Clinical and Swallowing Characteristics Related With Respiratory Infection in Parkinsonism Patients.

OBJECTIVE: To investigate the clinical and swallowing characteristics related to respiratory infection in patients with parkinsonism. METHODS: One hundred and forty-two patients with parkinsonism who underwent videofluoroscopic swallowing studies (VFSS) were enrolled in this study. The initial clinical and VFSS characteristics were compared between patients with and without a history of respiratory infection in the past year. A multivariate logistic regression model was applied to identify clinical and swallowing characteristics related to respiratory infections. RESULTS: Patients with respiratory infections were older (74.75±10.20 years vs. 70.70±8.83 years, p=0.037), had a higher Hoehn and Yahr (H&Y) stage (stage IV-V, 67.9% vs. 49.1%; p=0.047), and were more likely to have a diagnosis of idiopathic Parkinson's disease (IPD) (67.9% vs. 41.2%, p=0.011) than those without respiratory infections. Among VFSS findings, bolus formation, premature bolus loss, oral transit time, pyriform sinus residues, pharyngeal wall coatings, and penetration/aspiration were significantly worse in patients with respiratory infections (p<0.05). Regarding clinical characteristics, higher H&Y stage (odds ratio [OR], 3.174; 95% confidence interval [CI], 1.226-8.216; p=0.017) and diagnosis of IPD (OR, 0.280, 95% CI, 0.111-0.706; p=0.007) were significantly related to respiratory infections in the multivariate analysis. Among VFSS findings, pyriform sinus residue (OR, 14.615; 95% CI, 2.257-94.623; p=0.005) and premature bolus loss (OR, 5.151; 95% CI, 1.047-25.338; p=0.044) were also significantly associated with respiratory infection. CONCLUSION: This study suggests that disease severity, diagnosis, pyriform sinus residue, and premature bolus loss observed in VFSS are associated with respiratory infection in patients with parkinsonism.

Marine Microbial-Derived Resource Exploration: Uncovering the Hidden Potential of Marine Carotenoids.

Microbes in marine ecosystems are known to produce secondary metabolites. One of which are carotenoids, which have numerous industrial applications, hence their demand will continue to grow. This review highlights the recent research on natural carotenoids produced by marine microorganisms. We discuss the most recent screening approaches for discovering carotenoids, using in vitro methods such as culture-dependent and culture-independent screening, as well as in silico methods, using secondary metabolite Biosynthetic Gene Clusters (smBGCs), which involves the use of various rule-based and machine-learning-based bioinformatics tools. Following that, various carotenoids are addressed, along with their biological activities and metabolic processes involved in carotenoids biosynthesis. Finally, we cover the application of carotenoids in health and pharmaceutical industries, current carotenoids production system, and potential use of synthetic biology in carotenoids production.

Efficacy of Modified Cervical and Shoulder Retraction Exercise in Patients With Loss of Cervical Lordosis and Neck Pain.

OBJECTIVE: To explore if the modified cervical and shoulder retraction exercise program restores cervical lordosis and reduces neck pain in patients with loss of cervical lordosis. METHODS: This study was a retrospective analysis of prospectively collected data. Eighty-three patients with loss of cervical lordosis were eligible. The eligible patients were trained to perform the modified cervical and shoulder retraction exercise program by a physiatrist, and were scheduled for a follow-up 6 to 8 weeks later to check the post-exercise pain intensity and lateral radiograph of the cervical spine in a comfortable position. The parameters of cervical alignment (4-line Cobb's angle, posterior tangent method, and sagittal vertical axis) were measured from the lateral radiograph. RESULTS: Forty-seven patients were included. The mean age was 48.29±14.47 years. Cervical alignment and neck pain significantly improved after undergoing the modified cervical and shoulder retraction exercise program (p≤0.001). The upper cervical lordotic angle also significantly improved (p=0.001). In a subgroup analysis, which involved dividing the patients into two age groups (<50 years and ≥50 years), the change of the sagittal vertical axis was significantly greater in the <50 years group (p=0.021). CONCLUSION: The modified cervical and shoulder retraction exercise program tends to improve cervical lordosis and neck pain in patients with loss of cervical lordosis.

Anti-CotH3 antibodies protect mice from mucormycosis by prevention of invasion and augmenting opsonophagocytosis.

Mucorales are fungal pathogens that cause mucormycosis, a lethal angioinvasive disease. Previously, we demonstrated that Rhizopus, the most common cause of mucormycosis, invades endothelial cells by binding of its CotH proteins to the host receptor GRP78. Loss of CotH3 renders the fungus noninvasive and attenuates Rhizopus virulence in mice. Here, we demonstrate that polyclonal antibodies raised against peptides of CotH3 protected diabetic ketoacidotic (DKA) and neutropenic mice from mucormycosis compared to mice treated with control preimmune serum. Passive immunization with anti-CotH3 antibodies enhanced neutrophil inlfux and triggered Fc receptor-mediated enhanced opsonophagocytosis killing of Rhizopus delemar. Monoclonal antibodies raised against the CotH3 peptide also protected immunosuppressed mice from mucormycosis caused by R. delemar and other Mucorales and acted synergistically with antifungal drugs in protecting DKA mice from R. delemar infection. These data identify anti-CotH3 antibodies as a promising adjunctive immunotherapeutic option against a deadly disease that often poses a therapeutic challenge.

Low skeletal muscle mass and radiographic osteoarthritis in knee, hip, and lumbar spine: a cross-sectional study.

BACKGROUND: Although several studies have shown that low skeletal muscle mass is correlated with knee osteoarthritis, no studies have investigated the correlation between skeletal muscle mass and hip and lumbar spine osteoarthritis (OA). AIM: This study aimed to delineate the relationship between low skeletal muscle mass and radiographic OA (ROA) of the knee, hip, and lumbar spine. METHODS: This is a cross-sectional study using the public data obtained from the Fifth Korean National Health and Nutrition Examination Survey (2010-2011). We included subjects aged ≥ 50 years who completed the surveys (3813 subjects). ROA was assessed by knee, hip, and lumbar spine radiographs and defined as Kellgren/Lawrence (KL) grade of at least 2 in the knee and lumbar spine, whereas KL grade ≥ 1 in the hip. Multivariate logistic regression analyses were performed to evaluate the effects of low skeletal muscle mass on radiographic joint degeneration. RESULTS: Appendicular skeletal muscle mass (ASM) was higher in subjects with healthy joints than in subjects with knee and lumbar spine ROA (18.9 ± 0.1 kg vs. 17.1 ± 0.2 kg, P < 0.0001 and 18.6 ± 0.1 kg vs. 17.4 ± 0.2 kg, P < 0.0001, respectively), whereas it was higher in those with ROA than in those with healthy hip (17.9 ± 0.1 kg vs. 19.1 ± 0.2 kg P < 0.0001). On multivariate logistic regression analysis, lower skeletal muscle mass independently associated with knee ROA [odds ratio (OR) 1.348; 95% confidence interval (CI) 1.037-1.752]. However, it was inversely associated with lumbar spine ROA (OR 0.786; 95% CI 0.623-0.991). CONCLUSION: Low skeletal muscle mass was independently associated with knee ROA alone, whereas it was inversely associated with lumbar spine ROA. These opposite results might originate from measuring the area of ASM.

APX001 Is Effective in the Treatment of Murine Invasive Pulmonary Aspergillosis.

Invasive pulmonary aspergillosis (IPA) due to Aspergillus fumigatus is a serious fungal infection in the immunosuppressed patient population. Despite the introduction of new antifungal agents, mortality rates remain high, and new treatments are needed. The novel antifungal APX001A targets the conserved Gwt1 enzyme required for the localization of glycosylphosphatidylinositol-anchored mannoproteins in fungi. We evaluated the in vitro activity of APX001A against A. fumigatus and the in vivo activity of its prodrug APX001 in an immunosuppressed mouse model of IPA. APX001A inhibited the growth of A. fumigatus with a minimum effective concentration of 0.03 µg/ml. The use of 50 mg/kg 1-aminobenzotriazole (ABT), a suicide inhibitor of cytochrome P450 enzymes, enhanced APX001A exposures (area under the time-concentration curve [AUC]) 16- to 18-fold and enhanced serum half-life from ∼1 to 9 h, more closely mimicking human pharmacokinetics. We evaluated the efficacy of APX001 (with ABT) in treating murine IPA compared to posaconazole treatment. Treatment of mice with 78 mg/kg once daily (QD), 78 mg/kg twice daily, or 104 mg/kg QD APX001 significantly enhanced the median survival time and prolonged day 21 postinfection overall survival compared to the placebo. Furthermore, administration of APX001 resulted in a significant reduction in lung fungal burden (4.2 to 7.6 log10 conidial equivalents/g of tissue) versus the untreated control and resolved the infection, as judged by histopathological examination. The observed survival and tissue clearance were comparable to a clinically relevant posaconazole dose. These results warrant the continued development of APX001 as a broad-spectrum, first-in-class treatment of invasive fungal infections.

PCR-Based Approach Targeting Mucorales-Specific Gene Family for Diagnosis of Mucormycosis.

Mucormycosis is an aggressive, life-threatening infection caused by fungi in the order Mucorales. The current diagnosis of mucormycosis relies on mycological cultures, radiology and histopathology. These methods lack sensitivity and are most definitive later in the course of infection, resulting in the prevention of timely intervention. PCR-based approaches have shown promising potential in rapidly diagnosing mucormycosis. The spore coating protein homolog encoding CotH genes are uniquely and universally present among Mucorales. Thus, CotH genes are potential targets for the rapid diagnosis of mucormycosis. We infected mice with different Mucorales known to cause human mucormycosis and investigated whether CotH could be PCR amplified from biological fluids. Uninfected mice and those with aspergillosis were used to determine the specificity of the assay. CotH was detected as early as 24 h postinfection in plasma, urine, and bronchoalveolar lavage (BAL) samples from mice infected intratracheally with Rhizopus delemar, Rhizopus oryzae, Mucor circinelloides, Lichtheimia corymbifera, or Cunninghamella bertholletiae but not from samples taken from uninfected mice or mice infected with Aspergillus fumigatus Detection of CotH from urine samples was more reliable than from plasma or BAL fluid. Using the receiver operating characteristic method, the sensitivity and the specificity of the assay were found to be 90 and 100%, respectively. Finally, CotH was PCR amplified from urine samples of patients with proven mucormycosis. Thus, PCR amplification of CotH is a promising target for the development of a reliable, sensitive, and simple method of early diagnosis of mucormycosis.