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Enteroaggregative Escherichia coli (EAEC) strains have been linked to several outbreaks of severe diarrhea around the world, and this bacterium is now commonly resistant to antibiotics. As part of the pathophysiology of EAEC, the characteristic pattern of adherence looks like stacked bricks on the intestinal epithelium. This phenotype depends on an aggregative adhesion plasmid (pAA), which codes for a regulatory protein named AggR. The AggR protein is a master regulator that transcriptionally actives the main virulence genes in this E. coli pathotype, such as those that encode the aggregative adhesion fimbriae, dispersin and its secretion apparatus, Aar regulatory protein, and type VI secretion system. Several reports have shown that AggR positively affects most EAEC virulence genes, functioning as a classic transcriptional activator in the promoter region of these genes, interacting with the RNA polymerase. This minireview article integrates the information about virulence determinants of EAEC controlled by the AggR regulator. [ABSTRACT FROM AUTHOR]

This study examined the influence of PPARG activation by pioglitazone (PG) on the mRNA of core clock, inflammation‐ and metabolism‐related genes in the mouse kidney medulla as well as urinary sodium/potassium excretion rhythms disrupted by reverse feeding. Mice were assigned to daytime feeding and nighttime feeding groups. PG 20 mg/kg was administered at 7 am or 7 pm. On day 8 of the feeding intervention, mice were killed at noon and midnight. Kidney medulla expression of Arntl, Clock, Nr1d1, Cry1, Cry2, Per1, Per2, Nfe2l2, Pparg, and Scnn1g was determined by qRT PCR. We measured urinary K+, Na+, urine volume, food, and H2O intake. The reverse feeding uncoupled the peripheral clock gene rhythm in mouse kidney tissues. It was accompanied by a decreased expression of Nfe2l2 and Pparg as well as an increased expression of Rela and Scnn1g. These changes in gene expressions concurred with an increase in urinary Na+, K+, water excretion, microcirculation disorders, and cell loss, especially in distal tubules. PG induced the restoration of diurnal core clock gene expression as well as Nfe2l2, Pparg, Scnn1g mRNA, and decreased Rela expressions, stimulating Na+ reabsorption and inhibiting K+ excretion. PG intake at 7 pm was more effective than at 7 am. [ABSTRACT FROM AUTHOR]

Introduction: In this cross-sectional study, we investigated the 1-year prevalence and related factors in the general population with an experience of chronic dizziness. Methods: This study analyzed persons (n = 5,163) who respond to dizziness and nutrition questionnaire from participant of Korean National Health and Nutrition Examination Survey (KNHANES, 2019-2020). Results: Of individuals over 40 years, 25.3% of the general population (61.6% females) reported either dizziness or imbalance for the past year. Moreover, 4.8% of the patients reported they suffered fromchronic dizziness or imbalance for more than 3 months. In multiple regression analysis, patients with chronic dizziness were older, females, had lower body mass index (BMI), had stress awareness, and had a history of tinnitus within 1 year (>5 min per episode). Relative to normal body weight, both overweight and mild obesity (obesity stages 1 and 2) were associated with a significantly lower risk of chronic dizziness. Overweight, obesity stage 1, and obesity stage 2 had odds ratios of 0.549 [95% confidence interval (CI), 0.332-0.910], 0.445 (95% CI, 0.273-0.727), and 0.234 (95% CI, 0.070-0.779), respectively. Conclusions: In this study, the prevalence of chronic dizziness in the general population was 4.8%. Our study demonstrated that overweight and mild obesity were independently associated with a lower risk of chronic dizziness in adults for the past year. Therefore, the optimal BMI for patients with dizziness should be defined and managed according to an integrated care pathway. [ABSTRACT FROM AUTHOR]

The attachment of enteropathogenic Escherichia coli (EPEC) to intestinal epithelial cells is facilitated by several adhesins; however, the individual host-cell receptors for pili-mediated adherence have not been fully characterized. In this study, we evaluated the hypothesis that the E. coli common pilus (ECP) tip adhesin protein EcpD mediates attachment of EPEC to several extracellular matrix (ECM) glycoproteins (fibronectin, laminin, collagens I and IV, and mucin). We found that the ΔecpA mutant, which lacks production of the EcpA filament but retains EcpD on the surface, adhered to these glycoproteins below the wild-type levels, while the ΔecpD mutant, which does not display EcpA or EcpD, bound significantly less to these host glycoproteins. In agreement, a purified recombinant EcpD subunit bound significantly more than EcpA to laminin, fibronectin, collagens I and IV, and mucin in a dose-dependent manner. These are compelling data that strongly suggest that ECP-producing EPEC may bind to host ECM glycoproteins and mucins through the tip adhesin protein EcpD. This study highlights the versatility of EPEC to bind to different host proteins and suggests that the interaction of ECP with the host's ECM glycoproteins may facilitate colonization of the intestinal mucosal epithelium. [ABSTRACT FROM AUTHOR]

Background: Diarrheagenic E. coli (DEC) pathogenicity relies on the interaction of bacteria with the host's gut environment, which is regulated by the resident microbiota. Previously, we identified indicative bacterial species of gut microbiota in DEC-positive stool samples from children. Here, we evaluated the role of two indicative species, Citrobacter werkmanii (CW) and Escherichia albertii (EA), in the virulence of two DEC pathotypes, Shiga toxin-producing (STEC) and enteroaggregative (EAEC) Escherichia coli. Methods: We determined the effect of supernatants obtained from CW and EA cultures on the gene expression of STEC strain 86-24 and EAEC strain 042 by RNA-seq analysis. We evaluated IL-8 secretion fromT84 cells infected with these DEC strains in the presence or absence of the supernatant from EA. The effect of the supernatant fromEA on the growth and adherence of STEC and EAEC to cells was also evaluated. Finally, we studied the effect of the EA supernatant on the STEC-induced inflammation mediated by the long polar fimbriae (Lpf) in T84 cells and the expression of plasmid-encoded toxin (Pet) in EAEC. Results: RNA-seq analysis revealed that several virulence factors in STEC and EAEC were upregulated in the presence of supernatants from CW and EA. Interestingly, an increase in the secretion of IL-8 was observed in cells infected with STEC or EAEC in the presence of a supernatant from EA. Similar results were observed with the supernatants obtained from clinical strains of E. albertii. The supernatant from EA had no effect on the growth of STEC and EAEC, or on the ability of these DEC strains to adhere to cells. We found that Pet toxin in EAEC was upregulated in the presence of a supernatant from EA. In STEC, using mutant strains for Lpf fimbriae, our data suggested that these fimbriae might be participating in the increase in IL-8 induced by STEC in cells in the presence of a supernatant from EA. Conclusion: Supernatant obtained from an indicative species of DEC-positive diarrhea could modulate gene expression in STEC and EAEC, and IL-8 secretion induced by these bacteria. These data provide new insights into the effect of gut microbiota species in the pathogenicity of STEC and EAEC. [ABSTRACT FROM AUTHOR]

Aim: The objective of this research was to determine the static postural control differences measured from a force platform in Type 2 diabetes mellitus (T2DM) and healthy control groups with different levels of body mass index (BMI), and detect the static postural control difference between T2DM and healthy control groups stratified by different BMI category. This research also explored the relationship of BMI and static postural performance. Methods: We recruited 706 participants with T2DM and 692 healthy controls who were sufficiently matched for age, gender, and BMI in this cross-sectional study. The participants were stratified into three groups by BMI: normal weight, overweight, and obesity. All participants performed two-legged static stance postural control assessment on a firm force platform. The Center of Pressure (CoP) parameters were collected under eyes-open and eyes-closed conditions. Mann–Whitney U test was used to compare the static postural control parameters within each BMI category in both groups. The static postural control parameters among different weight groups were compared by Kruskal–Wallis test, post hoc pair-wise comparison were conducted. Generalized linear model was conducted to examine the association between BMI and static postural control parameters while controlling for confounding factors. Results: Healthy control group had statistical difference in most CoP parameters compared to T2DM group based on all BMI categories. Normal weight participants presented significant difference compared with overweight and/or obesity for total track length (TTL) and velocity of CoP displacements in Y direction (V-Y) under eyes-open condition, and for most CoP parameters under eyes-closed condition in both groups. There were statistically significant correlations between BMI and most static postural control parameters under only eyes-closed condition according to the result of generalized linear model. Conclusion: T2DM patients had impaired static postural control performance compared to healthy controls at all BMI categories. The findings also indicated the association between BMI and static postural control, where higher BMI individuals showed more static postural instability in both T2DM and healthy controls. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is more frequent in elderly patients. Mechanisms contributing to AKI (tubular cell death, inflammatory cell infiltration, impaired mitochondrial function, and prolonged cell-cycle arrest) have been linked to cellular senescence, a process implicated in regeneration failure and progression to fibrosis. However, the molecular and pathological basis of the age-related increase in AKI incidence is not completely understood. To explore these mechanisms, experimental AKI was induced by folic acid (FA) administration in young (3-months-old) and old (1-year-old) mice, and kidneys were evaluated in the early phase of AKI, at 48 h. Tubular damage score, KIM-1 expression, the recruitment of infiltrating immune cells (mainly neutrophils and macrophages) and proinflammatory gene expression were higher in AKI kidneys of old than of young mice. Tubular cell death in FA-AKI involves several pathways, such as regulated necrosis and apoptosis. Ferroptosis and necroptosis cell-death pathways were upregulated in old AKI kidneys. In contrast, caspase-3 activation was only found in young but not in old mice. Moreover, the antiapoptotic factor BCL-xL was significantly overexpressed in old, injured kidneys, suggesting an age-related apoptosis suppression. AKI kidneys displayed evidence of cellular senescence, such as increased levels of cyclin dependent kinase inhibitors p16ink4a and p21cip1, and of the DNA damage response marker γH2AX. Furthermore, p21cip1 mRNA expression and nuclear staining for p21cip1 and γH2AX were higher in old than in young FA-AKI mice, as well as the expression of senescence-associated secretory phenotype (SASP) components (Il-6, Tgfb1 , Ctgf, and Serpine1). Interestingly, some infiltrating immune cells were p21 or γH2AX positive, suggesting that molecular senescence in the immune cells ("immunosenescence") are involved in the increased severity of AKI in old mice. In contrast, expression of renal protective factors was dramatically downregulated in old AKI mice, including the antiaging factor Klotho and the mitochondrial biogenesis driver PGC-1α. In conclusion, aging resulted in more severe AKI after the exposure to toxic compounds. This increased toxicity may be related to magnification of proinflammatory-related pathways in older mice, including a switch to a proinflammatory cell death (necroptosis) instead of apoptosis, and overactivation of cellular senescence of resident renal cells and infiltrating inflammatory cells. [ABSTRACT FROM AUTHOR]

Introduction: Although vestibular rehabilitation therapy (VRT) methods are relatively popular in treating patients with body balance deficits of vestibular origin, only limited studies have been conducted into customized exercises for unilateral vestibular hypofunction (UVH). Furthermore, very little evidence is available on the outcomes of VRT in the elderly population with chronic UVH. Materials and Methods: A total of 21 patients, aged 61 to 74 years, with UVH participated in this study. The dizziness handicap inventory (DHI) was performed immediately before, and 2 and 8 weeks after treatment. Results: All patients showed a reduction in DHI scores during the study. The average decrease in DHI score was 25.98 points after 2 weeks' intervention (P<0.001) and 32.54 points at the end of the study. This improvement was observed in all DHI subscores, and was most profound in the functional aspect. The correlation between the degree of final recovery and canal paresis was not significant (P>0.05). There were no relationships between the scores and gender. Conclusion: Our study demonstrates that VRT is an effective method for the management of elderly patients with UVH, and shows maximal effect on functional aspects. [ABSTRACT FROM AUTHOR]

Background: Dizziness is one of the most prevalent symptoms in old age and tends to increase with age. Aims: To report physical functioning, health-related aspects and gender differences in elderly persons with and without dizziness in a population-based sample of 75-year-olds. Methods: A cross-sectional sample of 75-year-olds from Gothenburg, Sweden ( n = 675, 398 women and 277 men) was examined by means of questionnaires and functional tests. The questions concerned dizziness/imbalance, physical activity level, walking habits, falls efficacy, number of falls, subjective health or general fatigue and medication. The tests included were self-selected and maximum gait speed, stair climbing capacity, one leg stance and grip strength. Results: More women than men reported dizziness/imbalance (40 vs 30 %, p < 0.001). Persons with dizziness, compared to those without dizziness, less often regularly exercised at a moderate intensity level (summer: 62 vs 74 %, p < 0.001; winter: 41 vs 51 %, p < 0.001), less often took a daily walk ( p < 0.05), had lower scores on the FES(S) ( p < 0.001), more often reported general fatigue ( p < 0.001), more often had fallen in the previous year (40 vs 23 %, p < 0.001) and had a higher intake of medical drugs (4.6 vs 3.3, p < 0.001). They also performed worse regarding gait speed, stair climbing and one leg stance ( p < 0.001), but there was no difference in grip strength. Conclusion: Older persons with dizziness are less physically active, have worse lower extremity function, are more often fallers and report lower self-rated health than persons without dizziness. [ABSTRACT FROM AUTHOR]

Enteroaggregative Escherichia coli (EAEC) infections are still one of the most important etiologic pathogens of diarrhea in children worldwide. EAEC pathogenesis comprises three stages: adherence and colonization, production of toxins, and diarrhea followed by inflammation. Previous studies have demonstrated that EAEC strains have the ability to bind to fibronectin (FN); however, the role this extracellular matrix protein plays in the inflammatory response induced by EAEC remains unknown. In this study, we postulated that FN-mediated adherence of EAEC strains to epithelial cells increases the expression of pro-inflammatory genes. To verify this hypothesis, we infected HEp-2 and HT-29 cells, in both the presence and absence of FN, with EAEC reference strain 042. We quantified IL-8 secretion and the relative expression of a set of genes regulated by the NF-kB pathway. Although FN increased EAEC adherence, no changes in IL-8 protein secretion or IL8 gene expression were observed. Similar observations were found in HEp-2 cells transfected with FN-siRNA and infected with EAEC. To evaluate the involvement of AAF/II fimbriae, we infected HEp-2 and HT-29 cells, in both the presence and absence of FN, with an EAEC 042aafA mutant strain transformed with a plasmid harboring the native aafA gene with a site-directed mutation in Lys72 residue (K72A and K72R strains). No changes in IL-8 secretion were observed. Finally, SEM immunogold assay of cells incubated with FN and infected with EAEC revealed that AAF fimbriae can bind to cells either directly or mediated by FN. Our data suggests that FN participates in AAF/II fimbriae-mediated adherence of EAEC to epithelial cells, but not in the inflammatory response of cells infected by this pathogen. [ABSTRACT FROM AUTHOR]

The article discusses the case of an adult patient with benign paroxysal positional vertigo and whether canalith repositioning procedure (CRP) can help the patient. Topics discussed include the benign paroxysmal positional vertigo (BPPV) experienced by patients with a change in the head's position, treatment of the posterior canal BPPV with a particle repositioning maneuver like canalith repositioning maneuver and other treatments such as the Brandt-Daroff exercises.

Background: Autologous epidermal basal cell suspension therapy has been proven to be one of the most effective treatments for full-thickness wounds. However, we found there remain obvious defects that significantly confined the utilization and function of the epidermal basal cells (EBCs), especially the epidermal stem cells (ESCs) in it. This study investigated whether precoating fibronectin (FN) on the wound bed before spraying EBCs could overcome these defects and further explored its possible mechanisms. Methods: In the in vitro study, EBCs were isolated from the donor skin of patients who needed skin grafting. Different concentrations of FN were used to precoat culture dishes before cell culture; the adherent efficiency, proliferation and migration ability of ESCs were analyzed and compared with traditional collagen IV precoating. In the in vivo study, Sprague–Dawley (SD) rats with full-thickness skin wounds were selected as full-thickness wounds' model. For the experiment groups, 20 μg/ml FN was precoated on the wound bed 10 min before EBC spray. The quality of wound healing was estimated by the residual wound area rate, wound healing time, and hematoxylin and eosin (H&E) staining. Expression of ESC markers, neovascular markers, inflammation markers, and collagen formation and degradation markers was elucidated by immunohistochemistry (IHC), immunofluorescence (IF), western blot (WB), and RT-qPCR analysis. Results: The in vitro study showed that the dishes precoated with 20 μg/ml FN had a similar adherent efficiency and colony formation rate with collagen IV, but it could improve the proliferation and migration of ESCs significantly. Similarly, in the in vivo study, precoating FN on wound bed before EBC spray also significantly promote wound healing by improving ESCs' utilization efficiency, promoting angiogenesis, decreasing inflammations, and regulating collagen formation and degradation. Conclusion: FN precoating wound bed before EBC spray could significantly promote full-thickness wound healing by improving the utilization and function of the ESCs and further by promoting angiogenesis, decreasing inflammations, and regulating collagen formation and degradation. [ABSTRACT FROM AUTHOR]