Bone attenuation on routine chest CT correlates with bone mineral density on DXA in patients with COPD

Chronic obstructive pulmonary disease (COPD), although primarily a disease of the lungs, is associated with extrapulmonary effects such as muscle weakness and osteoporosis. Fractures owing to osteoporosis cause significant morbidity and mortality, particularly in patients with COPD. To prevent osteoporotic fractures, it is important to diagnose osteoporosis in an early stage and to start anti‐osteoporotic therapy in at‐risk patients. Because routine chest computed tomography (CT) is increasingly used to assess the extent of emphysema and airways disease in patients with COPD, we investigated whether simple attenuation measurement of the thoracic spine on routine chest CT may provide useful information on bone health in patients with COPD. Fifty‐eight patients with moderate to very severe COPD were included in our study. The average attenuation of thoracic vertebrae 4, 7, and 10 on chest CT was correlated with the lowest bone mineral density (BMD) of the hip and lumbar spine (L₁ to L₄) on dual‐energy X‐ray absorptiometry (DXA) in patients with COPD. The inter‐ and intra‐observer variabilities of the attenuation measurements were low as shown by Bland‐Altman plots. Pearson's correlation coefficient between the average attenuation of the three thoracic vertebrae and the lowest BMD of the hip and lumbar spine was high (r = 0.827, p < 0.001). A receiver‐operating characteristic (ROC) analysis of the area under the curve for osteoporosis was 0.969 (p < 0.001), corresponding to an attenuation threshold of 147 Hounsfield Units (HU). In conclusion, our data demonstrated that bone attenuation measured on routine chest CT correlated strongly with BMD assessed on DXA in patients with COPD. Routine chest CT may provide useful information on bone health in patients with COPD. © 2012 American Society for Bone and Mineral Research.     

A family with Stickler syndrome type 2 has a mutation in the COL11A1 gene resulting in the substitution of glycine 97 by valine in alpha 1 (XI) collagen

Stickler syndrome (hereditary arthro-ophthalmopathy) is the commonest inherited cause of retinal detachment and one of the commonest autosomal dominant connective tissue dysplasias. There is clinical and locus heterogeneity with about two thirds of families linked to the gene encoding type II procollagen (COL2A1). Families with Sticklers syndrome type 1 have a characteristic congenital vitreous anomaly and are linked without recombination to markers at the COL2A1 locus. In contrast families with the type 2 variety have a different vitreo- retinal phenotype and are not linked to the COL2A1 gene. Type XI collagen is a quantitatively minor fibrillar collagen related to type V collagen and associated with the more abundant type II collagen fibrils. A mutation in COL11A2, the gene for alpha 2 (XI) procollagen, has recently been found in a family described as having Stickler syndrome, although there was no ocular involvement. Here we show for the first time that a family with the full Type 2 Stickler syndrome including vitreous and retinal abnormalities is linked to the COL11A1 gene and characterise the mutation as a Glycine to Valine substitution at position 97 of the triple helical domain caused by a single base G-- >T mutation. These results are the first to provide confirmation that type XI collagen is an important structural component of human vitreous. They also support previous work suggesting that mutations in the genes encoding collagen XI can give rise to some manifestations of Stickler syndrome, but of these, only mutations in COL11A1 will give the full syndrome including the vitreo-retinal features.      

Online Prevention Aimed at Lifestyle Behaviors: A Systematic Review of Reviews

Background

Interventions aimed at behavior change are increasingly being delivered over the Internet. Although research on intervention effectiveness has been widely conducted, their true public health impact as indicated by reach, effectiveness, and use is unclear.

Objective

The aim of this paper is to (1) review the current literature on online prevention aimed at lifestyle behaviors, and (2) identify research gaps regarding reach, effectiveness, and use.

Methods

A systematic search in PubMed revealed relevant literature published between 2005 and 2012 on Internet-delivered behavior change interventions aimed at dietary behaviors, physical activity, alcohol use, smoking, and condom use. Our search yielded 41 eligible reviews, which were analyzed in terms of reach, effectiveness, and use according to the RE-AIM framework.

Results

According to health priorities, interventions are largely targeted at weight-related behaviors, such as physical activity and dietary behavior. Evaluations are predominantly effect-focused and overall effects are small, variable, and not sustainable. Determinants of effectiveness are unclear; effectiveness cannot yet be unambiguously attributed to isolated elements. Actual reach of interventions is undiversified, mostly reaching participants who are female, highly educated, white, and living in high-income countries. One of the most substantial problems in online prevention is the low use of the interventions, a phenomenon seen across all behavior domains.

Conclusions

More research is needed on effective elements instead of effective interventions, with special attention to long-term effectiveness. The reach and use of interventions need more scientific input to increase the public health impact of Internet-delivered interventions.     

TP53 codon 72 polymorphism and risk of conjunctival squamous cell carcinoma in Uganda

Background: The most common TP53 gene polymorphism, which alters the amino acid sequence of the oncosuppressor p53 protein, is located at the codon 72, resulting in either Pro72 or Arg72 p53 variant. Several studies have associated this polymorphism with different types of cancer. We have analyzed the distribution and the role of TP53 Arg72 and Pro72 alleles in conjunctival neoplasia. Method: The study included 41 invasive conjunctival squamous cell carcinoma (ICSCC), 33 conjunctival intraepithelial neoplasia of grade 3 (CIN3), 33 of moderate grade (CIN1 and CIN2), and 115 controls from Uganda, a sub-Saharan country with the highest incidence rate of conjunctival neoplasia in the World, particularly in the era of AIDS. The TP53 Arg/Arg codon 72 genotype was detected in 21.9% of ICSCC and in 18.2% of CIN3 but only in 6% of CIN1–2 and in 5.2% of controls (P < 0.05). Results: These data show an increased risk of ICSCC (odds ratio (OR) = 6.2, 95% confidence interval (CI): 1.6–24.6) and CIN3 (OR = 4.1, 95% CI: 1.0–18.0) associated with TP53 Arg homozygosity, not observed in CIN1–2 lesions (OR = 0.8, 95% CI: 0.1–5.1). Moreover, the frequency of the Arg homozygosity was similar in HIV-positive and HIV-negative groups. We conclude that TP53 Arg/Arg codon 72 genotype is a relevant risk factor for invasive squamous cell carcinoma of the conjunctiva and for CIN3 in the Ugandan population. Discussion: The absence of statistically significant difference in the distribution of TP53 Arg72 or Pro72 encoding alleles between HIV-positive and -negative subjects, affected by conjunctival neoplasia, suggests that HIV infection and/or the associated immunodeficiency represent further independent risk factors for ICSCC.     

Induction of neutralizing antibodies and cytotoxic T lymphocytes in Balb/c mice immunized with virus-like particles presenting a gp120 molecule from a HIV-1 isolate of clade A

We have recently developed a candidate HIV-1 vaccine based on virus-like particles (VLPs) expressing a gp120 from an Ugandan HIV-1 isolate of the clade A (HIV-VLP(A)s). In vivo immunogenicity experiments were performed in Balb/c mice, with an immunization schedule based on a multiple-dose regimen of HIV-VLP(A)s without adjuvants, showing a significant induction of both humoral and cellular immunity. The Env-specific cellular response was investigated in vitro, scoring for both the proliferative response of T helper cells and the cytolytic activity of cytotoxic T lymphocytes (CTLs). Furthermore, immune sera showed >50% neutralization activity against both the autologous field isolate and the heterologous T cell adapted B-clade HIV-1(IIIB) viral strain. This is one of the first examples of HIV-1 vaccines based on antigens derived from the A clade, which represents >25% of all isolates identified world wide. In particular, the A clade is predominant in sub-Saharan countries, where 70% of the global HIV-1 infections occur, and where vaccination is the only rational strategy for an affordable prevention against HIV-1 infection.     

HIV-Gag VLPs presenting trimeric HIV-1 gp140 spikes constitutively expressed in stable double transfected insect cell line

We have previously described the establishment and characterization of a stably transfected insect cell line for the constitutive and efficient expression of Pr55 HIV Gag proteins, which auto-assemble into enveloped Virus-Like Particles (VLPs) released into the cell culture supernatant. Such HIV-Gag VLPs have been shown to elicit a specific systemic humoral response in vivo, proving the appropriate antigenic presentation of the HIV Gag protein to the immune system. Here we describe the establishment of a stable double transfected insect cell line for the constitutive and reproducible production of Pr55Gag-VLPs expressing on their surface trimeric forms of HIV-1 envelope glycoproteins. The persistence of HIV coding genes has been verified in clonal resistant insect cells, the protein expression and conformation has been verified by Western blot analysis. The resulting HIV-VLPs have been visualized by standard transmission electron microscopy and their immunogenicity has been evaluated in vivo. This represents, to our knowledge, the first example of stable double transfected insect cell line for the constitutive production of enveloped HIV-Gag VLPs presenting trimeric HIV-gp140 on their surface.     

A novel system for providing compatible blood to patients during surgery: "self-service" electronic blood banking by nursing staff

BACKGROUND: A good blood bank must be able to provide compatible blood units promptly to operating room patients with minimal wastage. A "self- service" by nursing staff blood banking system that is safe, efficient, and well-accepted has been developed. STUDY DESIGN AND METHODS: Specific blood units are no longer assigned to surgical patients who have a negative pretransfusion antibody screen, irrespective of the type of surgery. A computer-generated list of the serial numbers of all group-identical blood units currently in the blood bank inventory is provided for each patient. The units themselves are not labeled with a patient's name. The group O list will be provided for group O patients, the group A list for group A patients, and so forth. Should the patient require transfusion during surgery, the operating room nurses go to the refrigerator, remove any group-identical unit, and check the serial number of the unit against the serial numbers on the patient's list. If the serial number is on that list, the blood bank will accept responsibility for compatibility. The system was implemented in 1995. RESULTS: Since implementation, a total of 2154 patients have undergone operations at this hospital. Thirty-two patients received more than 10 units of red cells each. There were no transfusion errors. The crossmatch-to-transfusion ratio was reduced from 1.67 to 1.12. Turnaround time for supplying additional or urgent units to patients in operating room was shortened from 33 to 2.5 minutes. There was no incidence of a blood unit's serial number not being on the list. Work by nurses and technical staff was reduced by nearly 50 percent. CONCLUSION: The "self-service" (by nursing staff) blood banking system described is safe and efficient. It saves staff time and can be easily set up.