S-9-PAHSA's neuroprotective effect mediated by CAIII suppresses apoptosis and oxidative stress in a mouse model of type 2 diabetes.

BACKGROUND: With the rapidly increasing prevalence of metabolic diseases such as type 2 diabetes mellitus (T2DM), neuronal complications associated with these diseases have resulted in significant burdens on healthcare systems. Meanwhile, effective therapies have remained insufficient. A novel fatty acid called S-9-PAHSA has been reported to provide metabolic benefits in T2DM by regulating glucose metabolism. However, whether S-9-PAHSA has a neuroprotective effect in mouse models of T2DM remains unclear. METHODS: This in vivo study in mice fed a high-fat diet (HFD) for 5 months used fasting blood glucose, glucose tolerance, and insulin tolerance tests to examine the effect of S-9-PAHSA on glucose metabolism. The Morris water maze test was also used to assess the impact of S-9-PAHSA on cognition in the mice, while the neuroprotective effect of S-9-PAHSA was evaluated by measuring the expression of proteins related to apoptosis and oxidative stress. In addition, an in vitro study in PC12 cells assessed apoptosis, oxidative stress, and mitochondrial membrane potential with or without CAIII knockdown to determine the role of CAIII in the neuroprotective effect of S-9-PAHSA. RESULTS: S-9-PAHSA reduced fasting blood glucose levels significantly, increased insulin sensitivity in the HFD mice and also suppressed apoptosis and oxidative stress in the cortex of the mice and PC12 cells in a diabetic setting. By suppressing oxidative stress and apoptosis, S-9-PAHSA protected both neuronal cells and microvascular endothelial cells in in vivo and in vitro diabetic environments. Interestingly, this protective effect of S-9-PAHSA was reduced significantly when CAIII was knocked down in the PC12 cells, suggesting that CAIII has a major role in the neuroprotective effect of S-9-PAHSA. However, overexpression of CAIII did not significantly enhance the protective effect of S-9-PAHSA. CONCLUSION: S-9-PAHSA mediated by CAIII has the potential to exert a neuroprotective effect by suppressing apoptosis and oxidative stress in neuronal cells exposed to diabetic conditions. Furthermore, S-9-PAHSA has the capability to reduce fasting blood glucose and LDL levels and enhance insulin sensitivity in mice fed with HFD.

Human Adipose Tissue Lysate-Based Hydrogel for Lasting Immunomodulation to Effectively Improve Spinal Cord Injury Repair.

The long-term inflammatory microenvironment is one of the main obstacles to inhibit acute spinal cord injury (SCI) repair. The natural adipose tissue-derived extracellular matrix hydrogel shows effective anti-inflammatory regulation because of its unique protein components. However, the rapid degradation rate and removal of functional proteins during the decellularization process impair the lasting anti-inflammation function of the adipose tissue-derived hydrogel. To address this problem, adipose tissue lysate provides an effective way for SCI repair due to its abundance of anti-inflammatory and nerve regeneration-related proteins. Thereby, human adipose tissue lysate-based hydrogel (HATLH) with an appropriate degradation rate is developed, which aims to in situ long-term recruit and induce anti-inflammatory M2 macrophages through sustainedly released proteins. HATLH can recruit and polarize M2 macrophages while inhibiting pro-inflammatory M1 macrophages regardless of human or mouse-originated. The axonal growth of neuronal cells also can be effectively improved by HATLH and HATLH-induced M2 macrophages. In vivo experiments reveal that HATLH promotes endogenous M2 macrophages infiltration in large numbers (3.5 × 105/100 µL hydrogel) and maintains a long duration for over a month. In a mouse SCI model, HATLH significantly inhibits local inflammatory response, improves neuron and oligodendrocyte differentiation, enhances axonal growth and remyelination, as well as accelerates neurological function restoration.

Steccherins A-D, chamigrane-type sesquiterpenes from the fungus Steccherinum ochraceum with selective inhibition on B lymphocyte proliferation.

Four previously undescribed chamigrane sesquiterpenes, namely steccherins A-D, have been isolated from the fungus Steccherinum ochraceum. Their structures were elucidated by extensive spectroscopic analysis, as well as computational methods and single crystal X-ray diffraction. Steccherins A and B possess previously undescribed backbones which might be derived from normal chamigrane sesquiterpenes, especially that steccherin A possesses a spiro[5.6]dodecane carbon skeleton via a ring-rearrangement. Steccherins A, C, and D showed immunosuppressive activity with IC50 values ranging from 6.2 to 37.8 µM. The data suggested that these chamigrane sesquiterpenes have potential selective inhibition on LPS-induced B lymphocyte proliferation.

Identification of lactate-related subgroups and prognostic model in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that exhibits elevated glycolytic capacity. Lactate, as a byproduct of glycolysis, is considered a major oncometabolite that plays an important role in oncogenesis and remodeling of the tumor microenvironment. However, the potential roles of lactate in TNBC are not yet fully understood. In this study, our goal was to identify prognosis-related lactate genes (PLGs) and construct a lactate-related prognostic model (LRPM) for TNBC. METHODS: First, we applied lactate-related genes to classify TNBC samples using a hierarchical clustering algorithm. Then, we performed the log-rank analysis and the least absolute shrinkage and selection operator analysis to screen PLGs and construct the LRPM. The biological functions of the identified PLGs in TNBC were investigated using CCK8 assay and clone formation assay. Finally, we constructed a nomogram based on the lactate-risk score and tumor clinical stage. We used the operating characteristic curve and decision curve analysis to evaluate the predictive capability of the nomogram. RESULTS: Our results showed that the TNBC samples could be classified into two subgroups with different survival probabilities. Three genes (NDUFAF3, CARS2 and FH), which can suppress TNBC cell proliferation, were identified as PLGs. Moreover, the LRPM and nomogram exhibited excellent predictive performance for TNBC patient prognosis. CONCLUSION: We have developed a novel LRPM that enables risk stratification and identification of poor molecular subtypes in TNBC patients, showing great potential in clinical practice.

Pharmacokinetics of immediate and sustained-release formulations of paroxetine: Population pharmacokinetic approach to guide paroxetine personalized therapy in chinese psychotic patients.

Paroxetine is one of the most potent selective serotonin reuptake inhibitors (SSRIs) approved for treating depression, panic disorder, and obsessive-compulsive disorder. There is evidence linking genetic polymorphisms and nonlinear metabolism to the Paroxetine's pharmacokinetic (PK) variability. The purpose of the present study was to develop a population PK (PPK) model of paroxetine in Chinese patients, which was used to define the paroxetine's PK parameters and quantify the effect of clinical and baseline demographic factors on these PK characteristics. The study included 184 inpatients with psychosis (103 females and 81 males), with a total of 372 serum concentrations of paroxetine for PPK analyses. The total daily dosage ranged from 20 to 75 mg. One compartment model could fit the PKs characterize of paroxetine. Covariate analysis revealed that dose, formulation, and sex had a significant effect on the PK parameters of paroxetine; however, there was no evident genetic influence of CYP2D6 enzymes on paroxetine concentrations in Chinese patients. The study determined that the population's apparent distribution volume (V/F) and apparent clearance (CL/F), respectively, were 8850 and 21.2 L/h. The CL/F decreased 1-2-fold for each 10 mg dose increase, whereas the different formulations caused a decrease in V/F of 66.6%. Sex was found to affect bioavailability (F), which decreased F by 47.5%. Females had higher F values than males. This PPK model described data from patients with psychosis who received paroxetine immediate-release tablets (IR-T) and/or sustained-release tablets (SR-T). Paroxetine trough concentrations and relative bioavailability were different between formulations and sex. The altered serum concentrations of paroxetine resulting from individual variants and additive effects need to be considered, to optimize the dosage regimen for individual patients.

Relationship between Aspiration Pneumonia and Feeding Care among Home Care Patients with an In-Dwelling Nasogastric Tube in Taiwan: A Preliminary Study.

Home care patients have swallowing dysfunction and rely on an in-dwelling nasogastric tube (NGT) to complement oral food intake, supplement their diet, and maintain adequate nutritional status. This study explored the relationship between aspiration pneumonia (AP) and feeding care among home care patients with an in-dwelling NGT. This preliminary study employed a cross-sectional design. There were 35 patients who relied on an in-dwelling NGT to complement their oral intake of food (NGT-oral feeding) and their primary caregivers participated in this study. All of them developed AP in the past year. Factors involving food intake performance during mealtime of the home care patients and feeding care provided by the caregivers were simultaneously observed and recorded. Among the six risk factors univariately correlated with the incidence of AP, feeding in a noisy environment, using a large spoon to feed the participants, more than 5 mL of food per mouthful, food intake duration lasting > 30 min, swallowing twice for each mouthful of food, and coughing at least once every day remained significant in the logistic regression model (all p < 0.05). Four risk factors for AP were correlated with feeding care; the adjusted risk ratio ranged from 6.17 to 14.96 (all p < 0.05). In addition to each individual's food intake ability, improper feeding assistance was related to the risk factors for AP among home care patients with NGT-oral feeding. Thus, home caregivers should receive safe oral feeding education and training.

PRRT2 Mutation and Serum Cytokines in Paroxysmal Kinesigenic Dyskinesia.

OBJECTIVE: Paroxysmal kinesigenic dyskinesia (PKD) is a rare movement disorder PRRT2 gene mutations have been reported to cause PKD. However, the pathophysiological mechanism of PKD remains unclear, and it is unknown whether an inflammatory response is involved in the occurrence of this disease. We aimed to investigate the symptomatology, genotype, and serum cytokines of patients with PKD. METHODS: We recruited 21 patients with PKD, including 7 with familial PKD and 14 with sporadic PKD. Their clinical features were investigated, and blood samples were collected, and PRRT2 mutations and cytokine levels were detected. RESULTS: The mean age at PKD onset was 12.3±2.2 years old. Dystonia was the most common manifestation of dyskinesia, and the limbs were the most commonly affected parts. All attacks were induced by identifiable kinesigenic triggers, and the attack durations were brief (<1 min). Four different mutations from 9 probands were identified in 7 familial cases (71.4%) and 14 sporadic cases (28.6%). Two of these mutations (c.649dupC, c.620_621delAA) had already been reported, while other 2 (c.1018_1019delAA, c.1012+1G>A) were previously undocumented. The tumor necrosis factor (TNF)-α level in the PKD group was significantly higher than that in the age- and sex-matched control group (P=0.025). There were no significant differences in the interleukin (IL)-1ß, IL-2R, IL-6, IL-8, or IL-10 levels between the two groups. CONCLUSION: In this study, we summarized the clinical and genetic characteristics of PKD. We found that the serum TNF-α levels were elevated in patients clinically diagnosed with PKD, suggesting that an inflammatory response is involved in the pathogenesis of PKD.

Physical Frailty and Oral Frailty Associated with Late-Life Depression in Community-Dwelling Older Adults.

Late-life depression is a major mental health problem and constitutes a heavy public health burden. Frailty, an aging-related syndrome, is reciprocally related to depressive symptoms. This study investigated the associations of physical frailty and oral frailty with depression in older adults. This large-scale cross-sectional study included 1100 community-dwelling older adults in Taiwan. The participants completed a dental examination and questionnaires answered during personal interviews. The 15-item Geriatric Depression Scale was used to assess depression, and information on physical conditions and oral conditions was collected. Multivariable logistical regression analysis was conducted to examine associations of interest. Significant factors associated with depression were pre-physical frailty (adjusted odds ratio (aOR) = 3.61), physical frailty (aOR = 53.74), sarcopenia (aOR = 4.25), insomnia (aOR = 2.56), pre-oral frailty (aOR = 2.56), oral frailty (aOR = 4.89), dysphagia (aOR = 2.85), and xerostomia (aOR = 1.10). Depression exerted a combined effect on physical frailty and oral frailty (aOR = 36.81). Physical frailty and oral frailty were significantly associated with late-life depression in community-dwelling older adults in a dose-response manner. Developing physical and oral function interventions to prevent depression among older adults is essential.

Cerebral venous sinus thrombosis in pregnancy: A case report.

BACKGROUND: Cerebral venous thrombosis (CVT) is a rare but life-threatening disease in pregnant women. Anticoagulation is the first-line therapy for CVT management. However, some patients have poor outcomes despite anticoagulation. Currently, the endovascular treatment of CVT in pregnant women remains controversial. We report a rare case of CVT in a pregnant woman who was successfully treated with two stent retriever devices. CASE SUMMARY: The patient was a 29-year-old pregnant woman. She was first diagnosed with hyperemesis gravidarum due to severe nausea and vomiting for one week. As the disease progressed, she developed acute left hemiplegia. Imaging confirmed the diagnosis of superior sagittal sinus, right transverse sinus and sinus sigmoideus thrombosis. As anticoagulant therapy was ineffective, she underwent thrombectomy. After the mechanical thrombectomy, her headache diminished. Three weeks later, the patient was completely independent. At a 3-mo follow-up, no relapse of symptoms was observed. CONCLUSION: Mechanical thrombectomy may be an effective alternative therapy for CVT in pregnant women if anticoagulation therapy fails.

Dimethyl itaconate alleviates the pyroptosis of macrophages through oxidative stress.

Macrophages are involved in the pathophysiology of many diseases as critical cells of the innate immune system. Pyroptosis is a form of macrophage death that induces cytokinesis of phagocytic substances in the macrophages, thereby defending against infection. Dimethyl itaconate (DI) is an analog of itaconic acid with anti-inflammatory effects. However, the effect of dimethyl itaconate on macrophage pyroptosis has not been elucidated clearly. Thus, the present study aimed to analyze the effect of DI treatment on a macrophage pyroptosis model (Lipopolysaccharide, LPS + Adenosine Triphosphate, ATP). The results showed that 0.25 mM DI ameliorated macrophage pyroptosis and downregulated interleukin (IL)-1ß expression. Then, real-time quantitative polymerase chain reaction (RT-qPCR) was used to confirm the result of RNA-sequencing of the upregulated oxidative stress-related genes (Gclc and Gss) and downregulated inflammation-related genes (IL-12ß and IL-1ß). In addition, Gene Ontology (GO) enrichment analysis showed that differential genes were associated with transcript levels and DNA replication. Kyoto encyclopedia of genes and genomes (KEGG) enrichment showed that signaling pathways, such as tumor necrosis factor (TNF), Jak, Toll-like receptor and IL-17, were altered after DI treatment. N-acetyl-L-cysteine (NAC) reversed the DI effect on the LPS + ATP-induced macrophage pyroptosis and upregulated the IL-1ß expression. Oxidative stress-related protein Nrf2 is involved in the DI regulation of macrophage pyroptosis. Taken together, these findings suggested that DI alleviates the pyroptosis of macrophages through oxidative stress.

Impact of intravenous dexmedetomidine on postoperative bowel movement recovery after laparoscopic nephrectomy: A consort-prospective, randomized, controlled trial.

BACKGROUND: Postoperative ileus is a frequent postoperative complication, especially after abdominal surgery. Sympathetic excitation is the primary factor for postoperative ileus. Sympathetic activation becomes increased by surgical stress, postoperative pain, and inflammation. Dexmedetomidine (DEX) can inhibit sympathetic nerve activity, inflammation, and pain. AIM: To observe whether DEX promotes bowel movements in patients after laparoscopic nephrectomy. METHODS: One hundred and twenty patients undergoing laparoscopic nephrectomy were assigned to three groups: C (normal saline infusion), D1 (DEX 0.02 µg/kg/h), and D2 (DEX 0.04 µg/kg/h). The primary outcomes were the recorded times to first flatus, defecation, and eating after surgery. The secondary outcomes were postoperative pain, assessed using the numerical rating scale (NRS), adverse effects, and the duration of the postoperative hospital stay. RESULTS: The times to first flatus, defecation, and eating in groups D1 and D2 were significantly shorter than those in group C (P < 0.01). The NRS scores at 8 h and 24 h after surgery were significantly lower in groups D1 and D2 than in group C (P < 0.05). No adverse effects were observed (P > 0.05). CONCLUSION: Postoperative infusion of DEX at 0.04 µg/kg/h facilitates bowel movements in patients undergoing laparoscopic nephrectomy.

Awake fiberoptic intubation and use of bronchial blockers in ankylosing spondylitis patients.

BACKGROUND: Patients with ankylosing spondylitis (AS) combined with severe cervical fusion deformity have difficult airways. Awake fiberoptic intubation is the standard treatment for such patients. Alleviating anxiety and discomfort during intubation while maintaining airway patency and adequate ventilation is a major challenge for anesthesiologists. Bronchial blockers (BBs) have significant advantages over double-lumen tubes in these patients requiring one-lung ventilation. AIM: To evaluate effective drugs and their optimal dosage for awake fiberoptic nasotracheal intubation in patients with AS and to assess the pulmonary isolation effect of one-lung ventilation with a BB. METHODS: We studied 12 AS patients (11 men and one woman) with lung or esophageal cancer who underwent thoracotomy with a BB. Preoperative airway evaluation found that all patients had a difficult airway. All patients received an intramuscular injection of penehyclidine hydrochloride (0.01 mg/kg) before anesthesia. In the operating room, dexmedetomidine(0.5 µg/kg) was infused intravenously for 10 min, with 2% lidocaine for airway surface anesthesia, and a 3% ephedrine cotton swab was used to contract the nasal mucosa vessels. Before tracheal intubation, fentanyl (1 µg/kg) and midazolam (0.02 mg/kg) were administered intravenously. Awake fiberoptic nasotracheal intubation was performed in the semi-reclining position. Intravenous anesthesia was administered immediately after successful intubation, and a BB was inserted laterally. The pre-intubation preparation time, intubation time, facial grimace score, airway responsiveness score during the fiberoptic introduction, time of end tracheal catheter entry into the nostril, and lung collapse and surgical field score were measured. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were recorded while entering the operation room (T1), before intubation (T2), immediately after intubation (T3), 2 min after intubation (T4), and 10 min after intubation (T5). After surgery, all patients were followed for adverse reactions such as epistaxis, sore throat, hoarseness, and dysphagia. RESULTS: All patients had a history of AS (20.4 ± 9.6 years). They had a Willson's score of 5 or above, grade III or IV Mallampati tests, an inter-incisor distance of 2.9 ± 0.3 cm, and a thyromental (T-M) distance of 4.8 ± 0.7 cm. The average pre-intubation preparation time was 20.4 ± 3.4 min, intubation time was 2.6 ± 0.4 min, facial grimace score was 1.7 ± 0.7, airway responsiveness score was 1.1 ± 0.7, and pulmonary collapse and surgical exposure score was 1.2 ± 0.4. The SBP, DBP, and HR at T5 were significantly lower than those at T1-T4 (P < 0.05). While the values at T1 were not significantly different from those at T2-T4 (P > 0.05), they were significantly different from those at T5 (P < 0.05). Seven patients had minor epistaxis during endotracheal intubation, two were followed 24 h after surgery with a mild sore throat, and two had hoarseness without dysphagia. CONCLUSION: Patients with AS combined with severe cervical and thoracic kyphosis should be intubated using fiberoptic bronchoscopy under conscious sedation and topical anesthesia. Proper doses of penehyclidine hydrochloride, dexmedetomidine, fentanyl, and midazolam, combined with 2% lidocaine, administered prior to intubation, can provide satisfactory conditions for tracheal intubation while maintaining the comfort and safety of patients. BBs are safe and effective for one-lung ventilation in such patients during thoracotomy.

Association of Satellite Sign with Postoperative Rebleeding in Patients Undergoing Stereotactic Minimally Invasive Surgery for Hypertensive Intracerebral Haemorrhage.

There are few studies regarding imaging markers for predicting postoperative rebleeding after stereotactic minimally invasive surgery (MIS) for hypertensive intracerebral haemorrhage (ICH), and little is known about the relationship between satellite sign on computed tomography (CT) scans and postoperative rebleeding after MIS. This study aimed to determine the value of the CT satellite sign in predicting postoperative rebleeding in patients with hypertensive ICH who undergo stereotactic MIS. We retrospectively examined and analysed 105 patients with hypertensive ICH who underwent standard stereotactic MIS for hematoma evacuation within 72 h following admission. Postoperative rebleeding occurred in 14 of 65 (21.5%) patients with the satellite sign on baseline CT, and in 5 of the 40 (12.5%) patients without the satellite sign. This difference was statistically significant. Positive and negative values of the satellite sign for predicting postoperative rebleeding were 21.5% and 87.5%, respectively. Multivariate logistic regression analysis verified that baseline ICH volume and intraventricular rupture were independent predictors of postoperative rebleeding. In conclusion, the satellite sign on baseline CT scans may not predict postoperative rebleeding following stereotactic MIS for hypertensive ICH.

Dental Treatment Needs and Related Risk Factors among School Children with Special Needs in Taiwan.

The purpose of this study was to assess dental treatment needs (TNs) and related risk factors of children with disabilities (CD). This cross-sectional study recruited 484 CD, 6 to 12 years of age, from 10 special education schools in Taiwan. Dental status and TNs were examined and evaluated by well-trained dentists and based on the criteria set by the World Health Organization (1997). The results indicated that 61.78% required restorative dental treatment due to their dental caries. On average, each participant had 2.72 teeth that required treatment, and 6.38 surfaces required restoration. One-quarter of the participants (24.79%) required 1- or 2-surface restoration, and one out of three (36.98%) had more complex TNs (including 3 or more surfaces to be filled, pulp care, extraction, and more specialized care). The significant risk factors associated with restorative TNs among CD were those whose parents had lower socioeconomic status, frequent sweets intake, insufficient tooth-brushing ability, and poor oral health. Most of the CD had extensive unmet TNs for their caries and required complex treatment to recover the function of their teeth. Encouraging parents/caregivers to take their children for dental treatment, promoting awareness of the importance of dental hygiene, giving assistance to brushing their teeth after eating, and controlling and/or modifying sweet diet habits are necessary to reduce CD's dental caries, especially those with lower socioeconomic status parents/caregivers.

Restoration of bilateral motor coordination from preserved agonist-antagonist coupling in amputation musculature.

BACKGROUND: Neuroprosthetic devices controlled by persons with standard limb amputation often lack the dexterity of the physiological limb due to limitations of both the user's ability to output accurate control signals and the control system's ability to formulate dynamic trajectories from those signals. To restore full limb functionality to persons with amputation, it is necessary to first deduce and quantify the motor performance of the missing limbs, then meet these performance requirements through direct, volitional control of neuroprosthetic devices. METHODS: We develop a neuromuscular modeling and optimization paradigm for the agonist-antagonist myoneural interface, a novel tissue architecture and neural interface for the control of myoelectric prostheses, that enables it to generate virtual joint trajectories coordinated with an intact biological joint at full physiologically-relevant movement bandwidth. In this investigation, a baseline of performance is first established in a population of non-amputee control subjects ([Formula: see text]). Then, a neuromuscular modeling and optimization technique is advanced that allows unilateral AMI amputation subjects ([Formula: see text]) and standard amputation subjects ([Formula: see text]) to generate virtual subtalar prosthetic joint kinematics using measured surface electromyography (sEMG) signals generated by musculature within the affected leg residuum. RESULTS: Using their optimized neuromuscular subtalar models under blindfolded conditions with only proprioceptive feedback, AMI amputation subjects demonstrate bilateral subtalar coordination accuracy not significantly different from that of the non-amputee control group (Kolmogorov-Smirnov test, [Formula: see text]) while standard amputation subjects demonstrate significantly poorer performance (Kolmogorov-Smirnov test, [Formula: see text]). CONCLUSIONS: These results suggest that the absence of an intact biological joint does not necessarily remove the ability to produce neurophysical signals with sufficient information to reconstruct physiological movements. Further, the seamless manner in which virtual and intact biological joints are shown to coordinate reinforces the theory that desired movement trajectories are mentally formulated in an abstract task space which does not depend on physical limb configurations.

The Effectiveness of a Board Game-Based Oral Hygiene Education Program on Oral Hygiene Knowledge and Plaque Index of Adults with Intellectual Disability: A Pilot Study.

An oral hygiene board game was designed as an intervention tool and applied to explore the effectiveness for the oral health related knowledge (OHK) score and plaque index (PI) of adults with intellectual disability (ID). This one-group pre/post-test design study was conducted in a residential long-term care facility for 42 participants. The study had one pre-test (baseline) and three post-tests evaluated in both control and intervention stages, respectively. The participants participated in a 60-min oral hygiene board game twice a week during the intervention stage. Total OHK score and PI of the participants were recorded to determine the effectiveness of intervention. There were no differences in OHK score and PI between the two stages at baseline. The results in intervention stage demonstrated a significant gradual increase and reduction in the OHK score when compared with the control stage. A statistically significant improvement in the OHK score and PI (42.29% and -33.28%, respectively) at the end of intervention between two stages was recorded. This study proved a board game is deemed an effective education method applicable to promote the OHK and skills of ID adults.

Sesquiterpenoids and Xanthones from the Kiwifruit-Associated Fungus Bipolaris sp. and Their Anti-Pathogenic Microorganism Activity.

Nine previously undescribed sesquiterpenoids, bipolarisorokins A-I (1-9); two new xanthones, bipolarithones A and B (10 and 11); two novel sativene-xanthone adducts, bipolarithones C and D (12 and 13); as well as five known compounds (14-18) were characterized from the kiwifruit-associated fungus Bipolaris sp. Their structures were elucidated by extensive spectroscopic methods, electronic circular dichroism (ECD), 13C NMR calculations, DP4+ probability analyses, and single crystal X-ray diffractions. Many compounds exhibited anti-pathogenic microorganism activity against the bacterium Pseudomonas syringae pv. actinidiae and four pathogenic microorganisms.

Patterns of Deterioration in Moderate Patients With COVID-19 From Jan 2020 to Mar 2020: A Multi-Center, Retrospective Cohort Study in China.

Background: Around the globe, moderate cases account for the largest proportion of all coronavirus disease 2019 (COVID-19) patients, and deteriorated moderate patients contribute the most in mortality. However, published articles failed to address the deterioration details of moderate cases, especially on when and how they deteriorated. Methods: All moderate COVID-19 patients hospitalized in Guangdong Province from January 14 to March 16, 2020, were included in this multicenter retrospective cohort study and were divided into deteriorated and non-deteriorated groups according to clinical status. Symptoms and demographic, therapeutic, and laboratory test result characteristics were collected to explore the features of disease deterioration. Results: Of 1,168 moderate patients included, 148 (13%) deteriorated to severe (130 cases) or critical (18 cases) status. Over 20% of the older subgroup (>50 years old) showed deterioration. The median time for deterioration was 11 days after onset [interquartile range (IQR) 9-14 days]. In addition, 12.2% severe cases could further develop to critical status after 3 days (IQR 2-6.5 days) of having a severe condition. Respiratory dysfunction and hypoxia were the major manifestations as disease deterioration, while 76 cases (52.1%) showed respiratory rate >30 breaths/min, 119 cases (80.4%) showed SaO2 <93%, 100 cases (67.5%) had 201 < PaO2/FiO2 < 300, and 27 cases (18.9%) had blood lactic acid >2.0 mmol/L. In view of multiple organ dysfunction, 87.8% of acute respiratory distress syndrome (ARDS), 20.2% of acute kidney injury (AKI), 6.8% of coagulopathy, 4% of acute heart failure (AHF), 3.4% of acute hepatic injury (AHI), and 5.4% of shock occurred in deteriorated patients, while organ injury occurred in the following sequence: ARDS, AKI, AHF, coagulopathy, AHI, and shock. Conclusions: The deteriorated pattern of moderate COVID-19 patients is characterized as the 11th day from onset (IQR 9-14 days) being an important time point of disease deterioration with further exacerbation to critical condition in 3 days (IQR 2-6.5 days), A RDS followed by AKI being the typical modes of sequential organ damage.