Bioactive nano‐fibrous scaffold for vascularized craniofacial bone regeneration

There has been a growing demand for bone grafts for correction of bone defects in complicated fractures or tumours in the craniofacial region. Soft flexible membrane like material that could be inserted into defect by less invasive approaches; promote osteoconductivity and act as a barrier to soft tissue in growth while promoting bone formation is an attractive option for this region. Electrospinning has recently emerged as one of the most promising techniques for fabrication of extracellular matrix such as nano‐fibrous scaffolds that can serve as a template for bone formation. To overcome the limitation of cell penetration of electrospun scaffolds and improve on its osteoconductive nature, in this study, we fabricated a novel electrospun composite scaffold of polyvinyl alcohol (PVA)‐poly (ε) caprolactone (PCL)‐Hydroxyapatite based bioceramic (HAB), namely, PVA‐PCL‐HAB. The scaffold prepared by dual electrospinning of PVA and PCL with HAB overcomes reduced cell attachment associated with hydrophobic PCL by combination with a hydrophilic PVA and the HAB can contribute to enhance osteoconductivity. We characterized the physicochemical and biocompatibility properties of the new scaffold material. Our results indicate PVA‐PCL‐HAB scaffolds support attachment and growth of stromal stem cells; [human bone marrow skeletal (mesenchymal) stem cells and dental pulp stem cells]. In addition, the scaffold supported in vitro osteogenic differentiation and in vivo vascularized bone formation. Thus, PVA‐PCL‐HAB scaffold is a suitable potential material for therapeutic bone regeneration in dentistry and orthopaedics.     

Validation of 64Cu-ATSM damaging DNA via high-LET Auger electron emission

Radioactive copper (II) (diacetyl-bis N4-methylthiosemicarbazone) (Cu-ATSM) isotopes were originally developed for the imaging of hypoxia in tumors. Because the decay of a ⁶⁴Cu atom is emitting not only positrons but also Auger electrons, this radionuclide has great potential as a theranostic agent. However, the success of ⁶⁴Cu-ATSM internal radiation therapy would depend on the contribution of Auger electrons to tumor cell killing. Therefore, we designed a cell culture system to define the contributions to cell death from Auger electrons to support or refute our hypothesis that the majority of cell death from ⁶⁴Cu-ATSM is a result of high-LET Auger electrons and not positrons or other low-LET radiation. Chinese hamster ovary (CHO) wild type and DNA repair–deficient xrs5 cells were exposed to ⁶⁴Cu-ATSM during hypoxic conditions. Surviving fractions were compared with those surviving gamma-radiation, low-LET hadron radiation, and high-LET heavy ion exposure. The ratio of the D₁₀ values (doses required to achieve 10% cell survival) between CHO wild type and xrs5 cells suggested that ⁶⁴Cu-ATSM toxicity is similar to that of high-LET Carbon ion radiation (70 keV/μm). γH2AX foci assays confirmed DNA double-strand breaks and cluster damage by high-LET Auger electrons from ⁶⁴Cu decay, and complex types of chromosomal aberrations typical of high-LET radiation were observed after ⁶⁴Cu-ATSM exposure. The majority of cell death was caused by high-LET radiation. This work provides strong evidence that ⁶⁴Cu-ATSM damages DNA via high-LET Auger electrons, supporting further study and consideration of ⁶⁴Cu-ATSM as a cancer treatment modality for hypoxic tumors.     

Obsessive–Compulsive Disorder is Characterized by a Lack of Adaptive Coping Rather than an Excess of Maladaptive Coping

The present study aimed to elucidate the profile of coping in patients with obsessive–compulsive disorder (OCD) in order to discern whether the disorder is characterized by an excess of maladaptive coping skills and/or a lack of adaptive coping skills. Sixty individuals with OCD were compared with 110 individuals with depression and 1050 nonclinical controls on the Maladaptive and Adaptive Coping Styles Questionnaire (MAX). Psychopathology was assessed with the Obsessive–Compulsive Inventory-Revised (OCI-R), the Yale-Brown Obsessive–Compulsive Scale (Y-BOCS), and the Patient Health Questionnaire-9 for depression (PHQ-9). Individuals with OCD and depression displayed more maladaptive coping and avoidance as well as less adaptive coping than nonclinical controls. Importantly, adaptive coping was significantly lower in individuals with OCD than in those with depression at a medium effect size, whereas the clinical groups were indistinguishable on maladaptive coping and avoidance. Lack of adaptive coping was strongly correlated with resistance to symptoms and poor insight in OCD (Y-BOCS), even after controlling for depression. Lack of adaptive coping skills may represent a specific pathogenetic factor in OCD. Longitudinal studies need to clarify whether strengthening adaptive skills during childhood and adolescence may help to prevent the progression from subclinical to manifest OCD.     

Mycoplasma pneumoniae and Chlamydia pneumoniae in asthma: effect of clarithromycin

STUDY OBJECTIVES: To determine the effect of clarithromycin therapy in patients with asthma. DESIGN: Randomized, double blind, placebo-controlled trial. SETTING: A tertiary referral center. PATIENTS OR PARTICIPANTS: Fifty-five subjects with chronic, stable asthma recruited from the general Denver, CO, community. INTERVENTIONS: Patients underwent airway evaluation for Mycoplasma pneumoniae and Chlamydia pneumoniae by polymerase chain reaction (PCR) and culture, followed by treatment with clarithromycin, 500 bid, or placebo for 6 weeks. MEASUREMENTS AND RESULTS: Outcome variables were lung function, sinusitis as measured by CT, and the inflammatory mediators tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, IL-4, IL-5, and IL-12 messenger RNA (mRNA) measured via in situ hybridization, in airway biopsies, and BAL. Mycoplasma or chlamydia were detected by PCR in 31 of 55 asthmatics. Treatment resulted in a significant improvement in the FEV(1), but only in the PCR-positive subjects (2.50 +/- 0.16 to 2.69 +/- 0.19 L, mean +/- SEM; p = 0.05). This was not appreciated in the PCR-negative subjects (2.59 +/- 0.24 to 2.54 +/- 0.18 L, p = 0.85) or the PCR-positive or PCR-negative subjects who received placebo. Sinus CTs revealed no change in sinusitis with clarithromycin treatment. In situ hybridization revealed no significant difference in baseline airway tissue or BAL-mediator expression between the PCR-positive and PCR-negative subjects. However, the PCR-positive subjects who received clarithromycin demonstrated a reduction in TNF-alpha (p = 0.006), IL-5 (p = 0.007), and IL-12 (p = 0.004) mRNA in BAL and TNF-alpha mRNA in airway tissue (p = 0.0009). The PCR-negative subjects who received clarithromycin only demonstrated a reduction in TNF-alpha (p = 0.01) and IL-12 (p = 0.002) mRNA in BAL and TNF-alpha mRNA in airway tissue (p = 0.004). There were no significant differences in cytokine expression in those subjects who received placebo. CONCLUSIONS: These observations support the hypothesis that clarithromycin therapy improves lung function, but only in those subjects with positive PCR findings for M pneumoniae or C pneumoniae.     

Unrecognized staphylococcal pyarthrosis with rheumatoid arthritis

Four patients whose rheumatoid arthritis (RA) was complicated by staphylococcal arthritis were identified. All patients had active, long-standing disease with destructive changes. Affected joints included hip (two patients), knee (one patient), and shoulder (one patient). Pain and loss of motion in the affected joint were prominent, but toxic features of pyogenic infections--hectic fever, chills, sweats, local warmth, or erythema--were conspicuously absent. Two patients had moderate fever and three patients had mild leukocytosis. No patient was leukopenic. When present, fever was attributed to infected decubiti or urinary tract infection and treated with antibiotics. Therapy with corticosteroids and nonsteroidal antiinflammatory drugs (NSAIDs) probably masked symptoms and delayed the correct diagnosis. Purulent synovial effusions were discovered serendipitously--during arthrography (knee), attempted Girdlestone procedure (hip), and aspiration prior to steroid injection (shoulder). Sepsis was included in the preoperative diagnoses only once (hip). Prior instrumentation (aspiration or injection) of the affected joint was not a feature in any patients, although one patient had undergone insertion of a knee prosthesis one year prior to sepsis. Infectious organisms were Staphylococcus aureus in three patients and Staphylococcus epidermidis in one. Severe sequelae ensued in three of four patients: death from recurrent sepsis (one patient), loss of prosthesis leading to knee arthrodesis (one patient), and protracted sepsis with additional pyarthrosis (one patient). The only patient to regain preseptic joint function (shoulder) had not been on long-standing corticosteroids. Pyarthrosis must be considered in RA patients with unusually painful or stiff joints even in the absence of toxic symptoms.     

Microstructure and long-term stability of solder joints on nickel-plated aluminium formed during short soldering times

Within this work, we demonstrate that an easy soldering process in combination with wet chemical coating is suitable to realize a strong and reliable solder interconnection of Al substrates, even at short soldering times <5 s in ambient air. The microstructure of solder joints on wet chemically treated aluminum foils is investigated. A single and double zincate pre-treatment are compared to activate the Al surface, followed by electroless Ni plating. The quality of the solderable Ni surface is characterized by contact angle measurements, yielding good wettability (<60°), which is also achieved after isothermally heating (250 °C) the Ni-coated Al foils for 100 min. The microstructure of the Sn62Pb36Ag2 solder joints is investigated by SEM and EDX of cross sections, directly after soldering as well as after isothermal aging at 85 °C. Under the used soldering conditions, with a soldering temperature at about 280 °C, diffusion zones <500 nm were identified. Nonetheless, high peel forces after soldering >5 N mm⁻¹ show stable values under aging conditions of 85 °C for 1000 hours. This could be correlated to a mixed fracture pattern, promoting the high adhesion due to the absence of a dominant failure mechanism.

High mechanical reliability of tin-based solder joints processed by joining copper and nickel-coated aluminium with short soldering times in ambient air.