Purpose To prepare mesoporous silica-based delivery systems capable of simultaneous delivery of drugs and nucleic acids. Methods The surface of mesoporous silica nanoparticles (MSN) was modified with poly(ethylene glycol) (PEG) and poly(2-(dimethylamino)ethylmethacrylate) (PDMAEMA) or poly (2-(diethylamino)ethylmethacrylate) (PDEAEMA). The particles were then loaded with a lysosomotropic agent chloroquine (CQ) and complexed with plasmid DNA or siRNA. The ability of the synthesized particles to deliver combinations of CQ and nucleic acids was evaluated using luciferase plasmid DNA and siRNA targeting luciferase and GAPDH. Results The results show a slow partial MSN dissolution to form hollow silica nanoparticles in aqueous solution. The biological studies show that polycation-modified MSN are able to simultaneously deliver CQ with DNA and siRNA. The co-delivery of CQ and the nucleic acids leads to a significantly increased transfection and silencing activity of the complexes compared with MSN not loaded with CQ. Conclusion PEGylated MSN modified with polycations are promising delivery vectors for combination drug/nucleic acid therapies.

efects of the cranium may result from various causes: traumatic loss, neurosurgical intervention, skull tumors, infection, and congenital abnormalities. 1 The purpose of cranioplasty is to accurately restore the integrity and surface morphology of the skull using a permanent and durable reconstruction. This is done for both cosmetic and functional purposes. 2 The choice of reconstruction in cranioplasty may be divided into two broad categories: autologous bone and alloplastic materials. Autologous bone provides reparative capabilities and the potential for at least partial consolidation and revascularization. It features superior infection resistance and is less likely to extrude. However, it is also susceptible to resorption, can be difficult to shape, and is associated with donor-site morbidity. 3,4 Alloplastic materials were designed to circumvent these problems. They provide permanent shape and volume retention, but do not incorporate into the skeleton and are more susceptible to both infection and extrusion. 5 The recent advent of computer-designed, patient-specific, three-dimensional implants has revolutionized cranioplasty. Even in experienced

BackgroundAnimal bites are typically harmless, but in rare cases infections introduced by such bites can be fatal. Capnocytophaga canimorsus, found in the normal oral flora of dogs, has the potential to cause conditions ranging from minor cellulitis to fatal sepsis. The tendency of C. canimorsus infections to present with varied symptoms, the organism’s fastidious nature, and difficulty of culturing make this a challenging diagnosis. Rarely, bacterial cytotoxins such as those produced by C. canimorsus may act as causative agents of TTP, further complicating the diagnosis. Early recognition is crucial for survival, and the variability of presentation must be appreciated. We present the first known case of C. canimorsus infection resulting in TTP that initially presented as splenic infarction.Case presentation72-year-old Caucasian male presented with a four-day history of abdominal pain, nausea, vomiting, diarrhea, and intermittent confusion. On presentation, vital signs were stable and the patient was afebrile. Physical examination was unremarkable apart from petechiae on the inner left thigh, and extreme diffuse abdominal pain to palpation and percussion along with positive rebound tenderness. Initial investigations revealed leukocytosis with left shift and thrombocytopenia, but normal liver enzymes, cardiac enzymes, lipase, INR and PTT. Abdominal CT demonstrated a non-enhancing spleen and hemoperitoneum, suggesting complete splenic infarction. Although the patient remained afebrile, he continued deteriorating over the next two days with worsening thrombocytopenia. After becoming febrile, he developed microangiopathic hemolytic anemia and hemodynamic instability, and soon after was intubated due to hypoxic respiratory failure and decreased consciousness. Plasma exchange was initiated but subsequently stopped when positive blood cultures grew a gram-negative organism. The patient progressively improved following therapy with piperacillin-tazobactam, which was switched to imipenem, then meropenem when Capnocytophaga was identified.ConclusionsThere is a common misconception amongst practitioners that the presence of systemic infection excludes the possibility of TTP and vice versa. This case emphasizes that TTP may occur secondary to a systemic infection, thereby allowing the two processes to coexist. It is important to maintain a wide differential when considering the diagnosis of either TTP or C. canimorsus infection since delays in treatment may have fatal consequences.

Although a rare entity, it is important to consider congenital calvarial hemangioma in the differential diagnosis of slow growing skull lesions due to the possibility of complications as a result of the hemangioma's intracranial extension, and the potential for treatment. En bloc resection has classically been described as a treatment for such lesions, although our case demonstrates that medical treatment with propranolol therapy may be appropriate in certain situations.

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Objective: Cleft lip (CL) repair at 3 months is chosen mostly out of convention and offers minimal functional benefit. Potentially, a better cosmetic outcome is possible by delaying repair. This study examines parental perceptions around repair at 3 months to determine if current guidelines are appropriate. Design: Retrospective cross-sectional survey. Setting: Tertiary-care institution. Participants: Parents of children with CL AE P under age 6 years who underwent CL repair from 2004 to 2011 at our center were surveyed (n ¼ 64). Response rate was 61% (n ¼ 37). Methods: Open-ended survey asked about various aspects of parental perceptions before and after repair. Qualitative data analysis is used to interpret survey responses. Statistics: Fisher exact test using contingency tables to identify statistically significant results.Results: Nearly all (36/37) parents felt repair was important, citing reasons such as feeding, speech, and appearance. Most (28/37) felt surgery would fix the problem. A portion of parents (15/37) would delay repair if better aesthetics were possible later, but most would not (20/37). Most parents were satisfied with repair quality (33/37). On average, repair did not impact parent-child bonding, and eliminated negative interactions with strangers that parents found distressing. Conclusions: Arguably, positive parental perceptions of their child's condition reflect favorably on the child's well-being, and may outweigh any future aesthetic benefit. Therefore, current recommendations should be upheld. However, given that some parents would consider delaying repair, they could be offered this option. Future efforts should examine cultural factors, and aesthetic and developmental outcomes of repair at different ages to determine optimal repair timing.

A 44-year-old pathologist presented to the emergency department after sustaining a scalpel injury during a postmortem examination 16 hours previously. He had stabbed the dorsum of his left thumb overlying the interphalangeal joint and immediately irrigated the wound with water. At the time of presentation, he felt feverish, and had erythema and severe pain in his thumb. He was previously healthy, and did not smoke or have any known allergies. He was not taking any medications.The patient was given ceftriaxone empirically in the emergency department, and the plastic surgery service was consulted. Upon examination, he was afebrile and had a 0.5-cm laceration oriented obliquely over the dorsum of the interphalangeal joint of his thumb ( Figure 1A). There was a hemorrhagic blister distal to the laceration and minimal purpuric discolouration around the laceration. Erythema tracked proximally to the metacarpophalangeal joint of the thumb, with lymphangitic streaking extending into the axilla. There was no impairment of range of motion of the thumb, no substantial pain and no tenderness on axial loading of the interphalangeal or metacarpophalangeal joints. There was no pain upon palpation over the flexor sheath or the volar deep spaces of the hand. However, there was substantial pain upon palpation over the dorsal thumb. A radiograph of the hand showed no abnormality other than swelling of soft tissue.We suspected a localized subcutaneous infection and undertook a bedside incision and drainage. The hemorrhagic blister contained only blood and no pus. We extended the laceration overlying the interphalangeal joint and expressed a small amount of frank purulence. There was a 3 mm laceration in the extensor pollicis longus tendon overlying the interphalangeal joint, which communicated with the joint, but there was no purulence within the joint itself. The pus tracked proximally to the level of the metacarpophalangeal joint in a plane above the extensor pollicis longus tendon. We expressed all visible pus, irrigated copiously with 1 L of normal saline and packed the area with gauze. We continued to monitor the patient because of the rapid development of this infection and consulted the infectious diseases service.We reassessed the patient two hours later and, although he remained afebrile with normal blood pressure, PRACTICE | CASES