Human papillomavirus (HPV) vaccines as an option for preventing cervical malignancies: (how) effective and safe?

We carried out a systematic review of HPV vaccine pre- and post-licensure trials to assess the evidence of their effectiveness and safety. We find that HPV vaccine clinical trials design, and data interpretation of both efficacy and safety outcomes, were largely inadequate. Additionally, we note evidence of selective reporting of results from clinical trials (i.e., exclusion of vaccine efficacy figures related to study subgroups in which efficacy might be lower or even negative from peer-reviewed publications). Given this, the widespread optimism regarding HPV vaccines long-term benefits appears to rest on a number of unproven assumptions (or such which are at odd with factual evidence) and significant misinterpretation of available data. For example, the claim that HPV vaccination will result in approximately 70% reduction of cervical cancers is made despite the fact that the clinical trials data have not demonstrated to date that the vaccines have actually prevented a single case of cervical cancer (let alone cervical cancer death), nor that the current overly optimistic surrogate marker-based extrapolations are justified. Likewise, the notion that HPV vaccines have an impressive safety profile is only supported by highly flawed design of safety trials and is contrary to accumulating evidence from vaccine safety surveillance databases and case reports which continue to link HPV vaccination to serious adverse outcomes (including death and permanent disabilities). We thus conclude that further reduction of cervical cancers might be best achieved by optimizing cervical screening (which carries no such risks) and targeting other factors of the disease rather than by the reliance on vaccines with questionable efficacy and safety profiles.

Differential pattern of glycogen accumulation after protein phosphatase 1 glycogen-targeting subunit PPP1R6 overexpression, compared to PPP1R3C and PPP1R3A, in skeletal muscle cells

Background PPP1R6 is a protein phosphatase 1 glycogen-targeting subunit (PP1-GTS) abundant in skeletal muscle with an undefined metabolic control role. Here PPP1R6 effects on myotube glycogen metabolism, particle size and subcellular distribution are examined and compared with PPP1R3C/PTG and PPP1R3A/GM. Results PPP1R6 overexpression activates glycogen synthase (GS), reduces its phosphorylation at Ser-641/0 and increases the extracted and cytochemically-stained glycogen content, less than PTG but more than GM. PPP1R6 does not change glycogen phosphorylase activity. All tested PP1-GTS-cells have more glycogen particles than controls as found by electron microscopy of myotube sections. Glycogen particle size is distributed for all cell-types in a continuous range, but PPP1R6 forms smaller particles (mean diameter 14.4 nm) than PTG (36.9 nm) and GM (28.3 nm) or those in control cells (29.2 nm). Both PPP1R6- and GM-derived glycogen particles are in cytosol associated with cellular structures; PTG-derived glycogen is found in membrane- and organelle-devoid cytosolic glycogen-rich areas; and glycogen particles are dispersed in the cytosol in control cells. A tagged PPP1R6 protein at the C-terminus with EGFP shows a diffuse cytosol pattern in glucose-replete and -depleted cells and a punctuate pattern surrounding the nucleus in glucose-depleted cells, which colocates with RFP tagged with the Golgi targeting domain of β-1,4-galactosyltransferase, according to a computational prediction for PPP1R6 Golgi location. Conclusions PPP1R6 exerts a powerful glycogenic effect in cultured muscle cells, more than GM and less than PTG. PPP1R6 protein translocates from a Golgi to cytosolic location in response to glucose. The molecular size and subcellular location of myotube glycogen particles is determined by the PPP1R6, PTG and GM scaffolding.

Clinical studies of experimental vaccines.

PURPOSE OF REVIEW: The scope of this review is to provide the current status of HIV vaccine clinical development. A series of issues regarding the type of immune response stimulated by the candidate vaccines in the pipeline, the advances in the immune correlates of protection, the need for an effective decision-making process for selection of candidate vaccines into further clinical development and the rationale for clinical trials will also be discussed. RECENT FINDINGS: Efforts in the development of HIV vaccines inducing broad neutralizing antibodies have failed so far. The current pipeline is predominantly composed of candidate vaccines designed to induce cellular immunity and particularly T-cell response. For these reasons, these candidate vaccines have been termed 'T-cell vaccines'. A large number of candidate vaccines or vaccine combinations have entered phase I-II clinical trials in 2005. Furthermore, an adenovirus vector-based vaccine has entered proof-of-concept efficacy trial and a canarypox vector in combination with a protein-based vaccine is currently being evaluated in phase III clinical trials. T-cell vaccines have been shown to be safe and the most recent generation of these vaccines also has substantial immunogenicity. SUMMARY: Only clinical trials can provide the definitive answer to immune correlates of protection and vaccine efficacy.

Subunit composition of seed storage proteins in high-protein soybean genotypes

The objective of this work was to quantify the accumulation of the major seed storage protein subunits, β-conglycinin and glycinin, and how they influence yield and protein and oil contents in high-protein soybean genotypes. The relative accumulation of subunits was calculated by scanning SDS-PAGE gels using densitometry. The protein content of the tested genotypes was higher than control cultivar in the same maturity group. Several genotypes with improved protein content and with unchanged yield or oil content were developed as a result of new breeding initiatives. This research confirmed that high-protein cultivars accumulate higher amounts of glycinin and β-conglycinin. Genotypes KO5427, KO5428, and KO5429, which accumulated lower quantities of all subunits of glycinin and β-conglycinin, were the only exceptions. Attention should be given to genotypes KO5314 and KO5317, which accumulated significantly higher amounts of both subunits of glycinin, and to genotypes KO5425, KO5319, KO539 and KO536, which accumulated significantly higher amounts of β-conglycinin subunits. These findings suggest that some of the tested genotypes could be beneficial in different breeding programs aimed at the production of agronomically viable plants, yielding high-protein seed with specific composition of storage proteins for specific food applications.

Developmental changes in the heavy subunit of neurofilaments in the corpus callosum of the cat.

In the corpus callosum of the cat, the heavy subunit of neurofilaments (NFH) can be demonstrated with the monoclonal antibody NE14, as early as P11, not at P3, and only in a few axons. At P18-19 and more markedly at P29, many more callosal axons have become positive to NE14 and this is similar to what is found in the adult. In contrast, callosal axons become positive to the neurofilament antibody SMI-32 only between P29 and P39 and remain positive in the adult. Treatment with alkaline phosphatase prevents axonal staining with NE14, but results in SMI-32 staining of a few callosal axons as early as P11, but not at P3. Between P11 and P19 the number of axons stained with SMI-32 after alkaline phosphatase treatment increases, in parallel with that of axons stained with NE14. Thus NE14 appears to recognize a phosphorylated form of NFH, while SMI-32 appears to recognize an epitope of NFH which is either masked by phosphate or inaccessible until between P29 and P39, unless the tissue is treated with alkaline phosphatase. These two forms of NFH appear towards the end of the period of massive developmental elimination of callosal axons. They are also synchronous with changes in the spacing of neurofilaments quantified in a separate ultrastructural study. These cytoskeletal changes may terminate the juvenile-labile state of callosal axons and allow further axial growth of the axon.

Social factors related to the clinical severity of influenza cases in Spain during the A(H1N1)2009 virus pandemic

Background During the 2009 influenza pandemic, a change in the type of patients most often affected by influenza was observed. The objective of this study was to assess the role of individual and social determinants in hospitalizations due to influenza A (H1N1) 2009 infection. Methods We studied hospitalized patients (cases) and outpatients (controls) with confirmed influenza A (H1N1) 2009 infection. A standardized questionnaire was used to collect data. Variables that might be related to the hospitalization of influenza cases were compared by estimation of the odds ratio (OR) and 95% confidence intervals (CI) and the variables entered into binomial logistic regression models. Results Hospitalization due to pandemic A (H1N1) 2009 influenza virus infections was associated with non-Caucasian ethnicity (OR: 2.18, 95% CI 1.17 − 4.08), overcrowding (OR: 2.84, 95% CI 1.20 − 6.72), comorbidity and the lack of previous preventive information (OR: 2.69, 95% CI: 1.50 − 4.83). Secondary or higher education was associated with a lower risk of hospitalization (OR 0.56, 95% CI: 0.36 − 0.87) Conclusions In addition to individual factors such as comorbidity, other factors such as educational level, ethnicity or overcrowding were associated with hospitalization due to A (H1N1) 2009 influenza virus infections.

Iowa Influenza Surveillance Network: Weekly Activity Report Week 2, January 16, 2016

The Iowa Influenza Surveillance Network (IISN) was established in 2004, though surveillance has been conducted at the Iowa Department of Public Health. Schools and long-term care facilities report data weekly into a Web-based reporting system. Schools report the number of students absent due to illness and the total enrolled. Long-term care facilities report cases of influenza and vaccination status of each case. Both passively report outbreaks of illness, including influenza, to IDPH.

Iowa Influenza Surveillance Network: Weekly Activity Report Week 3, January 23, 2016

The Iowa Influenza Surveillance Network (IISN) was established in 2004, though surveillance has been conducted at the Iowa Department of Public Health. Schools and long-term care facilities report data weekly into a Web-based reporting system. Schools report the number of students absent due to illness and the total enrolled. Long-term care facilities report cases of influenza and vaccination status of each case. Both passively report outbreaks of illness, including influenza, to IDPH.

Iowa Influenza Surveillance Network: Monthly Activity Report, July 2015

The Iowa Influenza Surveillance Network (IISN) was established in 2004, though surveillance has been conducted at the Iowa Department of Public Health. Schools and long-term care facilities report data weekly into a Web-based reporting system. Schools report the number of students absent due to illness and the total enrolled. Long-term care facilities report cases of influenza and vaccination status of each case. Both passively report outbreaks of illness, including influenza, to IDPH.

Iowa Influenza Surveillance Network: Monthly Activity Report, June 2015

The Iowa Influenza Surveillance Network (IISN) was established in 2004, though surveillance has been conducted at the Iowa Department of Public Health. Schools and long-term care facilities report data weekly into a Web-based reporting system. Schools report the number of students absent due to illness and the total enrolled. Long-term care facilities report cases of influenza and vaccination status of each case. Both passively report outbreaks of illness, including influenza, to IDPH.

Iowa Influenza Surveillance Network: Monthly Activity Report, September 2015

The Iowa Influenza Surveillance Network (IISN) was established in 2004, though surveillance has been conducted at the Iowa Department of Public Health. Schools and long-term care facilities report data weekly into a Web-based reporting system. Schools report the number of students absent due to illness and the total enrolled. Long-term care facilities report cases of influenza and vaccination status of each case. Both passively report outbreaks of illness, including influenza, to IDPH.

Iowa Influenza Surveillance Network: Weekly Activity Report Week 4, January 30, 2016

The Iowa Influenza Surveillance Network (IISN) was established in 2004, though surveillance has been conducted at the Iowa Department of Public Health. Schools and long-term care facilities report data weekly into a Web-based reporting system. Schools report the number of students absent due to illness and the total enrolled. Long-term care facilities report cases of influenza and vaccination status of each case. Both passively report outbreaks of illness, including influenza, to IDPH.

Iowa Influenza Surveillance Network: Weekly Activity Report Week 5, February 6, 2016

The Iowa Influenza Surveillance Network (IISN) was established in 2004, though surveillance has been conducted at the Iowa Department of Public Health. Schools and long-term care facilities report data weekly into a Web-based reporting system. Schools report the number of students absent due to illness and the total enrolled. Long-term care facilities report cases of influenza and vaccination status of each case. Both passively report outbreaks of illness, including influenza, to IDPH.

Iowa Influenza Surveillance Network: Weekly Activity Report Week 6, February 13, 2016

The Iowa Influenza Surveillance Network (IISN) was established in 2004, though surveillance has been conducted at the Iowa Department of Public Health. Schools and long-term care facilities report data weekly into a Web-based reporting system. Schools report the number of students absent due to illness and the total enrolled. Long-term care facilities report cases of influenza and vaccination status of each case. Both passively report outbreaks of illness, including influenza, to IDPH.

Iowa Influenza Surveillance Network: Weekly Activity Report Week 7, February 20, 2016

The Iowa Influenza Surveillance Network (IISN) was established in 2004, though surveillance has been conducted at the Iowa Department of Public Health. Schools and long-term care facilities report data weekly into a Web-based reporting system. Schools report the number of students absent due to illness and the total enrolled. Long-term care facilities report cases of influenza and vaccination status of each case. Both passively report outbreaks of illness, including influenza, to IDPH.