Magnesium exposure increases hip fracture risks in patients with chronic kidney disease: a population-based nested case-control study.

This population-based study demonstrates a strong link between Mg-containing antacid exposure and hip fracture risk in nondialysis CKD and dialysis patients. As an Mg-containing antacid, MgO is also commonly used as a stool softener, which can be effortlessly replaced by other laxatives in CKD patients to maintain bone health. PURPOSE: Bone fracture is a severe complication in chronic kidney disease (CKD) patients, leading to disability and reduced survival. In CKD patients, blood magnesium (Mg) concentrations are usually above the normal range due to reduced kidney excretion of Mg. The present study examines the association between Mg-containing antacid exposure and the risk of hip fracture of CKD patients. METHODS: In this nationwide nested case-control study, we enrolled 44,062 CKD patients with hip fracture and 44,062 CKD matched controls, among which the mean age was 77.1 years old, and 87.9% was nondialysis CKD. RESULTS: As compared to non-users, Mg-containing antacid users were significantly more likely to experience hip fracture (adjusted odds ratio (OR) 1.36, 95% CI, 1.32 to 1.41; p < 0.001). Subgroup analysis showed that such risk exists in both nondialysis CKD patients and long-term dialysis patients. In contrast, aluminum or calcium-containing-antacid use did not reveal such association. Next, we examined the influence of Mg-containing antacid dosage on hip fracture risk, the adjusted ORs in the first quartile (Q1), Q2, Q3, and Q4 were 1.20 (95% CI, 1.15 to 1.25; p < 0.001), 1.35 (95% CI, 1.30 to 1.41; p < 0.001), 1.49 (95% CI, 1.43 to 1.56; p < 0.001), and 1.54 (95% CI, 1.47 to 1.61; p < 0.001), respectively, showing that such risk exists regardless of the antacid dosage. A receiver operating characteristic curve analysis demonstrated that the best cutoff value of the exposed Mg dose to discriminate the hip fracture is 532 mEq during the follow-up period. CONCLUSION: This population-based study demonstrates a strong link between Mg-containing antacid exposure and the hip fracture risk in both nondialysis CKD and dialysis patients.

[The application value of plasma heterogeneous nuclear ribonucleoprotein A2/B1, Aß42 and P-tau in the preoperative diagnosis of mild cognitive dysfunction].

Objective: To explore the application value of plasma heterogeneous nuclear ribonucleoprotein A2/B1(hnRNP A2B1), ß-amyloid 42(Aß42) and phosphorylated tau protein(P-tau) levels in elderly patients in the preoperative diagnosis of mild cognitive impairment(MCI). Methods: A total of 200 patients who underwent elective surgery at Tianjin Third Central Hospital from June 2020 to March 2021were Enrolled, regardless of gender, age 65-80 years old. According to the international MCI working group standards and the European Alzheimer's Disease Federation working group standards, patients were divided into MCI group and control group. There were 58 males and 42 females in each group. The patient's plasma hnRNP A2/B1, Aß42 and P-tau levels were detected before operation. The sensitivity, specificity and accuracy of the diagnosis of MCI were calculated. The receiver operating characteristic curve were drew to evaluate the diagnostic value of each index. Results: The plasma levels of hnRNP A2/B1, Aß42 and P-tau in the MCI group were 310.0 (275.1, 344.2), 34.5 (24.9, 42.5), 190.4 (150.4, 301.7) ng/L, respectively, which were significantly higher than those of the control group [272.7 (239.6, 291.5), 18.7 (14.7, 26.6), 140.0 (101.8, 217.5) ng/L]. The differences were statistically significant (all P<0.05). Taking the international MCI working group standard as the gold standard, the sensitivity, specificity and area under the ROC curve (AUC) of plasma hnRNP A2/B1 for predicting MCI were 80%, 61%, and 0.781, respectively. The sensitivity, specificity and AUC of plasma Aß42 for predicting MCI were 78%, 73%, and 0.744. The sensitivity, specificity, and AUC of P-tau for predicting MCI were 51%, 79%, and 0.675, respectively. The sensitivity, specificity and AUC of hnRNP A2/B1 and Aß42 in predicting MCI were not statistically significant (all P>0.05), but the sensitivity of both were higher than P-tau (all P<0.001). Compared with P-tau, the AUC of plasma hnRNP A2/B1 was higher when predicting MCI (P<0.05). When the three indicators were combined, the sensitivity was 82%, and the AUC was 0.842, both of which were the highest, but the specificity reduced (71%) (all P<0.05). Conclusions: Plasma hnRNP A2/B1 combined with Aß42 and P-tau levels can improve the sensitivity and accuracy of MCI diagnosis in elderly MCI patients before surgery, and have the greatest diagnostic efficiency. It has certain application value.

[Clinical characteristics of children infected with different subtypes/genotypes of human respiratory syncytial virus in Beijing from 2009 to 2017].

Objective: To explore the different clinical characteristics of children infected with different subtype/genotype of human respiratory syncytial virus (HRSV) in Beijing. Methods: Respiratory specimens for positive HRSV were randomly collected from children with acute respiratory tract infection (ARTI) in the epidemic season of HRSV from November of each year to January of the next year during 2009 and 2017. G genes of HRSV were amplified and sequenced for subtyping and genotyping by bioinformatics analysis. Clinical data were collected and analyzed. Results: Out of 590 children, 376 (63.7%) with subtype A, and 214 (36.3) with subtype B. The annual dominant subtypes of HRSV from 2009 to 2017 were B-A-A-B-AB-A-A-B-A, respectively, whilst a total of 10 genotypes were detected with 95.8% assigned to genotype ON1 and NA1 of subtype A, and genotype BA9 of subtype B. Children infected with subtype B (96 cases, 44.9%) were more likely aged 0-3 month old than those with subtype A (118 cases, 31.4%) (P=0.001), and more likely to be admitted to Intensive Care Unit(ICU) ((124 cases, 57.9%) than those with subtype A (172 cases, 45.7%)) (P=0.005). Statistical significance were shown among children infected with genotype ON1, NA1 or BA9, in the possibility of infection in children aged 0-3 month (P=0.003), proportion of admission into ICU (P=0.007), length of stay in hospital (P=0.001), and clinical outcome (P=0.001), respectively. Conclusion: Children infected with different subtype or genotype of HRSV have different clinical characteristics, which stresses the important role of the monitoring HRSV subtypes and genotypes among children.

Hyperbaric oxygen inhibits the HMGB1/RAGE signaling pathway by upregulating Mir-107 expression in human osteoarthritic chondrocytes.

OBJECTIVE: MicroRNA (miRNA)107 expression is downregulated but high mobility group box 1 (HMGB-1), Toll-like receptors (TLRs), and receptor for advanced glycation end products (RAGE) are upregulated in osteoarthritic (OA) cartilage. We investigated mir-107/HMGB-1 signaling in OA after hyperbaric oxygen (HBO) treatment. DESIGN: MiR-107 mimic was transfected and the HMGB-1 was analyzed in OA chondrocytes. MiRNA targets were identified using bioinformatics and a luciferase reporter assay. After HBO treatment, the mRNA or protein levels of HMGB-1, RAGE, TLR2, TLR4, and inducible nitric oxide (NO) synthase (iNOS) and phosphorylation of mitogen-activated protein kinase (MAPK) were evaluated. The secreted HMGB-1 and matrix metalloproteases (MMPs) levels were quantified. Finally, we detected the HMGB-1 and iNOS expression in rabbit cartilage defects. RESULTS: Overexpression of miR-107 suppressed HMGB-1 expression in OA chondrocytes. The 3'UTR of HMGB-1 mRNA contained a 'seed-matched-sequence' for miR-107. MiR-107 was induced by HBO and a marked suppression of HMGB-1 was observed simultaneously in OA chondrocytes. Knockdown of miR-107 upregulated HMGB-1 expression in hyperoxic cells. HBO downregulated the mRNA and protein expression of HMGB-1, RAGE, TLR2, TLR4, and iNOS, and the secretion of HMGB-1. HBO decreased the nuclear translocation of nuclear factor (NF)-κB, downregulated the phosphorylation of MAPK, and significantly decreased the secretion of MMPs. Morphological and immunohistochemical observation demonstrated that HBO markedly enhanced cartilage repair and the area stained positive for HMGB-1 and iNOS tended to be lower in the HBO group. CONCLUSIONS: HBO inhibits HMGB-1/RAGE signaling related pathways by upregulating miR-107 expression in human OA chondrocytes.

Randomized trial of oral versus enteral feeding for patients with postoperative pancreatic fistula after pancreatoduodenectomy.

BACKGROUND: Whether continued oral feeding may have a negative impact on healing of postoperative pancreatic fistula (POPF) is unclear. The aim was to test the hypothesis that oral feeding is non-inferior to enteral feeding in closure of POPF after pancreatoduodenectomy, and to clarify the effects of oral feeding on the duration and grade of POPF. METHODS: This multicentre, non-inferiority randomized trial of oral or enteral feeding of patients with POPF after pancreatoduodenectomy recruited patients between August 2013 and September 2016. The primary efficacy outcome was the 30-day fistula closure rate. The prespecified non-inferiority margin was 15 per cent. Other efficacy outcomes included grade of fistula, and hospital stay and costs. RESULTS: A total of 114 patients were included, and received oral (57) or enteral (57) feeding. The two groups were balanced in baseline characteristics and no patient was lost to follow-up. In intention-to-treat analysis, oral feeding was non-inferior to enteral feeding in terms of 30-day fistula closure rate (88 versus 89 per cent respectively; difference -1·8 per cent, lower limit of 95 per cent c.i. -14·4 per cent; P = 0·020 for non-inferiority). Compared with enteral feeding, oral feeding significantly reduced hospital costs and duration of stay. No significant differences were noted in the number of patients whose POPF evolved into grade B/C, or other outcomes. CONCLUSION: Oral feeding in patients with POPF after pancreatoduodenectomy did not increase the duration or grade of POPF, and was associated with reduced duration of stay and hospital costs. Registration number: NCT01755260 (http://www.clinicaltrials.gov).

Validation of a nomogram to predict the risk of cancer in patients with intraductal papillary mucinous neoplasm and main duct dilatation of 10 mm or less.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is premalignant pancreatic lesion. International guidelines offer limited predictors of individual risk. A nomogram to predict individual IPMN malignancy risk was released, with good diagnostic performance based on a large cohort of Asian patients with IPMN. The present study validated a nomogram to predict malignancy risk and invasiveness of IPMN using both Eastern and Western cohorts. METHODS: Clinicopathological and radiological data from patients who underwent pancreatic resection for IPMN at four centres each in Eastern and Western countries were collected. After excluding patients with missing data for at least one malignancy predictor in the nomogram (main pancreatic duct diameter, cyst size, presence of mural nodule, serum carcinoembryonic antigen and carbohydrate antigen (CA) 19-9 levels, and age). RESULTS: In total, data from 393 patients who fit the criteria were analysed, of whom 265 were from Eastern and 128 from Western institutions. Although mean age, sex, log value of serum CA19-9 level, tumour location, main duct diameter, cyst size and presence of mural nodule differed between the Korean/Japanese, Eastern and Western cohorts, rates of malignancy and invasive cancer did not differ significantly. Areas under the receiver operating characteristic (ROC) curve values for the nomogram predicting malignancy were 0·745 for Eastern, 0·856 for Western and 0·776 for combined cohorts; respective values for the nomogram predicting invasiveness were 0·736, 0·891 and 0·788. CONCLUSIONS: External validation of the nomogram showed good performance in predicting cancer in both Eastern and Western patients with IPMN lesions.

ANTECEDENTES: La neoplasia mucinosa papilar intraductal (intraductal papillary mucinous neoplasm, IPMN) es una lesión pancreática premaligna. Las guías internacionales incluyen un número limitado de factores predictivos de riesgo individual. Para predecir el riesgo individual de malignidad del IPMN se ha propuesto un nomograma con un buen rendimiento diagnóstico, basado en una gran cohorte de pacientes asiáticos con IPMN. Este estudio validó el nomograma para predecir el riesgo de cáncer y de invasión de la IPMN utilizando cohortes tanto orientales como occidentales. MÉTODOS: Se recogieron datos clínico-patológicos y radiológicos de pacientes en los que se realizó una resección de páncreas por IPMN en 4 centros en países orientales y en 4 centros de países occidentales. Se excluyeron los pacientes en los que en el nomograma faltaba ≥ 1 factor(es) predictivo(s) de malignidad (diámetro del conducto pancreático principal, tamaño del quiste, presencia de nódulo mural, niveles séricos de CEA y CA19-9, y edad). RESULTADOS: En total, se analizaron datos de 393 pacientes que cumplían con los criterios de inclusión, de los cuales 265 eran de centros orientales y 128 de centros occidentales. Aunque la edad media, el sexo, el valor logarítmico del nivel sérico de CA19-9, la localización del tumor, el diámetro del conducto principal, el tamaño del quiste y la presencia de un nódulo mural difirieron entre las cohortes de Corea/Japón y las cohortes oriental y occidental, las tasas de malignidad y de cáncer invasivo no fueron significativamente diferentes. Las áreas bajo la curva operativa del receptor (area under the receiver operating curve, AUC) que mostró el nomograma para predecir la malignidad fueron: cohorte oriental: 0,745; cohorte occidental: 0,856 y cohortes combinadas: 0,776; y para predecir la invasión tumoral fueron: cohorte oriental: 0,736; cohorte occidental: 0,891, y cohortes combinadas: 0,788. CONCLUSIÓN: La validación externa del nomograma mostró un buen rendimiento en la predicción de cáncer, tanto en pacientes orientales como occidentales con lesiones IPMN.

Relationship between fasting plasma glucose and incidence of diabetes in children and adolescents.

AIM: To investigate the appropriate fasting plasma glucose threshold by which to define prediabetes in children and adolescents, based on its ability to predict incident paediatric diabetes. METHODS: In a nationwide survey of diabetes and renal disease conducted between 1992 and 2000 in all school-aged children in Taiwan, those with abnormal results in repeated urine tests received further physical examination and blood tests. Students who had blood tests for at least two time points were selected for the present study (N = 12 119). The incidence of paediatric diabetes, adjusted hazard ratio and predictive power of fasting plasma glucose were analysed. RESULTS: The incidence of paediatric diabetes increased with increasing fasting plasma glucose levels. Groups with fasting plasma glucose >5.6 mmol/l had a higher adjusted hazard ratio. The adjusted hazard ratio of incident diabetes for participants with higher fasting plasma glucose rose continuously when using a higher threshold for fasting plasma glucose. The area under the receiver-operating characteristic curve for fasting plasma glucose was 0.628 for predicting paediatric diabetes. The association between fasting plasma glucose and incident paediatric diabetes and the area under the receiver-operating characteristic curve were similar in boys and girls and were higher in the age group 12-18 years. According to receiver-operating characteristic curve analysis, the optimal thresholds, sensitivity and specificity were 4.75 mmol/l, 65% and 51%, respectively, for those aged 6-11 years and 5.19 mmol/l, 60% and 73%, respectively, for those aged 12-18 years. CONCLUSION: Fasting plasma glucose is associated with the incidence of paediatric diabetes. The results of the present study can be used as reference data to suggest a cut-off value to define paediatric prediabetes.

Association between lactic acid sting test scores, self-assessed sensitive skin scores and biophysical properties in Chinese females.

BACKGROUND: Lactic acid sting test (LAST) is a classical method to identify sensitive skin. However, some subjects with self-perceived sensitive skin are negative for LAST. OBJECTIVE: To determine whether LAST scores are associated with specific phenotype of sensitive skin. METHODS: A total of 292 subjects with self-perceived sensitive skin were enrolled in this study. The Sensitive Scale was used to evaluate the severity of burning, stinging, itching, tautness, erythema and scaling based on 0-10 scale scores. In addition to the assessment of LAST scores, epidermal biophysical properties were measured using an MPA system. RESULTS: The Sensitive Scale scores of stinging, itching, tautness and scaling were significantly different between the LAST-positive and -negative groups. However, burning and erythema scores did not differ between the LAST-positive and -negative groups. LAST scores were positively correlated with the Sensitive Scale scores for stinging, itching, tautness and scaling, but not for burning and erythema scores. Moreover, LAST scores negatively correlated with stratum corneum hydration, but positively with transepidermal water loss (TEWL) rates. CONCLUSIONS: Lactic acid sting test scores positively correlated with TEWL rates. LAST scores could be used to identify subjects with sensitive skin characterized mainly by stinging and itching, but not those mainly by burning and erythema.

CONTEXTE: Le test de la piqûre d'acide lactique (LAST) est une méthode classique pour identifier les peaux sensibles. Cependant, certaines personnes s'évaluant ayant une peau sensible sont négatifs au test LAST. OBJECTIF: Déterminer si le score du LAST est associé à un phénotype spécifique de peau sensible. MÉTHODES: Au total, 292 personnes s'évaluant ayant une peau sensible ont été inclus dans cette étude. L'échelle de sensibilité a été utilisée pour évaluer la sévérité de la brûlure, du picotements, de la démangeaison, de la tension, de l'érythème et des desquamations basée sur une échelle de 0-10. En plus de l'évaluation du score LAST, les propriétés biophysiques épidermiques ont été mesurées à l'aide d'un système MPA. RÉSULTATS: Les scores de l'échelle de sensibilité pour le picotement, les démangeaisons, la tension et la desquamation étaient significativement différents entre la groupe LAST positif et celle du LAST négatif. Cependant, les scores de la brûlure et de l'érythème n'étaient pas différents entre les deux groupes. Le score LAST était positivement corrélé avec les scores de l'échelle de sensibilité du picotement, des démangeaisons, de la tension et des desquamations, mais pas pour la brûlure et l'érythème. En plus, les scores LAST étaient négativement corrélés avec l'hydratation du stratum corneum, mais positivement corrélés avec le taux de perte en eau transépidermique (TEWL). CONCLUSIONS: Les scores LAST étaient corrélés positivement avec le taux de perte en eau transépidermique. Les scores LAST pourraient être utilisés pour identifier les personnes avec la peau sensible caractérisée principalement le picotement et les démangeaisons, mais pas la brûlure et l'érythème.

Cultivation of auricular chondrocytes in poly(ethylene glycol)/poly(ε-caprolactone) hydrogel for tracheal cartilage tissue engineering in a rabbit model.

Tissue engineering has the potential to overcome the limitations of tracheal reconstruction. To tissue-engineer a tracheal cartilage, auricular chondrocytes were encapsulated in a photocurable poly(ethylene glycol)/poly(ε-caprolactone) (PEG/PCL) hydrogel. Chondrogenic genes, including Sox9, Acan and Col2a1, were up-regulated in auricular chondrocytes after 2 weeks of in vitro cultivation in the PEG/PCL hydrogel. Co-cultivation of 70 % auricular chondrocytes and 30 % bone marrow mesenchymal stem cells (BMSCs) accelerated the chondrogenic genes' expression in the PEG/PCL hydrogel. Cartilaginous matrix markers, including proteoglycans and collagen type II, were detected in the chondrocytes-encapsulated PEG/PCL hydrogel after 4 weeks of in vitro cultivation. The higher expression level of cartilaginous matrix markers was observed in the PEG/PCL hydrogel with co-cultivation of 70 % chondrocytes and 30 % BMSCs. After 4 weeks of ectopic cultivation in rabbits, the cylindrical PEG/PCL structure was sustained with the use of a luminal silicon stent. However, without the stent, the construct collapsed under a compression force. No fibrosis or vessel ingrowth were found in the PEG/PCL hydrogel after 4 weeks of ectopic cultivation, whereas the auricular chondrocytes showed proteoglycans' accumulation and collagen type II production. Rabbit auricular chondrocytes could survive and retain chondrogenic ability in the PEG/PCL hydrogel under both in vitro and in vivo conditions. While the PEG/PCL hydrogel did not show sufficient mechanical properties for supporting the cylindrical shape of the construct, the high chondrogenesis level of chondrocytes in the PEG/PCL hydrogel displayed the potential of this material for tracheal tissue engineering.

Larval species composition and genetic structures of Carposina sasakii, Grapholita dimorpha, and Grapholita molesta from Korea.

Rapid determination of the larval species composition and understanding of their genetic structure is important to establish the appropriate management system for multiple species infesting in fruits. We established accurate and rapid diagnostic methods based on multiplex polymerase chain reaction (PCR) diagnostic techniques to discriminate the three major lepidopteran species in orchard, Carposina sasakii, Grapholita dimorpha, and Grapholita molesta. Each species was identified by amplifying species-specific PCR products (375 bp for C. sasakii, 125 and 234 bp for G. dimorpha, and 125 bp for G. molesta). Based on species composition analysis from six types of infested fruits, G. dimorpha constituted the highest proportion (47.8%), followed by 35.2 and 13.5% for G. molesta and C. sasakii, respectively. Interestingly, high prevalence was found in G. dimorpha and G. molesta for plum and peach, respectively. Based on genetic diversity analysis, the three insect species exhibited moderate or high haplotype diversity and low nucleotide diversity, ranging from 0.319 to 0.699 and 0.0006 to 0.0045, respectively. Demographic expansion was not detected according to either a neutrality test or mismatch distribution analysis. Moreover, no significant genetic structure corresponding to province, host plant, fruit type, or collection period was observed. These results suggest that the population of each species would have high dispersal ability following fruit-generating periods via intrinsic host adaptation ability regardless of the spatial and temporal conditions. Determination of larval composition on fruit is valuable for establishing appropriate management systems that take the species into consideration; additionally, population genetic approaches can be utilized to understand the effects of environmental factors (province, host fruit, fruit type, etc.) on population structures.

[Secretory carcinoma of the breast: clinical histopathologic and biological behaviors].

Objective: To investigate the clinicopathological and immunohistochemistrical features of secretory carcinoma of the breast (SCB), as well as its diagnosis and prognosis. Methods: Five cases of SCB were collected and specimens were fully drawn. Microscopic pathology examinations and immunohistochemistry(SP method)were performed. Results: Five cases were all female patients aged from 31 to 54 years old (with an average age of 38 years), and all patients initially presented with the painless breast lump, often near the areola. Macroscopically, all the tumors were relatively circumscribed, with a mean diameter of 2.1 cm(1.2-3.0 cm). Histologically, the tumors revealed different patterns (microcystic, solid, ductal, and so forth) and appeared large amounts of intracellular and extracellular eosinophilic PAS- and AB-PAS- positive secretory materials, as well as the granular eosinophilic cytoplasm. Immunohistochemistrically, the tumor cells were strongly positive for epithelial membrane antigen (EMA) and S-100. Three cases had negative expression for estrogen receptor (ER) and progesterone (PR), and two cases had weakly focal expression. Human epidermal growth factor receptor 2 (HER2) and P53 were negative, while only one case had weakly focal expression. The tumors were positive for CK7, CK5/6, CD10, but they were negative for CEA, smooth muscle actin (SMA) and P63 . The proliferation index of Ki-67 was 5%-8%. There was no patient with metastasis of the tumor in axillary lymph node. Except 1 case lost follow-up, and the rest had no recurrence or distant metastasis. Conclusions: SCB is very rare, with low malignancy, and has better prognosis, but it is usually classified as triple-negative breast cancer because of the immune phenotype. The correct diagnosis of this lesion depends on clinical characteristics, morphology and immunohistochemistry.

Homogeneity of Different Functional mRNA Indicators for Wound Age Estimation.

OBJECTIVES: To explore the homogeneity level of four different functional mRNA （PUM2, TAB2, Cx45 and CHRNA1） expressions in rats with skeletal muscle contusion. METHODS: The relative expressions of PUM2, TAB2, Cx45 and CHRNA1 mRNAs were detected by quantitative real-time reverse transcription-polymerase chain reaction （RT-qPCR）. The coefficient of variation （CV） of the relative expressions for different individuals in each injury group was calculated. The extreme value of CV, cumulative variability, and CVCV were compared. RESULTS: A high CV of PUM2 and TAB2 mRNAs appeared on several different time points. However, the CV of Cx45 and CHRNA1 mRNAs was relatively low. The cumulative variability from high to low was PUM2, CHRNA1, TAB2 and Cx45 mRNAs. The relative expression of PUM2 mRNA was significantly higher than that of TAB2, Cx45 and CHRNA1 mRNAs （ P<0.05）. There was no statistical significance （P>0.05） in the CVCV of the relative expression of TAB2, CHRNA1 and Cx45 mRNAs. CONCLUSIONS: As the mRNAs involving in biological process regulation, PUM2 and CHRNA1 mRNAs show a lowest individual homogeneity of the relative expression followed by TAB2 mRNA. As the mRNAs participating in the composition of cellular structure, Cx45 and CHRNA1 mRNAs show a high individual homogeneity of the relative expressions. The functional classification should be considered for the screening of the mRNA indicators used for wound age estimation.

ADAMTS and ADAM metalloproteinases in osteoarthritis - looking beyond the 'usual suspects'.

INTRODUCTION: Matrix metalloproteinases (MMPs) and 'aggrecanase' a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) are well established to play key roles in osteoarthritis (OA) through degradation of extracellular matrix (ECM) type II collagen and aggrecan, and are thus potential targets for development of OA therapies. OBJECTIVE: This paper aims to provide a comprehensive review of the expression and potential roles of other, lesser-known ADAMTSs and related adamalysins (or a disintegrin and metalloproteinases (ADAMs)) in cartilage, with a view to identifying potentially protective or homeostatic metalloproteinases in the joint and informing consequent selective inhibitor design. DESIGN: A comprehensive literature search was performed using PubMed terms 'osteoarthritis' and 'ADAMTS' or 'ADAM'. RESULTS: Several ADAMTSs and ADAMs were identified as having reportedly increased expression in OA. These include enzymes likely to play roles in cartilage matrix anabolism (e.g., the procollagen N-proteinases ADAMTS-2, ADAMTS-3 and ADAMTS-14), chondrocyte differentiation and proliferation (e.g., ADAM9, ADAM10, ADAM12), as well as enzymes contributing to cartilage catabolism (e.g., Cartilage oligomeric protein (COMP)-degrading ADAMTS-7 and ADAMTS-12). CONCLUSIONS: In addition to the well-characterised MMPs, ADAMTS-4 and ADAMTS-5, many other ADAMTSs and ADAMs are expressed in cartilage and several show significantly altered expression in OA. Studies aimed at elucidating the pathophysiological roles of these enzymes in cartilage will contribute to our understanding of OA pathogenesis and enable design of targeted inhibitors that effectively target metalloproteinase-mediated cartilage degradation while sparing cartilage repair pathways.

Landing strategies focusing on the control of tibial rotation in the initial contact period of one-leg forward hops.

Anterior cruciate ligament (ACL) reconstruction (ACLR) surgeries successfully restore anterior tibial translation but not tibial rotation. This study aimed to explore landing strategies focusing on the control of tibial rotation at landing when the ACL is most vulnerable. Three groups of male subjects (50 ACLRs, 26 basketball players, and 31 controls) participated in one-leg forward hop tests for determining the tibial rotatory landing strategies adopted during the initial landing phase. The differences in knee kinematics and muscle activities between internal and external tibial rotatory (ITR, ETR) landing strategies were examined. A higher proportion of basketball players (34.6%) were found to adopt ITR strategies (controls: 6.5%), exhibiting significantly greater hopping distance and knee strength. After adjusting for hopping distance, subjects adopting ITR strategies were found to hop faster with straighter knees at foot contact and with greater ITR and less knee adduction angular displacement during the initial landing phase. However, significantly greater angular displacement in knee flexion, greater medial hamstring activities, and greater co-contraction index of hamstrings and medial knee muscles were also found during initial landing. Our results support the importance of the recruitments of medial hamstrings or the local co-contraction in assisting the rotatory control of the knee during initial landing for avoiding ACL injuries.

Zinc treatment increases the titre of 'Candidatus Liberibacter asiaticus' in huanglongbing-affected citrus plants while affecting the bacterial microbiomes.

AIMS: Huanglongbing (HLB)-affected citrus often display zinc deficiency symptoms. In this study, supplemental zinc was applied to citrus to determine its effect on Candidatus Liberibacter asiaticus (Las) titre, HLB symptoms, and leaf microbiome. METHODS AND RESULTS: HLB-affected citrus were treated with various amounts of zinc. The treatments promoted Las growth and affected microbiomes in citrus leaves. Phylochip(™) -based results indicated that 5475 of over 50 000 known Operational Taxonomic Units (OTUs) in 52 phyla were detected in the midribs of HLB-affected citrus, of which Proteobacteria was the most abundant, followed by Firmicutes and Actinobacteria. In comparison, the microbiomes of zinc-treated diseased plants had overall more OTUs with higher amounts of Proteobacteria, but decreased percentages of Firmicutes and Actinobacteria. In addition, more OTUs of siderophore-producing bacteria were present. Only zinc-sensitive Staphylococcaceae had higher OTU's in the diseased plants without zinc treatments. CONCLUSIONS: Although HLB-affected citrus appear zinc deficient, zinc amendments increased the pathogen levels and shifted the microbiome. SIGNIFICANCE AND IMPACT OF THE STUDY: HLB is currently the most devastating disease of citrus worldwide. Zinc is often applied to HLB-affected citrus due to zinc deficiency symptoms. This study provided new insights into the potential effects of zinc on HLB and the microbial ecology of citrus.

Brassinosteroid (BR) biosynthetic gene lhdd10 controls late heading and plant height in rice (Oryza sativa L.).

KEY MESSAGE: A Brd2 allele suppresses heading date by altering the expression of heading date regulators such as OsMADS50 , and also negatively regulates chlorophyll biosynthesis. Heading date and plant height are important determinants of yield in rice (Oryza sativa L.). In this study, we characterized a late heading, dwarf mutant known as lhdd10 selected following ethyl methane sulfonate (EMS)-treatment of ssp. indica cultivar 93-11. lhdd10 showed late heading, dwarfness and slightly darker-green leaves than wild-type 93-11 under long-day and short-day conditions. We isolated lhdd10 by map-based cloning; it encoded a putative FAD-linked oxidoreductase protein (a brassinosteroid biosynthetic gene) that localized to the nucleus. LHDD10 was constitutively expressed in various tissues, but more so in shoot apices and panicles. Our data showed that lhdd10 influences heading date by controlling the expression of heading date regulators, such as OsMADS50 in both LD and SD conditions. lhdd10 also negatively regulated expression of chlorophyll biosynthetic genes to reduce the chlorophyll content. Our data indicated that BRs play important roles in regulating heading date and chlorophyll biosynthesis. This work provides material that will allow study of how BRs regulate heading date in rice.

Responses to thermal and salinity stress in wild and farmed Pacific oysters Crassostrea gigas.

The Pacific oyster Crassostrea gigas was introduced from Japan to many countries in the world for oyster farming, resulting in the establishment of wild populations in intertidal zones and resource competition with local faunas. This study examined physiological responses of wild oysters and farmed oysters to thermal (15°C, 25°C, 37°C and 44°C) and salinity stress (39, 50 and 60ppt). The wild oysters produced more 72kDa heat shock proteins when the temperature increased from 15°C to 25°C and 37°C and the salinity increased from 39 to 50 and 60ppt. However, the amount of 69kDa heat shock protein was similar between farmed and wild oysters when the temperature increased from 15°C to the sublethal temperature 37°C, but it was lower in wild oysters than in farmed oysters when the temperature increased from 15°C to the lethal temperature 44°C. In the tissues, wild oysters used more glycogen to promote metabolic activities by increasing the level of AEC (adenylate energy charge). The results suggest that farmed oysters might have limited ability to cope with heat stress due to low energy reserve and glycolysis activity for HSP synthesis. This study provides experimental evidence on differential responses between wild and farmed oysters to temperature and salinity changes, leading to a better understanding on the pattern of distribution for invading oyster species in the marine environment and the adaptation of marine invertebrates to the threat of climate change.

Characterization and Antibacterial Activity of Oil-In-Water Nano-Emulsion Formulation Against Candidatus Liberibacter asiaticus.

Nano-emulsion is a promising delivery system for increasing pesticide use and enhancing the therapeutic efficiency against pathogens. The pathogen Candidatus Liberibacter asiaticus (Las) that causes destructive citrus huanglongbing (HLB) resides in citrus phloem, which makes it difficult to treat with chemicals. Based on various physiochemical characteristics of oils, surfactants, and organic solvents, an oil-in-water (O/W) nano-emulsion formulation was developed and optimized to combat citrus HLB. The nano-emulsion was formulated through a spontaneous emulsification method for efficient delivery of ampicillin into the citrus phloem using bark application. The nano-emulsion that was prepared from Cremophor EL (viscous oil), acetone (water miscibility organic solvent), and Span 80/Tween 80 (surfactant) formed a small droplet size (17.33 ± 0.52 nm) and exhibited an improved absorption rate. Peak concentration was detected at 2 days posttreatment and the maximum concentration (Cmax) and relative bioavailability (RBA) of ampicillin in HLB-affected citrus were 71.86 ± 35.38 ng/g and 267.25% ± 44.1%, respectively. The peak concentration of Amp appeared at 6 days posttreatment in the citrus trees that were treated with Amp alone and their Cmax and RBA were 56.44 ± 32.59 ng/g and 100%, respectively. The same nano-emulsion was used to deliver five different antimicrobials to control citrus HLB through bark application. We found that the droplet size of the antimicrobials in the nano-emulsion was significantly reduced and the nano-emulsion also enhanced the therapeutic efficiency of validoxylamine A alone and in combination with actidione as well as sulfadimoethoxine sodium against Las. Therefore, this study provides an efficient bark application nano-emulsion formulation for citrus HLB control.