Worldwide genomic diversity of the human papillomaviruses-53, 56, and 66, a group of high-risk HPVs unrelated to HPV-16 and HPV-18

Among more than 200 human papillomavirus (HPV) types presumed to exist, 18 "high-risk" HPV types are frequently found in anogenital cancer. The best studied types are HPV-16 and 18, which are only distantly related to one another and form two separate phylogenetic branches, each including six closely related types. HPV-30, 53, 56, and 66 form a third phylogenetic branch unrelated to HPV-16 and 18. Worldwide comparison of HPV-16 and 18 isolates revealed a distribution of variant genomes that correlated with the geographic origin and the ethnicity of the infected cohort and led to the concept of unique African, European, Asian, and Native American HPV-16 and 18 variants. Here, we address the question whether similar phylogenies are found for HPV-53, 56, and 66 by determining the sequence of the long control regions (LCR) of these HPVs in samples from Europe, Asia, and Africa, and from immigrant societies in North and South America. Phylogenetic trees calculated from point mutations and a few insertions/deletions affecting 2-4.2% of the nucleotide sequences were distinct for each of the three HPVs and divergent from HPV-16 and 18. In contrast to the "star-phylogenies" formed by HPV-16 and 18 variants, 44 HPV-53 isolates represented nine variants, which formed two deep dichotomic branches reminiscent of the beginning split into two new taxa, as recently observed for subtypes of HPV-44 and 68. A total of 66 HPV-56 isolates represented 17 variants, which formed three branches preferentially containing European, Asian, and African variants. Variants of a fourth branch, deeply separated from the other three, were characterized by a 25 bp insertion and created a dichotomy rather than star-like phylogeny. As it contained isolates from cohorts in all continents, it may have evolved before the spread of humans into all continents. 18 of 31 HPV-66 isolates represented the prototype clone, which was found in all parts of the world, while the remaining 13 clones formed 11 branches without any geographic association. Our findings confirm the notion of a quantitatively limited genomic diversity of each HPV type with some correlation to the geographic origin of the sample. In addition, we observed in some variants of these three HPV types mutations that affect the amino acid sequence of the E6 oncoproteins and the L1 capsid protein, supporting the possibility of immunogenic and oncogenic diversity between variants of any HPV type.     

Use of multiple PCR primer sets for optimal detection of human papillomavirus.

Using multiple PCR primer sets, we tried to optimize the detection of human papillomavirus (HPV) in DNA samples isolated from 361 frozen biopsy specimens from patients with invasive cervical carcinomas. The HPVs detected were placed into three distinct groups, including group I/Inex at Telelab (Skien, Norway) and group Ineg and group II at the Norwegian Radium Hospital (Oslo, Norway). The consensus primer sets were Oli-1b-oli-2i, My09-My11, Gp5-Gp6, and Gp(5+)-Gp6+ from the HPV L1 gene and CpI-CpIIG from the E1 gene. Using these consensus primers together with the type-specific primers from E6-E7, we found that 355 patients (98%) were HPV positive. Type-specific primers for HPV types 11, 16, 18, 31, 33, and 35 detected more HPV-infected patients than the most sensitive consensus primer set, while the three consensus primer sets My, Gp/Gp+, and Cp together detected more HPV-positive patients than the type-specific primers. Testing of sensitivity of the PCR with SiHa cells serially diluted in lymphocytes (HPV-negative cells) indicated a detection limit of 6,300 HPV type 16 DNA copies with consensus primers (My, Gp+, and Cp) and 126 original HPV type 16 DNA copies with type-specific primers. Comparison of the amplification results for consensus L1 primers and type-specific E6-E7 primers indicated the presence of L1 deletions in 23 of 56 samples. The conclusion is that in PCR detection systems, multiple consensus primers and type-specific primers should be used in order to detect all patients harboring HPV.     

Expression of MHC class I heavy chain and beta2-microglobulin in rat brainstem motoneurons and nigral dopaminergic neurons

We demonstrate here that motoneurons and nigral dopaminergic neurons in the brainstem of the adult rat, with the exception of motoneurons innervating ocular muscles, display high levels of both MHC class I heavy chain and beta2-microglobulin mRNAs. These neurons also display interferon-gamma receptor mRNA. We find it striking that these particular neurons are those which are vulnerable to neurodegeneration in diseases such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS).     

An Overview of the Stability and Fretting Corrosion of Microgrooved Necks in the Taper Junction of Hip Implants

Fretting corrosion at the head–neck interface of modular hip implants, scientifically termed trunnionosis/taperosis, may cause regional inflammation, metallosis, and adverse local tissue reactions. The severity of such a deleterious process depends on various design parameters. In this review, the influence of surface topography (in some cases, called microgrooves/ridges) on the overall performance of the microgrooved head–neck junctions is investigated. The methodologies together with the assumptions and simplifications, as well as the findings from both the experimental observations (retrieval and in vitro) and the numerical approaches used in previous studies, are presented and discussed. The performance of the microgrooved junctions is compared to those with a smooth surface finish in two main categories: stability and integrity; wear, corrosion, and material loss. Existing contradictions and disagreements among the reported results are reported and discussed in order to present a comprehensive picture of the microgrooved junctions. The current research needs and possible future research directions on the microgrooved junctions are also identified and presented.     

Evaluating changes in pulse transit time drop index in patients with obstructive sleep apnea before and during CPAP therapy

Airflow limitation in patients with obstructive sleep apnea (OSA) leads to arousal, increased sympathetic nervous system activity, and elevated blood pressure, which causes a decrease in pulse transit time (PTT). The present study aims to evaluate the effect of CPAP therapy on PTT in patients with moderate to severe OSA. This was a cross‐sectional study. Split‐night polysomnography (PSG) study was performed for each participant with apnea‐hypopnea index (AHI) ≥ 15 before and during CPAP therapy. The PTT was calculated as the time interval between the R wave of the electrocardiogram and the following arrival point in fingertip photoplethysmography. PTT drop was defined as a fall in the PTT curve of ≥15 ms lasting at least for 3 s and at most for 30 s. PTT drop index was defined as the number of drops in PTT that occur per hour of sleep. A total of 30 patients were included. PTT significantly increased, and PTT drop index significantly decreased during CPAP therapy (P < 0.001). PTT was significantly correlated to sleep efficiency (r _s = −0.376, P = 0.049) and oxygen desaturation index (ODI) (r _s = −0.428, P = 0.018). PTT drop index was strongly correlated to AHI (r _s = 0.802, P < 0.001), respiratory disturbance index (RDI) (r _s = 0.807, P < 0.001), ODI (r _s = 0.693, P < 0.001), arousal index (r _s = 0.807, P < 0.001), and periodic leg movement (PLM) index (r _s = 0.400, P = 0.035). Overall, the findings from this study indicated that the PTT drop index is a non‐invasive and useful marker for evaluating the severity of OSA and the effectiveness of treatment in patients with moderate to severe OSA.     

Correlation of optic nerve sheath diameter measurements by computed tomography and magnetic resonance imaging

BackgroundTraditionally, intracranial pressure is measured by direct ventriculostomy, which is invasive. Noninvasive measures such as bedside ultrasound and magnetic resonance imaging have been advocated and utilized recently to assess the intracranial pressure. The role of this study is to determine the degree of agreement between measurements of the optic nerve sheath diameter by computed tomography (CT) and magnetic resonance imaging (MRI).Materials and MethodsRetrospective chart review of 100 consecutive patients who had both MRI and CT scan of the head from January 1, 2011, until March 31, 2013, at our center was performed. A discrepancy of 0.2 mm between the 2 measurements was set as acceptable difference. The measurements of optic nerve sheath diameter (ONSD) were compared for agreement between the 2 modalities using the method by Bland and Altman.ResultsA total of 100 patients with both MRI and CT scan of the head were selected. Of these 100 patients, 24 were male and 76 were female. The average age was 63 years. No ONSD abnormality was detected in any of the patients. The discrepancy in measurements of the ONSD between CT and MRI in transverse plane was less than the predetermined cut-off value of 0.2 mm. Within-subject variance was estimated at 0.0058 for both CT and MRI.ConclusionComparable results without significant discrepancy as predetermined by the study groups were obtained from CT scan. Measurement of ONSD by CT scan can be used to indirectly asses the intracranial pressure in addition to clinical assessment and other signs of increased intracranial pressure on CT scan.     

Real time optic nerve sheath diameter measurement during lumbar puncture

Measurement of optic nerve sheath diameter (ONSD) using point of care ultrasound has been used to indirectly assess the intracranial pressure (ICP) particularly in conditions where it is raised. Direct pressure measurements using probes reaching the ventricle system correlated with ONSD using ultrasound. Attempts were made to measure the ONSD pre and post lumbar puncture (LP) after draining cerebrospinal fluid (CSF) as well as post ventricular shunt placement. We report ONSD measurement and demonstrate dynamic changes during LP in a patient with known idiopathic intracranial hypertension (IIH).     

Quadriceps force production during straight leg raising at different hip positions with and without concomitant ankle dorsiflexion

Objective

Due to the significant prevalence of knee disorders and patellofemoral pain syndrome, as well as the importance of quadriceps strengthening in knee rehabilitation programs, it is necessary to specify the best method to activate and strengthen the quadriceps muscles. The current study aimed at comparing the maximum generated isometric force during an active straight-leg-raising (SLR) maneuver in a sitting position by changing the hip rotational position with and without the simultaneous contraction of the ankle dorsiflexor muscles.