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.

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.

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.

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.

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.

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.

Removal of nitrogen and phosphorus from the secondary effluent in tertiary denitrifying biofilters combined with micro-coagulation.

Effective control of nitrogen and phosphorus in secondary effluent can reduce or avoid the eutrophication of receiving water bodies. Two denitrifying biofilters (DNBFs) packed with different sizes of quartz sands combined with micro-coagulation were operated for simultaneous removal of nitrogen and phosphorus from the secondary effluent. The quartz sand size in one DNBF was 2-4 mm (DNBFS), and in the other was 4-6 mm (DNBFL). In both DNBFs, methanol was used as the electron donor and different organic carbon to nitrogen (C/N) ratios were applied. Under C/N ratios of 1.5, 1.25, and 0.75 g/g, the nitrate nitrogen (NO3(-)-N) removal percentages were 73%, 77%, and 50% in DNBFS, and 43%, 25%, and 21% in DNBFL; the effluent total phosphorus concentrations were 0.15, 0.14, and 0.18 mg/L in DNBFS, and 0.29, 0.35, and 0.24 mg/L in DNBFL. The performance of both biofilters was quite stable within a backwashing cycle. The NO3(-)-N reduction rates were 1.31, 1.10, and 0.48 mg/(L·min) in DNBFS, and 0.97, 0.27, and 0.10 mg/(L·min) in DNBFL. For biomass detached from both biofilters, their denitrifying activities were similar. Biofilm biomass in DNBFS was higher than that in DNBFL, inducing a high denitrification efficiency in DNBFS.

Recruitment of the prefrontal cortex and cerebellum in Parkinsonian rats following skilled aerobic exercise.

Exercise modality and complexity play a key role in determining neurorehabilitative outcome in Parkinson's disease (PD). Exercise training (ET) that incorporates both motor skill training and aerobic exercise has been proposed to synergistically improve cognitive and automatic components of motor control in PD patients. Here we introduced such a skilled aerobic ET paradigm in a rat model of dopaminergic deafferentation. Rats with bilateral, intra-striatal 6-hydroxydopamine lesions were exposed to forced ET for 4weeks, either on a simple running wheel (non-skilled aerobic exercise, NSAE) or on a complex wheel with irregularly spaced rungs (skilled aerobic exercise, SAE). Cerebral perfusion was mapped during horizontal treadmill walking or at rest using [(14)C]-iodoantipyrine 1week after the completion of ET. Regional cerebral blood flow (rCBF) was quantified by autoradiography and analyzed in 3-dimensionally reconstructed brains by statistical parametric mapping. SAE compared to NSAE resulted in equal or greater recovery in motor deficits, as well as greater increases in rCBF during walking in the prelimbic area of the prefrontal cortex, broad areas of the somatosensory cortex, and the cerebellum. NSAE compared to SAE animals showed greater activation in the dorsal caudate-putamen and dorsal hippocampus. Seed correlation analysis revealed enhanced functional connectivity in SAE compared to NSAE animals between the prelimbic cortex and motor areas, as well as altered functional connectivity between midline cerebellum and sensorimotor regions. Our study provides the first evidence for functional brain reorganization following skilled aerobic exercise in Parkinsonian rats, and suggests that SAE compared to NSAE results in enhancement of prefrontal cortex- and cerebellum-mediated control of motor function.

Ring-Oven Washing Technique Integrated Paper-based Immunodevice for Sensitive Detection of Cancer Biomarker.

A paper-based microfluidic immunodevice has recently attracted considerable interest for point-of-care testing (POCT) and a washing procedure was used as a standard procedure in immunoassay to eliminate the nonspecific binding protein from a paper surface. However, the traditional washing method cannot get rid of the nonspecific binding protein more completely to get a lower background. In this work, a novel washing strategy with a ring-oven technique integrated on a paper-based immunodevice was presented, which can effectively wash a nonspecific binding protein and enable a low background for sensitive detection of the carcinoembryonic antigen (CEA). By immobilizing the antibody on the detection area and incorporating the temperature-controlled ring-oven under the paper-based device, the continuous washing solution can carry the nonspecific binding protein to the waste area freely by capillary force and then the waste area dried quickly by heating. The paper device, which is matched to the size of the ring-oven, is composed of eight microfluidic channels by the simple and rapid paper-cutting fabrication method. With the HRP-catalyzed 3,3',5,5'-tetramethylbenzidine (TMB)-H2O2 colorimetric detection method, a lower detection limit of 0.03 ng/mL CEA can be obtained by enzyme-linked immunosorbent assay (ELISA). The washing efficiency for the nonspecific binding protein was improved a lot compared to the traditional washing methods, and the established paper-based device can be used in the determination of CEA in human serum with high sensitivity. The paper-based device provides a new washing strategy for sensitive immunoassay and point-of-care diagnostics.

Isolation and molecular typing of Cronobacter spp. in commercial powdered infant formula and follow-up formula.

Cronobacter spp. (Enterobacter sakazakii) are important foodborne pathogens. Infections with this pathogen can lead to neonatal meningitis, necrotizing enterocolitis, and bacteremia. This study examined Cronobacter spp. contamination in commercial powdered infant formulas (PIFs) and follow-up formulas (FUFs) in China. Forty-nine of 399 samples were contaminated with Cronobacter spp. and 10.2% of the isolates were resistant to cefotaxime; in contrast, all of the tested isolates were susceptible to amikacin, amoxicillin/clavulanic acid, cefepime, ciprofloxacin, imipenem, and meropenem. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) analyses produced a total of 16 PFGE banding patterns and 11 sequence types (STs), including 7 novel STs. In summary, the rates at which Cronobacter spp. were isolated from commercial PIF and FUF samples in China were relatively high, and the isolated strains exhibited high susceptibility in vitro to most antibiotics. The PFGE method exhibited higher typing capability than the MLST method, and molecular typing results revealed that the contamination of PIF and FUF with Cronobacter spp. in China may be mainly due to the addition of contaminated materials. Thus, the development of more effective control strategies during the manufacturing process is needed.

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.

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.

Change in IgG1 Fc N-linked glycosylation in human lung cancer: age- and sex-related diagnostic potential.

The interactions of IgG Fc region with Fc receptors are optimized by the tailoring of a single-conserved N-linked glycosylation site at Asn-297. Our previous study has demonstrated that the age-related Fc-glycosylation change is featured by sex specificity and that the Fc-glycosylation has the potential for disease discrimination. Here, we conducted a Fourier transform ion cyclotron resonance MS-based profiling study involving 410 control individuals and 259 lung cancer (LC) patients. As compared to healthy controls, the marked increase in IgG1 Fc-agalactosylation and decrease in galactosylation were observed in LC patients. The binary logistic regression in combination with the receiver operating characteristic curve was used to determine the diagnostic ability of IgG1 Fc-glycosylation. It was found that this diagnostic ability was both sex and age dependent. Additionally, the change in Fc-glycosylation upon many different physiological and pathological conditions was retrospectively discussed. The data furthered the understanding of the immune-associated change in human LC, and also might be useful in the future attempts for Fc-glycosylation-associated diagnostic evaluations and clinical assays.

Lipid profiling for early diagnosis and progression of colorectal cancer using direct-infusion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry.

RATIONALE: Colorectal cancer (CRC) has attracted increasing attention due to its common occurrence and worldwide distribution. METHODS: Direct-infusion positive and negative ion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (DI-ESI(±)-FTICR MS) was applied to analyze the serum metabolites from 52 CRC patients and 52 healthy controls. Metabolites whose inter-group intensities were determined to be statistically significant by univariate and multivariate statistical analyses were further identified by a combination of the Human Metabolome Database, accurate mass measurement, isotopic abundance distribution simulation, and tandem mass spectrometry. Orthogonal partial least square discriminant analysis (OPLS-DA), based on the data from DI-ESI(±)-FTICR MS, revealed a remarkable discrimination among early stage patients, late stage patients, and healthy controls. RESULTS: A total of 15 differentially expressed metabolites were identified and categorized into four lipid classes. Each lipid class demonstrated specific changing trends in CRC progression. Biomarker panel 1 containing palmitic amide, oleamide, hexadecanedioic acid, octadecanoic acid, eicosatrienoic acid, LPC(18:2), LPC(20:4), LPC(22:6), myristic acid and LPC(16:0) achieved excellent diagnostic accuracy with area under the ROC curve (AUC) of 0.991, a sensitivity of 0.981 and a specificity of 1.000 for differentiating early stage patients from healthy controls, which was better than the carcinoembryonic antigen biomarker. CONCLUSIONS: Our study revealed that the consideration of CRC stages would be necessary in diagnostic biomarker discovery, as well as that attention should be paid to the facile loss of methyl chloride from the [M + Cl](-) form of LPC(16:0) in its tandem mass spectrum.

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.

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.

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.

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.

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.

Bone marrow progenitor cells repair rat hepatic sinusoidal endothelial cells after liver injury.

BACKGROUND & AIMS: Damage to hepatic sinusoidal endothelial cells (SECs) initiates sinusoidal obstruction syndrome (SOS), which is most commonly a consequence of myeloablative chemoirradiation or ingestion of pyrrolizidine alkaloids such as monocrotaline (Mct). This study examines whether SECs are of bone marrow origin, whether bone marrow repair can be a determinant of severity of liver injury, and whether treatment with progenitor cells is beneficial. METHODS: Mct-treated female rats received infusion of male whole bone marrow or CD133(+) cells at the peak of sinusoidal injury. The Y chromosome was identified in isolated SECs by fluorescent in situ hybridization. Bone marrow suppression was induced by irradiation of both lower extremities with shielding of the abdomen. RESULTS: SECs in uninjured liver have both hematopoietic (CD45, CD33) and endothelial (CD31) markers. After Mct-induced SOS, infusion of bone marrow-derived CD133(+) progenitor cells replaces more than one quarter of SECs. All CD133(+) cells recovered from the SEC fraction after injury are CD45(+). CD133(+)/CD45(+) progenitors also repaired central vein endothelium. Mct suppresses CD133(+)/CD45(+) progenitors in bone marrow by 50% and in the circulation by 97%. Irradiation-induced bone marrow suppression elicited SOS from a subtoxic dose of Mct, whereas infusion of bone marrow during the necrotic phase of SOS nearly eradicates histologic features of SOS. CONCLUSIONS: SECs have both hematopoietic and endothelial markers. Bone marrow-derived CD133(+)/CD45(+) progenitors replace SECs and central vein endothelial cells after injury. Toxicity to bone marrow progenitors impairs repair and contributes to the pathogenesis of SOS, whereas timely infusion of bone marrow has therapeutic benefit.