Intra- and inter-rater consistency of dual assessment by radiologist and neurologist for evaluating DWI-ASPECTS in ischemic stroke.

OBJECTIVES: To estimate the intra -and inter-rater consistency of radiologist and neurologist working in pairs attributing DWI-ASPECTS (Diffusion Alberta Stroke Program Early CT Score) in patients with acute middle cerebral artery ischemic stroke referred for mechanical thrombectomy, intravenous thrombolysis or bridging therapy. METHODS: Five neurologists and 5 radiologists working in pairs and in hour period scored independently and in two reading sessions anonymized DWI-ASPECTS of 80 patients presenting with acute anterior ischaemic stroke in our center. We measured agreement between pairs using intraclass correlation coefficients (ICCs). A Fleiss kappa was used for dichotomized (0-6;7-10) and trichotomized (0-3;4-6;7-10) ASPECTS. The interrater distribution of the score in the trichotomized (0-3;4-6;7-10) ASPECTS was calculated. We determined the interrater (Cohen kappa) and intrarater (Fleiss kappa) agreement on the ASPECTS regions. RESULTS: The average DWI-ASPECTS was 6.35 (SD±2.44) for the first reading, and 6.47 (SD±2.44) for the second one. The ICC was 0.853 (95%CI, 0.798-0.896) for the interrater, and 0.862 (95%CI, 0.834-0.885) for the intrarater evaluation. Kappa coefficients were high for dichotomized (k=0.75) and trichotomized (k=0.64) ASPECTS. Evaluators agreement on the ASPECTS category (0-3), (4-6) and (7-10) was 88, 76 and 93% respectively. The anatomic region infarcted was well identified (k=0.70-0.77), except for the internal capsula (k=0.57). Interrater agreement was fair for M5 (k=0.37), moderate for internal capsula (0.52) and substantial for the other regions (0.60-0.79). CONCLUSIONS: Reliability of DWI-ASPECTS is good when determined by radiologist and neurologist working in pairs, which corresponds to our current clinical practice. However, discrepancies are possible for cut-off determination, which may impact the indication of thrombectomy, and for the determination of the exact infarcted region. Agreement to propose category (4-6) is lower than for (0-3) and (8-10) ASPECTS categories.

Biofilm formation - what we can learn from recent developments.

Although biofilms have been observed early in the history of microbial research, their impact has only recently been fully recognized. Biofilm infections, which contribute to up to 80% of human microbial infections, are associated with common human disorders, such as diabetes mellitus and poor dental hygiene, but also with medical implants. The associated chronic infections such as wound infections, dental caries and periodontitis significantly enhance morbidity, affect quality of life and can aid development of follow-up diseases such as cancer. Biofilm infections remain challenging to treat and antibiotic monotherapy is often insufficient, although some rediscovered traditional compounds have shown surprising efficiency. Innovative anti-biofilm strategies include application of anti-biofilm small molecules, intrinsic or external stimulation of production of reactive molecules, utilization of materials with antimicrobial properties and dispersion of biofilms by digestion of the extracellular matrix, also in combination with physical biofilm breakdown. Although basic principles of biofilm formation have been deciphered, the molecular understanding of the formation and structural organization of various types of biofilms has just begun to emerge. Basic studies of biofilm physiology have also resulted in an unexpected discovery of cyclic dinucleotide second messengers that are involved in interkingdom crosstalk via specific mammalian receptors. These findings even open up new venues for exploring novel anti-biofilm strategies.

Directional K+ channel insertion in a single phospholipid bilayer: Neutron reflectometry and electrophysiology in the joint exploration of a model membrane functional platform.

We investigated the insertion of small potassium (K+) channel proteins (KcvMA-1D and KcvNTS) into model membranes and the lipid-protein structural interference, combining neutron reflectometry and electrophysiology. Neutron reflectometry experiments showed how the transverse structure and mechanical properties of the bilayer were modified, upon insertion of the proteins in single model-membranes, either supported on solid substrate or floating. Parallel electrophysiology experiments were performed on the same channels reconstituted in free-standing planar lipid bilayers, of both typical composition and matched to the neutron reflectometry experiment, assessing their electrical features. Functional and structural results converge in detecting that the proteins, conical in shape, insert with a directionality, cytosolic side first. Our work addresses the powerful combination of the two experimental approaches. We show here that membrane structure spectroscopy and ion channel electrophysiology can become synergistic tools in the analysis of structural-functional properties of biomimetic complex environment.

Tectonics of a K⁺ channel: The importance of the N-terminus for channel gating.

The small K⁺ channel Kcv represents the pore module of complex potassium channels. It was found that its gating can be modified by sensor domains, which are N-terminally coupled to the pore. This implies that the short N-terminus of the channel can transmit conformational changes from upstream sensors to the channel gates. To understand the functional role of the N-terminus in the context of the entire channel protein, we apply combinatorial screening of the mechanical coupling and long-range interactions in the Kcv potassium channel by reduced molecular models. The dynamics and mechanical connections in the channel complex show that the N-terminus is indeed mechanically connected to the pore domain. This includes a long rang coupling to the pore and the inner and outer transmembrane domains. Since the latter domains host the two gates of the channel, the data support the hypothesis that mechanical perturbation of the N-terminus can be transmitted to the channel gates. This effect is solely determined by the topology of the channel; sequence details only have an implicit effect on the coarse-grained dynamics via the fold and not through biochemical details at a smaller scale. This observation has important implications for engineering of synthetic channels on the basis of a K⁺ channel pore.

Imaging in osteogenesis imperfecta: Where we are and where we are going.

Osteogenesis imperfecta (OI) is a rare phenotypically and genetically heterogeneous group of inherited skeletal dysplasias. The hallmark features of OI include bone fragility and susceptibility to fractures, bone deformity, and diminished growth, along with a plethora of associated secondary features (both skeletal and extraskeletal). The diagnosis of OI is currently made on clinical grounds and may be confirmed by genetic testing. However, imaging remains pivotal in the evaluation of this disease. The aim of this article is to review the current role played by the various radiologic techniques in the diagnosis and monitoring of OI in the postnatal setting as well as to discuss recent advances and future perspectives in OI imaging. Conventional Radiography and Dual-energy X-ray Absorptiometry (DXA) are currently the two most used imaging modalities in OI. The cardinal radiographic features of OI include generalized osteopenia/osteoporosis, bone deformities, and fractures. DXA is currently the most available technique to assess Bone Mineral Density (BMD), specifically areal BMD (aBMD). However, DXA has important limitations and cannot fully characterize bone fragility in OI based on aBMD. Novel DXA-derived parameters, such as Trabecular Bone Score (TBS), may provide further insight into skeletal changes induced by OI, but evidence is still limited. Techniques like Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) can be useful as problem-solvers or in specific settings, including the evaluation of cranio-cervical abnormalities. Recent evidence supports the use of High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT) as a promising tool to improve the characterization of bone fragility in OI. However, HR-pQCT remains a primarily research technique at present. Quantitative Computed Tomography (QCT) is an alternative to DXA for the determination of BMD at central sites, with distinct advantages but considerably higher radiation exposure. Quantitative Ultrasound (QUS) is a portable, inexpensive, and radiation-free modality that may complement DXA evaluation, providing information on bone quality. However, evidence of usefulness of QUS in OI is poor. Radiofrequency Echographic Multi Spectrometry (REMS) is an emerging non-ionizing imaging method that holds promise for the diagnosis of low BMD and for the prediction of fracture risk, but so far only one published study has investigated its role in OI. To conclude, several different radiologic techniques have proven to be effective in the diagnosis and monitoring of OI, each with their own specificities and peculiarities. Clinicians should be aware of the strategic role of the various modalities in the different phases of the patient care process. In this scenario, the development of international guidelines including recommendations on the role of imaging in the diagnosis and monitoring of OI, accompanied by continuous active research in the field, could significantly improve the standardization of patient care.

Bioelectrical Impedance Vector Analysis (BIVA) for the monitoring of body composition in pregnancy.

BACKGROUND/OBJECTIVES: During pregnancy, body composition alterations can be considered as markers of complications and in this context, a non-invasive and low-cost method such as Bioelectrical Impedance Vector Analysis (BIVA), can be employed to monitor such changes. This study aimed at identifying body compartments trend during physiological pregnancy. SUBJECTS/METHODS: Classic and specific BIVA variables have been measured in a sample of 37 pregnant women approximately every 4 weeks of gestation and once postpartum. Researchers used both longitudinal and cross-sectional approach. The first case included data of women from the 11th to the 15th week along with data from the 28th to the 32nd week of gestation. The cross-sectional approach regarded two more specific moments (11th-12th weeks and 30th-31st weeks) and data within two months postpartum RESULTS: The longitudinal approach showed a significant decrease in classic BIVA variables (R/H, Xc/H, Z/H p < 0.001) and a shortening of the vector, pointing out that TBW and hydration increased significantly. Specific vector length increased significantly, indicating a physiological gain of FM% (p < 0.01). The cross-sectional approach showed lower values of R/H, Xc/H, Z/H between 12th-13th and 30th-31st weeks (p < 0.01), while in the postpartum period values tended to those registered at the beginning of pregnancy. No changes have been found for the phase angle in both approaches, indicating that ECW/ICW ratio remained constant CONCLUSIONS: Among physiological pregnancies, bioelectric values showed a coherent trend and these results represent a first contribution to support routine exams, leading to an early detection of anomalous values potentially correlated to pathologies.

Do ion levels in hip resurfacing differ from metal-on-metal THA at midterm?

BACKGROUND: Metal-on-metal Birmingham hip resurfacing (MOM-BHR) is an alternative to metal-on-metal total hip arthroplasty (MOM-THA), especially for young and/or active patients. However, wear resulting in increased serum ion levels is a concern. QUESTIONS/PURPOSES: We asked whether (1) serum chromium (Cr), cobalt (Co), and molybdenum (Mo) concentrations would differ between patients with either MOM-BHR or MOM-THA at 5 years, (2) confounding factors such as gender would influence ion levels; and (3) ion levels would differ at 2 and 5 years for each implant type. PATIENTS AND METHODS: Ions were measured in two groups with either MOM-BHR (n = 20) or MOM-THA (n = 35) and a mean 5-year followup, and two groups with either MOM-BHR (n = 15) or MOM-THA (n = 25) and a mean 2-year followup. Forty-eight healthy blood donors were recruited for reference values. RESULTS: At 5 years, there were no differences in ion levels between patients with MOM-BHR or MOM-THA. Gender was a confounding factor, and in the MOM-BHR group at 5 years, Cr concentrations were greater in females compared with those of males. Mean ion levels were similar in patients with 2 and 5 years of followup for each implant type. Ion levels in patients were sevenfold to 10-fold higher than in controls. CONCLUSIONS: As the metal ion concentrations in the serum at 5 years were in the range reported in the literature, we do not believe concerns regarding excessive metal ion levels after MOM-BHR are justified. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Guidelines for Authors for a complete description of level of evidence.

A potassium channel protein encoded by chlorella virus PBCV-1.

The large chlorella virus PBCV-1, which contains double-stranded DNA (dsDNA), encodes a 94-codon open reading frame (ORF) that contains a motif resembling the signature sequence of the pore domain of potassium channel proteins. Phylogenetic analyses of the encoded protein, Kcv, indicate a previously unidentified type of potassium channel. The messenger RNA encoded by the ORF leads to functional expression of a potassium-selective conductance in Xenopus laevis oocytes. The channel blockers amantadine and barium, but not cesium, inhibit this conductance, in addition to virus plaque formation. Thus, PBCV-1 encodes the first known viral protein that functions as a potassium-selective channel and is essential in the virus life cycle.

Chlamydia trachomatis serovar distribution and other concurrent sexually transmitted infections in heterosexual men with urethritis in Italy.

The distribution of Chlamydia trachomatis serovars among 157 heterosexual male patients with urethritis and the presence of coinfections with other sexually transmitted infections were studied. One hundred seventeen (74.5%) patients, with a mean age of 33.7 years, were Italians, whereas 40 (25.5%) were immigrants coming from eastern European countries, Africa, and South America. All the immigrants and 82 (70.0%) Italian patients reported sex with prostitutes. Out of 157 patients, 73 (46.5%) were found positive for C. trachomatis in urethral secretions and eight different C. trachomatis serovars were identified. The most common serovars were E (n = 18; 24.7%), D (n = 15; 20.5%), G (n = 14;19.2%), and F (n = 12; 16.4%). The sequencing data showed a high degree of conservation of the omp1 gene. Thirty-six (46.7%) out of the 73 C. trachomatis-positive patients were coinfected with another sexually transmitted infection. The most common coinfection was gonorrhoea detected in 22 (30.1%) patients, followed by condyloma in eight (8.2%) patients, syphilis in five (6.8%), and HIV in three (4.1%).

A two-year prospective and retrospective multi-center study of the TriboFit® Hip System.

The first 50 cases using a polycarbonate-urethane acetabular component in the TriboFit® Hip System for human hip reconstruction were reviewed. The average follow-up for cases not revised or deceased prior to 24 months was 28.0 months. The clinical results were similar to those reported in the literature for the same indications and follow-up. Therefore, with 2 to 4 years follow-up, it can be concluded that the TriboFit® Hip System is as safe and effective for use as a hip replacement system in femoral neck fracture patients as traditional hemiarthroplasty systems, and in osteoarthritis patients as a total hip system made of traditional bearing materials.

Functional assessment in patients with osteoporotic wrist fractures treated with external fixation: a review of randomized trials.

INTRODUCTION: Osteoporosis is a chronic and progressive condition that leads to decreased bone mass and skeletal fragility which may result in fractures, disability, pain, deformity and even death. Fractures of the wrist are the most common symptomatic fracture related to osteoporosis in which up to 80% of the persons with this fracture type have low bone mass. External fixation is minimally-invasive and is used in particular for the treatment of displaced, unstable fractures. OBJECTIVE: The present systematic review will present functional outcome assessment in randomized controlled trials in the aged with distal radius fractures and treated with external fixation. MATERIALS AND METHODS: Multiple databases including Medline, EMBASE, CINAHL, AMED and OVID Healthstar were searched. MESH headings such as: "Radius fractures" or "wrist injuries" were used in combination with "randomized controlled trials". Studies were included if the surgical treatment was external fixation, mean patient age was 50 years and over, and were in the English language. RESULTS: The primary focus of wrist outcome assessments in patients treated with external fixation were based on traditional measures such as wrist range of movement and grip strength reflecting the need to shift the focus in future protocols towards measuring a patient's functional ability, measuring the difficulty of task performance and compensatory mechanisms. Furthermore, it is essential to take into account more evidence of instrument development before clinicians can reliably choose the best measure to assess the aged treated with external fixation.

14-3-3 proteins regulate the potassium channel KAT1 by dual modes.

KAT1 is a cloned plant potassium channel belonging to the superfamily of Shaker-like Kv channels. Previous studies have shown that 14-3-3 proteins significantly increase KAT1 current by modifying the channel open probability. Employing a 14-3-3 scavenger construct to lower the long-term availability of endogenous 14-3-3 proteins, we found that 14-3-3 proteins not only control the voltage dependency of the channel but also the number of channels in the plasma membrane.

Cancer in kidney transplantation.

Cancer in the transplanted kidney is rare, and its clinical and surgical management can be controversial. We report 3 cases of cancer in renal transplantation (1 case of renal cell carcinoma and 2 cases of transitional cell carcinoma) and their treatment. Our data and those reported in the literature suggest that these cancers can be treated like a neoplasm in the general population. However, a higher number of cases and longer follow-up periods are necessary to confirm our findings.

Prevalence of multidrug-resistant organisms in migrant children admitted to an Italian cardiac surgery department, 2015-2016.

Screening on hospital admission to identify multidrug-resistant organism (MDRO) colonization is a frequently discussed topic. We report the results of microbiological screening in 141 Italian and 354 migrant children candidates for cardiac surgery conducted in 2015-2016. In all, 25% of Italian children and more than 65.4% of African and Romanian children carried at least one MDRO (meticillin-resistant Staphylococcus aureus; extended-spectrum ß-lactamase enzymes; carbapenemase producers; and vancomycin-resistant enterococci). Based on our findings, we propose that non-geographically limited approaches are needed to improve infection prevention and control.

CT Features of an unusual calcified schwannoma of the superior laryngeal nerve.

We report the CT findings in a patient with a lateral neck mass histologically diagnosed as a laryngeal schwannoma but presenting some uncommon CT features. CT showed unusual calcified components, very rarely observed and potentially misleading for diagnosis. However, this imaging feature can be found in ancient schwannomas. Our case is, therefore, a very rare one and reviews the main differential diagnoses.

Current augmentation fixation techniques for the osteoporotic patient.

Osteoporosis is defined as the deterioration of microarchitecture and overall poor bone quality, which represents a risk of implant fixation failure when patients with osteoporosis are surgically treated. Fragility fractures in elderly patients, typically at the hip, spine and wrist, should be assessed by the orthopaedic surgeon prior to surgery in order to select the most appropriate technique necessary to overcome failures and other complications associated with reduced osteofixation. In this review, advanced methods of augmenting implant fixation in osteoporotic bone are described including polymethylmethacrylate (PMMA), bone grafts, calcium phosphate implants, calcium phosphate cements, calcium phosphate coatings, modified implants and pharmaceutical augmentation concepts. The indication for these techniques should be based on the quantitative assessment of the osteoporotic quality of bone evaluated by dual energy X-ray absorptiometry (DXA).

Feasibility of a psychoeducational family intervention for people with bipolar I disorder and their relatives: Results from an Italian real-world multicentre study.

BACKGROUND: Despite several guidelines recommend the use of psychoeducational family interventions (PFIs) as add-on in the treatment of patients with bipolar I disorder, their implementation on a large scale remains limited. The aim of the present study is to identify obstacles for the feasibility of PFIs in routine care. METHODS: This was a multicentre, real-world, controlled, outpatient trial, carried out in 11 randomly recruited Italian mental health centres. Two mental health professionals from each center attended a modular training course on PFI and provided the intervention. Difficulties and benefits experienced by mental health professionals in implementing the intervention were assessed through the Family Intervention Schedule (FIS-R), which was administered six times. RESULTS: Sixteen out of the 22 recruited professionals completed the training and administered the PFI to 70 patients with bipolar I disorder and their relatives. The retention rate of families receiving the intervention was 93%. Mental health professionals reported high levels of organizational difficulties, several benefits in their daily clinical work and low levels of intervention-related difficulties. The most important organizational obstacles were related to the need to integrate the intervention with other work responsibilities and to the lack of time to carry out the intervention. These difficulties did not decrease over time. Intervention-related difficulties were rated as less problematic since the first time assessment and tended to improve over time. LIMITATIONS: Low number of recruited professionals; use of a not previously validated assessment instrument. CONCLUSIONS: PFIs are feasible in routine care for the treatment of patients with bipolar I disorder and their relatives, and main obstacles are related to the organization/structure of mental health centres, and not to the characteristics of the intervention itself.

The human gene coding for HCN2, a pacemaker channel of the heart.

Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, underlying 'pacemaker' currents (I(f)/Ih), are involved in pacemaker activity of cardiac sinoatrial node myocytes and central neurons. Several cDNAs deriving from four different genes were recently identified which code for channels characterized by six transmembrane domains and a cyclic nucleotide binding domain. We report here the identification of the human HCN2 gene and show that its functional expression in a human kidney cell line generates a current with properties similar to the native pacemaker f-channel of the heart. The hHCN2 gene maps to the telomeric region of chromosome 19, band p13.3. This is the first identification of a genetic locus coding for an HCN channel.