Hybrid scaffolds of Mg alloy mesh reinforced polymer/extracellular matrix composite for critical‐sized calvarial defect reconstruction

The challenge of developing scaffolds to reconstruct critical‐sized calvarial defects without the addition of high levels of exogenous growth factor remains relevant. Both osteogenic regenerative efficacy and suitable mechanical properties for the temporary scaffold system are of importance. In this study, a Mg alloy mesh reinforced polymer/demineralized bone matrix (DBM) hybrid scaffold was designed where the hybrid scaffold was fabricated by a concurrent electrospinning/electrospraying of poly(lactic‐co‐glycolic acid) (PLGA) polymer and DBM suspended in hyaluronic acid (HA). The Mg alloy mesh significantly increased the flexural strength and modulus of PLGA/DBM hybrid scaffold. In vitro results demonstrated that the Mg alloy mesh reinforced PLGA/DBM hybrid scaffold (Mg‐PLGA@HA&DBM) exhibited a stronger ability to promote the proliferation of bone marrow stem cells (BMSCs) and induce BMSC osteogenic differentiation compared with control scaffolding materials lacking critical components. In vivo osteogenesis studies were performed in a rat critical‐sized calvarial defect model and incorporated a variety of histological stains and immunohistochemical staining of osteocalcin. At 12 weeks, the rat model data showed that the degree of bone repair for the Mg‐PLGA@HA&DBM scaffold was significantly greater than for those scaffolds lacking one or more of the principal components. Although complete defect filling was not achieved, the improved mechanical properties, promotion of BMSC proliferation and induction of BMSC osteogenic differentiation, and improved promotion of bone repair in the rat critical‐sized calvarial defect model make Mg alloy mesh reinforced PLGA/DBM hybrid scaffold an attractive option for the repair of critical‐sized bone defects where the addition of exogenous isolated growth factors is not employed.     

Evaluation of specific humoral immune response and cross reactivity against <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> antigens induced in mice immunized with liposomes composed of total lipids extracted from <Emphasis Type="Italic">Mycobacterium smegmatis</Emphasis>

The development of a new tuberculosis (TB) vaccine has become one of the main objectives of the scientific community. Protein antigens have been widely explored as subunit TB vaccines, however lipid antigens could be equally important to be used or included in such a vaccine. The aim of this study was to demonstrate the potential of a liposome formulation composed of an extract of lipids from Mycobacterium smegmatis (Ms) as a TB vaccine candidate. We evaluated the immunogenicity of this formulation as well as the cross reactive response against antigens from Mycobacterium tuberculosis (MTb) in BALB/c mice. We determined the anti-liposome IgG response in sera from TB patients and from healthy subjects who displayed a positive (PPD+) or negative (PPD-) tuberculin skin test. A significant increase in anti-liposome IgG (p<0.05) was detected in animals immunized with Bacille Calmette-Guérin (BCG) compared with all groups, and in the group immunized with liposomes from Ms (LMs) compared to animals immunized with either LMs adjuvanted with aluminium (LMs-A) or the negative control group (phosphate buffered saline, PBS) respectively. With respect to the cross reactive response against a cocktail of cell wall antigens (CWA) from MTb, significantly higher IgG levels were observed in animals immunized with BCG and LMs compared to negative controls and either, aluminium-adjuvanted liposomes (LMs-A) or montanide (LMs-M) (p<0.05). Furthermore, the anti-liposome IgG response was significantly superior in sera from pulmonary TB patients compared to PPD+ and PPD- healthy subjects (p<0.001) suggesting the expression of these antigens in vivo during active MTb infection. The results obtained provide some evidence for the potential use of liposomes containing total lipid extracts of Ms as a TB vaccine candidate.     

Association between long-term aspirin use and periodontal attachment level in humans: a cross-sectional investigation

Background: Pharmaceutical inhibition of host response pathways may be an adjunctive or alternative strategy for treating periodontal diseases. In addition to inhibition of prostaglandin synthesis, aspirin is known to modify the action of cyclo‐oxygenase, changing its activity to a lipoxygenase and leading to formation of lipoxins which have a proresolving effect. This study evaluated the periodontal attachment level of subjects on long‐term low dose aspirin therapy. Methods: Oral hygiene index simplified, clinical attachment loss and bleeding index were recorded for 162 subjects who were on long‐term (>6 months) low dose (75 mg and 150 mg) aspirin therapy (study group) and 146 subjects not taking the drug (control group). Results: Mean clinical attachment loss was 2.38 ± 0.49 mm in the control group and 2.01 ± 0.69 mm in the study group. The difference was statistically significant at p < 0.001. Correlation analysis suggested that there was a negative correlation between clinical attachment loss and duration of aspirin intake but the clinical attachment loss was not significantly different in the two dosage groups. Conclusions: The results of this study suggest that low dose aspirin may reduce the risk of periodontal attachment loss. This hypothesis needs to be tested by larger sample sized prospective cohort studies.     

Proteomic characterization of HIV-modulated membrane receptors, kinases and signaling proteins involved in novel angiogenic pathways

Background  

Kaposi's sarcoma (KS), hemangioma, and other angioproliferative diseases are highly prevalent in HIV-infected individuals. While KS is etiologically linked to the human herpesvirus-8 (HHV8) infection, HIV-patients without HHV-8 and those infected with unrelated viruses also develop angiopathies. Further, HIV-Tat can activate protein-tyrosine-kinase (PTK-activity) of the vascular endothelial growth factor receptor involved in stimulating angiogenic processes. However, Tat by itself or HHV8-genes alone cannot induce angiogenesis in vivo unless specific proteins/enzymes are produced synchronously by different cell-types. We therefore tested a hypothesis that chronic HIV-replication in non-endothelial cells may produce novel factors that provoke angiogenic pathways.     

Outcome of surgery on infants younger than 1 month with congenital glaucoma

PURPOSE: To determine the visual outcomes and surgical and anesthetic complication rates of patients with newborn glaucoma operated within 1 month of age. DESIGN: Retrospective, consecutive, noncomparative case series. PARTICIPANTS: All children with newborn glaucoma who underwent surgery between January 1990 and December 2000 were included. METHODS: The medical records of 25 consecutive patients (47 eyes) who underwent primary combined trabeculotomy and trabeculectomy either bilaterally in a single session or unilaterally were reviewed retrospectively. Outcomes were evaluated using Kaplan-Meier survival analysis. MAIN OUTCOME MEASURES: Clinical outcome assessment included corneal clarity, intraocular pressure (IOP), bleb characteristics, visual acuity, refractive errors, and identification of surgical and anesthetic complications. RESULTS: The mean follow-up was 3.1+/-1.8 years (range, 9.5 months-7.4 years). The mean preoperative IOP was 26.9+/-5.2 mmHg (range, 14-42 mmHg). At the final follow-up visit, the mean IOP was 14.5+/-3.8 mmHg (range, 8-28 mmHg). The percentage reduction in IOP was 43.3+/-21.5 (P<0.0001). Twelve-, 24-, and 36-month survival rates for complete success for IOP control were 89.4%, 83.6%, and 71.7%, respectively, which were maintained for 7 years of follow-up. After surgery, complete clearance of corneal edema was achieved in 66% of the eyes. Data on visual acuity was available for 19 patients. Final best spectacle-corrected visual acuity was 20/40 or better in the better eye in 5 patients (26.3%), 7 patients (36.8%) obtained 20/60 or better in the better eye, 8 patients (42.1%) achieved final visual acuity of less than 20/60 to 20/200 in the better eye (low vision), and four patients obtained less than 20/400 visual acuity in the better eye (blind) according to World Health Organization criteria. However, there was no eye with absent perception of light in the better eye. Myopia (mean spherical equivalent, 4.6+/-3.2 diopters) was the most common refractive error, present in approximately half of the eyes (n = 23; 53.8%). There were no significant intraoperative or postoperative complications in any patient. Anesthesia-related complications developed in 2 patients; however, they were resuscitated successfully. CONCLUSIONS: Primary combined trabeculotomy-trabeculectomy offers a viable surgical option in infants that have cloudy corneas at birth as a result of congenital glaucoma. It is associated with a favorable visual outcome and a low rate of anesthetic complications in an Indian population.     

Bilateral optic neuritis in pregnancy

A 25-year old primigravida at 11-weeks period of amenorrhoea presented with bilateral optic neuritis following Varicella Zoster viral (VZV) infection. She was serologically positive for systemic lupus erythematosus but negative for virus. The exact pathogenesis of the patient's severe optic neuritis, adduction and neurological deficit was unknown. The initiation of high dose steroids for optic neuritis was a big clinical dilemma in a pregnant patient with viral infection. The patient was treated with high dose steroids after three days of commencement of antiviral treatment. At 6 months after presentation, her visual acuity in the right eye was 6/36 with perception to light in the left.     

Orexin (hypocretin) gene transfer diminishes narcoleptic sleep behavior in mice

Gene transfer has proven to be an effective neurobiological tool in a number of neurodegenerative diseases, but it is not known if it can correct a sleep disorder. Narcolepsy is a neurodegenerative sleep disorder linked to the loss of neurons containing the neuropeptide orexin, also known as hypocretin. Here, a replication-defective herpes simplex virus-1 amplicon-based vector was constructed to transfer the gene for mouse prepro-orexin into mice with a genetic deletion of the orexin gene. After in vitro tests confirmed successful gene transfer into cells, the gene vector was delivered to the lateral hypothalamus of orexin knockout (KO) mice where the orexin peptide was robustly expressed in the somata and processes of numerous neurons, and the peptide product was detected in the cerebrospinal fluid. During the 4-day life-span of the vector the incidence of cataplexy declined by 60%, and the levels of rapid eye movement sleep during the second half of the night were similar to levels in wild-type mice, indicating that narcoleptic sleep-wake behavior in orexin KO mice can be improved by targeted gene transfer.     

Investigation of optimal schedule of concurrent radiotherapy with S-1 for oral squamous cell carcinoma

In the present study, we examined the appropriate schedule of S-1 medication in the combination with radiation by investigating the safety, the clinical efficacy, and antitumor effects on tumors in nude mice. In the patients with oral squamous cell carcinoma (OSCC), S-1 was given orally according to a 4-week application followed by 2-week rest regimen (4-week regimen), or a 2-week application followed by a 1-week rest regimen (2-week regimen). Radiation was given (2 Gy/day; 5 days/week) for a total of 60 Gy. In nude mouse models, human oral cancer cell lines were used as subcutaneous xenografts in nude mice. The mice were treated by S-1 (10 mg/kg) and radiation (1 Gy) with a 4-week regimen or a 2-week regimen. Apoptotic cells were detected by TUNEL method. In the patients with OSCC, the response rate with the 4-week regimen was 100% and the response rate with the 2-week regimen was 92.3%. However, a high frequency of adverse effect was found in the 4-week regimen when compared to the 2-week regimen. Grade 3 toxicity of leukopenia, neutropenia and stomatitis were seen in 3 cases, grade 3 toxicity of anorexia and nausea were seen in 2 cases, and grade 3 toxicity of decrease of hemoglobin level, heartburn/dyspepsia and increase of bilirubin level were seen in a case of the 4-week regimen. On the other hand, grade 3 toxicity of stomatitis, anorexia, nausea, heartburn/dyspepsia and increase of bilirubin level were seen in a case of the 2-week regimen. In nude mouse models, the 2-week regimen was more effective than the 4-week regimen. In addition, significant increase in the percentage of apoptotic cells was observed in the tumors treated with the 4-week regimen when compared with the tumors treated with the 2-week regimen. No loss of body weight was observed in mice treated with the 2-week regimen during the experimental period. These results suggested that the 2-week regimen might reduce adverse effects, and enhance therapeutic effects compared to the 4-week regimen. Briefly, this 2-week regimen may be a useful concurrent chemo-radiotherapy improving the quality of life (QOL) of patients with OSCC.     

Daytime sleeping, sleep disturbance, and circadian rhythms in the nursing home.

OBJECTIVE: This study reports the frequency of abnormal daytime sleeping and identifies factors related to daytime sleeping, nighttime sleep disturbance, and circadian rhythm abnormalities among nursing home residents. METHODS: The authors conducted secondary analysis of data collected under usual care conditions within a nonpharmacologic sleep intervention trial. All residents from four Los Angeles nursing homes were screened for daytime sleeping (asleep>or=15% of observations, 9:00 am-5:00 pm). Consenting residents with daytime sleeping had two nights of wrist actigraphy to assess nighttime sleep disturbance (asleep<80%, 10:00 pm-6:00 am). Residents with nighttime sleep disturbance completed an additional 72-hour wrist actigraphy recording to assess circadian activity rhythms and light exposure. RESULTS: Sixty-nine percent of 492 observed residents had daytime sleeping, of whom 60% also had disturbed nighttime sleep. Sleep disturbance and daytime sleeping were rarely documented in medical records. Residents spent one-third of the day in their rooms, typically in bed, and were seldom outdoors or exposed to bright light. More time in bed and less social activity were significant predictors of daytime sleepiness. Ninety-seven percent of residents assessed had abnormal circadian rhythms. More daytime sleeping and less nighttime sleep were associated with weaker circadian activity rhythms. Later circadian rhythm acrophase (peak) was associated with more bright light exposure. CONCLUSION: Daytime sleepiness, nighttime sleep disturbance, and abnormal circadian rhythms were common in nursing home residents. Modifiable factors (e.g., time in bed) are associated with sleep/wake abnormalities. Mental health specialists should consider the complexity of factors causing sleep problems in nursing home residents.