Prevalence of cognitive impairment using the Montreal Cognitive Assessment questionnaire among patients with systemic lupus erythematosus: a cross-sectional study at two tertiary centres in Malaysia.

INTRODUCTION: Cognitive impairment is a common neuropsychiatric manifestation of systemic lupus erythematosus (SLE). However, it is not routinely assessed for despite its high prevalence and significant disease burden. AIMS: This study aimed to determine the prevalence of mild cognitive impairment (MCI) using the Montreal Cognitive Assessment (MoCA) and its associated factors among patients diagnosed with SLE in Malaysia. METHODS: A total of 200 SLE patients were recruited prospectively from the outpatient clinics of two tertiary hospitals in Malaysia. Standardized clinical interview was utilized to obtain information on socio-demographic characteristics. All patients were then assessed using the MoCA questionnaire for presence of cognitive impairment; the Patient Health Questionnaire 9 (PHQ-9) for presence of depressive symptoms; and the Wong-Baker Faces Pain Scale (WBFPS) for severity of pain. The evaluation of disease activity and severity were performed by the treating rheumatologists and nephrologists using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics Damage Index (SLICC DI). RESULTS: The prevalence of MCI was 35%. The significant associated factors from the bivariate analysis were male gender (p = 0.04), educational level (p = 0.00), WBFPS score (p = 0.035) and anticardiolipin IgM (p = 0.01). Further analysis using logistic regression model found that male gender (OR = 7.43, 95% confidence interval 1.06-52.06, p = 0.04), lower educational level (OR = 4.4, 95% confidence interval 1.47-13.21, p = 0.01) and presence of anticardiolipin IgM (OR = 6.81, 95% confidence interval 1.45-32.01, p = 0.031) were associated with impaired MoCA scores. Also, increasing pain scores increased the risk of patients being affected by cognitive impairment. CONCLUSION: Over one-third of patients with SLE in our cohort were found to have MCI. Risk factors included male gender, lower educational level, higher pain score and presence of anticardiolipin IgM. Physicians are encouraged to perform routine screening to detect cognitive dysfunction in patients with SLE in their clinical practice as part of a more comprehensive management.

Suicidal ideation in systemic lupus erythematosus: NR2A gene polymorphism, clinical and psychosocial factors.

Background Systemic lupus erythematosus (SLE) patients are a high-risk population for suicide. Glutamatergic neurosystem genes have been implicated in the neurobiology of depression in SLE and suicidal behaviour in general. However, the role of glutamate receptor gene polymorphisms in suicidal behaviour among SLE patients remains unclear in the context of established clinical and psychosocial factors. We aimed to investigate the association of NR2A gene polymorphism with suicidal ideation in SLE while accounting for the interaction between clinical and psychosocial factors. Methods A total of 130 SLE patients were assessed for mood disorders (MINI International Neuropsychiatric Interview), severity of depression (Patient Health Questionnaire-9), suicidal behaviour (Columbia-Suicide Severity Rating Scale), socio-occupational functioning (Work and Social Adjustment Scale), recent life events (Social Readjustment Rating Scale) and lupus disease activity (SELENA-SLE Disease Activity Index). Eighty-six out of the 130 study participants consented for NR2A genotyping. Results Multivariable logistic regression showed nominal significance for the interaction effect between the NR2A rs2072450 AC genotype and higher severity of socio-occupational impairment with lifetime suicidal ideation in SLE patients ( p = 0.038, odds ratio = 1.364, 95% confidence interval = 1.018-1.827). However, only the association between lifetime mood disorder and lifetime suicidal ideation remained significant after Bonferroni correction ( p < 0.001, odds ratio = 33.834, 95% confidence interval = 7.624-150.138). Conclusions Lifetime mood disorder emerged as a more significant factor for suicidal ideation in SLE compared with NR2A gene polymorphism main and interaction effects. Clinical implications include identification and treatment of mood disorders as an early intervention for suicidal behaviour in SLE. More adequately-powered gene-environment interaction studies are required in the future to clarify the role of glutamate receptor gene polymorphisms in the risk stratification of suicidal behaviour among SLE patients.

Independent determinants of periodontitis in Yemeni adults: A case-control study.

OBJECTIVES: The relative importance of risk factors of periodontitis varies from one population to another. In this study, we sought to identify independent risk factors of periodontitis in a Yemeni population. METHODS: One hundred and fifty periodontitis cases and 150 healthy controls, all Yemeni adults 30-60 years old, were recruited. Sociodemographic data and history of oral hygiene practices and oral habits were obtained. Plaque index (PI) was measured on index teeth. Periodontal health status was assessed using Community Periodontal Index (CPI) and Clinical Attachment Loss (CAL) according to WHO. Periodontitis was defined as having one or more sextants with a CPI score ≥ 3. Multiple logistic regression modelling was employed to identify distal, intermediate and proximal determinants of periodontitis, while ordinal regression was used to identify those of CAL scores. RESULTS: In logistic regression, PI score was associated with the highest odds of periodontitis (OR = 82.9) followed by cigarette smoking (OR = 12.8), water pipe smoking (OR = 10.2), male gender (OR = 3.4) and age (OR = 1.19); on the other hand, regular visits to the dentist (OR = 0.05), higher level of education (OR = 0.37) and daily dental flossing (OR = 0.95) were associated with lower odds. Somewhat similar associations were seen for CAL scores (ordinal regression); however, qat chewing was identified as an additional determinant (OR = 4.69). CONCLUSION: Water pipe smoking is identified as a risk factor of periodontitis in this cohort in addition to globally known risk factors. Adjusted effect of qat chewing is limited to CAL scores, suggestive of association with recession.

Quantitative analysis of classical and new putative periodontal pathogens in subgingival biofilm: a case-control study.

BACKGROUND AND OBJECTIVES: A number of species/phylotypes have been newly implicated as putative periopathogens. The objective of this study was to explore associations among classical and new pathogens in subgingival biofilm and to assess their relative importance to chronic periodontitis. MATERIAL AND METHODS: Pooled subgingival biofilm samples were obtained from 40 patients with chronic periodontitis and 40 healthy controls. Taqman q-PCR assays were used to determine the absolute and relative counts of Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Parvimonas micra, Filifactor alocis, oral Synergistetes and oral TM7s. Microbial associations were assessed using cluster analysis. Different statistical models were used to explore associations between microbial parameters and periodontitis. RESULTS: The median log and relative counts were lowest for TM7s (4.4 and 0.0016%, respectively) and highest for oral Synergistetes (7.2 and 1.4%, respectively). Oral Synergistetes clustered strongly with the red complex, particularly T. forsythia (100% rescaled similarity). All species/phylotypes except TM7s were significantly associated with periodontitis (Mann-Whitney test; p ≤ 0.005). However, P. gingivalis and F. alocis lost association after adjusting for confounders (ordinal regression). In receiving operator characteristic curve analysis, the log counts of oral Synergistetes were the best markers of periodontitis (82.5% sensitivity and specificity), followed by those of T. forsythia, P. micra and T. denticola. In prediction analysis, however, P. micra was the only microbial predictor of periodontal parameters. CONCLUSIONS: Oral Synergistetes are presented here as new members of the red complex, with relative importance to periodontitis exceeding that of the classical members. P. micra is shown as an important periodontal pathogen warranting more attention.

Job satisfaction and perceived future roles of Malaysian dental therapists: findings from a national survey.

OBJECTIVE: To assess Malaysian dental therapists' perceptions of their job satisfaction and future roles. METHODS: A nationwide postal survey involving all Malaysian dental therapists who met the inclusion criteria (n = 1726). RESULTS: The response rate was 76.8%. All respondents were females; mean age 35.4 years (SD = 8.4). Majority were married (85.5%) and more than one-half had a working experience of <10 years (56.1%). Majority worked in community dental service (94.3%) and in urban areas (61.7%). Overall, they were highly satisfied with most aspects of their career. However, they were least satisfied with administrative workload (58.1%), career advancement opportunities (51.9%) and remuneration package; specifically income (45.2%), allowances (45.2%) and non-commensurate between pay and performance (44.0%). Majority perceived their role as very important in routine clinical tasks such as examination and diagnosis, preventive treatment, extraction of deciduous teeth and oral health promotion. However, fewer than one-half consider complex treatment such as placement of preformed crowns on deciduous teeth (37.1%) and extraction of permanent teeth (37.2%) as very important tasks. CONCLUSION: Majority expressed high career satisfaction with most aspects of their employment but expressed low satisfaction in remuneration, lack of career advancement opportunities and administrative tasks. We conclude that most Malaysian dental therapists have positive perceptions of their current roles but do not favour wider expansion of their roles. These findings imply that there was a need to develop a more attractive career pathway for therapists to ensure sustainability of effective primary oral healthcare delivery system for Malaysia's children.

Outcome of Endoprosthesis used in Limb Salvage Surgery in a Malaysian Orthopaedic Oncology Centre.

Introduction: To describe the duration of survival among bone tumour patients with endoprosthesis reconstruction and to determine frequency of implant failure, revision of surgery, and amputation after endoprosthesis reconstruction. Materials and methods: A retrospective cross-sectional review of all patients with either primary bone tumour or secondary bone metastases treated with en bloc resection and endoprosthesis reconstruction from January 2008 to December 2020. Results: A total of 35 failures were recorded among the 27 (48.2%) patients with endoprostheses. Some of the patients suffered from one to three types of modes of failure on different timelines during the course of the disease. Up to eight patients suffered from more than one type of failure throughout the course of the disease. Out of all modes of failure, local recurrence (type 5 failure) was the most common, accounting for 25.0% of all failure cases. Four patients (7.1%) eventually underwent amputation, which were either due to infection (2 patients) or disease progression causing local recurrence (2 patients). Conclusion: The overall result of endoprosthesis reconstruction performed in our centre was compatible with other centres around the world. Moreover, limb salvage surgery should be performed carefully in a selected patient group to maximise the benefits of surgery.

Attitudes towards the use of fluorides for oral health among Islamic clerics in Kelantan Province, Malaysia.

OBJECTIVE: To assess the knowledge, attitudes and practices of Imams (Islamic clerics) concerning fluoride toothpaste and fluoridated water to improve oral health in Kelantan. BASIC RESEARCH DESIGN: Cross sectional study of Imams in 65 registered mosques in Pasir Puteh district, Kelantan. METHOD AND PARTICIPANTS: Face-to-face interview, using structured questionnaire and some open ended questions. RESULTS: Most of the 83 interviewees (82% participation rate) were unsure whether their toothpaste contained fluoride (64%), only 25% were sure. More than one-third (37%) were using fluoridated piped water. Most (87%) had little knowledge of fluorides and more than two-thirds (69%) had lacked positive attitudes towards its use. Television (54%) was the most common source of information about fluorides, followed by newspapers (9%). The main reasons given among the few who opposed fluoride use were i) fear of dangerous side effects (4%) and ii) uncertainty about the halal status of fluoride (2%), Attitudes were not associated with the use of fluoridated water supply (p=0.999), age (p=0.103), income (p=0.540) and location (p=0.999). CONCLUSION: Over two-thirds of Imams had little knowledge of and lacked positive attitudes towards fluoride use in toothpaste and piped water supplies.

A universal combinatorial design of antibody framework to graft distinct CDR sequences: a bioinformatics approach.

Antibody (Ab) humanization is crucial to generate clinically relevant biologics from hybridoma-derived monoclonal antibodies (mAbs). In this study, we integrated antibody structural information from the Protein Data Bank with known back-to-mouse mutational data to build a universal consensus of framework positions (10 heavy and 7 light) critical for the preservation of the functional conformation of the Complimentarity Determining Region of antibodies. On the basis of FR consensus, we describe here a universal combinatorial library suitable for humanizing exogenous antibodies by CDR-grafting. The six CDRs of the murine anti-human EGFR Fab M225 were grafted onto a distinct (low FR sequence similarity to M225) human FR sequence that incorporates at the 17 FR consensus positions the permutations of the naturally observed amino acid diversities. Ten clones were selected from the combinatorial library expressing phage-displayed humanized M225 Fabs. Surprisingly, 2 of the 10 clones were found to bind EGFR with stronger affinity than M225. Cell-based assays demonstrated that the 10 selected clones retained epitope specificity by blocking EGFR phosphorylation and thus hindering cellular proliferation. Our results suggest that there is a universal and structurally rigid near-CDR set of FR positions that cooperatively support the binding conformation of CDRs.

Therapeutic high affinity T cell receptor targeting a KRASG12D cancer neoantigen.

Neoantigens derived from somatic mutations are specific to cancer cells and are ideal targets for cancer immunotherapy. KRAS is the most frequently mutated oncogene and drives the pathogenesis of several cancers. Here we show the identification and development of an affinity-enhanced T cell receptor (TCR) that recognizes a peptide derived from the most common KRAS mutant, KRASG12D, presented in the context of HLA-A*11:01. The affinity of the engineered TCR is increased by over one million-fold yet fully able to distinguish KRASG12D over KRASWT. While crystal structures reveal few discernible differences in TCR interactions with KRASWT versus KRASG12D, thermodynamic analysis and molecular dynamics simulations reveal that TCR specificity is driven by differences in indirect electrostatic interactions. The affinity enhanced TCR, fused to a humanized anti-CD3 scFv, enables selective killing of cancer cells expressing KRASG12D. Our work thus reveals a molecular mechanism that drives TCR selectivity and describes a soluble bispecific molecule with therapeutic potential against cancers harboring a common shared neoantigen.

Role of Mg(NO3)2 as Defective Agent in Ameliorating the Electrical Conductivity, Structural and Electrochemical Properties of Agarose-Based Polymer Electrolytes.

Polymer electrolytes based on agarose dissolved in DMSO solvent complexed with different weight percentages of Mg(NO3)2 ranging from 0 to 35 wt% were prepared using a solution casting method. Electrochemical impedance spectroscopy (EIS) was applied to study the electrical properties of this polymer electrolyte, such as ionic conductivity at room and different temperatures, dielectric and modulus properties. The highest conducting film has been obtained at 1.48 × 10-5 S·cm-1 by doping 30 wt% of Mg(NO3)2 into the polymer matrix at room temperature. This high ionic conductivity value is achieved due to the increase in the amorphous nature of the polymer electrolyte, as proven by X-ray diffractometry (XRD), where broadening of the amorphous peak can be observed. The intermolecular interactions between agarose and Mg(NO3)2 are studied by Fourier transform infrared (FTIR) spectroscopy by observing the presence of -OH, -CH, N-H, CH3, C-O-C, C-OH, C-C and 3,6-anhydrogalactose bridges in the FTIR spectra. The electrochemical properties for the highest conducting agarose-Mg(NO3)2 polymer electrolyte are stable up to 3.57 V, which is determined by using linear sweep voltammetry (LSV) and supported by cyclic voltammetry (CV) that proves the presence of Mg2+ conduction.