Antifungal efficacy of natural antiseptic products against Candida auris.

Candida auris is an emerging fungal pathogen responsible for healthcare-associated infections and outbreaks with high mortality around the world. It readily colonizes the skin, nares, respiratory and urinary tract of hospitalized patients, and such colonization may lead to invasive Candida infection in susceptible patients. However, there is no recommended decolonization protocol for C. auris by international health authorities. The aim of this study is to evaluate the susceptibility of C. auris to commonly used synthetic and natural antiseptic products using an in vitro, broth microdilution assay. Synthetic antiseptics including chlorhexidine, povidone-iodine, and nystatin were shown to be fungicidal against C. auris. Among the natural antiseptics tested, tea tree oil and manuka oil were both fungicidal against C. auris at concentrations less than or equal to 1.25% (v/v). Manuka honey inhibited C. auris at 25% (v/v) concentrations. Among the commercial products tested, manuka body wash and mouthwash were fungicidal against C. auris at concentrations less than or equal to 0.39% (w/v) and 6.25% (v/v) of products as supplied for use, respectively, while tea tree body wash and MedihoneyTM wound gel demonstrated fungistatic properties. In conclusion, this study demonstrated good in vitro antifungal efficacy of tea tree oil, manuka oil, manuka honey, and commercially available antiseptic products containing these active ingredients. Future studies are warranted to evaluate the effectiveness of these antiseptic products in clinical settings.

Candida auris is an emerging superbug fungus that poses a serious threat to global public health. The excellent antifungal efficacy of natural antiseptics and their commercial hygiene products provide new insights into the development of an alternative decolonization regimen against C. auris.

Evaluation of patients treated with direct-acting anti-viral therapy for chronic hepatitis C and their risk of hepatocellular carcinoma in Hong Kong.

BACKGROUND & AIM: To evaluate the risk of early hepatocellular carcinoma (HCC) in chronic hepatitis C patients treated with direct-acting antivirals (DAAs) in Hong Kong, as it has not been studied before in this locality. METHODS: Three hundred thirty-three consecutive chronic hepatitis C patients treated with DAAs from two hospitals over the past 6 years were identified. Kaplan-Meier method was used to calculate cumulative HCC incidence. Cox regression was used to identify factors associated with HCC development. RESULTS: During a median follow-up of 23.4 months after DAA started, 15 (5.4%, 95% CI 3.3-8.7%) out of 279 total included patients developed HCC. The overall sustained virological response (SVR) rate was 98.9%. The 1-year cumulative incidence for de-novo HCC and HCC recurrence were 0.8 and 30.9%, respectively (log-rank test p < 0.001). The 1-year cumulative HCC incidence for patients without and with cirrhosis were 0.7 and 5.1%, respectively (log-rank test p = 0.036). Univariate analysis showed that significant factors associated with HCC after DAA were: history of treated HCC, cirrhosis, evidence of portal hypertension, higher AFP at the start or end of DAA therapy, higher bilirubin, lower platelets, lower albumin, and older age. From receiver operating characteristic curve analysis, the optimal cut-off level of AFP for predicting HCC was 10.5 ng/mL at the start and 5.6 ng/mL at the end of DAA therapy. CONCLUSIONS: The risk of early HCC recurrence remains high despite achieving SVR following DAA therapy, whereas the risk of early de-novo HCC occurence is low. AFP levels, both at the start and end of DAA therapy, can be useful in stratifying risks of HCC development.

The impact of tubular dysfunction and its relationship with acute kidney injury in children.

BACKGROUND: Tubular dysfunction can cause electrolyte disturbances with potentially serious consequences. We studied the epidemiology and outcomes of electrolyte disturbances and tubular dysfunction among critically ill children and evaluated their relationships with acute kidney injury (AKI). METHODS: We conducted a prospective cohort study recruiting children aged 1 month to ≤ 18 years old admitted to the pediatric intensive care unit (PICU) from 6/2020 to 6/2021. The serum levels of sodium, potassium, calcium, phosphate, and magnesium were reviewed and simultaneous urinary investigations for tubular function were performed among children with electrolyte disturbances. RESULTS: Altogether there were 253 episodes of admission. The median (interquartile) age was 4.9 (1.3-11.0) years and 58.1% were male. The median number of electrolyte disorders was 3 (2-4) types. Hypophosphatemia (74.2%), hypocalcemia (70.3%) and hypermagnesemia (52.9%) were the three commonest types of disturbances. Urinary electrolyte wasting was commonly observed among children with hypomagnesemia (70.6%), hypophosphatemia (67.4%) and hypokalemia (28.6%). Tubular dysfunction was detected in 82.6% of patients and urinary ß2-microglobulin level significantly correlated with the severity of tubular dysfunction (p < 0.001). The development of tubular dysfunction was independent of AKI status. Tubular dysfunction was associated with mortality (p < 0.001) and was an independent predictor of PICU length of stay (LOS) (p < 0.001). The incorporation of the tubular dysfunction severity into the AKI staging system improved the prediction of PICU LOS. CONCLUSIONS: Tubular dysfunction was associated with both morbidity and mortality in critically ill children and its assessment may help to capture a more comprehensive picture of acute kidney insult.

Harnessing immunomodulation to combat sarcopenia: current insights and possible approaches.

Sarcopenia is a complex age-associated syndrome of progressive loss of muscle mass and strength. Although this condition is influenced by many factors, age-related changes in immune function including immune cell dynamics, and chronic inflammation contribute to its progression. The complex interplay between the immune system, gut-muscle axis, and autophagy further underscores their important roles in sarcopenia pathogenesis. Immunomodulation has emerged as a promising strategy to counteract sarcopenia. Traditional management approaches to treat sarcopenia including physical exercise and nutritional supplementation, and the emerging technologies of biophysical stimulation demonstrated the importance of immunomodulation and regulation of macrophages and T cells and reduction of chronic inflammation. Treatments to alleviate low-grade inflammation in older adults by modulating gut microbial composition and diversity further combat sarcopenia. Furthermore, some pharmacological interventions, nano-medicine, and cell therapies targeting muscle, gut microbiota, or autophagy present additional avenues for immunomodulation in sarcopenia. This narrative review explores the immunological underpinnings of sarcopenia, elucidating the relationship between the immune system and muscle during ageing. Additionally, the review discusses new areas such as the gut-muscle axis and autophagy, which bridge immune system function and muscle health. Insights into current and potential approaches for sarcopenia management through modulation of the immune system are provided, along with suggestions for future research directions and therapeutic strategies. We aim to guide further investigation into clinical immunological biomarkers and identify indicators for sarcopenia diagnosis and potential treatment targets to combat this condition. We also aim to draw attention to the importance of considering immunomodulation in the clinical management of sarcopenia.

Sarcopenia and Ageing.

Musculoskeletal ageing is a major health challenge as muscles and bones constitute around 55-60% of body weight. Ageing muscles will result in sarcopenia that is characterized by progressive and generalized loss of skeletal muscle mass and strength with a risk of adverse outcomes. In recent years, a few consensus panels provide new definitions for sarcopenia. It was officially recognized as a disease in 2016 with an ICD-10-CM disease code, M62.84, in the International Classification of Diseases (ICD). With the new definitions, there are many studies emerging to investigate the pathogenesis of sarcopenia, exploring new interventions to treat sarcopenia and evaluating the efficacy of combination treatments for sarcopenia. The scope of this chapter is to summarize and appraise the evidence in terms of (1) clinical signs, symptoms, screening, and diagnosis, (2) pathogenesis of sarcopenia with emphasis on mitochondrial dysfunction, intramuscular fat infiltration and neuromuscular junction deterioration, and (3) current treatments with regard to physical exercises and nutritional supplement.

First Report of Grovesinia moricola Causing Zonate Leaf Spot on Hernandia nymphaeifolia in Taiwan.

Hernandia nymphaeifolia (C. Presl) Kubitzki, a native tree of Taiwan, is a sea drift plant (Yang and Lu 1996). It is a salt- and wind-tolerant tree (Bezona et al. 2009) and was selected for the afforestation of badlands in coastal areas of Taiwan. In December 2022, all H. nymphaeifolia seedlings at a nursery in Wu-Lai, Taiwan were diseased and wilted with a similar progression. The initial symptom was small zonate white or gray lesions with water-soaked periphery on leaves. Then, expansion and fusion of leaf spots which caused leaf blight and defoliation were observed. Seedlings eventually wilted. Sporophores found on the host were generally hypophyllous, solitary, erect, and easily detachable. The upper portion of the sporophore was considered an individual conidium and consisted of a pyramidal head that was fusiform to ventricose, 206.3 to 501.8 µm (average: 378.0 ± 75.3 µm) long, and 63.6 to 104.5 µm (average: 85.0 ± 16.2 µm) wide at the broadest point (n=30). Branches within the pyramidal head were short, compact, and di- or trichotomously branched. The central stipe was hyaline, broad, septate, tapering toward an acute apex, and sometimes constricted at the basal septum. Sclerotia were gray or black, spherical, and 1.0 to 2.5 mm (n=10) in diameter and observed on older lesions. The fungus was isolated from infected tissue and sporophores and maintained on potato dextrose agar (PDA) at 20°C in darkness. Sclerotia were produced on PDA after 4 to 5 weeks and were irregular or spherical, but no sporophore was developed. The fungus was identified as Grovesinia moricola (I. Hino) Redhead based on morphological characteristics (Tomoko et al. 2006). Three DNA samples was obtained from the cultures isolated from the diseased leaf, sporophores and sclerotia. They were then amplified by PCR with primers for the internal transcribed spacer region (ITS; primers ITS5/ITS4) and the large subunit nuclear ribosomal RNA gene (LSU; primers LR0R/LR5) (Cho et al. 2017), and then sequenced respectively. The sequences were deposited into GenBank with accession nos. PP727191 to PP727193 and PP748518 to PP748520. BLAST analysis of the three isolates showed 100% identity to the sequences of G. moricola from Taiwan (OP550202, OP550203) for the ITS region and 99.9% identity to the sequence of G. moricola from the USA (MW013804) for the LSU rRNA gene. The specimens (FS2022-140) and the culture (Asco-0109) in this study were deposited into the herbarium of Taiwan Forestry Research Institute in Taiwan. Koch's postulates were performed by inoculating four 8-month-old, asymptomatic, potted H. nymphaeifolia plants; every plant was inoculated with sporophores from infected leaves on the upper surface of each of five leaves. Four uninoculated plants were kept in separate pots and served as controls. All plants were covered with transparent plastic bags individually and incubated in a growth chamber at 18 to 20°C with 8 h of light. Similar leaf spots and sporophores were observed after 2 to 4 days and 10 days on every inoculated plant but not on uninoculated plants. The pathogen with a similar colony on PDA was reisolated from the leaf spots of the inoculated plants. Molecular identification of the reisolated pathogen by the above method was carried out. The sequences showed 99.9% identity to the sequence of G. moricola, and were deposited into GenBank with accession nos. PQ157896 to PQ157897 (ITS region) and PQ157701 to PQ157702 (LSU rRNA gene). The pathogenicity test was repeated once. G. moricola is known to cause severe defoliation on woody and annual plants, including at least 73 host species and 36 families distributed in the eastern United States and Japan (Trolinger et al. 1978). This is the first report of G. moricola on H. nymphaeifolia in the world. Control of the disease would play an important role in maintaining healthy seedlings for the afforestation in Taiwan.

Comparative Analysis of Mitochondria Surrounding the Intercalated Discs in Heart Diseases-An Ultrastructural Pilot Study.

BACKGROUND: Mitochondria play a crucial role in adapting to fluctuating energy demands, particularly in various heart diseases. This study investigates mitochondrial morphology near intercalated discs in left ventricular (LV) heart tissues, comparing samples from patients with sinus rhythm (SR), atrial fibrillation (AF), dilated cardiomyopathy (DCM), and ischemic cardiomyopathy (ICM). METHODS: Transmission electron microscopy was used to analyze mitochondria within 0-3.5 µm and 3.5-7 µm of intercalated discs in 9 SR, 10 AF, 9 DCM, and 8 ICM patient samples. Parameters included mean size in µm2 and elongation, count, percental mitochondrial area in the measuring frame, and a conglomeration score. RESULTS: AF patients exhibited higher counts of small mitochondria in the LV myocardium, resembling SR. DCM and ICM groups had fewer, larger, and often hydropic mitochondria. Accumulation rates and percental mitochondrial area were similar across groups. Significant positive correlations existed between other defects/size and hydropic mitochondria and between count/area and conglomeration score, while negative correlations between count and size/other defects and between hydropic mitochondria and count could be seen as well. CONCLUSION: Mitochondrial parameters in the LV myocardium of AF patients were similar to those of SR patients, while DCM and ICM displayed distinct changes, including a decrease in number, an increase in size, and compromised mitochondrial morphology. Further research is needed to fully elucidate the pathophysiological role of mitochondrial morphology in different heart diseases, providing deeper insights into potential therapeutic targets and interventions.

Automated airway quantification associates with mortality in idiopathic pulmonary fibrosis.

OBJECTIVES: The study examined whether quantified airway metrics associate with mortality in idiopathic pulmonary fibrosis (IPF). METHODS: In an observational cohort study (n = 90) of IPF patients from Ege University Hospital, an airway analysis tool AirQuant calculated median airway intersegmental tapering and segmental tortuosity across the 2nd to 6th airway generations. Intersegmental tapering measures the difference in median diameter between adjacent airway segments. Tortuosity evaluates the ratio of measured segmental length against direct end-to-end segmental length. Univariable linear regression analyses examined relationships between AirQuant variables, clinical variables, and lung function tests. Univariable and multivariable Cox proportional hazards models estimated mortality risk with the latter adjusted for patient age, gender, smoking status, antifibrotic use, CT usual interstitial pneumonia (UIP) pattern, and either forced vital capacity (FVC) or diffusion capacity of carbon monoxide (DLco) if obtained within 3 months of the CT. RESULTS: No significant collinearity existed between AirQuant variables and clinical or functional variables. On univariable Cox analyses, male gender, smoking history, no antifibrotic use, reduced DLco, reduced intersegmental tapering, and increased segmental tortuosity associated with increased risk of death. On multivariable Cox analyses (adjusted using FVC), intersegmental tapering (hazard ratio (HR) = 0.75, 95% CI = 0.66-0.85, p < 0.001) and segmental tortuosity (HR = 1.74, 95% CI = 1.22-2.47, p = 0.002) independently associated with mortality. Results were maintained with adjustment using DLco. CONCLUSIONS: AirQuant generated measures of intersegmental tapering and segmental tortuosity independently associate with mortality in IPF patients. Abnormalities in proximal airway generations, which are not typically considered to be abnormal in IPF, have prognostic value. CLINICAL RELEVANCE STATEMENT: Quantitative measurements of intersegmental tapering and segmental tortuosity, in proximal (second to sixth) generation airway segments, independently associate with mortality in IPF. Automated airway analysis can estimate disease severity, which in IPF is not restricted to the distal airway tree. KEY POINTS: • AirQuant generates measures of intersegmental tapering and segmental tortuosity. • Automated airway quantification associates with mortality in IPF independent of established measures of disease severity. • Automated airway analysis could be used to refine patient selection for therapeutic trials in IPF.

Detection of early (T1) lung cancers and lepidic adenocarcinomas in sputum and bronchial cytology.

BACKGROUND: The lung is an extensively epithelialized organ, producing ample exfoliated material for sputum and bronchial cytology. In view of the updates in the World Health Organization classification of early (T1/≤ 3 cm) lung cancer with respect to adenocarcinomas with lepidic pattern, this study retrospectively reviews sputum and bronchial cytology paired with resection-confirmed lung cancers. METHODS: A computerized search for all lung resection specimens of carcinomas over a 20-year period was performed. Cytologic diagnoses of corresponding sputum and bronchial cytology were classified into five-tiered categories (C1-insufficient/inadequate, C2-benign, C3-atypia, C4-suspicious and C5-malignant). Reports and slides of the resection specimen were reviewed for reclassification of T1 cancers. RESULTS: Totally 472 and 383 sputum and bronchial cytology specimens respectively were included. Sensitivity for T1 lesions on sputum cytology were 10.6 %, 2.1 % and 0.5 % at cutoffs of atypia/C3, suspicious/C4 and malignant/C5 categories, lower than bronchial cytology (35.1 %, 15.5 %, 8.1 %; p < 0.001). T1 lesions correlated with lower detection rates, whereas squamous cell carcinoma histology, larger size and bronchial invasion were associated with increased detection rates in sputum and bronchial cytology (p < 0.050). Detection rates for abrasive bronchial cytology (brushing) were overall higher (p = 0.018- < 0.001), but on subgroup comparison, non-abrasive (aspiration, lavage and washing) cytology demonstrated favorable trends (p = 0.063-0.088) in detecting T1 lesions. Adenocarcinomas with lepidic pattern had lower suspicious/C4 (p = 0.040) or above and malignant/C5 (p = 0.019), but not atypia/C3 or above (p = 0.517) rates. CONCLUSIONS: Most adenocarcinomas with lepidic pattern are only diagnosed as atypia/C3 on cytology. With its modest sensitivity, interpretation of negative and indeterminate cytology results mandates caution.

The Pitfall of Over-Sedation During Recovery From Acute Kidney Injury.

A 14-year-old boy with movement disorder and epilepsy developed status dystonicus leading to rhabdomyolysis and subsequent acute kidney injury requiring continuous renal replacement therapy (CRRT). He was given multiple intravenous sedatives and analgesics to control his dystonia and dyskinesia. 8 days after admission, his condition had improved and a trial termination of CRRT was carried out. The sedatives and analgesics were switched to oral diazepam, morphine, clonidine, and chloral hydrate. However, his renal function did not recover fully. There was rising trend of serum creatinine level with evolving hyperphosphatemia and metabolic acidosis. He also gradually developed hypoventilation, hypercapnia and pinpoint pupils after weaning CRRT. The clinical impression was over-sedation resulting in hypoventilation and respiratory failure, contributed by the deteriorating renal function. Non-invasive ventilatory support was then started and CRRT was resumed. His condition improved over the next 24 hours. Dexmedetomidine infusion was used during CRRT and he slowly required stepping up of sedatives again. A separate set of dosage for all his oral sedative agents was prepared for his subsequent CRRT weaning challenge and no more over-sedative episode was then encountered. Our case illustrated that patients at recovery phase of AKI are susceptible to medication overdose, especially during the period of CRRT weaning. Sedatives and analgesics including morphine and benzodiazepines should be used with caution during this period and alternatives may need to be considered. Advanced planning of medication dosage adjustment is advised to reduce the risk of medication overdose.

Uterine CD56+ cell density and euploid miscarriage in women with a history of recurrent miscarriage: A clinical descriptive study.

In women with a history of recurrent miscarriage, the uterine CD56+ cell density in subjects with subsequent euploid miscarriage was significantly higher than those with subsequent aneuploid miscarriage. Both endometrial and embryonic factors should be investigated when interpreting uterine CD56+ cell density results relating to recurrent miscarriage.

Enhanced Ability of Plant-Derived PGT121 Glycovariants To Eliminate HIV-1-Infected Cells.

The activity of broadly neutralizing antibodies (bNAbs) targeting HIV-1 depends on pleiotropic functions, including viral neutralization and the elimination of HIV-1-infected cells. Several in vivo studies have suggested that passive administration of bNAbs represents a valuable strategy for the prevention or treatment of HIV-1. In addition, different strategies are currently being tested to scale up the production of bNAbs to obtain the large quantities of antibodies required for clinical trials. Production of antibodies in plants permits low-cost and large-scale production of valuable therapeutics; furthermore, pertinent to this work, it also includes an advanced glycoengineering platform. In this study, we used Nicotiana benthamiana to produce different Fc-glycovariants of a potent bNAb, PGT121, with near-homogeneous profiles and evaluated their antiviral activities. Structural analyses identified a close similarity in overall structure and glycosylation patterns of Fc regions for these plant-derived Abs and mammalian cell-derived Abs. When tested for Fc-effector activities, afucosylated PGT121 showed significantly enhanced FcγRIIIa interaction and antibody dependent cellular cytotoxicity (ADCC) against primary HIV-1-infected cells, both in vitro and ex vivo. However, the overall galactosylation profiles of plant PGT121 did not affect ADCC activities against infected primary CD4+ T cells. Our results suggest that the abrogation of the Fc N-linked glycan fucosylation of PGT121 is a worthwhile strategy to boost its Fc-effector functionality. IMPORTANCE PGT121 is a highly potent bNAb and its antiviral activities for HIV-1 prevention and therapy are currently being evaluated in clinical trials. The importance of its Fc-effector functions in clearing HIV-1-infected cells is also under investigation. Our results highlight enhanced Fc-effector activities of afucosylated PGT121 MAbs that could be important in a therapeutic context to accelerate infected cell clearance and slow disease progression. Future studies to evaluate the potential of plant-produced afucosylated PGT121 in controlling HIV-1 replication in vivo are warranted.

The imminent risk of a fracture-existing worldwide data: a systematic review and meta-analysis.

The overall incidence of imminent fracture after a prior fragility fracture was 7.58% in the first year and 11.58% in the first 2 years. Approximately half of re-fractures occurred in the first 2 years after a fragility fracture. Older patients that have suffered from a fragility fracture should be treated promptly, with immediate care and a secondary fracture prevention to prevent the high imminent risk of a fracture. INTRODUCTION: Imminent fractures refer to the fractures that occur within 2 years of an initial fracture. It is well known that the risk of a subsequent fracture is not constant with time and occurs shortly after the initial one. This systematic review and meta-analysis aimed to present the existing data on imminent fracture worldwide. METHODS: Literature search was conducted in Pubmed, Embase, and Web of Science databases until 26 October 2021 for studies reporting the incidence of imminent osteoporotic fractures among people aged 50 years or older. The overall incidence of imminent fracture was pooled and subgroup analyses of index fracture sites and regions on incidence of imminent fracture were performed, with the 95% confidence interval (CI) being calculated. Percentage of imminent fracture occurring in follow-up period was calculated and pooled by meta-analysis. Hazard ratio (HR) was used to estimate the gender differences on the imminent risk of fracture. RESULTS: A total of 1446 articles were identified. Nineteen observational studies were eligible for our systematic review, in which 18 were used for quantitative analysis. Pooled overall incidence of imminent fracture in the first year after an osteoporotic fracture was 7.58% (95% CI 5.84 to 9.31%) and cumulative incidence in the first 2 years was 11.58% (95% CI 8.94 to 14.21%). Subgroup analysis showed that in the first 2 years, the pooled incidence in Asia was 7.30% (95% CI 3.42 to 11.18%), whilst incidence in Europe/North America was 13.17% (95% CI 10.14 to 16.20%). In included studies with follow-up period of more than 5 years, pooled imminent fracture percentage in the first 2 years was 47.24% (95% CI 26.18 to 68.30%). Hazard ratio (HR) on gender showed that women had an overall slight increase in risk of imminent fractures (HR 1.18, 95% CI 1.11 to 1.25). CONCLUSION: The incidence of imminent fracture is high globally at 11.58%. Approximately half of all refractures occur in the first 2 years after an index fragility fracture. Older patients that have suffered from a fragility fracture should be treated promptly. Also, immediate care and secondary fracture prevention are necessary to prevent the high imminent risk of a fracture, especially within the first 2 years.

Contribution of coronal vertebral and IVD wedging to Cobb angle changes in adolescent idiopathic scoliosis during growth.

STUDY DESIGN: Prospective study BACKGROUND: Vertebral and intervertebral disc (IVD) wedging are often seen in patients with adolescent idiopathic scoliosis (AIS). However, the relationship between wedging and curve progression, and the change of wedging before bracing to final weaning is unknown. The aim of this study was to investigate the pattern and sequence of vertebral and IVD wedging development, and to determine the relationship between the change of wedging and curve progression in AIS during growth. METHODS: This was a prospective study of 32 AIS females with right-sided thoracic curves and/or left-sided lumbar curves who completed brace treatment. They were classified into progression and non-progression groups. Vertebral and IVD wedging were calculated for each spinal segment. The wedging pattern was first identified and then used to determine the sequence of wedging development. Percentage change in the sum of wedging during growth was calculated and compared. RESULTS: The sum of vertebral wedging for both groups was 2.4° to 8.7° more than that of IVD wedging in the thoracic spine but 8.7° to 17.7° less in the lumbar spine. Out of the 20 curves assessed, 5 thoracic curves and 1 lumbar curve developed vertebral wedging before IVD wedging, and 3 thoracic curves and 4 lumbar curves had the opposite pattern. The progression group had larger increases in sum of vertebral (40%) and IVD (28.6%) wedging as compared to the non-progression group (both 16.7%). A significant difference in wedging between the first and the latest visits was found in the progression group only (p < 0.05). CONCLUSION: Pattern and sequence of vertebral and IVD wedging were related to the location of the curve rather than the presence of curve progression. Progressed curves were associated with increased wedging during growth. LEVEL OF EVIDENCE: II.

Coapplication of Magnesium Supplementation and Vibration Modulate Macrophage Polarization to Attenuate Sarcopenic Muscle Atrophy through PI3K/Akt/mTOR Signaling Pathway.

Sarcopenia is an age-related geriatric syndrome characterized by the gradual loss of muscle mass and function. Low-magnitude high-frequency vibration (LMHFV) was shown to be beneficial to structural and functional outcomes of skeletal muscles, while magnesium (Mg) is a cofactor associated with better indices of skeletal muscle mass and strength. We hypothesized that LMHFV, Mg and their combinations could suppress inflammation and sarcopenic atrophy, promote myogenesis via PI3k/Akt/mTOR pathway in senescence-accelerated mouse P8 (SAMP8) mice and C2C12 myoblasts. Results showed that Mg treatment and LMHFV could significantly decrease inflammatory expression (C/EBPα and LYVE1) and modulate a CD206-positive M2 macrophage population at month four. Mg treatment also showed significant inhibitory effects on FOXO3, MuRF1 and MAFbx mRNA expression. Coapplication showed a synergistic effect on suppression of type I fiber atrophy, with significantly higher IGF-1, MyoD, MyoG mRNA (p < 0.05) and pAkt protein expression (p < 0.0001) during sarcopenia. In vitro inhibition of PI3K/Akt and mTOR abolished the enhancement effects on myotube formation and inhibited MRF mRNA and p85, Akt, pAkt and mTOR protein expressions. The present study demonstrated that the PI3K/Akt/mTOR pathway is the predominant regulatory mechanism through which LMHFV and Mg enhanced muscle regeneration and suppressed atrogene upregulation.

Symptom management in Chinese adults with end stage renal disease (ESRD).

BACKGROUND: With over $50 billion spent annually in the United Sates (U.S.) on patients with chronic kidney diseases, and an incidence of end-stage renal disease (ESRD) in Asian Americans that is 1.5 times higher than in Caucasians, there is a compelling need to improve symptom management strategies for this population. AIMS: 1) To identify common, bothersome symptoms and both Eastern and Western symptom-management strategies in older Chinese-American ESRD patients. 2) To validate the effectiveness of these symptom-management strategies through literature review and an expert panel. METHODS: 1) Older Chinese-Americans were surveyed to assess common ESRD symptoms and management strategies. 2) An umbrella review of patients' symptom-management strategies was conducted, and findings were confirmed by experts. RESULTS: 1) Thirty Chinese-American ESRD patients with an average age of 80 (SD = 13.08) reported strategies to manage fatigue, pain, sleep disturbance, dyspnea, anxiety, nausea and vomiting, constipation, and pruritus. 2) A total of 55 studies were included in the umbrella review. Evidence of varying quality and confirmation by experts supported the effectiveness of 33 symptom-management strategies used by Chinese-American ESRD patients. CONCLUSION: Further study is needed to understand why Chinese-American patients, on average, reported fewer symptoms compared with the general population but scored lower on quality of life measures; to validate reported amelioration strategies; to explore strategy effectiveness; and to uncover additional symptoms and strategies among older Chinese-Americans living with ESRD.

Structure of mouse cytosolic sulfotransferase SULT2A8 provides insight into sulfonation of 7α-hydroxyl bile acids.

Cytosolic sulfotransferases (SULTs) catalyze the transfer of a sulfonate group from the cofactor 3'-phosphoadenosine 5'-phosphosulfate to a hydroxyl (OH) containing substrate and play a critical role in the homeostasis of endogenous compounds, including hormones, neurotransmitters, and bile acids. In human, SULT2A1 sulfonates the 3-OH of bile acids; however, bile acid metabolism in mouse is dependent on a 7α-OH sulfonating SULT2A8 via unknown molecular mechanisms. In this study, the crystal structure of SULT2A8 in complex with adenosine 3',5'-diphosphate and cholic acid was resolved at a resolution of 2.5 Å. Structural comparison with human SULT2A1 reveals different conformations of substrate binding loops. In addition, SULT2A8 possesses a unique substrate binding mode that positions the target 7α-OH of the bile acid close to the catalytic site. Furthermore, mapping of the critical residues by mutagenesis and enzyme activity assays further highlighted the importance of Lys44 and His48 for enzyme catalysis and Glu237 in loop 3 on substrate binding and stabilization. In addition, limited proteolysis and thermal shift assays suggested that the cofactor and substrates have protective roles in stabilizing SULT2A8 protein. Together, the findings unveil the structural basis of bile acid sulfonation targeting 7α-OH and shed light on the functional diversity of bile acid metabolism across species.

Can we enhance osteoporotic metaphyseal fracture healing through enhancing ultrastructural and functional changes of osteocytes in cortical bone with low-magnitude high-frequency vibration?

Fragility fractures are related to the loss of bone integrity and deteriorated morphology of osteocytes. Our previous studies have reported that low-magnitude high-frequency vibration (LMHFV) promoted osteoporotic fracture healing. As osteocytes are known for mechanosensing and initiating bone repair, we hypothesized that LMHFV could enhance osteoporotic fracture healing through enhancing morphological changes in the osteocyte lacuna-canalicular network (LCN) and mineralization. A metaphyseal fracture model was established in female Sprague-Dawley rats to investigate changes in osteocytes and healing outcomes from early to late phase post-fracture. Our results showed that the LCN exhibited an exuberant outgrowth of canaliculi in the osteoporotic fractured bone at day 14 after LMHFV. LMHFV upregulated the E11, dentin matrix protein 1 (DMP1), and fibroblast growth factor 23 (FGF23), but downregulated sclerostin (Sost) in osteocytes. Moreover, LMHFV promoted mineralization with significant enhancements of Ca/P ratio, mineral apposition rate (MAR), mineralizing surface (MS/BS), and bone mineral density (BMD) in the osteoporotic group. Consistently, better healing was confirmed by microarchitecture and mechanical properties, whereas the enhancement in osteoporotic group was comparable or even greater than the normal group. This is the first report to reveal the enhancement effect of LMHFV on the osteocytes' morphology and functions in osteoporotic fracture healing.

AmplifEYE assisted colonoscopy versus standard colonoscopy: A randomized controlled study.

BACKGROUND AND AIM: AmplifEYE is a mucosal exposure device mounted to the tip of colonoscope to improve polyp or adenoma detection. We aim to compare the adenoma detection rates (ADR) of AmplifEYE-assisted colonoscopy (AC) with standard colonoscopy (SC). METHODS: We performed a randomized controlled trial involving patients aged 50 to 79 who underwent AC or SC in two centers. Procedures were performed by five experienced colonoscopists. RESULTS: Three hundred fifty-five patients were recruited, with 334 patients (170 AC and 164 SC) included into analysis. The ADR was numerically higher in AC (47.1%) versus SC (40.9%), P = 0.253. The polyp detection rate (PDR) in AC was 68.2% versus 54.3% in SC, P = 0.009, and serrated polyp detection rate (SDR) in AC was 37.6% versus 20.1% in SC, P < 0.001, both statistically significant higher in the study group. The mean cecal intubation time was shorter with AmplifEYE (8.0 min in AC vs 8.9 min in SC, P = 0.030), and there was no difference in pain score (3 in AC vs 4 in SC, P = 0.121). CONCLUSIONS: AmplifEYE-assisted colonoscopy significantly improved the PDR and SDR, while the ADR was numerically higher in AC that did not reach statistical significance. Using the device resulted in shorter cecal intubation time and did not cause more pain.

Nostalgia, reflection, brooding: Psychological benefits and autobiographical memory functions.

We sought to clarify the psychological profile of experimentally induced nostalgia, compared to two other modes of thinking about one's past-reflection and brooding-also experimentally induced. We tested both British and Chinese participants. Our main hypothesis was that nostalgia's profile is more positive in terms of six psychological benefits and seven autobiographical memory functions. The results were consistent with the hypothesis. In regard to psychological benefits, nostalgia (vs. reflection and brooding) increased positive affect, self-esteem, self-continuity, social connectedness, and meaning in life. Furthermore, nostalgia increased optimism relative to brooding (but not reflection). In regard to autobiographical memory functions, nostalgia (vs. reflection and brooding) led to higher boredom reduction, conversation, intimacy maintenance, and death preparation, as well as lower bitterness revival. Nostalgia also elevated teach/inform relative to brooding (but not reflection). The findings were similar for British and Chinese participants.