The use of small intestine in bladder reconstruction

Reconstruction of the bladder is a treatment available to patients who have a diseased or damaged bladder, and small bowel is the most commonly used tissue. Augmentation cystoplasty increases the total bladder capacity, whereas substitution cystoplasty replaces the whole organ. This is either drained through a continent cutaneous stoma or is reanastomosed to the urethra as an orthotopic reconstruction. Although the treatment for invasive bladder cancer has not changed greatly in the last few decades, the use of orthotopic bladder reconstruction allows for a great improvement in the quality of life for patients who undergo cystectomy. These reconstructive techniques can also be offered to patients with other forms of pelvic malignancy that involve the bladder.     

Comparison of motion restriction and trunk stiffness provided by three thoracolumbosacral orthoses (TLSOs)

The amounts of thoracic and lumbar spine motion restriction and passive trunk stiffness provided by three thoracolumbosacral orthoses (TLSOs) (Aspen TLSO, Boston Body Jacket, and CAMP TLSO) were compared. Ten subjects executed maximum trunk flexion, extension, and lateral bending motions. The spine motion was measured noninvasively with a thin strain gauge device (Flexducer), and passive trunk stiffness around the neutral posture was estimated from an electromyography-assisted biomechanical model. No significant differences in either the restriction of motion or the amount of added passive trunk stiffness were found between the three orthoses. The subjects also did not perceive any difference in the restriction of motion but rated the Aspen TLSO significantly more comfortable than the other two orthoses. The rigid custom orthosis design may not be important for restricting the spine motion and providing passive trunk stiffness, or there may be other measures that reflect better the function of orthoses.     

Ultrasound evaluation of the abductor hallucis muscle: Reliability study

Background

The Abductor hallucis muscle (AbdH) plays an integral role during gait and is often affected in pathological foot conditions. The aim of this study was to evaluate the within and between-session intra-tester reliability using diagnostic ultrasound of the dorso-plantar thickness, medio-lateral width and cross-sectional area, of the AbdH in asymptomatic adults.

Methods

The AbdH muscles of thirty asymptomatic subjects were imaged and then measured using a Philips HD11 Ultrasound machine. Interclass correlation coefficients (ICC) with 95% confidence intervals (CI) were used to calculate both within and between session intra-tester reliability.

Results

The within-session reliability results demonstrated for dorso-plantar thickness an ICC of 0.97 (95% CI: 0.99–0.99); medio-lateral width an ICC: of 0.97 (95% CI: 0.92–0.97) and cross-sectional area an ICC of 0.98 (95% CI: 0.98–0.99). Between-session reliability results demonstrated for dorso-plantar thickness an ICC of 0.97 (95% CI: 0.95 to 0.98); medio-lateral width an ICC of 0.94 (95% CI 0.90 to 0.96) and for cross-sectional area an ICC of 0.79 (95% CI 0.65 to 0.88).

Conclusion

Diagnostic ultrasound has the potential to be a reliable tool for evaluating the AbdH muscle in asymptomatic subjects. Subsequent studies may be conducted to provide a better understanding of the AbdH function in foot and ankle pathologies.     

Direct and reversible inhibitory effect of the tetrapeptide acetyl-N- Ser-Asp-Lys-Pro (Seraspenide) on the growth of human CD34+ subpopulations in response to growth factors

The tetrapeptide Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP, Seraspenide; Ipsen- Biotech, Paris, France), an inhibitor of murine spleen colony-forming units reduces the number and the percentage in DNA synthesis of progenitors from human unfractionated bone marrow. To determine whether AcSDKP may directly affect the growth potential of purified progenitors even at the most primitive level, CD34+HLA-DRhigh and CD34++HLA-DRlow cells were highly purified by cell sorting. Then, CD34+ subsets were stimulated in liquid culture with combinations of growth factors (GFs) and AcSDKP was added for 20 hours or 6 days and cells plated in methylcellulose. After a 20-hour incubation, we show that AcSDKP (at 10(-10) mol/L) significantly inhibits the colony formation of both CD34+ subsets. Moreover, when added daily for 6 days, AcSDKP: (1) reduces the proliferation of both CD34+ cell fractions stimulated by 3 or 7 GFs, and (2) decreases the number of progenitors generated from the CD34+HLA-DRhigh and CD34++HLA-DRlow cell fractions. Furthermore, we show for the first time, using both high proliferative potential cell and long-term culture initiating cell assays, that AcSDKP inhibits the most primitive cells contained in the CD34++HLA-DRlow subpopulation. Finally, by using limiting dilution assays we demonstrated that AcSDKP acts directly at a single cell level and that its inhibitory effect is reversible and dose dependent.     

Hybrid hollow silica particles: synthesis and comparison of properties with pristine particles

In the past decade, interest in hollow silica particles has grown tremendously because of their applications in diverse fields such as thermal insulation, drug delivery, battery cathodes, catalysis, and functional coatings. Herein, we demonstrate a strategy to synthesize hybrid hollow silica particles having shells made of either polymer-silica or carbon–silica. Hybrid shells were characterized using electron microscopy. The effect of hybrid shell type on particle properties such as thermal and moisture absorption was also investigated.

Hybrid hollow silica particles, which show different properties compared to their pristine counterparts, have been synthesized.

In the past decade, hollow particles have attracted a great deal of interest because of their unique properties (e.g., high surface area, low density, and encapsulated cavity) compared with their dense counterparts. Hollow particles of several materials, including polymers, silica, titania, carbon, and zinc oxide have been reported.^1–9 Among these, hollow silica particles have attracted great attention from scientists because of their low material cost; well understood chemistry; and potential applications in widespread areas such as thermal insulation, drug delivery, energy storage, phase change encapsulation, catalysis, and superhydrophobic coatings.^10–18 Hollow silica particles can be synthesized using various approaches, such as by employing polymer micelles, immiscible solvent emulsions, inorganic or polymer (e.g., polystyrene) particles, and bacterial or virus cells as templates; by etching solid silica particles; or by spray pyrolysis.^19–25 Polymer micelles or emulsions provide very small particles, but making larger particles and tuning particle size are challenges in this approach. Similarly, the obtained particles typically fuse with one another, and achieving individually separated particles is a challenging task. Inorganic template etching is a time-consuming process, and in many cases, rudiments of inorganic templates remain in the hollow particle cavity if etching is incomplete. Unconventional techniques such as spray drying are inexpensive, but particle size control is difficult. The use of polystyrene particles as templates is attracting much attention because polystyrene particles can be synthesized at low cost with controlled sizes. Polystyrene particle-based synthesis of hollow silica particles involves three steps: (1) synthesis of polystyrene particles, (2) deposition of silica shells on polystyrene particles, and (3) removal of the polystyrene core by burning or dissolving to obtain hollow silica particles.Synthesis of hollow silica particles having shells made of silica alone (pristine hollow particles) is well reported. Some previous efforts have been made to attach surfactant molecules to the surfaces of mesoporous (not hollow) hollow particles. For example, Zhang et al.²⁶ first made porous silica particles by using cetyltrimethylammonium bromide (CTAB) as the template. In the next step, sodium carbonate-based etching was used to create cavities inside the porous particles, thus leading to porous-hollow silica particles. Then, 3-mercaptopropyl-trimethoxysilane (MPTS) was used to attach thiol-group ending surfactants to the surface. Similarly, Ribeiro et al.²⁷ coated solid silica particles with poly(butyl methacrylate) to make superhydrophobic coatings. Similarly, hollow polymer particles have been reported by depositing a polymer layer around solid silica particles, followed by etching the silica core. The same hollow polymer particles were also converted to hollow carbon particles by pyrolysis of polymer.^28,31 However, in this work, shell is made of a single material – polymer or carbon.^28,31 To the best of our knowledge, no work has reported hollow particles with a hybrid shell – shell made of two layers of different materials (inner layer: silica and outer layer: polymer or carbon). Additionally, no previous report has investigated the effect of such an additional layer on the properties of the hollow silica particles. We envisage that such additional layers can change the properties, such as stability against moisture and thermal conductivity, of pristine hollow silica particles.We report the synthesis of hybrid hollow silica particles, characterize these hybrid particles, and compare their properties with the properties of pristine hollow silica particles. Our investigations reveal that by changing the coating material, several intrinsic properties of hollow silica particles can be modified.Hollow silica particles were synthesized by modifying previously reported strategies based on the use of polystyrene particles (synthesis details in ESI S1^†) as a template.¹ For synthesizing hollow silica particles, in a typical experiment, 0.25 g of polystyrene particles were mixed into 100 mL of ethanol/water (ethanol 80 mL, water 20 mL). A suitable amount of tetraethyl orthosilicate was added to make complete shells around the polystyrene particles. To increase the TEOS hydrolysis, 28–30% of ammonium hydroxide was used as a catalyst. Fig. 1a depicts a schematic of hollow particle formation. Fig. 1b shows an SEM image of the polystyrene particles used as templates, and Fig. 1c shows a transmission electron microscope (TEM) image of polystyrene core-silica shell particles. Fig. 1d shows an SEM and Fig. 1e shows a high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) image of hollow silica particles obtained after burning the polystyrene core by keeping the sample at 550 °C for 4 h.Open in a separate windowFig. 1(a) Schematic showing synthesis of hollow silica particles. (b) SEM image of polystyrene particles. (c) TEM image of polystyrene core coated with silica shell (core–shell). (d) SEM and (e) HAADF-STEM image of hollow silica particles.There are several polymers that can be used to form coatings on silica.^28–31 Among these, the use of resorcinol is well studied.^28,31 In a typical experiment, 0.25 g of hollow particles (0.25 g) were mixed in water (100 mL). Ammonium hydroxide (28–30%, 500 μL), resorcinol (0.1 g), and formaldehyde (150 μL) were added to this reaction mixture. The reaction was allowed to proceed overnight (≈16 h) to completion. Expected mechanism for polymer coating formation is explained in ESI S3.^†Fig. 2a shows a schematic of the process used to make a polymer (polyresorcinol) coating on a silica shell. Fig. 2b shows low-magnification (i) and high-magnification (ii) TEM images of polymer-coated hollow silica particles. The polymer coating can be clearly seen (light in contrast) around the silica shell (dense in contrast). Though TEM imaging confirmed the presence of a polymer coating on the surface of the silica, to further confirm the formation of the coating, we applied electron energy loss spectroscopy (EELS). Energy dispersive X-ray (EDX) imaging is easy to use and is a readily available technique for analysing materials; however, EDX has a very low sensitivity to low-atomic-weight elements such as carbon and oxygen. Therefore, it was not a suitable technique for confirming the polymer presence. In contrast, EELS is known for its high sensitivity to low-atomic-weight elements (e.g., carbon and oxygen). Fig. 2c shows scanning HAADF-STEM (i) and EELS (ii) images of the polymer-silica hybrid shell. The coating was quite uniform, with some thicker areas on the free surfaces of particles and some thinner areas at the joints in aggregated particles (ESI S2^†). Therefore, if individual uniform coatings are required, the original hollow particle samples must be properly disaggregated.Open in a separate windowFig. 2(a) Schematic showing the polymer coating process. (b) TEM images of polymer-coated silica particles. (c) HAADF-TEM (i) and EELS S map (ii) showing polymer and silica layers of hybrid shell.Additionally, we demonstrated the formation of hybrid hollow silica particles with outer layers made of carbon and inner layers made of silica. To form a carbon layer on a silica shell, the initial polymer coating was sintered in an inert atmosphere (argon) at 550 °C for 4 h. Fig. 3a shows a schematic of polymer layer conversion to a carbon layer. Under these conditions, polymer converts into carbon instead of being completely oxidized into carbon dioxide and water. After heating under an inert atmosphere, brown polymer-coated particles changed to black carbon-coated particles. Separate carbon (outer) and silica (inner) layers were observed in TEM (Fig. 3b) and EELS images (Fig. 3c).Open in a separate windowFig. 3(a) Schematic showing conversion of polymer coating to carbon coating. (b) TEM images of carbon-coated particles. (c) EELS element map showing the carbon layer on a silica shell.In addition to making hybrid shell hollow particles, we investigated whether the coating affected the properties (e.g., thermal conductivity and moisture absorption) of the pristine hollow silica particles. We measured the thermal conductivity of pristine, polymer-coated, and carbon-coated particles. The results showed that polymer-coated particles had the lowest thermal conductivity and carbon-coated particles had the highest thermal conductivity of the three types. The Fig. 4 plot shows the thermal conductivities of the three types of particles, and respective insets show photos of corresponding particle samples. More details of the measurements are provided in ESI-S3.^† As expected, the polymer silica particles had lower thermal conductivity (0.022 ± 0.002 W m⁻¹ K⁻¹) than pristine hollow particles (0.024 ± 0.002 W m⁻¹ K⁻¹), whereas carbon-coated particles had higher thermal conductivity (0.036 ± 0.004 W m⁻¹ K⁻¹) than both the pristine and the polymer-coated particles. This information provides a new tool to achieve or tune thermal properties of hollow silica particles as desired. For example, for high-thermal-insulation materials, polymer-coated particles are ideal; whereas carbon-coated particles are more suitable where somewhat higher thermal conductivity, but hydrophobicity is required. We were expecting that a carbon coating will increase electrical conductivity of hollow particles, however, we observed that even carbon coated particles had an electrical resistance in the megaOhm range, i.e., behave as electrically insulators (measurement details in ESI S3^†). Although the thermal conductivity of polymer-coated or carbon-coated hollow silica particles can be further modified by modifying the coating thickness, in the present work, we did not investigate the effect of coating thickness on thermal conductivity in detail. We expect the thinner the coating, the lower the thermal conductivity will be. We observed in both the polymer- and carbon-coated particles that the coatings were not uniform. Some particles had thick and others thin coatings, indicating that coating nucleation was not uniform, and the coatings may have begun forming earlier on some particles than on others. We observed that carbon–silica hollow particles are hydrophobic in nature, staying afloat on water for several hours (ESI Fig. S4^†) and mixing in water only after vigorous stirring. It appears that, with stirring, water molecules enter the hollow particle cavities through the pores present in the carbon and silica shells and wet the inner parts of the cavities, thus causing the particles to mix in water.Open in a separate windowFig. 4Effect of different types of coatings on the thermal conductivity of hollow silica particles. Insets show the photos of respective particles.Additionally, we compared the moisture absorption properties of pristine hollow silica particles with those of polymer- and carbon-coated hollow silica particles (Fig. 5). Moisture absorption/desorption experiments were performed using a dual vapor gravimetric sorption analyser. We observed that polymer-coated particles absorbed less humidity compared with pristine particles at the same relative humidity. However, both materials had similar isotherm profiles in which the moisture adsorption capacity increased at relatively higher moisture concentrations. The carbon-coated particles, on the other hand, showed a completely different isotherm behaviour: an immediate increase in adsorption capacity was observed between 30% and 50% relative humidity. A sharp increase in moisture absorption at higher relative humidity (between 30–50%) appears due to the entry of water vapors inside the particles because of porous nature of carbon layer. Similar shape of isotherms for pristine and polymer coated particles indicates that both of these particles had similar surface groups (–OH), but lower absorption in polymer coated particles compared to pristine particles indicates that its surface has a small number of moisture absorbing groups (–OH) compared to pristine particles. The hysteresis between adsorption and desorption isotherms was found to be minimal, indicating that the samples had similar performance for adsorption or desorption process. We expect this information to be helpful for applications such as developing water-stable coatings or insulation materials by using hollow silica particles.Open in a separate windowFig. 5Effect on moisture adsorption and desorption process. Plot showing behaviour of hollow particles under different relative humidity conditions for pristine and coated samples.     

Intracortical haematogenous osteomyelitis

We present an unusual case of haematogenous osteomyelitis in the diaphysis of the tibia of an adult leading to a subacute presentation with an extracortical abscess. Fluid from the abscess grew methicillin resistant Staphylococcus aureus (MRSA) on culture; MRSA with the same antibiogram had been grown from the patient’s blood seven years earlier following a bowel resection. Drainage of the abscess and curettage of the bone lesion together with appropriate antibiotic therapy led to resolution of the osteomyelitis.     

Low-dose recombinant properdin provides substantial protection against Streptococcus pneumoniae and Neisseria meningitidis infection

Modern medicine has established three central antimicrobial therapeutic concepts: vaccination, antibiotics, and, recently, the use of active immunotherapy to enhance the immune response toward specific pathogens. The efficacy of vaccination and antibiotics is limited by the emergence of new pathogen strains and the increased incidence of antibiotic resistance. To date, immunotherapy development has focused mainly on cytokines. Here we report the successful therapeutic application of a complement component, a recombinant form of properdin (P_n), with significantly higher activity than native properdin, which promotes complement activation via the alternative pathway, affording protection against N. menigitidis and S. pneumoniae. In a mouse model of infection, we challenged C57BL/6 WT mice with N. menigitidis B-MC58 6 h after i.p. administration of P_n (100 µg/mouse) or buffer alone. Twelve hours later, all control mice showed clear symptoms of infectious disease while the P_n treated group looked healthy. After 16 hours, all control mice developed sepsis and had to be culled, while only 10% of P_n treated mice presented with sepsis and recoverable levels of live Meningococci. In a parallel experiment, mice were challenged intranasally with a lethal dose of S. pneumoniae D39. Mice that received a single i.p. dose of P_n at the time of infection showed no signs of bacteremia at 12 h postinfection and had prolonged survival times compared with the saline-treated control group (P < 0.0001). Our findings show a significant therapeutic benefit of P_n administration and suggest that its antimicrobial activity could open new avenues for fighting infections caused by multidrug-resistant neisserial or streptococcal strains.Pneumococcal and meningococcal infectious diseases remain a serious threat to public health. Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and a major cause of otitis media, septicemia, and meningitis (1, 2). S. pneumoniae is responsible for ∼1.2 million deaths per year worldwide, with young children and immunocompromised patients at particular risk (3). Neisseria meningitidis causes epidemic bacterial meningitis and septicemia, with high mortality in children and young adults (4). The impact of meningococcal disease on human health is defined by both the risk and the severity of invasive meningococcal infections, with unacceptably high mortality rates, ranging from 10% in patients under optimal clinical therapy with the latest generation of antibiotics to up to 40% in patients with untreated septicemia. Almost one-third of those who survive invasive infections are left with long-term disabilities and long-term morbidity. Globally, the World Health Organization estimates that ∼1.2 million cases of invasive meningococcal infections occur annually, leading to more than 135,000 fatalities (5).Vaccination programs have reduced the rates of infection in developed countries, but neonates and elderly adults remain especially vulnerable (6, 7). The efficacy of vaccination is further limited by the emergence of new strains of S. pneumoniae and N. meningitidis.The complement system plays a major role in the host resistance to both pathogens (8–13). Complement is activated via three routes: the classical pathway, the lectin pathway, and the alternative pathway. Activation of the classical and lectin pathways is mediated by specific recognition molecules. Binding of C1q to the bacterial surface or the Fc region of antibody initiates the classical pathway. The lectin pathway is initiated by carbohydrate recognition molecules, including mannan-binding lectin, ficolins, and collectin 11, which bind directly to bacterial polysaccharides. Activation of the classical or lectin pathway leads to the formation of a C3 convertase (C4b2a), which splits C3 into the biologically active fragments, C3b and C3a. C3b can bind covalently to an activating surface, and hundreds of molecules of C3b can be deposited in close proximity to the C3 convertase complex. Accumulation of C3b close to C4b2a forms the classical pathway C5 convertase C4b2a(3b)_n, in which C4b and C3b form a binding site for C5, orienting it for cleavage by C2a (14, 15).The mechanisms initiating the alternative pathway are less well understood. It is widely accepted that the alternative pathway maintains a continuous state of low-rate activation, which is held in check by potent negative regulators of activation on nonactivating surfaces, such as the surface of host cells. Turnover of the alternative pathway is initiated either by the provision of C3b via the classical pathway, the lectin pathway, or complement-independent proteolysis of C3 or by the spontaneous hydrolysis of C3 to form C3(H₂O). C3b or C3(H₂O) bind factor B to form either the C3bB or C3(H₂O)B zymogen complex. In this complex, factor B is cleaved by factor D, releasing a Ba fragment. The activated C3bBb or C3(H₂O)Bb fragments are themselves C3 convertases, which in turn cleave more C3 into C3a and C3b. Unchecked, the accumulation of C3b rapidly leads to the formation of more alternative pathway convertase complexes, resulting in a physiologically critical positive feedback mechanism—the amplification loop of complement activation (16). The alternative pathway thus amplifies complement activation initiated by any of the three pathways, making it an attractive target for therapeutic intervention designed to modulate complement-mediated immunity and/or inflammatory processes (17).Deposition of C3b and iC3b on the bacterial surface is a key step in the immune response against S. pneumoniae, because complement-mediated opsonisation is essential for clearance of S. pneumoniae through phagocytosis (8). Lysis of bacteria, owing to formation of the membrane attack complex complex, is the critically important biological activity of complement in the defense against N. meningitidis (10). Inherited or acquired deficiencies of the alternative pathway are associated with a high risk of recurrent bacterial infection. Factor B deficiencies significantly increase the risk of S. pneumoniae and Pseudomonas aeruginosa infection (9, 18). In a mouse model of properdin deficiency, the severity of polymicrobial peritonitis was significantly greater in deficient mice compared with their WT littermates (19). Properdin deficiency in humans has been associated with a high risk of meningococcal infections, especially with unusual infective serotypes, such as W-135 and Y (10, 20, 21). In addition, opsonophagocytosis of S. pneumoniae was found to be severely compromised in properdin-deficient sera, and reconstitution of properdin-deficient sera with purified properdin restored the opsonic activity and killing of S. pneumoniae by polymorphonuclear leukocytes (22, 23).Properdin is the only known positive physiological regulator of complement activation. It stabilizes and extends the half-life of the surface-bound C3 convertase C3bBb, and inhibits its degradation by factor I (24–26). In their pioneering 1954 work, Pillemer et al. (26) first described properdin as a serum protein that mediates complement activation and antimicrobial activity in absence of antibodies.Properdin is present in serum at a concentration of ∼5–15 μg/mL (27). Unlike most other complement components, properdin is not synthesized in the liver but rather is expressed by other cells, including monocytes, T cells, mast cells, and granulocytes (19, 28–30). Properdin monomers can assemble into dimers (P₂), trimers (P₃), and tetramers (P₄), formed by head-to-tail association of monomers (each ∼53 kDa) (31, 32). Properdin aggregates, so-called “activated” properdin (P_n), are considered artificial higher-order oligomers formed during the purification of properdin from plasma or during subsequent freeze–thaw cycles (33). The functional activity of properdin increases with the size of the polymers formed (34). By increasing the half-life of the alternative pathway C3 convertase, properdin antagonizes the functional activity of complement factor H, an abundantly expressed plasma component, which promotes inactivation of the alternative pathway C3 convertase and of all C5 convertases of complement by accelerating the decay of these enzyme complexes through binding to complex-bound C3b and by serving as a cofactor in the factor I-mediated conversion of C3b to its inactive form, termed iC3b (35). Interestingly, the two pathogens used in this study were previously shown to express distinct microbial surface components that sequester factor H from host plasma, leading to resistance to the complement-mediated immune clearance of these pathogens (36, 37).In the present study, we addressed the role of the alternative pathway and the effect of administration of recombinant properdin as a tool for boosting alternative pathway activity to augment the immune response against S. pneumoniae or N. meningitidis.     

Moisture affinity of HDPE/phase-change material composites for thermal energy storage applications

Moisture adsoprtion can degrade the structural integrity of thermal energy storage devices and can negatively impact the capacity and charging/discharging behaviour. Steady-state and transient experiments are conducted at various operating temperatures to evaluate the moisture affinity of organic phase-change material (PCM) shape stabilized with high-density polyethylene (HDPE).

A composite HDPE/PCM filament for 3D printing thermal energy storage systems is naturally hydrophobic.