Biomimetic Hierarchically Arranged Nanofibrous Structures Resembling the Architecture and the Passive Mechanical Properties of Skeletal Muscles: A Step Forward Toward Artificial Muscle

Skeletal muscles are considered to date the best existing actuator in nature thanks to their hierarchical multiscale fibrous structure capable to enhance their strength and contractile performances. In recent years, driven by the growing of the soft robotics and tissue-engineering research field, many biomimetic soft actuators and scaffolds were designed by taking inspiration from the biological skeletal muscle. In this work we used the electrospinning technique to develop a hierarchically arranged nanofibrous structure resembling the morphology and passive biomechanical properties of skeletal muscles. To mimic the passive properties of muscle, a low-modulus polyurethane was used. Several electrospun structures (mats, bundles, and a muscle-like assembly) were produced with different internal 3D arrangements of the nanofibers. A thermal characterization through thermogravimetric and differential scanning calorimetry analysis investigated the physico-chemical properties of the material. The multiscale morphological similarities with the biological counterpart were verified by means of scanning electron microscopy investigation. The tensile tests on the different electrospun samples revealed that the muscle-like assembly presented slightly higher strength and stiffness compared to the skeletal muscle ones. Moreover, mathematical models of the mechanical behavior of the nanofibrous structures were successfully developed, allowing to better investigate the relationships between structure and mechanics of the samples. The promising results suggest the suitability of this hierarchical electrospun nanofibrous structure for applications in regenerative medicine and, if combined with active materials, in soft actuators for robotic

Tuning the Structure of Nylon 6,6 Electrospun Bundles to Mimic the Mechanical Performance of Tendon Fascicles

Tendon and ligament injuries are triggered by mechanical loading, but the specific mechanisms are not yet clearly identified. It is well established however, that the inflection and transition points in tendon stress-strain curves represent thresholds that may signal the onset of irreversible fibrillar sliding. This phenomenon often results in a progressive macroscopic failure of these tissues. With the aim to simulate and replace tendons, electrospinning has been demonstrated to be a suitable technology to produce nanofibers similar to the collagen fibrils in a mat form. These nanofibrous mats can be easily assembled in higher hierarchical levels to reproduce the whole tissue structure. Despite the fact that several groups have developed electrospun tendon-inspired structures, an investigation of the inflection and transition point mechanics is missing. Comparing their behavior with that of the natural counterpart is important to adequately replicate their behavior at physiological strain levels. To fill this gap, in this work fascicle-inspired electrospun nylon 6,6 bundles were produced with different collector peripheral speeds (i.e., 19.7 m s–1; 13.7 m s–1; 7.9 m s–1), obtaining different patterns of nanofibers alignment. The scanning electron microcopy revealed a fibril-inspired structure of the nanofibers with an orientation at the higher speed similar to those in tendons and ligaments (T/L). A tensile mechanical characterization was carried out showing an elastic-brittle biomimetic behavior for the higher speed bundles with a progressively more ductile behavior at slower speeds. Moreover, for each sample category the transition and the inflection points were defined to study how these points can shift with the nanofiber arrangement and to compare their values with those of tendons. The results of this study will be of extreme interest for the material scientists working in the field, to model and improve the design of their electrospun structures and scaffolds and enable building a new generation of artificial tendons and ligaments

The joint involvement in adult onset Still's disease is characterised by a peculiar magnetic resonance imaging and a specific transcriptomic profile

Adult onset Still's disease (AOSD) is a rare systemic autoinflammatory disease, characterised by fever, arthritis, and skin rash, and joint involvement is one of its clinical manifestations. The aims of this work were to assess joint involvement, to describe main patterns of involvement, and associated clinical characteristics. In this work, we aimed at assessing the joint involvement in AOSD by using MRI, to describe main patterns and associated clinical characteristics. In addition, we aimed at assessing the global transcriptomic profile of synovial tissues in AOSD to elucidate possible pathogenic pathways involved. We also evaluated the global transcriptomic profile of synovial tissues to elucidate possible pathogenic pathways involved in the disease. Thus, AOSD patients, who underwent to MRI exam on joints, were assessed to describe patterns of joint involvement and associated clinical characteristics. Some synovial tissues were collected for RNA-sequencing purposes. The most common MRI finding was the presence of synovitis on 60.5%, mainly in peripheral affected joints, with low to intermediate signal intensity on T1-weighted images and intermediate to high signal intensity on T2-fat-saturated weighted and STIR images. Bone oedema and MRI-bone erosions were reported on 34.9% and 25.6% MRI exams, respectively. Patients with MRI-bone erosions showed a higher prevalence of splenomegaly, a more frequent chronic disease course, lower levels of erythrocyte sedimentation rate, and ferritin. In AOSD synovial tissues, a hyper-expression of interleukin (IL)-1, IL-6, and TNF pathways was shown together with ferritin genes. In conclusion, in AOSD patients, the most common MRI-finding was the presence of synovitis, characterised by intermediate to high signal intensity on T2-fat-saturated weighted and STIR images. MRI-bone erosions and bone oedema were also observed. In AOSD synovial tissues, IL-1, IL-6, and TNF pathways together with ferritin genes resulted to be hyper-expressed

Incidence of maternal Toxoplasma infections in pregnancy in Upper Austria, 2000-2007

Sagel U, Krämer A, Mikolajczyk RT. Incidence of maternal Toxoplasma infections in pregnancy in Upper Austria, 2000-2007. BMC Infectious Diseases. 2011;11(1): 348.UNLABELLED: ABSTRACT: BACKGROUND: Despite three decades of prenatal screening program for toxoplasmosis in Austria, population-based estimates for the incidence of maternal infections with Toxoplasma gondii during pregnancy are lacking. We studied the incidence of primary maternal infections during pregnancy in the Federal State of Upper Austria. METHODS: Screening tests for 63,416 women and over 90,000 pregnancies (more than 84.5% of pregnancies in the studied region) in the time period between 01.01.2000 and 31.12.2007 were analysed. The incidence of toxoplasmosis was estimated indirectly by binomial and directly by interval censored regression. RESULTS: During the studied period, 66 acute infections (risk of 0.07% per pregnancy) were detected, but only 29.8% of seronegative women were tested at least three times during their pregnancies. The seroprevalence of Toxoplasma antibodies among all tested women was 31%. Indirectly estimated incidence (from differences in prevalence by age) was 0.5% per pregnancy, while directly estimated incidence (interval censored regression) was 0.17% per pregnancy (95% confidence interval: 0.13-0.21%). CONCLUSIONS: Calculating incidence from observed infections results in severe underreporting due to many missed tests and potential diagnostic problems. Using statistical modelling, we estimated primary toxoplasmosis to occur in 0.17% (0.13-0.21%) of all pregnancies in Upper Austria

Group B streptococcus serotype prevalence in reproductive-age women at a tertiary care military medical center relative to global serotype distribution

<p>Abstract</p> <p>Background</p> <p>Group B <it>Streptococcus </it>(GBS) serotype (Ia, Ib, II-IX) correlates with pathogen virulence and clinical prognosis. Epidemiological studies of seroprevalence are an important metric for determining the proportion of serotypes in a given population. The purpose of this study was to evaluate the prevalence of individual GBS serotypes at Madigan Healthcare System (Madigan), the largest military tertiary healthcare facility in the Pacific Northwestern United States, and to compare seroprevalences with international locations.</p> <p>Methods</p> <p>To determine serotype distribution at Madigan, we obtained GBS isolates from standard-of-care anogenital swabs from 207 women of indeterminate gravidity between ages 18-40 during a five month interval. Serotype was determined using a recently described molecular method of polymerase chain reaction by capsular polysaccharide synthesis (cps) genes associated with pathogen virulence.</p> <p>Results</p> <p>Serotypes Ia, III, and V were the most prevalent (28%, 27%, and 17%, respectively). A systematic review of global GBS seroprevalence, meta-analysis, and statistical comparison revealed strikingly similar serodistibution at Madigan relative to civilian-sector populations in Canada and the United States. Serotype Ia was the only serotype consistently higher in North American populations relative to other geographic regions (p < 0.005). The number of non-typeable isolates was significantly lower in the study (p < 0.005).</p> <p>Conclusion</p> <p>This study establishes PCR-based serotyping as a viable strategy for GBS epidemiological surveillance. Our results suggest that GBS seroprevalence remains stable in North America over the past two decades.</p

Multidisciplinary approach to prostatitis

The modern clinical research on prostatitis started with the work of Stamey and coworkers who developed the basic principles we are still using. They established the segmented culture technique for localizing the infections in the males to the urethra, the bladder, or the prostate and to differentiate the main categories of prostatitis. Such categories with slight modifications are still used according to the NIH classification: acute bacterial prostatitis, chronic bacterial prostatitis, Chronic Pelvic Pain Syndrome (CPPS) and asymptomatic prostatitis. Prostatic inflammation is considered an important factor in influencing both prostatic growth and progression of symptoms of benign prostatic hyperplasia and prostatitis. Chronic inflammation/neuroinflammation is a result of a deregulated acute phase response of the innate immune system affecting surrounding neural tissue at molecular, structural and functional levels. Clinical observations suggest that chronic inflammation correlates with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and benign prostatic hyperplasia (BPH) and an history of clinical chronic prostatitis significantly increases the odds for prostate cancer. The NIHNIDDK classification based on the use of the microbiological 4- glasses localization test or simplified 2-glasses test, is currently accepted worldwide. The UPOINT system identifies groups of clinicians with homogeneous clinical presentation and is used to recognize phenotypes to be submitted to specific treatments. The UPOINTS algorithm implemented the original UPOINT adding to the urinary domains (U), psycho-social (P), organspecific (O), infection (I), neurological (N), muscle tension and tenderness (T) a further domain related to sexuality (S). In fact sexual dysfunction (erectile, ejaculatory, libido loss) has been described in 46-92% of cases with a high impact on the quality of life of patients with CP/CPPS. Prostatic ultrasound represents the most popular imaging test in the work-up of either acute and chronic prostatitis although no specific hypo-hyperechoic pattern has been clearly associated with chronic bacterial prostatitis and CPPS. Use of a digital-processing software to calculate the extension of prostatic calcification area at ultrasound demonstrated a higher percentage of prostatic calcification in patients with chronic bacterial prostatitis. Multiparametric Magnetic Resonance Imaging (mpMRI) is the current state-of-the art imaging modality in the assessment of patients with prostate cancer although a variety of benign conditions, including inflammation, may mimic prostate cancer and act as confounding factors in the discrimination between neoplastic and non-neoplastic lesions. Bacteria can infect prostate gland by: ascending the urethra, reflux of urine into the prostatic ducts, direct inoculation of bacteria through inserted biopsy needles or hematogenous seeding. Enterobacteriaceae are the predominant pathogens in acute and chronic bacterial prostatitis, but an increasing role of Enterococci has been reported. Many strains of these uropathogens exhibit the ability to form biofilm and multidrug- resistance. Sexually Transmitted Infections (STI) agents, in particular Chlamydia trachomatis and Mycoplasma genitalium, have been also considered as causative pathogens of chronic bacterial prostatitis. On the contrary the effective role in genital diseases of other "genital mycoplasmas" is still a much debated issue. Sexually Transmitted Infections agents should be investigated by molecular methods in both patient and sexual partner. "Next generation" investigations, such as cytokine analysis, cytological typing of immune cells could help stratifying the immune response. Epigenetic dysregulation of inflammatory factors should be investigated according to systemic and compartment-specific signals. The search for biomarkers should also include evaluation of hormonal pathways, as measurement of estrogen levels in semen. Antimicrobials are the first line agents for the treatment of bacterial prostatitis. The success of antimicrobial treatment depends on the antibacterial activity and the pharmacokinetic characteristics of the drug which must reach high concentrations in prostate secretion and prostate tissue. Acute bacterial prostatitis can be a serious infection with a potential risk for urosepsis For iInitial treatment of severely ill patients, intravenous administration of high doses of bactericidal antimicrobials, such as broad-spectrum penicillins, third-generation cephalosporins or fluoroquinolones, is recommended in combination with an aminoglycoside. Use of piperacillin-tazobactam and meropenem is justified in presence of multiresistant gramnegative pathogens. The antibiotic treatment of chronic prostatitis is currently based on the use of fluoroquinolones that, given for 2 to 4 weeks, cured about 70% of men with chronic bacterial prostatitis. For the treatment of Chlamydial prostatitis macrolides were shown to be more effective than fluoroquinolones, whereas no differences were observed in microbiological and clinical efficacy between macrolides and tetracyclines for the treatment of infections caused by intracellular pathogens. Aminoglycosides and fosfomycin could be considered as a therapeutic alternative for the treatment of quinolone resistant prostatitis. Use of alpha-blockers in CP/CPPS patients with urinary symptoms and analgesics +/- non steroidal anti-inflammatory drugs (NSAID), in presence of pain demonstrated a reduction of symptoms reduction and an improvement of quality of life, although long term use of NSAID is limited by side effect profile. However, the multimodal therapeutic regimen by contemporary use of alphablockers, antibiotics and anti-inflammatory showed a better control of prostatitis symptoms than single drug treatment. Novel therapeutic substances for the treatment of pain, such as the cannabinoid anandamide would be highly interesting to test. An alternative for the treatment of chronic prostatitis/chronic pelvic pain syndrome is phytotherapy, as primary therapy or in association with other drugs. Quercetin, pollen extract, extract of Serenoa repens and other mixtures of herbal extracts showed a positive effect on symptoms and quality of life without side effects. The association of CP/CPPS with alterations of intestinal function has been described. Diet has its effects on inflammation by regulation of the composition of intestinal flora and direct action on the intestinal cells (sterile inflammation). Intestinal bacteria (microbiota) interacts with food influencing the metabolic, immune and inflammatory response of the organism. The intestinal microbiota has protective function against pathogenic bacteria, metabolic function by synthesis of vitamins, decomposition of bile acids and production of trophic factors (butyrate), and modulation of the intestinal immune system. The alteration of the microbiota is called "dysbiosis" causing invasive intestinal diseases pathologies (leaky gut syndrome and food intolerances, irritable bowel syndrome or chronic inflammatory bowel diseases) and correlating with numerous systemic diseases including acute and chronic prostatitis. Administration of live probiotics bacteria can be used to regulate the balance if intestinal flora. Sessions of hydrocolontherapy can represent an integration to this therapeutic approach. Finally, microbiological examination of sexual partners can offer supplementary information for treatment

Tendon Fascicle-Inspired Nanofibrous Scaffold of Polylactic acid/Collagen with Enhanced 3D-Structure and Biomechanical Properties

Surgical treatment of tendon lesions still yields unsatisfactory clinical outcomes. The use of bioresorbable scaffolds represents a way forward to improve tissue repair. Scaffolds for tendon reconstruction should have a structure mimicking that of the natural tendon, while providing adequate mechanical strength and stiffness. In this paper, electrospun nanofibers of two crosslinked PLLA/Collagen blends (PLLA/Coll-75/25, PLLA/Coll-50/50) were developed and then wrapped in bundles, where the nanofibers are predominantly aligned along the bundles. Bundle morphology was assessed via SEM and high-resolution x-ray computed tomography (XCT). The 0.4-micron resolution in XCT demonstrated a biomimetic morphology of the bundles for all compositions, with a predominant nanofiber alignment and some scatter (50-60% were within 12° from the axis of the bundle), similar to the tendon microstructure. Human fibroblasts seeded on the bundles had increased metabolic activity from day 7 to day 21 of culture. The stiffness, strength and toughness of the bundles are comparable to tendon fascicles, both in the as-spun condition and after crosslinking, with moderate loss of mechanical properties after ageing in PBS (7 and 14 days). PLLA/Coll-75/25 has more desirable mechanical properties such as stiffness and ductility, compared to the PLLA/Coll-50/50. This study confirms the potential to bioengineer tendon fascicles with enhanced 3D structure and biomechanical properties

Solid state MPD thruster with applied magnetic field

A solid state MPD thruster with applied magnetic field has been investigated. The MPDhas been operated with applied fields up to 0.4 T. Current, impulse bit and ablated masshave been measured. The thruster has shown a threshold value of the applied magnetic fieldover which it does not work, this threshold value increases with the shot energy. Away fromthis threshold value the current shows small variation with the applied field. The measuredvalues of the impulse bit are in accordance with the trends shown by previous investigationsand show a satisfactory agreement with the theoretical values calculated with one of theauthors’ theory