The clinical significance of cyclic citrullinated peptide antibodies: new data

Early diagnosis of rheumatoid arthritis (RA) is a challenge due to an insufficient specificity of its clinical signs and a low sensitivity of presently used clinico-laboratory criteria. Cyclic citrullinated peptide antibodies (CCPA) are nowadays considered the most promising diagnostic and prognostic RA marker. A heterogeneous group of citrullinated peptides are the target for CCPA. The sensitivity of CCPA is comparable to that of the rheumatoid factor (RF), while its specificity for this disease is much higher. CCPA detection may be very useful for diagnostics of early sero-negative RA, differential diagnosis between RA and other rheumatic diseases, and for the prognosis of severe erosive articular lesion. Simultaneous detection of RF and CCPA allow for early RA diagnostics, which is important for timely administration of a more aggressive basic antirheumatic therapy.     

Human Protoparvovirus DNA and IgG in Children and Adults with and without Respiratory or Gastrointestinal Infections

Three human protoparvoviruses, bufavirus (BuV), tusavirus (TuV) and cutavirus (CuV), have recently been discovered in diarrheal stool. BuV has been associated with diarrhea and CuV with cutaneous T-cell lymphoma, but there are hardly any data for TuV or CuV in stool or respiratory samples. Hence, using qPCR and IgG enzyme immunoassays, we analyzed 1072 stool, 316 respiratory and 445 serum or plasma samples from 1098 patients with and without gastroenteritis (GE) or respiratory-tract infections (RTI) from Finland, Latvia and Malawi. The overall CuV-DNA prevalences in stool samples ranged between 0–6.1% among our six patient cohorts. In Finland, CuV DNA was significantly more prevalent in GE patients above rather than below 60 years of age (5.1% vs 0.2%). CuV DNA was more prevalent in stools among Latvian and Malawian children compared with Finnish children. In 10/11 CuV DNA-positive adults and 4/6 CuV DNA-positive children with GE, no known causal pathogens were detected. Interestingly, for the first time, CuV DNA was observed in two nasopharyngeal aspirates from children with RTI and the rare TuV in diarrheal stools of two adults. Our results provide new insights on the occurrence of human protoparvoviruses in GE and RTI in different countries.     

Visual field findings after a ruptured intracranial aneurysm

Background

Visual field defects (VFDs) negatively affect activities of daily living and rehabilitation following aneurysmal subarachnoid haemorrhage (aSAH). The aim here was to assess VFDs in patients with aSAH and their associations with age, gender, aSAH severity, and clinical outcome.

Methods

Patients admitted to Helsinki University Central Hospital and treated during 2011 were participants in this prospective study. Findings obtained with the Octopus 900 perimeter (Haag-Streit Inc, Koenic, Switzerland), the Goldmann perimeter (Haag-Streit Inc, Bern, Switzerland), or the confrontation visual field test on admission and 3 days, 14 days, 2 to 4 months, and 6 months postoperatively were assigned to 16 classes. Associations between post-chiasmal VFDs and relevant clinical, radiological, and demographic data were analysed with uni- and multivariate logistic regression.

Results

Of 105 survivors at 6 months, 20 (19 %) had VFDs occurring for aneurysm- or operation-related reasons; homonymous hemianopias or quadrantanopias were the most common finding, occurring in 16 patients (15 %). Posterior ischaemic optic neuropathy presented in two patients (2 %). Ten survivors (10 %) no longer fulfilled visual field requirements for driving licences. Significant associations emerged between VFDs at 6 months and the Hunt and Hess (H&H), World Federation of Neurosurgical Societies (WFNS), and Fisher grades on admission, presence of intracerebral haemorrhage (ICH), hydrocephalus, or postoperative infarction, and higher modified Rankin Scale scores at 6 months. Multivariate logistic regression showed the H&H grade and presence of ICH to independently predict VFDs.

Conclusions

Assessing VFDs is advisable, especially among patients with poor-grade aSAH (H&H grade IV or V) and ICH.     

Traumatic near amputation secondary to hippopotamus attack: lessons for surgeons

A 34-y-old man presented to Naivasha District Hospital (NDH) in Naivasha Town, Kenya, with near-complete below-knee amputation and hemorrhage after a hippopotamus attack. Residents from the University of Washington (UW), Departments of Surgery, Anesthesia, and Medicine, were rotating at NDH with the Clinical Education Partnership Initiative, a joint venture of UW and University of Nairobi. These providers met the patient in the operating theater. The leg was mangled with severely traumatized soft tissues and tibia–fibula fractures. The visiting UW Surgery resident (R3) and an NDH medical officer (second-year house officer) performed emergency below-knee completion amputation—the first time either had performed this operation. The three major vessel groups were identified and ligated. Sufficient gastrocnemius and soleus were preserved for future stump construction. The wound was washed out, packed with betadine-soaked gauze, and wrapped in an elasticized bandage. Broad-spectrum antibiotics were initiated. Unfortunately, the patient suffered infection and was revised above the knee. After a prolonged course, the patient recovered well and was discharged home. NDH house officers and UW trainees collaborated successfully in an emergency and conducted the postoperative care of a patient with a serious and challenging injury. Their experience highlights the importance of preparedness, command of surgical basics, humility, learning from mistakes, the expertise of others, a digitally connected surgical community, and the role of surgery in global health. These lessons will be increasingly pertinent as surgical training programs create opportunities for their residents to work in developing countries; many of these lessons are equally applicable to surgical practice in the developed world.     

Trichothecene mycotoxins activate NLRP3 inflammasome through a P2X7 receptor and Src tyrosine kinase dependent pathway

Inflammasome is an intracellular molecular platform of the innate immunity that is a key mediator of inflammation. The inflammasome complex detects pathogens and different danger signals, and triggers cysteine protease caspase-1-dependent processing of pro-inflammatory cytokines IL-1β, and IL-18 in dendritic cells and macrophages. Previously, we have shown that water-damaged building associated trichothecene mycotoxins, including roridin A, trigger IL-1β and IL-18 secretion in human macrophages. However, the molecular basis as well as mechanism behind this trichothecene-induced cytokine secretion has remained uncharacterized. Here, we show that the trichothecene-induced IL-1β secretion is dependent on NLRP3 inflammasome in human primary macrophages. Pharmacological inhibition and small interfering RNA approach showed that the trichothecene-induced NLRP3 inflammasome activation is mediated through ATP-gated P2X₇ receptor. Moreover, we show that trichothecene-triggered NLRP3 inflammasome activation is dependent on Src tyrosine kinase activity. In addition, gene silencing of c-Cbl, a negative autophagy-related regulator of c-Src, resulted in enhanced secretion of IL-1β and IL-18 in response to trichothecene mycotoxin stimulation in human macrophages. In conclusion, our results suggest that roridin A, a fungal trichothecene mycotoxin, acts as microbial danger signals that trigger activation of NLRP3 inflammasome through P2X₇R and Src tyrosine kinase signaling dependent pathway in human primary macrophages.     

Correlation of Statistical Distributions of the Dimension of Yeast Cells Attached to the Substrate and Its Surface Electrical Potential

The ability of cells to adhere to substrates is an important factor for the effectiveness of biotechnologies and bioimplants. This research demonstrates that the statistical distribution of the sizes of the cells (Saccharomyces cerevisiae) attached to the substrate surface correlates with the statistical distribution of electrical potential on the substrate’s surface. Hypothetically, this behavior should be taken into consideration during the processing of surfaces when cell adhesion based on cell size is required.