanking transcriptional start sites was significantly different in 3 genes in MBs, and 10 genes in MTs. SC derived MBs isolated from study participants with spastic CP exhibited fundamental differences in DNA methylation compared to controls at multiple levels of organization that may reveal new targets for studies of mechanisms contributing to muscle dysregulation in spastic CP. [ABSTRACT FROM AUTHOR]

Simple Summary: Several central and peripheral nervous system disorders are responsible for neurogenic bladder (NB) in dogs and cats. In this review, the authors summarized the neurological diseases causing neurogenic bladder comparable with human medicine. For the first time, the authors provided an overview of the epidemiology, prevalence, clinical findings, diagnosis and prognosis of the NB in dogs and cats compared with humans. Lower urinary tract disease (LUTD) includes abnormalities in the structure and function of the bladder and the urethra. LUTD caused by neurological disease is defined neurogenic bladder (NB). The integrity of the central nervous system (CNS) and peripheral nervous system (PNS) is required to explicate normal micturition, maintaining the proper function of bladder and urethra. The location and type of neurological lesions influence the pattern of clinical manifestations, potential treatment, and prognosis. Though, in dogs and cats, spinal cord injury is considered mainly responsible for bladder and/or urethra incompetence, other disorders, congenital or acquired, involving CNS or PNS, could play a role in NB. In veterinary medicine, the information about the epidemiology, prevalence, etiopathogenesis, diagnosis and treatment of NB are scattered. The aim of this study is to provide an overview of the epidemiology, prevalence, clinical findings, diagnosis and prognosis for NB in dogs and cats compared with humans. [ABSTRACT FROM AUTHOR]

The aim of this study is to define, for the first time, human methylone and HMMC plasma pharmacokinetics following controlled administration of 50–200 mg methylone to 12 male volunteers. A new LC-MS/MS method was validated to quantify methylone, MDMA, and their metabolites in plasma. The study was a randomized, cross-over, double-blinded and placebo-controlled study, with a total of 468 plasma samples collected. First, 10 µL of MDMA-d5, MDA-d5 and methylone-d3 internal standards were added to 100 µL of plasma. Two mL of chloroform and ethyl acetate 9:1 (v/v) were then added, mixed well and centrifuged. The supernatant was fortified with 0.1 mL acidified methanol and evaporated under nitrogen. Samples were reconstituted with a mobile phase and injected into the LC-MS/MS instrument. The method was fully validated according to OSAC guidelines (USA). Methylone plasma concentrations increased in a dose-proportional manner, as demonstrated by the increasing maximum concentration (Cmax) and area under the curve of concentrations (AUC). Methylone Cmax values were reported as 153, 304, 355 and 604 ng/mL, AUC0–24 values were reported as 1042.8, 2441.2, 3524.4 and 5067.9 h·ng/mL and T1/2 values as 5.8, 6.4, 6.9 and 6.4 h following the 50, 100, 150 and 200 mg doses, respectively. Methylone exhibited rapid kinetics with a Tmax of 1.5 h for the 50 mg dose and 2 h approximately after all the other doses. HMMC exhibited faster kinetics compared to methylone, with a Cmax value that was 10–14-fold lower and an AUC0–24 value that was 21–29-fold lower. Methylone pharmacokinetics was linear across 50–200 mg oral doses in humans, unlike the previously described non-linear oral MDMA pharmacokinetics. An LC-MS/MS method for the quantification of methylone, MDMA and their metabolites in human plasma was achieved. Methylone exhibited linear pharmacokinetics in humans with oral doses of 50–200 mg. [ABSTRACT FROM AUTHOR]

Time-restricted feeding (TRF) and Ramadan fasting (RF) have been recently associated with several health outcomes. However, it is not yet clear if they are superior to existing treatments in terms of glucose metabolism, insulin action, and weight loss. This review aims to summarize the current data on the effects of these regimes on body weight, body composition, and glycemia. An electronic search was conducted in PUBMED and SCOPUS databases up to August 2022. Twenty-four records met the inclusion criteria and underwent a risk-of-bias assessment. The main outcomes were: (a) TRF may result in moderate weight loss in individuals with overweight/obesity; when TRF is combined with caloric restriction, weight loss is >5% of the initial body weight, (b) 14 h of fasting may be as effective as 16 h in terms of weight loss, and (c) TRF may lead to improved insulin sensitivity and glycemic responses/variability throughout the day in individuals with overweight/obesity. Concerning RF, only two studies were available and thus, conclusions were not drawn. TRF may be an effective nutritional approach for weight loss, and the amelioration of glycemic control and insulin sensitivity in individuals with overweight/obesity. However, more long-term, well-designed studies are needed. [ABSTRACT FROM AUTHOR]

This paper describes one healthcare system's approach to strategically deploying genetic specialists and pharmacists to support the implementation of a precision medicine program. In 2013, Sanford Health initiated the development of a healthcare system-wide precision medicine program. Here, we report the necessary staffing including the genetic counselors, genetic counseling assistants, pharmacists, and geneticists. We examined the administrative and electronic medical records data to summarize genetic referrals over time as well as the uptake and results of an enterprise-wide genetic screening test. Between 2013 and 2020, the number of genetic specialists employed at Sanford Health increased by 190%, from 10.1 full-time equivalents (FTEs) to 29.3 FTEs. Over the same period, referrals from multiple provider types to genetic services increased by 423%, from 1438 referrals to 7517 referrals. Between 2018 and 2020, 11,771 patients received a genetic screening, with 4% identified with potential monogenic medically actionable predisposition (MAP) findings and 95% identified with at least one informative pharmacogenetic result. Of the MAP-positive patients, 85% had completed a session with a genetics provider. A strategic workforce staffing and deployment allowed Sanford Health to manage a new genetic screening program, which prompted a large increase in genetic referrals. This approach can be used as a template for other healthcare systems interested in the development of a precision medicine program. [ABSTRACT FROM AUTHOR]

Background: The lack of a national table informing the caffeine contents in foods, drinks, dietary supplements, and medications sold in Brazil added to the noncompulsory disclosure of caffeine contents on labels of food products makes it difficult to estimate caffeine consumption in the Brazilian population. Therefore, this study aimed to develop the Brazilian Caffeine Content Table (BraCaffT). Methods: A systematic search for caffeine levels in foods, drinks, recipes, supplements, and medications was performed through a literature review, afterward collecting data from the United States Department of Agriculture Food Data Central, information from manufacturers' and websites, and the Brazilian official medication guide. Subsequently, data systematization was performed in a spreadsheet with standardized values presented in mg of caffeine per 100 g or 100 mL of food or drink and a capsule or pill for medications and some dietary supplements. Results: The BraCaffT presents 57 items, divided into 11 categories: coffees, teas and infusions, cocoa powder, chocolates, cocoa-based beverages, desserts, soft drinks, energy drinks, guaraná powder, dietary supplements, and medications. Conclusions: The BraCaffT emerges as an instrument of great relevance and wide applicability in clinical contexts, in academic research, and as a database for the Brazilian population to better understand the amounts of caffeine in foods, drinks, dietary supplements, and medications consumed daily favoring a safe intake. [ABSTRACT FROM AUTHOR]

Simple Summary: Periodontal disease represents a worldwide health problem. Human periodontal pathogens such as Treponema denticola, Porphyromonas gingivalis, Tannerella forsythia and Aggregatibacter actinomycetemcomitans are the cause of inflammatory response resulting in periodontitis. Porphyromonas gulae is mostly involved in periodontitis in dogs; however, it is not a common pathogen in humans. This study deals with the prevalence of periodontal pathogens in Slovak patients with periodontitis. Furthermore, based on the previous findings of animal-to-human transmission of periodontal pathogens, this study also assesses the possible bacterial transmission between animals and their owners. The highest prevalence in Slovak patients amongst the monitored periodontal pathogens had T. forsythia. In regard to the limited information available on T. forsythia, antibiotic sensitivity of this bacterium was evaluated. Most of the T. forsythia isolates were susceptible to antibiotics, namely amoxicillin-clavulanic acid, clindamycin and moxifloxacin, while they were resistant to metronidazole. Moreover, the transmission of P. gulae between animals and their owners was confirmed. Based on the similarity of P. gulae with human P. gingivalis, there arises the question as to whether P. gulae can also be involved in the periodontitis pathogenesis in humans. However, more studies are required for further clarification. Oral health and diseases are greatly influenced by oral bacteria. During dysbiosis, bacterial composition changes, which can lead to periodontitis. Periodontitis in humans is associated with periodontal pathogens such as Treponema denticola, Porphyromonas gingivalis, Tannerella forsythia and Aggregatibacter actinomycetemcomitans. Animal-to-human transmission of some of these pathogens has also been reported. The aim of this study was to evaluate the prevalence of periodontal pathogens in Slovak patients and to assess the possible risk of transmission of these pathogens from animals to their owners. The presence of periodontal pathogens in dental plaque was monitored by PCR. Amplified products were analysed using Sanger sequencing. T. forsythia isolates were assessed for the susceptibility to different antibiotics using the disk diffusion method. In humans, T. denticola, P. gingivalis, T. forsythia and A. actinomycetemcomitans were present in 69.23%, 69.23%, 100% and 84.62%, respectively. Most isolates of T. forsythia were susceptible to amoxicillin-clavulanic acid, clindamycin and moxifloxacin, but they were resistant to metronidazole. The transmission of T. forsythia from animals to their owners was not proven based on sequence analysing. On the other hand, transmission of Porphyromonas gulae was confirmed, but the risk of its involvement in the pathogenesis of periodontitis in humans must be further investigated. [ABSTRACT FROM AUTHOR]

The biogenetic law (recapitulation law) states that ontogenesis recapitulates phylogenesis. However, this law can be distorted by the modification of development. We showed the recapitulation of phylogenesis during the differentiation of various cell types, using a meta-analysis of human single-cell transcriptomes, with the control for cell cycle activity and the improved phylostratigraphy (gene dating). The multipotent progenitors, differentiated from pluripotent embryonic stem cells (ESC), showed the downregulation of unicellular (UC) genes and the upregulation of multicellular (MC) genes, but only in the case of those originating up to the Euteleostomi (bony vertebrates). This picture strikingly resembles the evolutionary profile of regulatory gene expansion due to gene duplication in the human genome. The recapitulation of phylogenesis in the induced pluripotent stem cells (iPSC) during their differentiation resembles the ESC pattern. The unipotent erythroblasts differentiating into erythrocytes showed the downregulation of UC genes and the upregulation of MC genes originating after the Euteleostomi. The MC interactome neighborhood of a protein encoded by a UC gene reverses the gene expression pattern. The functional analysis showed that the evolved environment of the UC proteins is typical for protein modifiers and signaling-related proteins. Besides a fundamental aspect, this approach can provide a unified framework for cancer biology and regenerative/rejuvenation medicine because oncogenesis can be defined as an atavistic reversal to a UC state, while regeneration and rejuvenation require an ontogenetic reversal. [ABSTRACT FROM AUTHOR]

Over the years, molecular typing of methicillin-resistant S. aureus (MRSA) has allowed for the identification of endemic MRSA strains and pathogenic strains. After reaching a peak of predominance in a given geographic region, MRSA strains are usually replaced by a new strain. This process is called clonal replacement and is observed worldwide. The worldwide spread of hospital-associated MRSA (HA-MRSA), community-associated MRSA (CA-MRSA) and livestock-associated MRSA (LA-MRSA) clones over the last few decades has allowed this microorganism to be currently considered a pandemic. In Portugal, most HA-MRSA infections are associated with EMRSA-15 (S22-IV), New York/Japan (ST5-II) and Iberian (ST247-I) clones. Regarding the strains found in the community, many of them are frequently associated with the hospital environment, namely the Pediatric, Brazilian and Iberian clones. On the other hand, a strain that is typically found in animals, MRSA clonal complex (CC) 398, has been described in humans as colonizing and causing infections. The ST398 clone is found across all animal species, particularly in farm animals where the economic impact of LA-MRSA infections can have disastrous consequences for industries. In contrast, the EMRSA-15 clone seems to be more related to companion animals. The objective of this review is to better understand the MRSA epidemiology because it is, undoubtedly, an important public health concern that requires more attention, in order to achieve an effective response in all sectors. [ABSTRACT FROM AUTHOR]

Usutu virus (USUV) and West Nile virus (WNV) are phylogenetically closely related arboviruses. These viruses mainly follow an enzootic cycle involving mosquitoes and birds, but they occasionally infect humans and other mammals, inducing neurotropic disorders. Since the discovery of USUV, only two human cases have been reported in Africa, including one in Burkina Faso in 2004. Since then, no studies have been conducted to measure the extent of the circulation of this virus in Burkina Faso, and no study regarding the circulation of WNV has been conducted. Our study aimed to determine the seroprevalence of USUV and WNV in blood donations and in animals (horses, dogs, chickens and pigeons) and to perform molecular screening in patients with febrile fever and in Culex quinquefasciatus and Aedes aegypti mosquitoes. The prevalence of USUV and WNV was studied by serological (ELISA and microneutralization tests) and molecular analyses (RT-qPCR) of mosquito, dog, domestic bird, horse, and human samples in Burkina Faso between 2019 and 2021. We detected a very active transmission of both viruses in Burkina Faso. WNV and USUV seroprevalence is particularly high in humans (19.16% and 14.17%, respectively) and horses (17.28% and 6.17%). Molecular screening did not detect WNV or USUV in the mosquito or human samples tested. Our study shows an active spread of USUV and WNV in Burkina Faso, especially for WNV. This study highlights the value of developing surveillance programs to better prevent, detect, and alert people to USUV and WNV circulation in both primary and incidental hosts. [ABSTRACT FROM AUTHOR]

Heterogeneity in virulence potential of L. monocytogenes subgroups have been associated with genetic elements that could provide advantages in certain environments to invade, multiply, and survive within a host. The presence of gene mutations has been found to be related to attenuated phenotypes, while the presence of groups of genes, such as pathogenicity islands (PI), has been associated with hypervirulent or stress-resistant clones. We evaluated 232 whole genome sequences from invasive listeriosis cases in human and ruminants from the US and Europe to identify genomic elements associated with strains causing three clinical outcomes: central nervous system (CNS) infections, maternal-neonatal (MN) infections, and systemic infections (SI). Phylogenetic relationships and virulence-associated genes were evaluated, and a gene-based and single nucleotide polymorphism (SNP)-based genome-wide association study (GWAS) were conducted in order to identify loci associated with the different clinical outcomes. The orthologous results indicated that genes of phage phiX174, transfer RNAs, and type I restriction-modification (RM) system genes along with SNPs in loci involved in environmental adaptation such as rpoB and a phosphotransferase system (PTS) were associated with one or more clinical outcomes. Detection of phenotype-specific candidate loci represents an approach that could narrow the group of genetic elements to be evaluated in future studies. [ABSTRACT FROM AUTHOR]

Breast cancer recurrence is an important outcome for patients and healthcare systems, but it is not routinely reported in cancer registries. We developed an algorithm to identify patients who experienced recurrence or a second case of primary breast cancer (combined as a "second breast cancer event") using administrative data from the population of Ontario, Canada. A retrospective cohort study design was used including patients diagnosed with stage 0-III breast cancer in the Ontario Cancer Registry between 1 January 2009 and 31 December 2012 and alive six months post-diagnosis. We applied the algorithm to healthcare utilization data from six months post-diagnosis until death or 31 December 2013, whichever came first. We validated the algorithm's diagnostic accuracy against a manual patient record review (n = 2245 patients). The algorithm had a sensitivity of 85%, a specificity of 94%, a positive predictive value of 67%, a negative predictive value of 98%, an accuracy of 93%, a kappa value of 71%, and a prevalence-adjusted bias-adjusted kappa value of 85%. The second breast cancer event rate was 16.5% according to the algorithm and 13.0% according to manual review. Our algorithm's performance was comparable to previously published algorithms and is sufficient for healthcare system monitoring. Administrative data from a population can, therefore, be interpreted using new methods to identify new outcome measures. [ABSTRACT FROM AUTHOR]

Leishmaniases are human and animal parasitic diseases transmitted by phlebotomine sand flies. Globalization is an important driver of the burden and in the current dynamics of these diseases. A systematic review of articles published between 2000 and 2021 was conducted using the PubMed search engine to identify the epidemiology and clinical management of imported human leishmaniases as a fundamental step to better manage individual cases and traveler and migrant health from a global perspective. A total of 275 articles were selected, representing 10,341 human imported cases. Identified drivers of changing patterns in epidemiology include conflict and war, as well as host factors, such as immunosuppression, natural and iatrogenic. Leishmania species diversity associated with different clinical presentations implies diagnostic and treatment strategies often complex to select and apply, especially in non-endemic settings. Thus, diagnostic and management algorithms for medical clinical decision support are proposed. Increased surveillance of non-endemic cases, whether in vulnerable populations such as refugees/migrants and immunocompromised individuals or travelers, could improve individual health and mitigate the public health risk of introducing Leishmania species into new areas. [ABSTRACT FROM AUTHOR]

Glycation reactions play a key role in post-translational modifications of amino acids in food proteins. Questions have arisen about a possible pathophysiological role of dietary glycation compounds. Several studies assessed the metabolic fate of dietary glycation compounds into blood and urine, but studies about saliva are rare. We investigated here the dietary impact on salivary concentrations of the individual Maillard reaction products (MRPs) N-ε-fructosyllysine, N-ε-carboxymethyllysine (CML), N-ε-carboxyethyllysine (CEL), pyrraline (Pyr), and methylglyoxal-derived hydroimidazolone 1 (MG-H1). Quantitation was performed using stable isotope dilution analysis (LC-MS/MS). We describe here, that a low MRP diet causes a significant lowering of salivary levels of Pyr from 1.9 ± 0.4 ng/mL to below the LOD and MG-H1 from 2.5 ± 1.5 ng/mL to 0.7 ± 1.8 ng/mL. An impact on the salivary protein fraction was not observed. Furthermore, salivary Pyr and MG-H1 levels are modified in a time-dependent manner after a dietary intervention containing 1.2 mg Pyr and 4.7 mg MG-H1. An increase in mean salivary concentrations to 1.4 ng/mL Pyr and 4.2 ng/mL MG-H1 was observed within 30–210 min. In conclusion, saliva may be a useful tool for monitoring glycation compound levels by using Pyr and MG-H1 as biomarkers for intake of heated food. [ABSTRACT FROM AUTHOR]

Obesity is a complex chronic, relapsing, progressive disease. Association studies have linked microbiome alterations with obesity and overweight. However, the results are not always consistent. An integrated analysis of 4282 fecal samples (2236 control (normal weight) group, 1152 overweight, and 894 simple obesity) was performed to identify obesity-associated microbial markers. Based on a random effects model and a fixed effects model, we calculated the odds ratios of the metrics, including bacterial alpha-diversity, beta-diversity, Bacteroidetes/Firmicutes ratio, common genera, and common pathways, between the simple obesity and control groups as well as the overweight and control groups. The random forest model was trained based on a single dataset at the genus level. Feature selection based on feature importance ranked by mean decrease accuracy and leave-one-out cross-validation was conducted to improve the predictive performance of the models. Chao1 and evenness possessed significant ORs higher than 1.0 between the obesity and control groups. Significant bacterial community differences were observed between the simple obesity and the control. The ratio of Bacteroidetes/Firmicutes was significantly higher in simple obesity patients. The relative abundance of Lachnoclostridium and Faecalitalea were higher in people with simple obesity, while 23 genera, including Christensenellaceae_R-7_group, Akkermansia, Alistipes, and Butyricimonas, etc., were significantly lower. The random forest model achieved a high accuracy (AUC = 0.83). The adenine and adenosine salvage pathway (PWY-6609) and the L-histidine degradation I pathway (HISDEG-PWY) were clustered in obese patients, while amino acid biosynthesis and degradation pathways (HISDEG-PWY, DAPLYSINESYN-PWY) were decreased. This study identified obesity microbial biomarkers, providing fertile targets for the management of obesity. [ABSTRACT FROM AUTHOR]

Phytoene (PT) and phytofluene (PTF) are colourless carotenoids presents in the human diet and in blood, faeces and tissues and are biologically active. However, there is very little data on these carotenoids. This study aims to assess PT and PTF concentrations in serum from healthy Spanish normolipemic subjects (n = 101, 45–65 years) and the effect of a fruit and vegetable dietary intervention (4 weeks, n = 29) on PT and PTF concentration in serum and faeces and dietary intake. Serum and faecal concentrations were analysed by HPLC and dietary intake by 3 × 24 h recalls. PT showed higher concentrations than PTF in serum, faeces and in the dietary intake. Considering both studies, PT and PTF concentrations in serum were 0.16 ± 0.07 and 0.05 ± 0.04 µmol/L, respectively, in faeces 17.7 ± 20.3 and 6.5 ± 7.9 µg/g, respectively, and in dietary intake the median was 2.4 and 0.6 mg/p/day, respectively. Carrots and tomatoes were the major dietary contributors of these carotenoids. The dietary intervention did not cause significant variations in the PT and PTF intake or serum concentrations, but a lower concentration in faeces was observed for the fruit group (PT: p = 0.024; PTF isomer-3: p = 0.034). These data highlight the need for further research on the activities of these carotenoids in humans. [ABSTRACT FROM AUTHOR]

Malassezia spp. are commensals of the skin, oral/sinonasal cavity, lower respiratory and gastrointestinal tract. Eighteen species have been recovered from humans, other mammals and birds. They can also be isolated from diverse environments, suggesting an evolutionary trajectory of adaption from an ecological niche in plants and soil to the mucocutaneous ecosystem of warm-blooded vertebrates. In humans, dogs and cats, Malassezia-associated dermatological conditions share some commonalities. Otomycosis is common in companion animals but is rare in humans. Systemic infections, which are increasingly reported in humans, have yet to be recognized in animals. Malassezia species have also been identified as pathogenetic contributors to some chronic human diseases. While Malassezia species are host-adapted, some species are zoophilic and can cause fungemia, with outbreaks in neonatal intensive care wards associated with temporary colonization of healthcare worker's hands from contact with their pets. Although standardization is lacking, susceptibility testing is usually performed using a modified broth microdilution method. Antifungal susceptibility can vary depending on Malassezia species, body location, infection type, disease duration, presence of co-morbidities and immunosuppression. Antifungal resistance mechanisms include biofilm formation, mutations or overexpression of ERG11, overexpression of efflux pumps and gene rearrangements or overexpression in chromosome 4. [ABSTRACT FROM AUTHOR]

Associations between diet and DNA methylation may vary among subjects with different metabolic states, which can be captured by clustering populations in metabolically homogenous subgroups, called metabotypes. Our aim was to examine the relationship between habitual consumption of various food groups and DNA methylation as well as to test for effect modification by metabotype. A cross-sectional analysis of participants (median age 58 years) of the population-based prospective KORA FF4 study, habitual dietary intake was modeled based on repeated 24-h diet recalls and a food frequency questionnaire. DNA methylation was measured using the Infinium MethylationEPIC BeadChip providing data on >850,000 sites in this epigenome-wide association study (EWAS). Three metabotype clusters were identified using four standard clinical parameters and BMI. Regression models were used to associate diet and DNA methylation, and to test for effect modification. Few significant signals were identified in the basic analysis while many significant signals were observed in models including food group-metabotype interaction terms. Most findings refer to interactions of food intake with metabotype 3, which is the metabotype with the most unfavorable metabolic profile. This research highlights the importance of the metabolic characteristics of subjects when identifying associations between diet and white blood cell DNA methylation in EWAS. [ABSTRACT FROM AUTHOR]

Dietary cholesterol has been suggested to increase the risk of cardiovascular disease (CVD). Phytosterols, present in food or phytosterol-enriched products, can reduce cholesterol available for absorption. The present study aimed to investigate the association between habitual intake of total and individual plant sterols (β-sitosterol, campesterol, and stigmasterol) or a diet combined with phytosterol-enriched products and CVD in a cross-section of Polish adults, participants of the Multicenter National Health Survey II (WOBASZ II). Among men (n = 2554), median intakes of plant sterols in terciles ranged between 183–456 mg/d and among women (n = 3136), 146–350 mg/d in terciles. The intake of phytosterols, when consumed with food containing phytosterols, including margarine, ranged between 184–459 mg/d for men and 147–352 mg/d for women. Among both men and women, beta-sitosterol intake predominated. Plant sterol intake was lower among both men and women with CVD (p = 0.016) compared to those without CVD. Diet quality, as measured by the Healthy Diet Index (HDI), was significantly higher in the third tercile of plant sterol intake for both men and women and the entire study group (p < 0.0001). This study suggests that habitual dietary intake of plant sterols may be associated with a lower chance of developing CVD, particularly in men. [ABSTRACT FROM AUTHOR]

Fetuin-A, a plasma multifunctional protein known to play a role in insulin resistance, is usually presented as a liver secreted protein. However, fetuin-A adipose tissue production has been also described. Here, we evaluated fetuin-A production by the liver and the adipose tissue during metabolic dysfunction-associated fatty liver disease (MAFLD)-non-alcoholic steatohepatitis (NASH) development. Fetuin-A was evaluated by enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), Western blot, and immunofluorescence in male foz−/− mice fed a normal diet (ND) or a high fat diet (HFD) at various timepoints and in MAFLD-NASH patients. Foz−/− mice fed a short-term HFD developed liver steatosis, insulin resistance, and increased circulating levels of fetuin-A compared to ND-fed mice. In mice and patients with NASH, fetuin-A was located not only in healthy or steatotic hepatocytes but also in some macrophages forming lipogranulomas. In both mice and humans, a significant amount of fetuin-A was present in the adipose tissue compared to the liver. However, messenger ribonucleic acid levels and cell culture experiments indicate that fetuin-A is produced by the liver but not by the adipose tissue. In conclusion, fetuin-A is produced by steatotic hepatocytes at early timepoints in MAFLD and correlates with insulin resistance both in mice and humans. In NASH, fetuin-A also co-localizes with activated liver macrophages and could be interpreted as a signal released by damaged hepatocytes. [ABSTRACT FROM AUTHOR]

A characteristic feature of Alzheimer's disease (AD) is the formation of neuronal extracellular senile plaques composed of aggregates of fibrillar amyloid β ( Aβ ) peptides, with the Aβ1-42 peptide being the most abundant species. These Aβ peptides have been proposed to contribute to the pathophysiology of the disease; however, there are few tools available to test this hypothesis directly. In particular, there are no data that establish a dose-response relationship between Aβ peptide expression level and disease. We have generated a panel of transgenic Caenorhabditis elegans strains expressing the human Aβ1-42 peptide under the control of promoter regions of two pan-neuronal expressed genes, snb-1 and rgef-1 . Phenotypic data show strong age-related defects in motility, subtle changes in chemotaxis, reduced median and maximum lifespan, changes in health span indicators, and impaired learning. The Aβ1-42 expression level of these strains differed as a function of promoter identity and transgene copy number, and the timing and severity of phenotypes mediated by Aβ1-42 were strongly positively correlated with expression level. The pan-neuronal expression of varying levels of human Aβ1-42 in a nematode model provides a new tool to investigate the in vivo toxicity of neuronal Aβ expression and the molecular and cellular mechanisms underlying AD progression in the absence of endogenous Aβ peptides. More importantly, it allows direct quantitative testing of the dose-response relationship between neuronal Aβ peptide expression and disease for the first time. These strains may also be used to develop screens for novel therapeutics to treat Alzheimer's disease.

Leukemia is a prevalent pediatric cancer with significant challenges, particularly in relapsed or refractory cases. Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a personalized cancer treatment, modifying patients' T cells to target and destroy resistant cancer cells. This study reviews the current therapeutic options of CAR-T therapy for leukemia, addressing the primary obstacles such as antigen escape and T-cell exhaustion. We explore dual-targeting strategies and their potential to improve treatment outcomes by preventing the loss of target antigens. Additionally, we examine the mechanisms of T-cell exhaustion and strategies to enhance CAR-T persistence and effectiveness. Despite remarkable clinical successes, CAR-T therapy poses risks such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Our findings highlight the need for ongoing research to optimize CAR-T applications, reduce toxicities, and extend this innovative therapy to a broader range of hematologic malignancies. This comprehensive review aims to provide valuable insights for improving leukemia treatment and advancing the field of cancer immunotherapy.

Docetaxel is a commonly used taxane chemotherapeutic agent in the treatment of a variety of cancers, including breast cancer, ovarian cancer, prostate cancer, non-small cell lung cancer, gastric cancer, and head and neck cancer. Docetaxel exerts its anti-cancer effects through inhibition of the cell cycle and induction of proapoptotic activity. However, docetaxel also impacts rapidly proliferating normal cells in the scalp hair follicles (HFs), rendering the HFs vulnerable to docetaxel-induced cell death and leading to chemotherapy-induced alopecia (CIA). In severe cases, docetaxel causes persistent or permanent CIA (pCIA) when hair does not grow back completely six months after chemotherapy cessation. Hair loss has severe negative impacts on patients' quality of life and may even compromise their compliance with treatment. This review discusses the notable prevalence of docetaxel-induced CIA and pCIA, as well as their prevention and management. At this moment, scalp cooling is the standard of care to prevent CIA. Treatment options to promote hair regrowth include but are not limited to minoxidil, photobiomodulation (PBMT), and platelet-rich plasma (PRP). In addition, a handful of current clinical trials are exploring additional agents to treat or prevent CIA. Research models of CIA, particularly ex vivo human scalp HF organ culture and in vivo mouse models with human scalp xenografts, will help expedite the translation of bench findings of CIA prevention and/or amelioration to the clinic.

Lung cancer remains a formidable health challenge due to its high mortality and morbidity rates. Non-small cell lung cancer (NSCLC) constitutes approximately 85% of all lung cancer cases, with small cell lung cancer (SCLC) accounting for the remainder. Both NSCLC and SCLC cells express receptor tyrosine kinases, which may be overexpressed or mutated in lung cancer, leading to increased activation. The c-Met receptor tyrosine kinase, crucial for cell transformation and tumor growth, invasion, and metastasis, became the focus of our study. We used an E1B55KD-deleted, replication-selective oncolytic adenovirus (Ad.What), driven by the c-Met promoter, targeting lung cancer cells with c-Met overexpression, thus sparing normal cells. Previous studies have shown the enhanced antitumor efficacy of oncolytic adenoviruses when combined with chemotherapeutic agents. We explored combining rapamycin, a selective mTOR inhibitor with promising clinical trial outcomes for various cancers, with Ad.What. This combination increased infectivity by augmenting the expression of coxsackievirus and adenovirus receptors and αV integrin on cancer cells and induced autophagy. Our findings suggest that combining a c-Met promoter-driven oncolytic adenovirus with rapamycin could be an effective lung cancer treatment strategy, offering a targeted approach to exploit lung cancer cells' vulnerabilities, potentially marking a significant advancement in managing this deadly disease.

Presbycusis, also referred to as age-related hearing loss (ARHL), is a multifaceted condition caused by the natural aging process affecting the auditory system. Genome-wide association studies (GWAS) in human populations can identify potential genes linked to ARHL. Despite this, our knowledge of the biochemical and molecular mechanisms behind the condition remains incomplete. This study aims to evaluate a potential protective tool for ARHL treatment by comparing human blood-based target gene-miRNA associations regulated in ARHL. To identify promising target genes for ARHL, we utilized an mRNA assay. To determine the role of miRNA in ARHL, we investigated the expression profile of miRNA in whole blood in ARHL patients with real-time polymerase chain reaction (RT-qPCR). A reporter gene assay was performed to confirm the regulation of candidate genes by microRNA. Through RT-qPCR validation analysis, we finally confirmed the relationship between ARHL and the role of the interferon-gamma (IFNG) gene. This gene can be regarded as an age-related gene. Through gene ontology (GO) analysis, it has been found that these genes are enriched in pathways related to apoptosis. Among them, IFNG induces an inflammatory response, apoptotic cell death, and cellular senescence. We found that miR-409-3p downregulates the expression of the IFNG in vitro. In addition, the downregulation of the IFNG by miRNA 409-3p promoted cell apoptosis and suppressed proliferation. In conclusion, our study produced gene signatures and associated microRNA regulation that could be a protective key for ARHL patients. IFNG genes and miR-409-3p should be investigated for their usefulness as a new biomarker for treatment modality.

The blue crab ( Callinectes sapidus ), originally from the western Atlantic Ocean, has recently spread to the Mediterranean and is now considered one of the one hundred most invasive species in that region. This opportunistic species, known for its adaptability to different temperatures and salinities, negatively impacts biodiversity and human activities such as fishing and tourism in the Mediterranean. However, the blue crab is gaining interest as a potential food resource due to its high nutritional value and delicate, sweet flavor. Its meat is rich in protein (14% to 30%), omega-3 fatty acids (EPA and DHA) and other essential nutrients beneficial for human health such as vitamins, and minerals. Utilizing this species in the production of new foods could help mitigate the negative impact of its invasiveness and offer economic opportunities. One challenge with this potential resource is the generation of waste. Approximately 6-8 million tonnes of crab shells are produced worldwide each year, leading to disposal problems and concerns regarding environmental sustainability. To improve economic and environmental sustainability, there is a need to valorize these residues, which are an important source of proteins, lipids, chitin, minerals, and pigments that can be processed into high-value-added products. However, especially in areas with industrial pollution, attention should be paid to the heavy metal (Cd and As) contents of blue crab shells. Studies suggest that blue crab by-products can be used in various sectors, reducing environmental impacts, promoting a circular economy, and creating new industrial opportunities.

To accurately study human organ function and disease 'in the dish', it is necessary to develop reliable cell-based models that closely track human physiology. Our interest lay with the liver, which is the largest solid organ in the body. The liver is a multifunctional and highly regenerative organ; however, severe liver damage can have dire consequences for human health. A common cause of liver damage is adverse reactions to prescription drugs. Therefore, the development of predictive liver models that capture human drug metabolism patterns is required to optimise the drug development process. In our study, we aimed to identify compounds that could improve the metabolic function of stem cell-derived liver tissue. Therefore, we screened a compound library to identify additives that improved the maturity of in vitro -engineered human tissue, with the rationale that by taking such an approach, we would be able to fine-tune neonatal and adult cytochrome P450 metabolic function in stem cell-derived liver tissue.

The field of reproductive biology has made significant progress in recent years, identifying specific molecular players that influence oocyte development and function. Among them, sirtuin 3 (SIRT3) has attracted particular attention for its central role in mediating mitochondrial function and cellular stress responses in oocytes. So far, studies have demonstrated that the knockdown of SIRT3 leads to a decrease in blastocyst formation and an increase in oxidative stress within an embryo, underscoring the importance of SIRT3 in maintaining the cellular redox balance critical for embryonic survival and growth. Furthermore, the literature reveals specific signaling pathways, such as the SIRT3- Glycogen synthase kinase-3 beta (GSK3β) deacetylation pathway, crucial for mitigating oxidative stress-related anomalies in oocyte meiosis, particularly under conditions like maternal diabetes. Overall, the emerging role of SIRT3 in regulating oocyte mitochondrial function and development highlights the critical importance of understanding the intricate connections between cellular metabolism, stress response pathways, and overall reproductive health and function. This knowledge could lead to the development of novel strategies to support oocyte quality and fertility, with far-reaching implications for assisted reproductive technologies and women's healthcare. This commentary aims to provide an overview of the importance of SIRT3 in oocytes by synthesizing results from a multitude of studies. The aim is to elucidate the role of SIRT3 in oocyte development, maturation, and aging and to identify areas where further research is needed.

For patients with locally advanced/metastatic urothelial carcinoma (la/mUC), first-line (1L) treatment with platinum-based chemotherapy (PBC) followed by avelumab 1L maintenance (1LM) is a recommended therapy per treatment guidelines in patients without disease progression. However, contemporary real-world (rw) data among patients receiving this treatment are necessary to understand clinical outcomes and optimal treatment sequencing. This retrospective cohort study analyzed rw treatment patterns and clinical outcomes, including overall survival (rwOS) and progression-free survival (rwPFS), in patients with la/mUC receiving avelumab 1LM. From the Flatiron Health database, 214 patients who received avelumab 1LM following 1L PBC were included. From the start of avelumab 1LM, median rwOS was 23.8 months (95% CI: 18.2-not estimable [NE]) and median rwPFS was 5.1 months (95% CI: 4.1-7.0). A total of 96 patients received second-line (2L) therapy, with 53 receiving enfortumab vedotin (EV). From the start of 2L EV, median rwOS was 11.2 months (95% CI: 6.8-NE) and median rwPFS was 4.9 months (95% CI: 3.9-8.8). Treatment patterns and clinical outcomes in this study align with guidelines and outcomes observed in the JAVELIN Bladder 100 and EV-301 clinical trials and other rw studies, supporting the use of 1L PBC followed by avelumab 1LM and 2L EV for eligible patients.

Sestrins are a conserved family of stress-responsive proteins that play a crucial role in cellular metabolism, stress response, and ageing. Vertebrates have three Sestrin genes ( SESN1 , SESN2 , and SESN3 ), while invertebrates encode only one. Initially identified as antioxidant proteins that regulate cell viability, Sestrins are now recognised as crucial inhibitors of the mechanistic target of rapamycin complex 1 kinase (mTORC1), a central regulator of anabolism, cell growth, and autophagy. Sestrins suppress mTORC1 through an inhibitory interaction with the GATOR2 protein complex, which, in concert with GATOR1, signals to inhibit the lysosomal docking of mTORC1. A leucine-binding pocket (LBP) is found in most vertebrate Sestrins, and when bound with leucine, Sestrins do not bind GATOR2, prompting mTORC1 activation. This review examines the evolutionary conservation of Sestrins and their functional motifs, focusing on their origins and development. We highlight that the most conserved regions of Sestrins are those involved in GATOR2 binding, and while analogues of Sestrins exist in prokaryotes, the unique feature of eukaryotic Sestrins is their structural presentation of GATOR2-binding motifs.

Salivary gland cancers (SGC) are rare tumours with limited availability of systemic therapies. Some SGC subtypes overexpress HER2, and this represents a potential therapeutic target, but the evidence base is limited. This study sought to analyse real-world data on the efficacy of HER2-directed therapies in SGC. This is a retrospective observational study using anonymised data from commercial compassionate-use access registrations and a privately funded pharmacy prescribing register. Treatment duration was defined as the time from drug initiation to treatment discontinuation. Kaplan-Meier analysis of treatment duration was performed using R for Windows (v4.3.2). A case report is also provided of an exceptional responder. Eighteen patients were identified who received HER2-directed therapies for HER2-positive recurrent/metastatic SGC, and complete data on treatment duration was available for 15/18. Histology was salivary duct carcinoma in 13/18 patients, adenocarcinoma NOS in 4/18, and carcinoma ex pleomorphic adenoma in 1/18. The median treatment duration was 8.3 months (95% CI: 6.41-not reached), and the range was 1.0-47.0 months. Choice of HER2-directed therapy varied, with ado-trastuzumab emtasine being the most common (9/18). At the time of analysis, HER2-directed therapy was ongoing for 9/15, discontinued due to disease progression for 4/15, discontinued due to toxicity for 1/15, and 1/15 was discontinued for an unspecified reason. An exceptional responder experienced a complete response with a treatment duration of 47.0 months. These real-world data are comparable to the median PFS observed with HER2-directed therapies in phase II trials and support the use of HER2-directed therapies in this group.

As a natural preservative, nisin is widely used in the food industry, while its application in biomedicine is limited due to its susceptibility to interference from external conditions. In this study, a nanoparticle-hydrogel composite system was designed to encapsulate and release nisin. Nisin nanoparticles were identified with a smooth, spherical visual morphology, particle size of 122.72 ± 4.88 nm, polydispersity coefficient of 0.473 ± 0.063, and zeta potential of 23.89 ± 0.37 mV. Based on the sample state and critical properties, three temperature-sensitive hydrogels based on chitosan were ultimately chosen with a rapid gelation time of 112 s, outstanding reticular structure, and optimal swelling ratio of 239.05 ± 7.15%. The composite system exhibited the same antibacterial properties as nisin, demonstrated by the composite system's inhibition zone diameter of 17.06 ± 0.83 mm, compared to 20.20 ± 0.58 mm for nisin, which was attributed to the prolonged release effect of the hydrogel at the appropriate temperature. The composite system also demonstrated good biocompatibility and safety, making it suitable for application as short-term wound dressings in biomedicine due to its low hemolysis rate of less than 2%. In summary, our nanoparticle-based hydrogel composite system offers a novel application form of nisin while ensuring its stability, thereby deepening and broadening the employment of nisin.

Sacituzumab Govitecan (SG) is an antibody-drug conjugate (ADC) comprised of an anti-Trop-2 IgG1 molecule conjugated to SN-38, the active metabolite of irinotecan, via a pH-sensitive hydrolysable linker. As a result of recent Canadian funding for SG in advanced hormone receptor (HR)-positive breast cancer and triple-negative breast cancer (TNBC), experience with using SG and managing adverse events (AEs) has grown. This review presents a summary of evidence and adverse event recommendations derived from Canadian experience, with SG use in metastatic TNBC for extrapolation and guidance in all indicated settings. SG is dosed at 10 mg/kg on day 1 and day 8 of a 21-day cycle. Compared to treatment of physicians' choice (TPC) the phase III ASCENT and TROPiCS-02 studies demonstrated favorable survival data in unresectable locally advanced or metastatic TNBC and HR-positive HER2 negative metastatic breast cancer, respectively. The most common AEs were neutropenia, diarrhea, nausea, fatigue, alopecia, and anemia. This review outlines AE management recommendations for SG based on clinical trial protocols and Canadian guidelines, incorporating treatment delay, dose reductions, and the use of prophylactic and supportive medications.

Nuclear bodies are structures in eukaryotic cells that lack a plasma membrane and are considered protein condensates, DNA, or RNA molecules. Known nuclear bodies include the nucleolus, Cajal bodies, and promyelocytic leukemia nuclear bodies. These bodies are involved in the concentration, exclusion, sequestration, assembly, modification, and recycling of specific components involved in the regulation of ribosome biogenesis, RNA transcription, and RNA processing. Additionally, nuclear bodies have been shown to participate in cellular processes such as the regulation of transcription of the cell cycle, mitosis, apoptosis, and the cellular stress response. The dynamics and functions of these bodies depend on the state of the cell. It is now known that both DNA and RNA viruses can direct their proteins to nuclear bodies, causing alterations in their composition, dynamics, and functions. Although many of these mechanisms are still under investigation, it is well known that the interaction between viral and nuclear body proteins is necessary for the success of the viral infection cycle. In this review, we concisely describe the interaction between viral and nuclear body proteins. Furthermore, we focus on the role of the nucleolus in RNA virus infections. Finally, we discuss the possible implications of the interaction of viral proteins on cellular transcription and the formation/degradation of non-coding RNAs.