Notes

Co-modification using MSC membrane and Smartphone helps prevent Fe3O4-induced lung toxicity within these animals via AMPK-ULK1 axis.
Mean MDS-UPDRS score was positively associated with dysphagia severity on SSQ and SWAL-QOL. HRPIM in PD compared with controls showed impaired UES relaxation parameters, with shorter RT, and elevated IRP and IBP. MaxAdm was not affected. The overall pharyngeal contractility was significantly higher in PD. Only the IBP and IRP were associated with PD severity and only IBP was significantly associated with dysphagia severity. UES dysfunction leading to increased flow resistance is common in patients with PD and correlates with dysphagia severity. Increased flow resistance may suggest impaired UES relaxation and/or impaired neuromodulation to bolus volume.NEW & NOTEWORTHY In Parkinson's disease, objective assessment of swallow function with high-resolution impedance manometry identifies upper esophageal sphincter dysfunction leading to increased flow resistance.Background The study encompasses findings from a prospective quantitative screening of women family caregivers for depression as part of a larger mixed methods study designed to develop and validate a caregiver burden inventory for the home-based palliative care programme in Kerala, India. Aim We assessed the proportion of women caregivers screening positive for depression and explored the associated factors. Methods The Primary care Screening Questionnaire for Depression (PSQ4D) was used to screen participants for depression. Other variables analysed were caregiver and patient related factors, stresses, strains, support received, caregiver burden and quality of life domain variables as per the EuroQol EQ-5D-5L instrument. Results Forty women (20.0%, 95% Confidence Intervals [CI] 14.46% - 25.54%) screened positive for depression on the PSQ4D. This was more likely if the care recipient was the spouse, if the care recipient had cancer, if the caregiver perceived a moderate or high physical/psychological burden, or a high financial burden. Pain/ discomfort when included had an adjusted odds ratio (AOR) of 8.2 (95% CI 2.6-26.0) and tended to decrease the AOR of all other significantly associated variables, except cancer diagnosis in the care recipient. Conclusion Depression levels among women caregivers in primary palliative care settings in Kerala seem comparable to prevalence levels among women in the general population. Those caregivers reporting pain/ discomfort should be screened for depression using simple locally validated measures. Depression is associated with higher caregiver burden and poorer quality of life. Screening and treatment of depression may help mitigate these situations.It is well known that humans physiologically or pathologically respond to high altitude, with these responses accompanied by alterations in the gut microbiome. To investigate whether gut microbiota modulation can alleviate high-altitude-related diseases, we administered probiotics, prebiotics, and synbiotics in rat model with altitude-related cardiac impairment after hypobaric hypoxia challenge and observed that all three treatments alleviated cardiac hypertrophy as measured by heart weight-to-body weight ratio and gene expression levels of biomarkers in heart tissue. Entinostat ic50 The disruption of gut microbiota induced by hypobaric hypoxia was also ameliorated, especially for microbes of Ruminococcaceae and Lachnospiraceae families. Metabolome revealed that hypobaric hypoxia significantly altered the plasma short-chain fatty acids (SCFAs), bile acids (BAs), amino acids, neurotransmitters, and free fatty acids, but not the overall fecal SCFAs and BAs. The treatments were able to restore homeostasis of plasma amino acids and neurotransmitters to a certain degree, but not for the other measured metabolites. This study paves the way to further investigate the underlying mechanisms of gut microbiome in high-altitude related diseases and opens opportunity to target gut microbiome for therapeutic purpose. IMPORTANCE Evidence suggests that gut microbiome changes upon hypobaric hypoxia exposure; however, it remains elusive whether this microbiome change is a merely derivational reflection of host physiological alteration, or it synergizes to exacerbate high-altitude diseases. We intervened gut microbiome in the rat model of prolonged hypobaric hypoxia challenge and found that the intervention could alleviate the symptoms of pathological cardiac hypertrophy, gut microbial dysbiosis, and metabolic disruptions of certain metabolites in gut and plasma induced by hypobaric hypoxia. Our study suggests that gut microbiome may be a causative factor for high-altitude-related pathogenesis and a target for therapeutic intervention.The prevalence of tuberculosis (TB) and human immunodeficiency virus (HIV) coinfection in Nigeria is currently around 19.1%. This indicates that the two diseases are still a burden on the nation"s health. The aim of this study was to evaluate the diagnostic microbiology capacity and the barriers in performing assay for TB and HIV at peripheral district-level hospital-based laboratories in Oyo State, Nigeria. Diagnostic microbiology capacity was estimated using a scale of 100-point where scores ≤ 49% were categorized as low, 50-79% fair and ≥80% good. Barriers to diagnosis were summarized in proportions. The diagnostic microbiology capacity revealed that 6 (35.3%) and 11 (64.7%) of the laboratories had "fair" and "low" capacity, respectively, to detect TB in cerebrospinal fluid/sputum. In testing for HIV, 3 (17.6%) of the laboratories had "fair capacity" and 14 (82.4%) had "low capacity" to detect CD4 count and HIV antibodies in blood serum. The major diagnostic barriers in almost all (94.1%) the laboratories were lack of culture supplies and nonavailability of reagents/testing kits. There was no diagnostic microbiology service with good capacity to facilitate case detection of HIV and TB at the peripheral hospitals. Hence there is a need to improve the supply of reagents, culture stock and testing kits. This will facilitate the detection of TB and HIV cases in peripheral communities. IMPORTANCE This study provided a snapshot knowledge of testing capabilities and commodity availability at state laboratories. The findings should inform the action of stakeholders to improve diagnostic microbiology capacity, consequently enhancing diagnostic measures in detecting human immunodeficiency virus and Mycobacterium tuberculosis.The COVID-19 causing coronavirus (SARS-CoV-2) remains a public health threat worldwide. SARS-CoV-2 enters human lung cells via its spike glycoprotein binding to angiotensin-converting enzyme 2 (ACE2). Notably, the cleavage of the spike by the host cell protease furin in virus-producing cells is critical for subsequent spike-driven entry into lung cells. Thus, effective targeted therapies blocking the spike cleavage and activation in viral producing cells may provide an alternate strategy to break the viral transmission cycle and to overcome disease pathology. Here we engineered and described an antibody-based targeted strategy, which directly competes with the furin mediated proteolytic activation of the spike in virus-producing cells. The described approach involves engineering competitive furin substrate residues in the IgG1 Fc-extended flexible linker domain of SARS-CoV-2 spike targeting antibodies. Considering the site of spike furin cleavage and SARS-CoV-2 egress remains uncertain, the experimental stratentry and chain of the infection cycle, the solution described here of an antibody Fc-conjugated furin competing peptide is significant. In a scenario where spike mutational drifts do not interfere with the Fc-conjugated antibody's epitope, the proposed furin competing strategy confers a broad-spectrum targeting design to impede the production of efficiently transmissible SARS-CoV-2 viral particles. In addition, the proposed approach is plug-and-play against other potentially deadly viruses that exploit secretory pathway independent host protease machinery to gain cellular entry and subsequent transmissions to host cells.Methicillin-resistant Staphylococcus aureus (MRSA) sequence type (ST) 22, especially the epidemic MRSA-15 (EMRSA-15), has been one of the most important disease-causing clones transmitting rapidly within and between hospitals globally. However, the genetic features and evolution of Chinese MRSA ST22 remain to be determined. Herein, we performed comparative genomics analysis of 12 ST22 community-associated (CA) MRSA isolates from China with 9 Chinese ST22 CA-MSSA isolates and 284 ST22 genomes from global sources, to clarify the genotypic features and potential transmission of MRSA ST22 strains isolated in China. Phylogenetic reconstruction and time estimation suggested that the Chinese subclade emerged around 2006, and the ST22-SCCmec V clone may have evolved from the native ST22-MSSA clone rather than spread from other regions, indicating that the Chinese ST22-MRSA-V clone is independent of the EMRSA-15 and Gaza clone, with differences in lukSF-PV and tsst-1 carriage. Virulence assays suggested that the ST22-he genotypic features and potential transmission of MRSA ST22 strains isolated from China. Our results suggested that the Chinese subclade is highly virulent, and emerged around 2006. We also demonstrated that the ST22-SCCmec V may have evolved from the native ST22-MSSA clone rather than spread from other regions, and the high virulence potential of these ST22 strains may be attributed to the high expression of agr based on the results of virulence assays of Chinese ST22 clones. Our findings are of great importance for providing insights into the epidemiology and pathogenicity of global and Chinese ST22 clones.Colistin is widely used in agriculture and aquaculture as prophylaxis, particularly in Asia. Recently, mcr-1 and other mobilizable genes conferring colistin resistance have spread globally in community and hospital populations. Characterizing mcr-1 mobile genetic elements and host genetic background is important to understand the transmission of this resistance mechanism. We conducted whole-genome sequencing of 94 mcr-1-positive Escherichia coli isolates (Mcr1-Ec isolates) from human and animal feces, food, and water in a community cohort (N = 87) and from clinical specimens from a referral hospital (N = 7) in northern Vietnam. mcr-1 was plasmid-borne in 71 and chromosomally carried in 25 (2 isolates contain one copy on chromosome and one copy on a plasmid) of 94 E. coli isolates from the community and hospital settings. All seven clinical isolates carried mcr-1 on plasmids. Replicon types of mcr-1-carrying plasmids included IncI2, IncP, IncX4, and IncFIA single replicons and combinations of IncHI2, IncN, andon of mcr-1 in different reservoirs. The widespread use of colistin in agriculture, where a high diversity of bacteria are exposed, has allowed the selection and evolution of various transmission mechanisms that will make it a challenge to get rid of. Colocalization of mcr-1 and other antibiotic resistance genes (ARGs) on multireplicon plasmids adds another layer of complexity to the rapid dissemination of mcr-1 genes among community and hospital bacterial populations and to the slow pandemic of antimicrobial resistance (AMR) in general.Microbial keratitis is a devastating disease that can cause eye damage and blindness and can be the result of infections by several common ocular pathogens. Importantly, some of these pathogens, such as Acanthamoeba, are particularly unsusceptible to biocides in common contact lens care solutions. Therefore, the disinfection efficacy of preservative-free (PF) disinfection systems against bacteria, fungi, and Acanthamoeba trophozoites and cysts should be assessed as products with the most potential to be efficacious against resistant organisms. PF disinfection systems were analyzed for antimicrobial efficacy. These were the one-step (hydrogen peroxide-based) Clear Care and Clear Care Plus systems and the two-step (povidone-iodine-based) Cleadew system. Stand-alone challenges using bacteria, fungi, and Acanthamoeba were prepared according to the International Standards Organization method 14729. These same challenges were also conducted in the presence of the following contact lenses Boston RGP, Acuvue Oasys, Biofinity, Ultra, and 2-week PremiO.
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