Major histocompatibility complex class II (HLA-DRB and -DQB) allele frequencies in Botswana: association with human immunodeficiency virus type 1 infection

Southern Africa is facing an unprecedented public health crisis due to the high prevalence of human immunodeficiency virus type 1 (HIV-1). Vaccine development and testing efforts, mainly based on elicitation of HIV-specific T cells, are under way. To understand the role of human leukocyte antigen (HLA) class II alleles in HIV pathogenesis and to facilitate HLA-based HIV-1 vaccine design, we analyzed the frequencies of HLA class II alleles within the southern African country of Botswana. Common HLA class II alleles were identified within the Botswana population through the molecular genotyping of DRB and DQB1 loci. The DRB1 allele groups DRB1*01, DRB1*02/15, DRB1*03, DRB1*11, and DRB1*13 were encountered at frequencies above 20%. Within the DQB1 locus, DQB1*06 (47.7%) was the most common allele group, followed by DQB1*03 (39.2%) and DQB1*04 (25.8%). We found that DRB1*01 was more common in HIV-negative than in HIV-positive individuals and that those who expressed DRB1*08 had lower median viral loads. We demonstrate that the frequencies of certain HLA class II alleles in this Botswana population differ substantially from those in North American populations, including African-Americans. Common allele groups within Botswana cover large percentages of other African populations and could be targeted in regional vaccine designs.     

Enhanced molecular volume of conservatively pegylated Hb: (SP-PEG5K)6-HbA is non-hypertensive

Recent studies have suggested that the "pressor effect" of acellular Hb is a consequence of perturbation of the macro-and microcirculatory system in multiple ways, and that PEGylation is an effective approach for controlling the same. In an attempt to confirm this concept, a new and simple thiolation mediated, maleimide chemistry-based conservative PEGylation protocol has been developed to conjugate multiple copies of PEG-chains to Hb. This approach combines the high reactivity of maleimides towards thiols with the propensity of iminothiolane to derivatize the epsilon-amino groups of proteins into reactive thiol groups, with conservation of their positive charge. One of the PEGylated products, namely (SP-PEG5K)6-HbA, that carries on an average six copies of PEG5000 chains per Hb, is non-hypertensive in hamster top load and in rat 50% exchange transfusion models. This hexa-PEGylated-Hb has (i) a hydrodynamic volume corresponding to that of an oligomerized Hb of 256kDa, (ii) a molecular radius of approximately 6.8 nm, (iii) high oxygen affinity, (iv) lowered Bohr effect, and (v) increased viscosity and colloidal osmotic pressure. These properties of (SP-PEG5K)6-HbA are consistent with the emerging new paradigms for the design of Hb based oxygen carriers and confirm the concept that the "pressor effect" of Hb is a multifactorial event. The thiolation mediated maleimide chemistry-based PEGylation protocol described here for the generation of (SP-PEG5K)6-Hb is simple, highly efficient, and is carried out under oxy conditions. The results demonstrate that a non-hypertensive PEG-Hb can be generated by conjugation of a lower number of PEG chains than previously reported.     

Evaluation of surface and build-up region dose for intensity-modulated radiation therapy in head and neck cancer

Despite much development, there remains dosimetric uncertainty in the surface and build-up regions in intensity-modulated radiation therapy treatment plans for head and neck cancers. Experiments were performed to determine the dosimetric discrepancies in the surface and build-up region between the treatment planning system (TPS) prediction and experimental measurement using radiochromic film. A head and neck compression film phantom was constructed from two semicylindrical solid water slabs. Treatment plans were generated using two commercial TPSs (PINNACLE3 and CORVUS) for two cases, one with a shallow (approximately 0.5 cm depth) target and another with a deep (approximately 6 cm depth) target. The plans were evaluated for a 54 Gy prescribed dose. For each case, two pieces of radiochromic film were used for dose measurement. A small piece of film strip was placed on the surface and another was inserted within the phantom. Overall, both TPSs showed good agreement with the measurement. For the shallow target case, the dose differences were within +/- 300 cGy (5.6% with respect to the prescribed dose) for PINNACLE3 and +/- 240 cGy (4.4%) for CORVUS in 90% of the region of interest. For the deep target case, the dose differences were +/- 350 (6.5%) for PINNACLE3 and +/- 260 cGy (4.8%) for CORVUS in 90% of the region of interest. However, it was found that there were significant discrepancies from the surface to about 0.2 cm in depth for both the shallow and deep target cases. It was concluded that both TPSs overestimated the surface dose for both shallow and deep target cases. The amount of overestimation ranges from 400 to 1000 cGy (approximately 7.4% to 18.5% with respect to the prescribed dose, 5400 cGy).     

Extralobar pulmonary sequestration with an associated cyst of mixed bronchogenic and esophageal type--a case report.

We report an unusual case of extralobar pulmonary sequestration (ELS) with an associated cyst of mixed bronchogenic and esophageal type. A 58-year-old woman was incidentally found to have a 6 x 6 x 5 cm sized mass in the right superior mediastinum. The mass consisted of sequestrated pulmonary tissue and an unilocular cyst with a direct communication. The cyst could not be easily classified because it was lined by squamous or respiratory epithelium with two distinct muscle layers and bronchial glands. Bronchial cartilage was present in close proximity to the ELS. This unusual combination of ELS with a foregut cyst might be a part of bronchopulmonary foregut malformation, attributed to a common embryologic pathogenesis.     

Assault injury rates,social capital,and fear of neighborhood crime

This study develops an explanatory framework for fear of neighborhood crime based on respondents' social context and local rates of assault injuries. Rates of assault injuries within zip codes are based on hospital discharge records. We find that only four variables have a significant unique contribution to fear of crime: respondent's sex, perceptions of neighborhood social capital, and the rates of struck by/against assault injuries for the 10–24 and 50+ age groups. We also find that the perception of neighborhood social capital moderates the impact of assault injury rates on fear of crime; those who perceive a high level of neighborhood social capital exhibit less sensitivity to assault injury rates. We include a map of assault injury rates and fear of crime by ZIP Code and describe the community context related to our results. © 2007 Wiley Periodicals, Inc. J Comm Psychol 35: 483–498, 2007.     

A study on facial features of children with Williams syndrome in China based on three‐dimensional anthropometric measurement technology

To describe special facial features of children with Williams syndrome in China by using method of three‐dimensional craniofacial anthropometry. Using three‐dimensional stereo photogrammetric device, 14 craniofacial anthropometric measurements were performed and five indices were calculated in 52 children with Williams syndrome and 208 age and sex matched controls of Han Chinese ethnicity. Except intercanthal width, mouth breadth, morphological face height, nasal height‐breadth index, nasal breadth‐depth index, morphological ear index, the Williams syndrome group under 3 years old were smaller than the control group in the other 12 variables. Compared with the control group, the Williams syndrome group aged 3–5 years old had smaller biocular breadth, nasal length, nasorostral angle, bitragal breadth, ear width, morphological ear index and face depth. The Williams syndrome group aged above 6 years old had smaller biocular breadth, nasal breadth, bitragal breadth, ear width, ear length and face depth than the control group. The craniofacial variability index of the Williams syndrome group was greater than the control group. Greater variation was found among children with Williams syndrome than normal in China, specifically at eye, nose, ear and face shape, which demonstrate the usefulness of three‐dimensional stereo photogrammetric analysis in supporting accurate diagnose of the patient with Williams syndrome.     

Poly(ethylene glycol)-containing Hydrogels for Oral Protein Delivery Applications

Novel pH-sensitive hydrogels were developed as suitable candidates for carriers in bioMEMS devices as well as for oral delivery of therapeutic peptides and proteins due to their ability to respond to environmental pH change. Macromonomers containing various PEG molecular weights were synthesized and used to prepare P(MAA-g-EG) hydrogels were by photopolymerization. P(MAA-g-EG) hydrogels showed a drastic change of the equilibrium swelling ratio between pH 2.2 and 7.0. At pH 7.0, hydrogels with PEGMA2000 exhibited higher swelling ratio than hydrogels with PEGMA1000. For both hydrogels with PEGMA1000 and PEGMA2000, the swelling mechanism became more relaxation-controled as the environmental pH changed from 2.2 to 7.0 due to the ionization of the functional groups in polymer networks at high pH. In vitro release studies of insulin were conducted. P(MAA-g-EG) hydrogels exhibited drastic increase of insulin release as the pH of the medium was changed from acidic to basic. Insulin release from P(MAA-g-EG) hydrogels with PEGMA2000 was slower than from hydrogels with PEGMA1000 at both low and high pH. These results were used to design and improve protein release behavior from these carriers.     

GSTP1 polymorphism,cigarette smoking and cervical cancer risk in Korean women

Previous studies have suggested that glutathione S-transferase (GST) genotypes may play a role in determining susceptibility to cervical cancer, though the data have often been conflicting. The objective of this study was to examine the effect of GSTP1 polymorphism on cervical carcinogenesis. The studied subjects, patients who were pathologically diagnosed with invasive cervical cancer yielding positive results for human papillomavirus (HPV) (n=342), were compared to healthy, normal, female controls (n=707). DNA from peripheral blood samples from studied subjects whose GSTP1 specific sequences had been determined by PCR with allele-specific primers were reviewed in comparison with the normal controls. The genetic susceptibility of GSTP1 (11q 13.1) in cervical carcinogenesis was determined by examining the effect of gene and environmental factors by the different histopathologic types of invasive cervical cancers. In assessing polymorphism GSTP1, the percentages of individuals homozygous for the A allele, homozygous for the G allele, and heterozygous for the two alleles were 66.8%, 3.9%, and 29.3%, respectively, in the control group, and 64.3%, 4.1%, and 31.6%, respectively, among in women with cervical cancer. Compared with GSTP1 G allele positive (GA or G/G), the odds ratio (OR) (95% confidence interval) for GSTP1 A/A was 1.0 (0.7 - 1.4) for invasive cervical cancer. However, the risk increased with GSTP1 A/A among ever smokers (3.9, 1.7 - 8.9, p-value=0.0012) compared with GSTP1 G allele positive among nonsmokers. In particular, this risk was higher among women with squamous cell carcinoma (4.7, 2.0 - 10.8, p=0.0003). Polymorphism of GSTP1 among smoking women was associated with a higher risk of developing cervical cancer.     

United we stand? The effects of a couple-coping intervention on adjustment to early stage breast or gynecological cancer

Cancer diagnosis affects the psychological well-being of both patients and their partners, and effective coping has been suggested to be a conjoint process of mutual support. Ninety-four married women with early stage cancer and their partners were randomly assigned to couples-based coping training (CanCOPE), individual coping training for the woman, or a medical education control. Couples' observed support communication and self-reported psychological distress, coping effort, and sexual adjustment were assessed at diagnosis, after cancer surgery, and at 6- and 12-month follow-ups. CanCOPE produced significant improvements in couples' supportive communication, reduced psychological distress and coping effort, and improved sexual adjustment. Training in couples rather than individual coping was more effective in facilitating adaptation to cancer.