Alterations of the CD4+, CD8+ T Cell Subsets, Interleukins-1β, IL-10, IL-17, Tumor Necrosis Factor-α and Soluble Intercellular Adhesion Molecule-1 in Rheumatoid Arthritis and Osteoarthritis: Preliminary Observations

Rheumatoid arthritis is a multisystem disease with underlying immune mechanisms. Osteoarthritis is a debilitating, progressive disease of diarthrodial joints associated with the aging process. Although much is known about the pathogenesis of rheumatoid arthritis and osteoarthritis, our understanding of some immunologic changes remains incomplete. This study tries to examine the numeric changes in the T cell subsets and the alterations in the levels of some cytokines and adhesion molecules in these lesions. To accomplish this goal, peripheral blood and synovial fluid samples were obtained from 24 patients with rheumatoid arthritis, 15 patients with osteoarthritis and six healthy controls. The counts of CD4 (+) and CD8 (+) T lymphocytes were examined using flow cytometry. The levels of some cytokines (TNF-alpha, IL1-beta, IL-10, and IL-17) and a soluble intercellular adhesion molecule-1 (sICAM-1) were measured in the sera and synovial fluids using enzyme linked immunosorbant assay. We found some variations in the counts of T cell subsets, the levels of cytokines and sICAM-1 adhesion molecule between the healthy controls and the patients with arthritis. High levels of IL-1beta, IL-10, IL-17 and TNF-alpha (in the serum and synovial fluid) were observed in arthritis compared to the healthy controls. In rheumatoid arthritis, a high serum level of sICAM-1 was found compared to its level in the synovial fluid. A high CD4(+)/CD8(+) T cell ratio was found in the blood of the patients with rheumatoid arthritis. In rheumatoid arthritis, the cytokine levels correlated positively with some clinicopathologic features. To conclude, the development of rheumatoid arthritis and osteoarthritis is associated with alteration of the levels of some cytokines. The assessment of these immunologic changes may have potential prognostic roles.     

Computational prediction of methylation status in human genomic sequences

Epigenetic effects in mammals depend largely on heritable genomic methylation patterns. We describe a computational pattern recognition method that is used to predict the methylation landscape of human brain DNA. This method can be applied both to CpG islands and to non-CpG island regions. It computes the methylation propensity for an 800-bp region centered on a CpG dinucleotide based on specific sequence features within the region. We tested several classifiers for classification performance, including K means clustering, linear discriminant analysis, logistic regression, and support vector machine. The best performing classifier used the support vector machine approach. Our program (called hdfinder) presently has a prediction accuracy of 86%, as validated with CpG regions for which methylation status has been experimentally determined. Using hdfinder, we have depicted the entire genomic methylation patterns for all 22 human autosomes.     

The psychometric properties of the Iranian version of revised prenatal coping inventory (Nu PCI) in healthy pregnant women: a confirmatory factor analysis

The Revised Prenatal Coping Inventory (Nu PCI) is a self-report instrument that focuses on the coping styles of pregnant women during the prenatal period. The present study aimed to translate the scale and evaluate the psychometric properties of the Iranian version of the Nu PCI in healthy pregnant women. Beaton’s recommendations have been used for the translation and cultural adaptation of this scale. Reliability, content, and face validity were performed to assess the psychometric properties of the scale. The results indicated that the Nu PCI was successfully translated into the Persian language, with both the total scale and subscales exhibiting both content validity and internal consistency. Confirmatory factor analyses revealed that the conceptual three-factor structure of the measure had good fit indices. Reliability was evaluated using internal consistency. Cronbach Alpha coefficient was 0.92 and intra-class correlation coefficient (ICC) was 0.91. Therefore, the Nu PCI is a reliable instrument to measure prenatal coping patterns in primigravida healthy pregnant women.     

Impact of 226C>T MSH2 gene mutation on cancer phenotypes in two HNPCC-associated highly-consanguineous families from Kuwait: emphasis on premarital genetic testing

Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC) is one of the commonest cancer susceptibility syndromes. It is characterized by early onset colon cancer and a variety of extracolonic tumours. Germline mutations in the DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS1, and PMS2) are responsible for this disorder. Identifying an affected individual depends on the tumour histopathology, family history that fulfils the Amsterdam and/or Bethesda criteria, tumour immunohistochemistry, microsatellite instability, and finally molecular analysis of an affected member. It is a laborious, time consuming and expensive procedure, which needs the effort of a multi-disciplinary team. However, once the diagnosis is established and germline defect is identified, other high risk pre-symptomatic carriers could be offered intensive surveillance and management as a preventive measure against cancer development. Here, we present two large highly consanguineous HNPCC-families from Kuwait in whom a founder MSH2 mutation was identified. The relationship between this mutation and cancer expressivity in two large consanguineous families harbouring other genetic defects is discussed. Moreover, we shed light on the challenges pertaining to diagnosis, screening, premarital counselling of couples and prenatal diagnosis of offspring with biallelic MSH2 gene mutation.     

Transport Mechanisms and Dielectric Features of Mg-Doped ZnO Nanocrystals for Device Applications

Magnesium-doped zinc oxide “ZnO:Mg” nanocrystals (NCs) were fabricated using a sol gel method. The Mg concentration impact on the structural, morphological, electrical, and dielectric characteristics of ZnO:Mg NCs were inspected. X-ray diffraction (XRD) patterns display the hexagonal wurtzite structure without any additional phase. TEM images revealed the nanometric size of the particles with a spherical-like shape. The electrical conductivity of the ZnO NCs, thermally activated, was found to be dependent on the Mg content. The impedance spectra were represented via a corresponding circuit formed by a resistor and constant phase element (CPE). A non-Debye type relaxation was located through the analyses of the complex impedance. The conductivity diminished with the incorporation of the Mg element. The AC conductivity is reduced by raising the temperature. Its plot obeys the Arrhenius law demonstrating a single activation energy during the conduction process. The complex impedance highlighted the existence of a Debye-type dielectric dispersion. The various ZnO:Mg samples demonstrate high values of dielectric constant with small dielectric losses for both medium and high-frequency regions. Interestingly, the Mg doping with 3% content exhibits colossal dielectric constant (more than 2 × 10⁴) over wide temperature and frequency ranges, with Debye-like relaxation. The study of the electrical modulus versus the frequency and at different temperatures confirms the non-Debye relaxation. The obtained results reveal the importance of the ZnO:Mg NCs for device applications. This encourages their application in energy storage.     

The Scottish RD survey 10 years on: the increasing incidence of retinal detachments

BackgroundThe Scottish RD Survey reported an incidence of 12.05/100,000/yr in 2009. Data published from Denmark recently confirmed a 50% increase in RD presentations over the last 16 years. We set out to repeat the Scottish RD survey to determine if a similar trend has been observed in Scotland.MethodsAll 16 Scottish VR surgeons, who make up the collaboration of Scottish VR Surgeons (SCVRs) were asked to prospectively record all primary RDs presenting from 12th August 2019 to 11th August 2020. For consistency, the case definitions were the same as for the 2009 Scottish RD Survey. Basic demographic and clinical features were recorded. Age specific incidence was calculated from mid-year population estimates for 2019 obtained from the National Records of Scotland.ResultsThere were 875 RRDs recorded, which gives an updated incidence of 16.02/100,000/year in Scotland. 62.8% occurred in males and the greatest increases were seen in males aged 50–59 (p = 0.0094), 60–69 (p = 0.0395) and females aged 40–49 (p = 0.0312) and 50–59 (p = 0.0024). The proportion of pseudophakic RRDs in this study is 29.4% (253/860). Compared to the 21.6% in the 2010 study, this represents a 28% increase (χ² = 11.03, p = 0.0009). The proportion of macula-off RRDs remained generally stable at 58%.ConclusionOur study confirms that RRD is becoming more common in the UK, reflecting almost identical findings from Denmark. This trend is in part due to increasing myopia, increasing pseudophakia, and possibly other factors. This should be considered when planning VR services and allocating resources in the future.Subject terms: Health occupations, Epidemiology     

The diabesity health economic crisis—the size of the crisis in a European island state following a cross-sectional study

Background

Diabetes type 2 and obesity are well-established global epidemics and contributors to clinical, social and economic health burdens. The prevalence rates of these diseases are still on the rise among countries resulting in a corresponding public health burden. The Mediterranean island of Malta, known for it’s high diabetes and obesity rates, provides a good fundamental basis to portray the economical health burden of these diseases.

Method

A recent randomised stratified representative cross-sectional survey conducted in Malta tackling diabetes, obesity and other determinants, was used to work out the population prevalence of these diseases. The cost burden of diabetes and obesity, based on published data, was incorporated to the established population prevalence rates, in order to estimate the Maltese economical burden. Projections to the year 2050 by a bottom-up prevalence based design were performed.

Results

One eight of the Maltese adults (25 to 64 years) suffered from diabetes out of which approximately 10,000 adults were unaware of the disease. Alarmingly, more than a third of the Maltese population suffer from obesity. The approximate health care costs (direct and indirect) for the diabetic adult population was of €29,159,217 (€21,994,676 - €38,919,121) annually, amounting to 3.64% (2.75–4.875%) of the total health expenditure in Malta. The obesity cost burden was of €23,732,781 (€21,514,972-€26,049,204) annually contributing for 2.97% (2.69–3.26%) of the total health expenditure. The projected prevalence and costs for 2050 exhibited an estimated cost burden increase of €33,751,487 (€25,458,606–€45,048,473) for the diabetes mellitus population and €46,532,294 (€42,183,889–€51,074,049) for the obese population. These projected cost burdens are expected to increase exponentially the total health care expenditure in Malta by 2050.

Conclusion

Having an understanding of the prevalence and the economic cost burden of diabetes and obesity within a country, along with projections of the expected burden will enable policy and public health officials to clearly visualize this growing problem. It also helps in establishing effective preventive strategies and screening programs targeting these epidemics.

     

Dentists' and Parents' Attitude Toward Nitrous Oxide Use in Kuwait

The aim of this study was to investigate the attitude of dentists in Kuwait toward the use of nitrous oxide sedation as a behavior management technique (BMT) for pediatric patients and assess their training in nitrous oxide sedation. In addition, we assessed parents'' knowledge of and attitude toward the use of nitrous oxide as a BMT for their children. The objective was to determine if nitrous oxide sedation is being provided and utilized as a means to enhance dental care for pediatric patients. A cross-sectional survey was randomly distributed to both groups of interest: parents accompanying their children to the dentist and licensed dentists in Kuwait. Participants had to meet certain inclusion criteria to be included in the survey and had to complete the entire questionnaire to be part of the analysis. A total of 381 parents completed the questionnaires. The majority of parents responded that they were unaware of nitrous oxide sedation and were not aware of it as a BMT (79%). Two thirds of the parent would accept nitrous oxide sedation if recommended by a dentist treating their children. Two hundred and one dentists completed the survey and met the inclusion criteria. The majority (74.5%) of dentists were willing to use nitrous oxide as a BMT. However, only 6% were utilizing nitrous oxide sedation and providing it to their child patient if indicated. The main reasons for this huge gap are lack of facilities/equipment and lack of training as indicated by the dentists. This study showed that parents are accepting nitrous oxide sedation as a BMT for their children. It also showed the willingness of the dentists to provide such BMT to their patients. The lack of training and lack of equipment are the main barriers to providing such service to the patients. More training courses and more facilities should be provided to eliminate such barriers.Key Words: Nitrous oxide, Kuwait, Minimal sedationManaging a child''s behavior during dental treatment is an important factor in delivering safe and effective dental care. Various nonpharmacological and pharmacological techniques are recommended by the American Academy of Pediatric Dentistry to enable the dental practitioner to perform quality oral health care for the uncooperative pediatric patient, and at the same time alleviate fear and anxiety, guide the child to be cooperative, and nurture a positive dental attitude in him/her.¹ In addition to tailoring various behavior management techniques (BMTs) to the individual child, it is also important for dental practitioners to utilize techniques consistent with their level of professional education and clinical experience.²Nitrous oxide sedation has a long history of safe use in dentistry and offers the clinician predictable clinical outcomes.³ It is considered a preferred technique for the pharmacological management of anxiety in pediatric dental patients in the dental office.^4,5Nitrous oxide sedation has been accepted as a popular pharmacological BMT in many Western countries, including the United States.^6,7 In 1996, a survey of the American Academy of Pediatric Dentistry membership revealed that 89% of pediatric dentists utilize nitrous oxide sedation, with most of them using it more than 5 times per week.⁸ Moreover, this sedation technique is the second most accepted BMT by parents in the United States.⁹ On the contrary, several studies showed that the majority of parents in Middle East countries did not accept nitrous oxide sedation as a BMT. One study, which was conducted in 2009, demonstrated that most parents in Kuwait prefer nonpharmacological techniques over pharmacological ones, and nitrous oxide sedation was rated as one of the least acceptable techniques.¹⁰ Similar findings were found by Al-Shalan and Alammouri for Saudi Arabian and Jordanian parents, respectively.^11,12In 2010, nitrous oxide sedation was officially approved and regulated by the Kuwaiti Dental Board. Prior to that date, dentists were unable to administer nitrous oxide in their dental offices despite training in its use. Many dentists referred patients to have general anesthesia if the patient needed pharmacological anxiety management. Therefore, 3 years after the approval of its use by dentists, the aim was to investigate the attitude of dentists in Kuwait toward the use of nitrous oxide sedation as a BMT for pediatric patients and assess their training in nitrous oxide sedation. In addition, parents'' knowledge and attitude toward the use of nitrous oxide as a BMT for their children was also assessed.