A case‐control study and meta‐analysis reveal the association between COX‐2 G‐765C polymorphism and primary end‐stage hip and knee osteoarthritis

Background

Osteoarthritis (OA) is a popular arthrosis featured as pain, limited joint activity, and deformity. Cyclooxygenase‐2 (COX‐2) has been reported to be up‐regulated in arthritic tissues and is integral to the progression of osteoarthritis (OA). Previous studies showed the COX‐2 promoter G‐765C polymorphism could influence COX‐2 expression. However, the relationship between the variant and OA risk is contrasting.

Methods

We conducted a case‐control study with 196 primary end‐stage hip and knee OA cases and 196 controls in a Chinese Han population. Subsequently, we integrated this case‐control study in a meta‐analysis to acquire greater statistical power. The results from our case‐control study using MassARRAY genotyping technology and binary logistic regression statistical methods.

Results

The variant carriers in the Chinese Han population had a lower primary end‐stage hip and knee OA susceptibility (C vs G: OR = 0.350, 95%CI: 0.154‐0.797, P = .012; GC vs GG: adjusted OR = 0.282, 95%CI: 0.118‐0.676, P = .005). Stratification studies indicated that a higher GC frequency in women decreased not only knee OA susceptibility but also unilateral knee OA risk. The meta‐analysis showed that the variant exhibited a significantly decreased OA risk through comparisons involving allelic, homozygous, heterozygous, and dominant models.

Conclusion

Our findings suggest that the COX‐2 G‐765C polymorphism exerts a protective effect against primary end‐stage knee osteoarthritis in a female Chinese Han population.

     

Memantine delayed N‐methyl‐D‐aspartate ‐induced convulsions in neonatal rats

Memantine (1‐amino‐3,5‐dimethyladamantane) is a moderate‐affinity uncompetitive antagonist of N‐methyl‐d‐aspartate (NMDA) receptors. In this study, we have explored the effect of memantine against N‐methyl‐d‐aspartate (NMDA)‐induced seizures in neonatal rats. Here, we evaluated various behavioral seizure abnormalities in neonatal rats (Sprague–Dawley; postnatal day 9) after an intraperitoneal administration of NMDA. Further, we explored whether an acute administration of memantine could protect these neonates against different phases of convulsions induced by NMDA. In a separate study, we have compared the effect of levetiracetam in the same animal model. Exogenous administration of NMDA (30 mg/kg., i.p.) in neonatal rats resulted in arrest of activity, emprosthotonos curvature (trunk is bent forward by the entire muscles), myoclonic jerks, and forelimb/hindlimb clonus. The clonus phase in neonates was followed by loss of righting reflex and continuous seizures (for more than 5 min) suggesting status epilepticus, tonic extension, and death. Pretreatment of memantine hydrochloride (10–30 mg/kg., i.p.) dose‐dependently delayed the onset of different phases of convulsions induced by NMDA. Memantine at the highest dose was found to be ataxic in rat neonates, while lower doses were free of any observed behavioral signs of toxicity. Levetiracetam (25 mg/kg., i.p.) when administered 30 min before the NMDA challenge blocked only the jerk phase and did not affect other phases of NMDA‐induced convulsions. These data indicated that memantine and other safer uncompetitive NMDA receptor antagonists may be protective in the management of neonatal seizures.     

Validation of loop‐mediated isothermal amplification to detect Helicobacter pylori and 23S rRNA mutations: A prospective,observational clinical cohort study

BackgroundIdentifying point mutations in 23S rRNA closely associated with clarithromycin resistance can increase the eradication rate of Helicobacter pylori (H pylori). In this study, we verified the sensitivity, specificity, and reliability of a newly developed loop‐mediated isothermal amplification (LAMP) assay kit to detect H pylori and 2143G and 2182C mutations in 23S rRNA.MethodsLAMP assay to detect H pylori and a mutant strain with 2143G and 2182C was conducted with the Isopollo^® H pylori & ClaR kit. A prospective, open‐label, observational study was conducted to validate the reliability of the LAMP assay in both a development cohort and a bedside direct LAMP cohort.ResultsThe LAMP assay had good sensitivity, as it could detect as few as 10–100 copies of H pylori and mutants with 2143G and 2182C in 23S rRNA, and good specificity, as it did not react with other bacterial species. In the development cohort with 622 participants, the LAMP assay showed good agreement with RUT for detecting H pylori (kappa value 0.923, P < .001) and had exactly the same results as sequencing analysis for 2143G and 2182C point mutations. The direct LAMP cohort including 93 patients had 97.7% (42/43) of concordance in detecting 2143G and 2182C point mutations compared to the PCR‐based sequencing analysis.ConclusionThe Isopollo^® H pylori & ClaR LAMP assay was a valid method for detecting H pylori and for 2143G and 2182C point mutations in 23S rRNA in a clinical setting.     

Cannabidiol reverses the mCPP‐induced increase in marble‐burying behavior

Cannabidiol (CBD), one of the main components of Cannabis sp., presents clinical and preclinical anxiolytic properties. Recent results using the marble‐burying test (MBT) suggest that CBD can also induce anticompulsive‐like effects. Meta‐chloro‐phenyl‐piperazine (mCPP) is a nonspecific serotonergic agonist (acting mainly at 5HT1A, 5HT2C and 5HT1D receptors) reported to increase symptoms in OCD patients and block the anticompulsive‐like effect of serotonin reuptake inhibitors (SRIs) in animal models. The aim of this study was to investigate the interference of CBD on mCPP effects in repetitive burying. Administration of mCPP showed dual effects in the MBT, increasing the number of buried marbles at lower (0.1 mg/kg) while decreasing it at higher doses (1 mg/kg), an effect not related to a general increase in anxiety‐like behavior. As found previously, CBD (30 mg/kg) and the positive control fluoxetine (FLX; 10 mg/kg) decreased burying behavior without changing general exploratory activity. A similar effect was found when subeffective doses of CBD (15 mg/kg) and FLX (3 mg/kg) were administered together. These subeffective doses alone were also able to block mCPP‐induced repetitive burying. The results, in addition to reinforcing a possible anticompulsive effect of CBD, also suggest that mCPP‐induced repetitive burying could be a useful test for the screening of compounds with presumed anticompulsive properties.     

Modified Carba NP Test: Simple and rapid method to differentiate KPC‐ and MBL‐producing Klebsiella species

Background

The aim of this study was to evaluate the modified Carba NP test to differentiate KPC (Klebsiella pneumoniae carbapenemase)‐ and MBL (metallo‐β‐lactamase)‐producing Klebsiella species.

Methods

A total of 508 non‐duplicate clinical isolates of Klebsiella spp. were processed by modified Carba NP and combined disc tests which were further confirmed by conventional polymerase chain reaction (PCR), a gold standard method for statistical analysis.

Results

Modified Carba NP test demonstrated 91.7% sensitivity, 100% specificity, 100% positive predictive value (PPV) and 99.8% negative predictive value (NPV) for KPC and 96.7%, 100%, 100%, and 99.5% for MBL detection, respectively.

Conclusion

The performance of modified Carba NP test was significantly better than combined disc test, fulfilling the requirement of simple and rapid test for clinical applications.

     

Successful treatment of immediate allogeneic myeloablative hematopoietic stem cell transplantation from a HLA‐mismatched sibling donor for active systemic epstein–barr virus‐positive T‐cell lymphoproliferative disease of childhood following primary acute epstein–barr virus infection

A 22‐year‐old female was admitted for sustained high fever and diagnosed with systemic Epstein–Barr virus‐positive T‐cell lymphoproliferative disease. As her clinical course was so aggressive, she immediately underwent allogeneic myeloablative bone marrow transplantation from an HLA‐mismatched sibling donor on hospital day 46. The patient has remained in complete remission for 3 years.     

Early‐onset hypoparathyroidism and chronic keratitis revealing APECED

Early diagnosis of potentially life‐threatening autoimmune polyendocrinopathy‐candidiasis‐ectodermal dystrophy (APECED) is crucial, but is often delayed due to the clinical heterogeneity of the disorder. Even in the absence of the classic disease triad of chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenocortical insufficiency, a diagnosis of APECED should be considered in children who have hypoparathyroidism and chronic keratitis, with a past medical history showing a mild and transient Candida infection.