Development and Validation of Questionnaire to Assess Knowledge about Cervical Cancer among Women Aged 20 to 65 years in Oman

Objective: This study aimed to develop and validate a questionnaire to assess awareness of cervical cancer, its risk factors, and methods of prevention among Arabic-speaking women aged 20 years and over. Methods: The study took place at primary healthcare institutions, Al Buraimi Governorate, Oman, between November 2018 to February 2019. In phase I, seventy items concerning cervical cancer and its prevention were generated through a literature review. In phase 2, the questionnaire was validated through calculating the content validity index (CVI) for both item level (I-CVI) and the scale level (S-CVI), in this phase a shortened English questionnaire of 55 items was formed, then rigorously translated to the Arabic language in phase III. The questionnaire was tested for reliability in two stages: A pilot and a large field test in phase IV. Results: A total of 55 out of 70 items formed the final version of the questionnaire. The final instrument had an S-CVI/Ave of 0.92. The questionnaire called the Knowledge in Cervical Cancer and Prevention Methods 55-items (KCCPM-55). The Cronbach alpha coefficient was 0.940 for the whole questionnaire, and ranged between 0.57 to 0.93 for each of the domains. Test-retest reliability was examined in a subsample of the total participants sample (r = 0.769, p < 0.001). Conclusion: The KCCPM-55 has been successfully developed in the Arabic language and found to be a valid and reliable instrument for assessing the level of knowledge about cervical cancer and prevention methods among women aged 20 to 65 years in Oman.     

Y-chromosomal evidence for a limited Greek contribution to the Pathan population of Pakistan

Three Pakistani populations residing in northern Pakistan, the Burusho, Kalash and Pathan claim descent from Greek soldiers associated with Alexander's invasion of southwest Asia. Earlier studies have excluded a substantial Greek genetic input into these populations, but left open the question of a smaller contribution. We have now typed 90 binary polymorphisms and 16 multiallelic, short-tandem-repeat (STR) loci mapping to the male-specific portion of the human Y chromosome in 952 males, including 77 Greeks in order to re-investigate this question. In pairwise comparisons between the Greeks and the three Pakistani populations using genetic distance measures sensitive to recent events, the lowest distances were observed between the Greeks and the Pathans. Clade E3b1 lineages, which were frequent in the Greeks but not in Pakistan, were nevertheless observed in two Pathan individuals, one of whom shared a 16 Y-STR haplotype with the Greeks. The worldwide distribution of a shortened (9 Y-STR) version of this haplotype, determined from database information, was concentrated in Macedonia and Greece, suggesting an origin there. Although based on only a few unrelated descendants, this provides strong evidence for a European origin for a small proportion of the Pathan Y chromosomes.     

Definition of a minimal region of deletion of chromosome 7 in uterine leiomyomas by tiling-path microarray CGH and mutation analysis of known genes in this region

Somatic interstitial deletions of chromosome segment 7q22-q31 in uterine leiomyomas are a frequent event, thought to be indicative of a tumor suppressor gene in the region. Previous LOH and CGH studies have refined this region to 7q22.3-q31, although the target gene has not been identified. Here, we have used tiling-path resolution microarray CGH to further refine the region and to identify homozygous deletions in fibroids. Furthermore, we have screened all manually annotated genes in the region for mutations. We have refined the minimum deleted region at 7q22.3-q31 to 2.79 Mbp and identified a second region of deletion at 7q34. However, we identified no pathogenic coding variation.     

Tumor necrosis factor-alpha induces changes in mitochondrial cellular distribution in motor neurons

Motor neuron (MN) mitochondrial abnormalities and elevation in spinal fluid levels of the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). The mechanism of neuron death in ALS remains unclear, along with the contributions of mitochondrial dysfunction and inflammation in the process. Cell cultures enriched for MN derived from embryonic rat spinal cords were established and directly exposed in vitro to recombinant TNF-alpha for varying lengths of time. Although cytokine exposure for up to 4 days failed to induce MN death, mitochondrial changes were observed shortly after initiating treatment. Our results demonstrate that TNF-alpha induced mitochondrial redistribution toward the soma in MN. We postulate that inflammation may precede, and in fact cause, the mitochondrial changes observed in ALS tissue.     

Pediatric medulloblastoma xenografts including molecular subgroup 3 and CD133+ and CD15+ cells are sensitive to killing by oncolytic herpes simplex viruses

Background

Childhood medulloblastoma is associated with significant morbidity and mortality that is compounded by neurotoxicity for the developing brain caused by current therapies, including surgery, craniospinal radiation, and chemotherapy. Innate therapeutic resistance of some aggressive pediatric medulloblastoma has been attributed to a subpopulation of cells, termed cancer-initiating cells or cancer stemlike cells (CSCs), marked by the surface protein CD133 or CD15. Brain tumors characteristically contain areas of pathophysiologic hypoxia, which has been shown to drive the CSC phenotype leading to heightened invasiveness, angiogenesis, and metastasis. Novel therapies that target medulloblastoma CSCs are needed to improve outcomes and decrease toxicity. We hypothesized that oncolytic engineered herpes simplex virus (oHSV) therapy could effectively infect and kill pediatric medulloblastoma cells, including CSCs marked by CD133 or CD15.

Methods

Using 4 human pediatric medulloblastoma xenografts, including 3 molecular subgroup 3 tumors, which portend worse patient outcomes, we determined the expression of CD133, CD15, and the primary HSV-1 entry molecule nectin-1 (CD111) by fluorescence activated cell sorting (FACS) analysis. Infectability and cytotoxicity of clinically relevant oHSVs (G207 and M002) were determined in vitro and in vivo by FACS, immunofluorescent staining, cytotoxicity assays, and murine survival studies.

Results

We demonstrate that hypoxia increased the CD133+ cell fraction, while having the opposite effect on CD15 expression. We established that all 4 xenografts, including the CSCs, expressed CD111 and were highly sensitive to killing by G207 or M002.

Conclusions

Pediatric medulloblastoma, including Group 3 tumors, may be an excellent target for oHSV virotherapy, and a clinical trial in medulloblastoma is warranted.     

An epidemiologic model for diabetes mellitus: incidence, prevalence, and mortality

An epidemiologic model is developed to describe the incidence, prevalence, and mortality of diabetes. Available data are reviewed, analyzed, and applied to the model. The model provides a framework for understanding diabetes on a population basis, and is useful in identifying needs and facilitating health care planning.     

Investigation of the human oesophagus as a new monitoring site for blood oxygen saturation

Pulse oximeter probes placed peripherally may fail to give accurate values of arterial blood oxygen saturation (SpO2) when peripheral perfusion is poor. Since central blood flow may be preferentially preserved, the oesophagus was suggested as an alternative monitoring site. A reflectance oesophageal photoplethysmographic (PPG) probe and a multiplexed data acquisition system, operating simultaneously at two wavelengths and incorporating an external three-lead electrocardiogram (ECG) reference channel, has been developed. It has been used to investigate the suitability of the oesophagus as a possible monitoring site for SpO2 in cases of compromised peripheral perfusion. Oesophageal PPG signals and standard ECG traces were obtained from 16 anaesthetized patients and displayed on a laptop computer. Measurable PPG signals with high signal-to-noise ratios at both infrared and red wavelengths were obtained from all five oesophageal depths investigated. The maximum PPG amplitude occurred at 25 cm from the upper incisors in the mid-oesophagus. The measured pulse transit times (PTTs) to the oesophagus were consistent with previous measurements at peripheral sites and had a minimum value of 67 +/- 30 ms at a depth of 30 cm. There was broad agreement between the calculated values of oesophageal SpO2 and those from a commercial finger pulse oximeter.