A Cross-Sectional Study on Awareness of Tuberculosis Control Among Post-Treatment Tuberculosis Patients in a City in China.

Purpose: This study aimed to investigate awareness of tuberculosis control among post-treatment tuberculosis patients, in order to provide a basis for future preventive and control work in this population. Patients and Methods: A cross-sectional descriptive study was conducted on post-treatment patients with tuberculosis in seven districts of Jinan City between July 2021 and December 2022. A face-to-face or telephone interviews using structured questionnaires for the research subjects were conducted by data collectors. Analyses were carried out first for all subjects, and then separately for male and female subjects. Results: A total of 837 valid questionnaires were collected, of which 495 were males and 342 were females. The awareness rate of the core TB knowledge was 82.46%. The ≥65 year group in the total group (OR=0.43, 95% CI: (0.28, 0.68)), male (OR=0.47, 95% CI: (0.27, 0.83)) and female group (OR=0.40, 95% CI: (0.19, 0.86)) was lower than that of the control group. Educational level and monthly income are the main factors of TB cognition in total group. People with university or higher education (OR=2.05, 95% CI: (1.38, 3.05)) and with a monthly income of ≥6,000 (OR=1.89, 95% CI: (1.10, 3.25)) had a higher awareness rate. The group with current residence in the city was more aware than the reference group. Conclusion: In the future, the communication of the main transmission route, suspicious symptoms, and cure of TB needs to be strengthened for the post-treatment TB patients. The elderly, those with secondary school education or below, agricultural workers and low-income people are the groups with weak knowledge of TB, and they are also the groups that need to be focused on health education. The above information should be focused on the above groups of people in order to educate them in a way that is easily acceptable to them.

The second cutaneous anthrax infection diagnosed by metagenomic next-generation sequencing: A case report.

RATIONALE: Anthrax is a severe zoonotic infectious disease caused by Bacillus anthracis. Most reported cases were traditionally diagnosed through culture and microscopy. We reported here the second case of cutaneous anthrax diagnosed by metagenomic next-generation sequencing (mNGS). PATIENT CONCERNS: A 63-year-old man had a history of contact with an unwell sheep, developing local redness and swelling on wrist. The dorsal side of the left hand and forearm, with tension blisters on the back of the left. DIAGNOSIS: B anthracis was detected from culturing and mNGS of tension blisters. INTERVENTIONS: On the second day of admission, the patient was administered 3.2 million units of penicillin every 6 hours, and isolated and closely observed. OUTCOMES: The patient improves and is discharged. LESSONS: Traditional bacterial cultures are time-consuming, while mNGS offers the advantage of accurate, quick, high-throughput, unbiased sequencing of all genetic material in a sample, which is a good technical tool for assisting in the diagnosis of rare pathogen infections.

Rare occurrence of pulmonary coinfection involving Aspergillus fumigatus and Nocardia cyriacigeorgica in immunocompetent patients based on NGS: A case report and literature review.

RATIONALE: In our search on PubMed, we found that reports of co-infections involving Aspergillus fumigatus and Nocardia cyriacigeorgica in the literature are notably scarce. Most cases have been documented in patients with compromised immune systems or underlying pulmonary conditions. In contrast, our patient did not present with any of these risk factors. Furthermore, there have been no recent incidents such as near-drowning or other accidents in the patient history. To the best of our knowledge, this case represents a hitherto unreported clinical scenario. To enhance comprehension, we conducted a comprehensive literature review by compiling a total of 20 case reports (spanning from 1984 to 2023) on co-infections involving Aspergillus and Nocardia species, retrieved from PubMed. PATIENT CONCERNS AND DIAGNOSIS: Chest CT revealed the presence of multiple nodules and clustered high-density shadows in both lungs. Bronchoscopy revealed mucosal congestion and edema in the apical segment of the right upper lobe of the lung, along with the presence of 2 spherical polypoid new organisms. The pathological analysis reported severe chronic inflammation with evidence of Aspergillus within the tissue. Next-Generation Sequencing of bronchoalveolar lavage fluid revealed the presence of reads corresponding to A fumigatus and N cyriacigeorgica. Positive cultures for A fumigatus and the Nocardia genus were yielded by prolonging the incubation of samples in the microbiology laboratory. INTERVENTIONS: Treatment with voriconazole for A fumigatus and sulfamethoxazole-trimethoprim for N cyriacigeorgica infection was given. OUTCOMES: The patient improved and was discharged. After 6 months of telephone follow-up, the patient reported no clinical symptoms, discontinued the medication on his own. LESSONS: A fumigatus and N cyriacigeorgica can manifest as a co-infection in immunocompetent patients. Clinicians should prioritize the significant advantages and value of NGS in detecting rare and mixed pathogens associated with pulmonary infections.

Exercise alters cortico-basal ganglia network metabolic connectivity: a mesoscopic level analysis informed by anatomic parcellation defined in the mouse brain connectome.

The basal ganglia are important modulators of the cognitive and motor benefits of exercise. However, the neural networks underlying these benefits remain poorly understood. Our study systematically analyzed exercise-associated changes in metabolic connectivity in the cortico-basal ganglia-thalamic network during the performance of a new motor task, with regions-of-interest defined based on mesoscopic domains recently defined in the mouse brain structural connectome. Mice were trained on a motorized treadmill for six weeks or remained sedentary (control), thereafter undergoing [14C]-2-deoxyglucose metabolic brain mapping during wheel walking. Regional cerebral glucose uptake (rCGU) was analyzed in 3-dimensional brains reconstructed from autoradiographic brain sections using statistical parametric mapping. Metabolic connectivity was assessed by calculating inter-regional correlation of rCGU cross-sectionally across subjects within a group. Compared to controls, exercised animals showed broad decreases in rCGU in motor areas, but increases in limbic areas, as well as the visual and association cortices. In addition, exercised animals showed (i) increased positive metabolic connectivity within and between the motor cortex and caudoputamen (CP), (ii) newly emerged negative connectivity of the substantia nigra pars reticulata with the globus pallidus externus, and CP, and (iii) reduced connectivity of the prefrontal cortex (PFC). Increased metabolic connectivity in the motor circuit in the absence of increases in rCGU strongly suggests greater network efficiency, which is also supported by the reduced involvement of PFC-mediated cognitive control during the performance of a new motor task. Our study delineates exercise-associated changes in functional circuitry at the subregional level and provides a framework for understanding the effects of exercise on functions of the cortico-basal ganglia-thalamic network.

Omni-media health education combined with nanodrug therapy on the creation of gastrointestinal microenvironment and the improvement of treatment compliance in patients with gastrointestinal tumors.

According to the randomization method, 82 patients can be divided into two groups, the control group and the study group, each with 41 patients participating in the investigation. All patients in the control group were cared for, and the study group used a health education model. The treatment mode of each group needs to adopt adherence, and it is necessary to maintain a healthy diet, smoking cessation and alcohol cessation, and regular review during the treatment of regular exercise and emotional regulation. To enable patients to accurately grasp health knowledge during treatment, score self-management ability (ESCA), and maintain a level of satisfaction with care. (1) In the study group, the standard treatment of patients directly reached 97.56%, regular review reached 95.12%, regular exercise reached 90.24%, the degree of smoking cessation reached 92.68%. (2) The mastery of disease and health knowledge in the first group (95.12%) was significantly higher than that of (78.05%) (P < 0.05). (3) After the intervention, the first group scored higher for self-responsibility (27.07 ± 3.15), self-awareness (25.59 ± 3.11), health knowledge (40.38 ± 4.54), and self-care skills (36.45 ± 3.19). (4) The nursing satisfaction level of the first group was (92.68%), which was significantly higher than that of the other group (75.61%). According to the conclusions, it can be shown that health education for tumor patients can improve patients' compliance with treatment and mastery of disease health knowledge, which is conducive to improving patients' self-management ability.

Virulence, antimicrobial resistance, and molecular characteristics of carbapenem-resistant Klebsiella pneumoniae in a hospital in Shijiazhuang City from China.

Carbapenem-resistant Klebsiella pneumoniae (CRKP), as one of the most common drug-resistant bacteria threatening human health, is hyper-resistant to multiple antimicrobial drugs and carbapenems, which can be dealt with only limited clinical treatment options. This study described the epidemiological characteristics of CRKP in this tertiary care hospital from 2016 to 2020. Specimen sources included blood, sputum, alveolar lavage fluid, puncture fluid, secretions from a burn wound, and urine. Among the 87 carbapenem-resistant strains, ST11 was the predominant isolate, followed by ST15, ST273, ST340, and ST626. These STs were in broad agreement with the STs defined by pulsed-field gel electrophoresis clustering analysis in discriminating clusters of related strains. Most CRKP isolates contained the blaKPC-2 gene, some isolates carried the blaOXA-1, blaNDM-1, and blaNDM-5 genes, and the isolates carrying carbapenem resistance genes were more resistant to the antimicrobials of ß-lactams, carbapenems, macrolides, and fluoroquinolone. The OmpK35 and OmpK37 genes were detected in all CRKP strains, and the Ompk36 gene was detected in some CRKP strains. All detected OmpK37 had 4 mutant sites, and OmpK36 had 11 mutant sites, while no mutant sites were found in OmpK35. More than half of the CRKP strains contained the OqxA and OqxB efflux pump genes. The virulence genes were most commonly combined with urea-wabG-fimH-entB-ybtS-uge-ycf. Only one CRKP isolate was detected with the K54 podoconjugate serotype. This study elucidated the clinical epidemiological features and molecular typing of CRKP, and grasped the distribution of drug-resistant genotypes, podocyte serotypes, and virulence genes of CRKP, providing some guidance for the subsequent treatment of CRKP infection.

A mind in motion: Exercise improves cognitive flexibility, impulsivity and alters dopamine receptor gene expression in a Parkinsonian rat model.

Cognitive impairment, particularly deficits in executive function (EF) is common in Parkinson's disease (PD) and may lead to dementia. There are currently no effective treatments for cognitive impairment. Work from our lab and others has shown that physical exercise may improve motor performance in PD but its role in cognitive function remains poorly eludicated. In this study in a rodent model of PD, we sought to examine whether exercise improves cognitive processing and flexibility, important features of EF. Rats received 6-hydroxydopamine lesions of the bilateral striatum (caudate-putamen, CPu), specifically the dorsomedial CPu, a brain region central to EF. Rats were exercised on motorized running wheels or horizontal treadmills for 6-12 weeks. EF-related behaviors including attention and processing, as well as flexibility (inhibition) were evaluated using either an operant 3-choice serial reaction time task (3-CSRT) with rule reversal (3-CSRT-R), or a T-maze task with reversal. Changes in striatal transcript expression of dopamine receptors (Drd1-4) and synaptic proteins (Synaptophysin, PSD-95) were separately examined following 4 weeks of exercise in a subset of rats. Exercise/Lesion rats showed a modest, yet significant improvement in processing-related response accuracy in the 3-CSRT-R and T-maze, as well as a significant improvement in cognitive flexibility as assessed by inhibitory aptitude in the 3-CSRT-R. By four weeks, exercise also elicited increased expression of Drd1, Drd3, Drd4, synaptophysin, and PSD-95 in the dorsomedial and dorsolateral CPu. Our results underscore the observation that exercise, in addition to improving motor function may benefit cognitive performance, specifically EF, and that early changes (by 4 weeks) in CPu dopamine modulation and synaptic connectivity may underlie these benefits.

Effect of 1 + N Extended Nursing Service on Functional Recovery of Colostomy Patients.

To many hospitals' management as well as to patients, the nursing service is one of the most important aspects. Many diseases like sugar, blood pressure, urine passage, and gas are a little bit dangerous to handle by patients themselves. The earlier stage models are unable to give good services to patients; therefore, an advanced JHE: Effect of 1 + N extended nursing service is necessary to crossover the above limitations. Colostomy and colorectal cancers are very dangerous syndromes thus, disease monitoring is so difficult. In this research work, an extended JHE: Effect of 1 + N extended nursing service modeling is discussed with experimental modeling. Apart from conventional nursing care provided by the observation group, it was given online training as well as service providing. Self-efficacy and self-care competence were assessed in both groups 6 months after the discharge. Quality of life and mental health were also assessed. Besides, their dimensional and total self-care ability scores, and the observation group's self-efficacy ratings were substantially higher than those of the control group (P 0.05) after the intervention. It was observed that the intervention group's 6-month adjustment to the stoma was statistically more favorable than the control group's (P 0.001), and only the intervention group showed a significantly major change (P 0.001) between their two evaluations. This proposed methodology can improve the accuracy rate by 93.23%, and succussive treatment rate of 92.14% had been attained.

Super Dominant Pathobiontic Bacteria in the Nasopharyngeal Microbiota Cause Secondary Bacterial Infection in COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) is a respiratory infectious disease responsible for many infections worldwide. Differences in respiratory microbiota may correlate with disease severity. Samples were collected from 20 severe and 51 mild COVID-19 patients. High-throughput sequencing of the 16S rRNA gene was used to analyze the bacterial community composition of the upper and lower respiratory tracts. The indices of diversity were analyzed. When one genus accounted for >50% of reads from a sample, it was defined as a super dominant pathobiontic bacterial genus (SDPG). In the upper respiratory tract, uniformity indices were significantly higher in the mild group than in the severe group (P < 0.001). In the lower respiratory tract, uniformity indices, richness indices, and the abundance-based coverage estimator were significantly higher in the mild group than in the severe group (P < 0.001). In patients with severe COVID-19, SDPGs were detected in 40.7% of upper and 63.2% of lower respiratory tract samples. In patients with mild COVID-19, only 10.8% of upper and 8.5% of lower respiratory tract samples yielded SDPGs. SDPGs were present in both upper and lower tracts in seven patients (35.0%), among which six (30.0%) patients possessed the same SDPG in the upper and lower tracts. However, no patients with mild infections had an SDPG in both tracts. Staphylococcus, Corynebacterium, and Acinetobacter were the main SDPGs. The number of SDPGs identified differed significantly between patients with mild and severe COVID-19 (P < 0.001). SDPGs in nasopharyngeal microbiota cause secondary bacterial infection in COVID-19 patients and aggravate pneumonia. IMPORTANCE The nasopharyngeal microbiota is composed of a variety of not only the true commensal bacterial species but also the two-face pathobionts, which are one a harmless commensal bacterial species and the other a highly invasive and deadly pathogen. In a previous study, we found that the diversity of nasopharyngeal microbiota was lost in severe influenza patients. We named the genus that accounted for over 50% of microbiota abundance as super dominant pathobiontic genus, which could invade to cause severe pneumonia, leading to high fatality. Similar phenomena were found here for SARS-CoV-2 infection. The diversity of nasopharyngeal microbiota was lost in severe COVID-19 infection patients. SDPGs in nasopharyngeal microbiota were frequently detected in severe COVID-19 patients. Therefore, the SDPGs in nasopharynx microbiota might invade into low respiratory and be responsible for secondary bacterial pneumonia in patients with SARS-CoV-2 infection.

A gut-derived metabolite alters brain activity and anxiety behaviour in mice.

Integration of sensory and molecular inputs from the environment shapes animal behaviour. A major site of exposure to environmental molecules is the gastrointestinal tract, in which dietary components are chemically transformed by the microbiota1 and gut-derived metabolites are disseminated to all organs, including the brain2. In mice, the gut microbiota impacts behaviour3, modulates neurotransmitter production in the gut and brain4,5, and influences brain development and myelination patterns6,7. The mechanisms that mediate the gut-brain interactions remain poorly defined, although they broadly involve humoral or neuronal connections. We previously reported that the levels of the microbial metabolite 4-ethylphenyl sulfate (4EPS) were increased in a mouse model of atypical neurodevelopment8. Here we identified biosynthetic genes from the gut microbiome that mediate the conversion of dietary tyrosine to 4-ethylphenol (4EP), and bioengineered gut bacteria to selectively produce 4EPS in mice. 4EPS entered the brain and was associated with changes in region-specific activity and functional connectivity. Gene expression signatures revealed altered oligodendrocyte function in the brain, and 4EPS impaired oligodendrocyte maturation in mice and decreased oligodendrocyte-neuron interactions in ex vivo brain cultures. Mice colonized with 4EP-producing bacteria exhibited reduced myelination of neuronal axons. Altered myelination dynamics in the brain have been associated with behavioural outcomes7,9-14. Accordingly, we observed that mice exposed to 4EPS displayed anxiety-like behaviours, and pharmacological treatments that promote oligodendrocyte differentiation prevented the behavioural effects of 4EPS. These findings reveal that a gut-derived molecule influences complex behaviours in mice through effects on oligodendrocyte function and myelin patterning in the brain.

Occupational class differences in outcomes after ischemic stroke: a prospective observational study.

BACKGROUND: Occupational class is an integral part of socioeconomic status. The studies focused on the occupational difference in ischemic stroke outcome in a Chinese population are limited. We aimed to investigate the associations between occupational class and the prognosis of patients with ischemic stroke in China. METHODS: We included 1484 ischemic stroke participants (mean age: 63.42 ± 11.26 years) from the prospective cohort study: Infectious Factors, Inflammatory Markers and Prognosis of Acute Ischemic Stroke (IIPAIS). Occupational class was categorized into white-collar workers, blue-collar workers and farmers in our study. Study outcomes were cardiovascular events and all-cause mortality within 12 months after ischemic stroke onset. We applied Cox proportional hazard model to evaluate the associations between the occupational class and study outcomes after ischemic stroke. RESULTS: Within 12 months after ischemic stroke, there were 106 (7.5%) cardiovascular events and 69 (4.9%) all-cause deaths. The Kaplan-Meier plots showed that white-collar workers had highest risk of cardiovascular events after 12-month follow-up (Log-rank P = 0.02). Multivariate adjusted hazard ratio and 95% confidence intervals (CIs) of farmers versus white-collar workers was 0.43(0.20-0.91) for cardiovascular events. No significant difference showed in blue-collar workers versus white-collar workers, with fully adjusted hazard ratio 0.62(95% CIs, 0.23-1.67). CONCLUSIONS: Compared with white-collar workers, farmers are associated with less risk of cardiovascular events at 12 months after ischemic stroke, while there are no significant differences in blue-collar workers.

Cognitive flexibility deficits in rats with dorsomedial striatal 6-hydroxydopamine lesions tested using a three-choice serial reaction time task with reversal learning.

Lesions of the dorsomedial striatum elicit deficits in cognitive flexibility that are an early feature of Parkinson's disease (PD), and presumably reflect alterations in frontostriatal processing. The current study aimed to examine deficits in cognitive flexibility in rats with bilateral 6-hydroxydopamine lesions in the dorsomedial striatum. While deficits in cognitive flexibility have previously been examined in rodent PD models using the cross-maze, T-maze, and a food-digging task, the current study is the first to examine such deficits using a 3-choice serial reaction time task (3-CSRT) with reversal learning (3-CSRT-R). Although the rate of acquisition in 3-CSRT was slower in lesioned compared to control rats, lesioned animals were able to acquire a level of accuracy comparable to that of control animals following 4 weeks of training. In contrast, substantial and persistent deficits were apparent during the reversal learning phase. Our results demonstrate that deficits in cognitive flexibility can be robustly unmasked by reversal learning in the 3-CSRT-R paradigm, which can be a useful test for evaluating effects of dorsomedial striatal deafferentation and interventions.

Ceftriaxone inhibits stress-induced bladder hyperalgesia and alters cerebral micturition and nociceptive circuits in the rat: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome research network study.

AIMS: Emotional stress plays a role in the exacerbation and development of interstitial cystitis/bladder pain syndrome (IC/BPS). Given the significant overlap of brain circuits involved in stress, anxiety, and micturition, and the documented role of glutamate in their regulation, we examined the effects of an increase in glutamate transport on central amplification of stress-induced bladder hyperalgesia, a core feature of IC/BPS. METHODS: Wistar-Kyoto rats were exposed to water avoidance stress (WAS, 1 hour/day x 10 days) or sham stress, with subgroups receiving daily administration of ceftriaxone (CTX), an activator of glutamate transport. Thereafter, cystometrograms were obtained during bladder infusion with visceromotor responses (VMR) recorded simultaneously. Cerebral blood flow (CBF) mapping was performed by intravenous injection of [14 C]-iodoantipyrine during passive bladder distension. Regional CBF was quantified in autoradiographs of brain slices and analyzed in three dimensional reconstructed brains with statistical parametric mapping. RESULTS: WAS elicited visceral hypersensitivity during bladder filling as demonstrated by a decreased pressure threshold and VMR threshold triggering the voiding phase. Brain maps revealed stress effects in regions noted to be responsive to bladder filling. CTX diminished visceral hypersensitivity and attenuated many stress-related cerebral activations within the supraspinal micturition circuit and in overlapping limbic and nociceptive regions, including the posterior midline cortex (posterior cingulate/anterior retrosplenium), somatosensory cortex, and anterior thalamus. CONCLUSIONS: CTX diminished bladder hyspersensitivity and attenuated regions of the brain that contribute to nociceptive and micturition circuits, show stress effects, and have been reported to demonstrated altered functionality in patients with IC/BPS. Glutamatergic pharmacologic strategies modulating stress-related bladder dysfunction may be a novel approach to the treatment of IC/BPS.

Lineage, Antimicrobial Resistance and Virulence of Citrobacter spp.

Citrobacter spp. are opportunistic human pathogens which can cause nosocomial infections, sporadic infections and outbreaks. In order to determine the genetic diversity, in vitro virulence properties and antimicrobial resistance profiles of Citrobacter spp., 128 Citrobacter isolates obtained from human diarrheal patients, foods and environment were assessed by multilocus sequence typing (MLST), antimicrobial susceptibility testing and adhesion and cytotoxicity testing to HEp-2 cells. The 128 Citrobacter isolates were typed into 123 sequence types (STs) of which 101 were novel STs, and these STs were divided into five lineages. Lineages I and II contained C. freundii isolates; Lineage III contained all C. braakii isolates, while Lineage IV and V contained C. youngae isolates. Lineages II and V contained more adhesive and cytotoxic isolates than Lineages I, III, and IV. Fifty-one of the 128 isolates were found to be multidrug-resistant (MDR, ≥3) and mainly distributed in Lineages I, II, and III. The prevalence of quinolone resistance varied with Lineage III (C. braakii) having the highest proportion of resistant isolates (52.6%), followed by Lineage I (C. freundii) with 23.7%. Seven qnrB variants, including two new alleles (qnrB93 and qnrB94) were found with Lineage I being the main reservoir. In summary, highly cytotoxic MDR isolates from diarrheal patients may increase the risk of severe disease.

Leaching behavior and potential ecological risk of heavy metals in Southwestern China soils applied with sewage sludge compost under acid precipitation based on lysimeter trials.

The ecological risk of heavy metals (HM) resulting from the use of sewage sludge compost (SSC) as an amendment to flower garden soil (FGS) and to abandoned phosphate mine soil (APMS) influenced by acid rain were simulated in lysimeter trials and the potential ecological risk index (PERI) was evaluated with minor modifications. The use of SSC indeed increased the mobility and release of HMs in FGS and APMS under conditions of acid rain. The leaching dynamics of HMs was found to be influenced by Fe/Al oxides and organic matter (OM) in the soil. The application of SSC as a fertilizer to barren APMS dramatically decreased the mobility of Cr, Cu and Pb by 51-56% due to their retention by particulate organic matter, while the leaching of As, Cd and Ni was increased as the result of competition with OM for available Fe/Al oxides (As) and proton-metal exchange reactions that occurred in HM-OM complexes (Cd and Ni). The ecological risk of FGS and APMS resulting from HM migration was actually low (PERI = 0.07-0.12), but the increased potential ecological risk resulting from the use of SSC were estimated to be moderate (a 16.0-33.5% increase in PERI for SSC-amended FGS) or high (a 140% increase in PERI for SSC-amended APMS). Ni, Cd and Cu were identified as the three main HMs responsible for increasing the ecological risk in soil which was mainly composed of fine-grained particles, whereas Cd and As were key ecological risks HMs in soil that was mainly composed of coarse-grained particles.

Voluntary exercise improves voiding function and bladder hyperalgesia in an animal model of stress-induced visceral hypersensitivity: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome research network study.

OBJECTIVE: The underlying mechanism of interstitial cystitis/bladder pain syndrome (IC/BPS) is not well understood and evaluation of current therapeutic interventions has not identified any generally effective treatments. Physical activity has shown beneficial effects on individuals suffering from chronic pain. Anxiety-prone rats exposed to water avoidance stress (WAS) develop urinary frequency and lower bladder sensory thresholds with high face and construct validity for the study of IC/BPS. The aim of this study was to evaluate the role of chronic voluntary exercise on urinary frequency, voiding function, and hyperalgesia in animals exposed to WAS. MATERIALS AND METHODS: Twenty-six female Wistar-Kyoto rats were exposed to WAS and thereafter randomized to either voluntary exercise for 3 weeks or sedentary groups. Voiding parameters were assessed at baseline, post-WAS, and weekly for 3 weeks. Before euthanasia, the animals underwent cystometrogram (CMG), external urinary sphincter electromyography, and assessment of visceromotor response (VMR) to isotonic bladder distension (IBD). RESULTS: WAS exposure resulted in adverse changes in voiding parameters. Compared with sedentary animals, animals in the voluntary exercise group had improved voiding parameters during metabolic cage and CMG testing, as well as improved bladder sensory thresholds as determined by VMR during IBD. CONCLUSION: Voluntary exercise in an animal model of chronic stress leads to improvement in voiding function and visceral bladder hyperalgesia.

Exercise modulates neuronal activation in the micturition circuit of chronically stressed rats: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome (MAPP) research network study.

BACKGROUND: Rats exposed to water avoidance stress (WAS) show increased urinary frequency, increased somatosensory nociceptive reflex responses, as well as altered brain responses to bladder distension, analogous to similar observations made in patients with urologic chronic pelvic pain syndrome (UCPPS). Exercise has been proposed as a potential treatment option for patients with chronic urinary frequency and urgency. We examined the effects of exercise on urinary voiding parameters and functional brain activation during bladder distension in rats exposed to WAS. METHODS: Adult, female Wistar Kyoto rats were exposed to 10 days of WAS and thereafter randomized to either voluntary exercise for 3 weeks or sedentary groups. Voiding parameters were assessed at baseline, post-WAS, and weekly for 3 weeks. Thereafter, cerebral blood flow (CBF) mapping was performed during isotonic bladder distension (20 cm H2O) after intravenous bolus injection of [14C]-iodoantipyrine. Regional CBF was quantified in autoradiographs of brain slices and analyzed in 3-D reconstructed brains by statistical parametric mapping. Functional connectivity was examined between regions of the micturition circuit through interregional correlation analysis. RESULTS: WAS exposure in sedentary animals (WAS/no-EX) increased voiding frequency and decreased urinary volumes per void. Exercise exposure in WAS animals (WAS/EX) resulted in a progressive decline in voiding frequency back to the baseline, as well as increased urinary volumes per void. Within the micturition circuit, WAS/EX compared to WAS/no-EX demonstrated a significantly lower rCBF response to passive bladder distension in Barrington's nucleus that is part of the spinobulbospinal voiding reflex, as well as in the periaqueductal gray (PAG) which modulates this reflex. Greater rCBF was noted in WAS/EX animals broadly across corticolimbic structures, including the cingulate, medial prefrontal cortex (prelimbic, infralimbic areas), insula, amygdala, and hypothalamus, which provide a 'top-down' decision point where micturition could be inhibited or triggered. WAS/EX showed a significantly greater positive brain functional connectivities compared to WAS/no-EX animals within regions of the extended reflex loop (PAG, Barrington's nucleus, intermediodorsal thalamic nucleus, pons), as well as within regions of the corticolimbic decision-making loop of the micturition circuit, with a strikingly negative correlation between these pathways. Urinary frequency was positively correlated with rCBF in the pons, and negatively correlated with rCBF in the cingulate cortex. CONCLUSION: Our results suggest that chronic voluntary exercise may decrease urinary frequency at two points of control in the micturition circuit. During the urine storage phase, it may diminish the influence of the reflex micturition circuit itself, and/or it may increase corticolimbic control of voiding. Exercise may be an effective adjunct therapeutic intervention for modifying the urinary symptoms in patients with UCPPS.

Fabrication of paper-based microfluidic device by recycling foamed plastic and the application for multiplexed measurement of biomarkers.

Microfluidic paper-based analytical devices (µPADs) are emerging as effective analytical platforms for point-of-care assays in resource-limited areas. Simple and cost-effective fabrication method still remains challenging on µPADs. A simple and cost-effective method for fabricating paper-based devices was presented in this work by using of dipping strategy with the recycled polystyrene in chloroform as the hydrophobic reagent. Adhesive tape was employed as mask to transfer the hydrophilic channel pattern to the paper substrate. With the single-sided adhesive tape stuck on the hydrophilic parts of the paper surface, the paper-based device was immersed in chloroform solution with dissolving recycling polystyrene for several seconds. Then the hydrophilic pattern can be achieved and all the other parts on the paper surface were hydrophobic. The adhesive tape was torn off from the hydrophilic parts. The highest contact angle value of 114° of the hydrophobic part was acquired with this simple fabrication method. By using of the sandwich-type immunoreactions and luminol-H2O2p-iodophenol (PIP) chemiluminescence(CL) system, three cancer biomarkers were simultaneously detected in human serum samples on µPADs with the linear range of 0.05-80.0 ng·mL-1 for carcinoembryonic antigen (CEA), 5.0-80.0 ng·mL-1 for alpha-fetal protein (AFP) and 1.0-50.0 ng·mL-1 for prostate-specific antigen (PSA). The fabricating strategy with recycling polystyrene and adhesive tape provides a versatile platform for prototyping of µPADs in both developed and resource constrained region.

Sex differences in insular functional connectivity in response to noxious visceral stimulation in rats.

Insular cortex (INS) plays a critical role in pain processing and shows sex differences in functional activation during noxious visceral stimulation. Less is known regarding functional interactions within the INS and between this structure and other parts of the brain. Cerebral blood flow mapping was performed using [14C]-iodoantipyrine perfusion autoradiography in male and female rats during colorectal distension (CRD) or no distension (controls). Forty regions of interest (ROIs) were defined anatomically to represent the granular, dysgranular, and agranular INS along the anterior-posterior (A-P) axis. Inter-ROI correlation matrices were calculated for each group to characterize intra-insular functional connectivity (FC). Results showed a clear FC segregation within the INS into an anterior (rostral to bregma +2.4 mm), a posterior (caudal to bregma -1.2 mm), and a mid INS subregion in between. Female controls showed higher FC density compared to males. During CRD, intra-insular FC density decreased greatly in females, but only modestly in males, with a loss of long-range connections between the anterior and mid INS noted in both sexes. New functional organization was characterized in both sexes by a cluster in the mid INS and primarily short-range FC along the A-P axis. Seed correlation analysis during CRD showed sex differences in FC of the anterior and mid agranular INS with the medial prefrontal cortex, thalamus, and brainstem areas (periaqueductal gray, parabrachial nucleus), suggesting sex differences in the modulatory aspect of visceral pain processing. Our findings suggest presence of substantial sex differences in visceral pain processing at the level of the insula.

Positive Allosteric Modulation of Cholinergic Receptors Improves Spatial Learning after Cortical Contusion Injury in Mice.

We examined benzyl quinolone carboxylic acid (BQCA), a novel M1 muscarinic-positive allosteric modulator, for improving memory and motor dysfunction after cerebral cortical contusion injury (CCI). Adult mice received unilateral motorsensory cortical CCI or sham injury. Benzyl quinolone carboxylic acid (BQCA; 5, 10, and 20 mg/kg, intraperitoneally [i.p.] × 2/day × 3-4 weeks) or vehicle (Veh) were administered, and weekly evaluations were undertaken using a battery of motor tests, as well as the Morris water maze. Thereafter, cerebral metabolic activation was investigated in awake animals during walking with [14C]-2-deoxygIucose autoradiography, comparing CCI mice previously treated with BQCA (20 mg/kg) or vehicle. Relative changes in local cerebral glucose uptake (rCGU) were evaluated in three-dimensional-reconstructed brains using statistical parametric mapping. CCI resulted in mild hyperactivity in the open field, and modest significant motor deficits, as well as significantly decreased spatial learning at 3 weeks. BQCA in CCI mice resulted in significantly improved spatial recall during the third week, with minimal effects on motor outcomes. CCI significantly decreased rCGU in the ipsilesional basal ganglia-thalamocortical circuit and in somatosensory regions, with relative increases noted contralaterally, as well as in the cerebellum. Significant decreases in rCGU were noted in subregions of the ipsilesional hippocampal formation, with significant increases noted contralesionally. BQCA compared to vehicle-treated mice showed modest, though significantly increased, rCGU in motor regions, as well as a partial reversal of lesion-related rCGU findings in subregions of the hippocampal formation. rCGU in ipsilesional posterior CA1 demonstrated a significant inverse correlation with latency to find the submerged platform. BQCA at 20 mg/kg had no significant effect on general motor activity, body weight, or acute motor, secretory, or respiratory symptoms. Results suggest that BQCA is a candidate compound to improve learning and memory function after brain trauma and may not suffer the associated central nervous system side effects typically associated with even modest doses of other cholinergic enhancers.