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Additionally, the capacity of the SF-based nanocarriers to offer intestinal protection against 5-FU-induced GI mucositis was evaluated in vivo using a mouse model that mimics the chemotherapy-associated gut mucositis occurring in colorectal cancer. Our studies show that silk fibroin nanoparticles efficiently deliver 5-FU to tumor cells in vitro while protecting against drug-induced GI mucositis in a mouse model.Commensal fungus-Candida albicans turn pathogenic during the compromised immunity of the host, causing infections ranging from superficial mucosal to dreadful systemic ones. C. albicans has evolved various adaptive measures which collectively contribute towards its enhanced virulence. Among fitness attributes, metabolic flexibility and vigorous stress response are essential for its pathogenicity and virulence. Metabolic flexibility provides a means for nutrient assimilation and growth in diverse host microenvironments and reduces the vulnerability of the pathogen to various antifungals besides evading host immune response(s). Inside the host micro-environments, C. albicans efficiently utilizes the multiple fermentable and non-fermentable carbon sources to sustain and proliferate in glucose deficit conditions. The utilization of alternative carbon sources further highlights the importance of understanding these pathways as the attractive and potential therapeutic target. A thorough understanding of metabolic flexibility and adaptation to environmental stresses is warranted to decipher in-depth insights into virulence and molecular mechanisms of fungal pathogenicity. In this review, we have attempted to provide a detailed and recent understanding of some key aspects of fungal biology. Particular focus will be placed on processes like nutrient assimilation and utilization, metabolic adaptability, virulence factors, and host immune response in C. albicans leading to its enhanced pathogenicity.Purpose To report a case of cytomegalovirus retinitis (CMVR) with hypopyon and intense ocular inflammation.Case report An 81-year-old female was referred to our hospital with a suspicion of postoperative endophthalmitis in the left eye. She had been treated with etoposide and prednisolone for non-Hodgkin's lymphoma. Examination revealed mutton-fat keratic precipitates and numerous infiltrating cells in the anterior chamber with hypopyon. The fundus was invisible due to intense vitreous opacity. Systemic and topical administration of antibiotics was started, and vitrectomy was performed. However, the ocular symptoms did not respond to treatment. Vitrectomy was repeated twice, but severe endophthalmitis findings recurred soon after surgery. Finally, a comprehensive viral PCR test using the intraocular fluid detected CMV with 3.34 × 109 copies/ml, leading to a diagnosis of CMV retinitis.Conclusions If the causative agent is not identified in endophthalmitis that develops in immunosuppressive patients, CMV may also be considered as the possible cause.

Schizophrenia is a neuropsychiatric disorder that affects approximately 1% of individuals worldwide. There are no available medications to treat cognitive impairment in this patient population currently. Preclinical evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve cognitive function. There is a need to evaluate how GLP-1RAs alter specific domains of cognition and whether they will be of therapeutic benefit in individuals with schizophrenia.

This paper summarizes the effects of GLP-1RAs on metabolic processes in the brain and how these mechanisms relate to improved cognitive function. We provide an overview of preclinical studies that demonstrate GLP-1RAs improve cognition and comment on their potential therapeutic benefit in individuals with schizophrenia.

To understand the benefits of GLP-1RAs in individuals with schizophrenia, further preclinical research with rodent models relevant to schizophrenia symptomology are needed. Moreover, preclinical studies must focus on using a wider range of behavioral assays to understand whether important aspects of cognition such as executive function, attention, and goal-directed behavior are improved using GLP-1RAs. Further research into the specific mechanisms of how GLP-1RAs affect cognitive function and their interactions with antipsychotic medication commonly prescribed is necessary.

To understand the benefits of GLP-1 RAs in individuals with schizophrenia, further preclinical research with rodent models relevant to schizophrenia symptomology are needed. Moreover, preclinical studies must focus on using a wider range of behavioral assays to understand whether important aspects of cognition such as executive function, attention, and goal-directed behavior are improved using GLP-1 RAs. Further research into the specific mechanisms of how GLP-1 RAs affect cognitive function and their interactions with antipsychotic medication commonly prescribed is necessary.

Deep brain stimulation (DBS) is an effective surgical treatment for patients with Parkinson's disease (PD). DBS therapy, particularly with the subthalamic nucleus (STN) target, has been linked to rare psychiatric complications, including depression, impulsivity, irritability, and suicidality. Stimulation-induced elevated mood states can also occur. These episodes rarely meet DSM-5 criteria for mania or hypomania.

The investigators conducted a chart review of 82 patients with PD treated with DBS.

Nine (11%) patients developed stimulation-induced elevated mood. Five illustrative cases are described (all males with STN DBS; mean age=62.2 years [SD=10.5], mean PD duration=8.6 years [SD=1.6]). Elevated mood states occurred during or shortly after programming changes, when more ventral contacts were used (typically in monopolar mode) and lasted minutes to months. Four patients experienced elevated mood at low amplitudes (1.0 V/1.0 mA); all had psychiatric risk factors (history of impulse-control disorder, dopirritable mood and psychomotor agitation that occur during or shortly after DBS programming changes and may be associated with increased goal-directed activity, impulsivity, grandiosity, pressured speech, flight of ideas, or decreased need for sleep and may persist beyond stimulation adjustments. This clinical phenomenon should be considered for inclusion in the bipolar disorder category in future DSM revisions, allowing for increased recognition and appropriate management.Objectives. To identify the association between Medicaid eligibility expansion and medical debt. Methods. We used difference-in-differences design to compare changes in medical debt for those gaining coverage through Louisiana's Medicaid expansion with those in nonexpansion states. We matched individuals gaining Medicaid coverage because of Louisiana's Medicaid expansion (n=196 556) to credit report data on medical debt and compared them with randomly selected credit reports of those living in Southern nonexpansion state zip codes with high rates of uninsurance (n=973 674). The study spanned July 2014 through July 2019. Results. One year after Louisiana Medicaid expansion, medical collections briefly rose before declining by 8.1 percentage points (95% confidence interval [CI]=-0.107, -0.055; P≤.001), or 13.5%, by the third postexpansion year. Balances also briefly rose before falling by 0.621 log points (95% CI=-0.817, -0.426; P≤.001), or 46.3%. Conclusions. Louisiana's Medicaid expansion was associated with a reduction in the medical debt load for those gaining coverage. These results suggest that future Medicaid eligibility expansions may be associated with similar improvements in the financial well-being of enrollees. (Am J Public Health. Published online ahead of print July 2, 2021 e1-e7. https//doi.org/10.2105/AJPH.2021.306316).The identification and isolation of highly infectious SARS-CoV-2-infected individuals is an important public health strategy. Rapid antigen detection tests (RADT) are promising tools for large-scale screenings due to timely results and feasibility for on-site testing. Nonetheless, the diagnostic performance of RADT in detecting infectious individuals is not yet fully determined. In this study, RT-qPCR and virus culture of RT-qPCR-positive samples were used to evaluate and compare the performance of the Standard Q COVID-19 Ag test in detecting SARS-CoV-2-infected and possibly infectious individuals. To this end, two combined oro- and nasopharyngeal swabs were collected at a routine SARS-CoV-2 diagnostic center. A total of 2,028 samples were tested, and 118 virus cultures were inoculated. SARS-CoV-2 infection was detected in 210 samples by RT-qPCR, representing a positive rate of 10.36%. The Standard Q COVID-19 Ag test yielded a positive result in 92 (4.54%) samples resulting in an overall sensitivity and specificity of 42.86 and 99.89%, respectively. For adjusted CT values of less then 20 (n = 14), less then 25 (n = 57), and less then 30 (n = 88), the RADT reached sensitivities of 100, 98.25, and 88.64%, respectively. All 29 culture-positive samples were detected by the RADT. Although the overall sensitivity was low, the Standard Q COVID-19 Ag test reliably detected patients with high RNA loads. In addition, negative RADT results fully corresponded with the lack of viral cultivability in Vero E6 cells. selleckchem These results indicate that RADT can be a valuable tool for the detection of individuals with high RNA loads that are likely to transmit SARS-CoV-2.

In this study, we investigated the in vitro and in vivo chondrogenic capacity of kartogenin (KGN)-enhanced bone marrow-derived mesenchymal stem cells (BMSCs) for cartilage regeneration.

To determine (1) whether functionalized nanographene oxide (NGO) can effectively deliver KGN into BMSCs and (2) whether KGN would enhance BMSCs during chondrogenesis in vitro and in vivo in an animal model.

Controlled laboratory study.

Functionalized NGO with line chain amine-terminated polyethylene glycol (PEG) and branched polyethylenimine (BPEI) were used to synthesize biocompatible NGO-PEG-BPEI (PPG) and for loading hydrophobic KGN molecules noncovalently via π-π stacking and hydrophobic interactions (PPG-KGN). Then, PPG-KGN was used for the intracellular delivery of hydrophobic KGN by simple mixing and co-incubation with BMSCs to acquire KGN-enhanced BMSCs. The chondrogenic efficacy of KGN-enhanced BMSCs was evaluated in vitro. In vivo, osteoarthritis (OA) was induced by anterior cruciate ligament transection in r-KGN-preconditioned BMSCs contributed to protection from joint space narrowing, pathological mineralization, OA development, and OA-induced pain, as well as improved tissue regeneration, as evidenced by radiographic, weightbearing, and histological findings.

Our results demonstrate that KGN-enhanced BMSCs showed markedly improved capacities for chondrogenesis and articular cartilage repair. We believe that this work demonstrates that a multifunctional nanoparticle-based drug delivery system could be beneficial for stem cell therapy. Our results present an opportunity to reverse the symptoms and pathophysiology of OA.

The intracellular delivery of KGN to produce BMSCs with enhanced chondrogenic potential may offer a new approach for the treatment of OA.

The intracellular delivery of KGN to produce BMSCs with enhanced chondrogenic potential may offer a new approach for the treatment of OA.

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