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The concomitant occurrence of renal cell carcinoma (RCC) and primary hyperparathyroidism is rare as these conditions are often identified by the presence of hypercalcemia, which might be missed in asymptomatic individuals. We present the case of a 58-year-old asymptomatic male detected to have a left abdominal mass during his routine medical follow-up. He was subsequently diagnosed with RCC. Further history revealed that his calcium levels had been persistently elevated for the past eight years but had never been investigated. Based on elevated parathyroid hormone levels and radiological findings, a diagnosis of primary hyperparathyroidism has also been made. A right inferior parathyroidectomy was performed, and the histopathological examination results showed a right parathyroid adenoma. Intraoperative intact PTH (iPTH) measurements confirmed the complete removal of the abnormal parathyroid gland. The postoperative calcium levels have returned to normal. To the best of our knowledge, this was the first reported case of concurrent primary hyperparathyroidism and RCC in our population. This case illustrates the importance of considering a broad differential when evaluating patients with hypercalcemia.

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Introduction Chronic kidney disease (CKD) is known to cause an increase in fibroblast growth factor 23 (FGF23). Periodontitis, a condition recognized as a risk factor for CKD, is also potentially associated with the increment of FGF23. This study aims to compare FGF23 levels in CKD patients with and without periodontitis and non-CKD patients with and without periodontitis. Correlation with serum phosphate, calcium, and intact parathyroid hormone (iPTH) was assessed. Additionally, associations between FGF23, calcium, phosphate, iPTH, creatinine, urea, plaque score, and bleeding score with periodontitis in CKD patients were determined. Method A total of 124 participants were categorized into four groups: CKD patients with periodontitis (n=31), CKD patients without periodontitis (n=32), periodontitis patients without CKD (n=32), and healthy population (n=29). The selected CKD patients include those from stages 3 and 4 (predialysis) patients. Serum levels of FGF23, calcium, phosphate, iPTH, creatinine, and urea were analyzed. Oral examinations were conducted to determine the presence and absence of periodontitis and assess plaque and bleeding scores. Result A significantly higher level of FGF23 was found in CKD compared to non-CKD groups; however, no difference was observed with the presence of periodontitis in both CKD and non-CKD. There was no significant correlation found between FGF23 and serum calcium, phosphate, or iPTH concerning periodontal status. Apart from the bleeding score, there was no association between FGF23, calcium, phosphate, iPTH, creatinine, urea, and plaque score with the presence of periodontitis in CKD patients. Conclusion The presence of periodontitis was not associated with higher FGF23 levels in CKD patients. Changes in FGF23, calcium, phosphate, iPTH, creatinine, urea, and plaque score could not be attributed to the presence of periodontitis in CKD patients.

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BACKGROUND: Rapid maxillary expansion (RME) has been proposed as an effective treatment for pediatric obstructive sleep apnea (OSA) and maxillary restriction in children. This study aimed to evaluate the effect of RME appliances on the nasomaxillary complex dimensions in children with OSA and maxillary constriction. METHODS: This prospective longitudinal study included 34 children aged 8-12 years with maxillary restriction and OSA confirmed by polysomnography who had completed RME therapy. The nasomaxillary complex is segmented into the nasal cavity, maxillary sinuses, and nasopharynx. The effect of RME on nasomaxillary complex dimensions was assessed pre and posttreatment using cone-beam computed tomography, analysis, while a second standard overnight polysomnography (PSG) was performed to assess changes in respiratory parameters. RESULTS: Significant improvements were observed, including inferior maxillary dislocation (S-S1 distance and N-ANS), increased anterior and posterior facial height, and a 5.43 events/h reduction in Apnea-Hypopnea Index (p < .001). The nasal cavity volume increased by 2439 (±584) mm3 (p < .001), nasopharynx size increased by 883 (±479) mm3 (p = .008), mid cross-sectional area increased by 31.74 (±14.50) mm2 (p < .001), and the distance between the right and left maxillary sinuses increased by 8.37 (±3.67) mm (p < .001) all exhibited positive changes, with some insignificant variations in volume change (p = .254). CONCLUSION: RME treatment was found to be effective in improving nasal cavity and nasopharyngeal dimensions, leading to improved respiratory parameters in children with OSA and maxillary constriction. While these results are promising, considerations about the potential long-term benefits of RME on future growth are important. The study provides valuable insights into the efficacy of RME as a treatment option for this pediatric population.

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Hindlimb suspension (HLS) mice exhibit osteoporosis of the hindlimb bones and may be an excellent model to test pharmacological interventions. We investigated the effects of inhibiting endoplasmic reticulum (ER) stress with 4-phenyl butyrate (4-PBA) on the morphology, physicochemical properties, and bone turnover markers of hindlimbs in HLS mice. We randomly divided 21 male C57BL/6J mice into three groups, ground-based controls, untreated HLS group and 4-PBA treated group (HLS+4PBA) (100mg/kg/day, intraperitoneal) for 21 days. We investigated histopathology, micro-CT imaging, Raman spectroscopic analysis, and gene expression. Untreated HLS mice exhibited reduced osteocyte density, multinucleated osteoclast-like cells, adipocyte infiltration, and reduced trabecular striations on micro-CT than the control group. Raman spectroscopy revealed higher levels of ER stress, hydroxyproline, non-collagenous proteins, phenylalanine, tyrosine, and CH2Wag as well as a reduction in proteoglycans and adenine. Furthermore, bone alkaline phosphatase and osteocalcin were downregulated, while Cathepsin K, TRAP, and sclerostin were upregulated. Treatment with 4-PBA partially restored normal bone histology, increased collagen crosslinking, and mineralization, promoted anti-inflammatory markers, and downregulated bone resorption markers. Our findings suggest that mitigating ER stress with 4-PBA could be a therapeutic intervention to offset osteoporosis in conditions mimicking hindlimb suspension.

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Background: The significance of the current study was to determine normative levels of PIVKA-II and AFP in patients with unresectable HCC and healthy participants. The second goal was to assess the roles of PIVKA-II and AFP in predicting radiological response after loco-regional therapy. Methods: This prospective cohort study enrolled consecutive samples of HCC patients and healthy controls. Venous blood samples were obtained at baseline and after interventions to determine serum levels of PIVKA-II and AFP using the chemiluminescent microparticle immunoassay method. Radiologic responses were determined based on the WHO criteria. Results: Fifty-four HCC patients (mean age 58.9 years, 49 males) and 40 healthy controls (mean age 33.5 years, 26 males) were recruited. The median serum levels of PIVKA-II and AFP in HCC vs. healthy controls were 988.4 vs. 24.2 mAU/ml and 13.6 vs. 1.7 ng/ml, respectively (both p < 0.001). With ROC curve analysis, the area under the curve (AUC) for PIVKA-II was 0.95 95% CI [0.90-0.99], and for AFP it was 0.98, 95% CI [0.95-1.0]). The cut-off value for PIVKA-II was 41.4 mAU/ml, and AFP was 4.8 ng/ml. PIVKA-II levels correlated significantly with radiological responses (r = 0.64, p = 0.02) but not AFP (r = 0.09, p = 0.2). Conclusion: PIVKA-II and AFP levels are distinctive between unresectable HCC and healthy controls. However, PIVKA-II, not AFP, can predict the radiological response after loco-regional therapy.

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Background: This study aimed to determine the agreement between intact parathyroid hormone (iPTH) and biointact parathyroid hormone (bio-PTH) assays and to correlate them with bone markers. Methods: This cross-sectional study included 180 patients with chronic kidney disease (CKD) stages 3b, 4 and 5D. We measured their iPTH, bio-PTH, 25-hydroxyvitaminD (25(OH)D), C-terminal telopeptide collagen (CTX), procollagen 1 intact N-terminal propeptide (P1NP), calcium, phosphate and alkaline phosphatase (ALP). Results: Higher iPTH than bio-PTH concentrations were seen in CKD stages 3b, 4 and 5D (58[62] versus 55[67] pg/mL, 94[85] versus 85[76] pg/mL and 378[481] versus 252[280] pg/mL, respectively). Both PTH assays showed good agreement among all the subjects, with an intraclass correlation coefficient of 0.832 (P-value < 0.001). The Passing-Bablok showed that the equation for the bio-PTH was PTH = 0.64 iPTH + 15.80, with r = 0.99. The Bland-Altman plots showed increased bias with an increasing PTH concentration. Both PTH assays showed a high positive correlation with CTX and P1NP, a moderate correlation with phosphate, a low correlation with ALP and calcium, and a negligible correlation with phosphate and 25(OH)D. Conclusion: The iPTH and bio-PTH assays were in agreement, but their bias increased with the PTH concentration. The unacceptable large bias indicates that the two assays cannot be used interchangeably. They had a variable correlation with the bone parameters.

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Chronic kidney disease (CKD) and chronic periodontitis (CP) contribute to the increased level of inflammatory biomarkers in the blood. This study hypothesized that successful periodontal treatment would reduce the level of inflammatory biomarkers in CKD patients. This prospective study recruited two groups of CP patients: 33 pre-dialysis CKD patients and 33 non-CKD patients. All patients underwent non-surgical periodontal therapy (NSPT). Their blood samples and periodontal parameters were taken before and after six weeks of NSPT. The serum level of high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and periodontal parameters were compared between groups. On the other hand, kidney function indicators such as serum urea and estimated glomerular filtration rate (eGFR) were only measured in CKD patients. Clinical periodontal parameters and inflammatory markers levels at baseline were significantly higher (p < 0.05) in the CKD group than in the non-CKD group and showed significant reduction (p < 0.05) after six weeks of NSPT. CKD patients demonstrated a greater periodontitis severity and higher inflammatory burden than non-CKD patients. Additionally, CKD patients with CP showed a good response to NSPT. Therefore, CKD patients' periodontal health needs to be screened for early dental interventions and monitored accordingly.

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Temporomandibular disorders (TMDs) are a type of idiopathic orofacial pain. Inflammation, particularly elevated circulating levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and interleukin-8 (IL-8), has been linked to pain symptoms. The purpose of this study was to compare hs-CRP, IL-6, and IL-8 biomarkers and pain intensity with different treatment strategies (LLLT, standard conservative treatment, and combination) for TMD patients. METHODS: A total of 32 participants were randomly included in the study and divided into three groups (Group I, Group II, and Group III) referred from the Dental Clinic, School of Dental Science, HUSM. Patients received LLLT (Groups II and III) in five sessions for the duration of 10 days. Patients in Groups I and III received standard conservative TMD treatment (diet and stress counseling, jaw exercises, physical therapy, which was a hot towel application) by the principal investigator. All blood samples for biomarkers were performed before starting treatments and directly after finishing the treatment protocols, where all results were recorded. RESULTS: The result showed a significant difference in the mean IL-8 (p = 0.001) between the three intervention groups (LLLT, standard treatment, and combined treatment). IL-6 showed an increase in the mean of IL-6 levels from baseline to post-treatment with a better mean in the LLLT treatment group without any significant differences. Additionally, there were no significant mean differences found between the groups and in the group for the hs-CRP biomarker. CONCLUSIONS: A statistically non-significant difference was found in hs-CRP and IL-6 before and after LLLT, conservative, and combined treatment strategies of TMD. A statistically significant difference was observed in the mean levels of IL-8 between the LLLT intervention group and the combined treatment group. Although there was no statistically significant correlation between pain intensity and biomarkers, a statistically significant difference was found in pain intensity before and after LLLT, conservative, and combined treatment strategies. TMJ degeneration could be exacerbated by elevated IL-8 levels. Thus, this can be an important biomarker to mark or identify the painful condition of TMJ.

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OBJECTIVE: This study was aimed to determine the levels of salivary receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) and its association with periodontal status among periodontitis patients. MATERIALS AND METHODS: A cross-sectional study was designed and performed at the Dental Clinic, Hospital Universiti Sains Malaysia (HUSM). Random sampling was employed to identify 88 participants into three groups: 30 mild periodontitis, 30 moderate to severe periodontitis, and 28 healthy (nonperiodontitis) patients. Periodontal parameters: periodontal pocket depth (PPD), clinical attachment level (CAL), plaque score (PS), and gingival bleeding index (GBI) were recorded. In total, 4 mL of unstimulated whole saliva was collected to determine the levels of salivary RANKL and OPG proteins by using ELISA technique. Data were analyzed by using SPSS software version 24.0. RESULTS: Mean values for PPD (5.3 ± 0.5) and CAL (5.6 ± 0.5) were observed higher for moderate to severe periodontitis as compared with values (4.4 ± 0.2) (4.5 ± 0.2) in mild periodontitis patients. The mean salivary RANKL and OPG was 0.23 ± 0.07 ng/mL and 1.78 ± 0.70 ng/mL respectively in moderate to severe periodontitis. Only salivary RANKL levels were significantly and positively correlated with all the clinical periodontal parameters. CONCLUSION: The levels of salivary RANKL were higher as opposed to lower OPG levels in periodontitis patients in contrast to healthy (nonperiodontitis) patients. RANKL levels were significantly associated with the periodontal parameters. Therefore, we can conclude that RANKL can potentially aid as an adjunctive diagnostic protein in evaluating periodontal disease.

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Objective: The aim of this systematic review was to evaluate the effectiveness of laser application in temporomandibular joint disorder. Methods: PubMed, SCOPUS, Science Direct, Web of Science, and Google Scholar electronic databases were searched systematically with restricting the languages to only English and year (January 2001 to March 2020), and studies were selected based on the inclusion criteria. Study quality and publication bias were assessed by using the Robvis, a software package of R statistical software. Results: This systematic review included 32 studies (1172 patients) based on the inclusion and exclusion criteria. Most of the studies reported significant reduction of pain by the use of the laser during TMD treatment. Two-thirds of the study (78.13%) found a better outcome comparing with conventional one. According to Robvis, 84.4% of the studies were high methodological studies with low risk of bias. Conclusion: TMD patients suffer with continuous pain for long time even after conventional treatment. Laser therapy shows a promising outcome of pain reduction for TMD patients. Therefore, laser therapy can be recommended for the TMD patients' better outcome. This trial is registered with PROSPERO (CRD42020177562).

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Numerous studies have been conducted in the previous years with an objective to determine the ideal biomarker or set of biomarkers in temporomandibular disorders (TMDs). It was recorded that tumour necrosis factor (TNF), interleukin 8 (IL-8), IL-6, and IL-1 were the most common biomarkers of TMDs. As of recently, although the research on TMDs biomarkers still aims to find more diagnostic agents, no recent study employs the biomarker as a targeting point of pharmacotherapy to suppress the inflammatory responses. This article represents an explicit review on the biomarkers of TMDs that have been discovered so far and provides possible future directions towards further research on these biomarkers. The potential implementation of the interactions of TNF with its receptor 2 (TNFR2) in the inflammatory process has been interpreted, and thus, this review presents a new hypothesis towards suppression of the inflammatory response using TNFR2-agonist. Subsequently, this hypothesis could be explored as a potential pain elimination approach in patients with TMDs.

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INTRODUCTION: Chronic kidney disease (CKD) is associated with periodontal disease due to its hyperinflammatory state. Limited studies have explored the prevalence of periodontal disease among CKD patients in Malaysia. OBJECTIVE: To assess the periodontal status of pre-dialysis CKD patients in Hospital Universiti Sains Malaysia. METHODS: A total of 46 pre-dialysis CKD patients who attended the nephrology clinic at Hospital Universiti Sains Malaysia were enrolled in this study. Periodontal examination was performed using the periodontal probing depth (PPD), clinical attachment loss (CAL) and plaque index. RESULTS: The majority of the CKD patients were Malay (95.7%) and 80.4% were males. The mean age of the patients was 58.5 years. Using PPD measurement, 37 (74.0%) of the patients had mild periodontitis, 9 (20.0%) had moderate periodontitis and 3 (6.0%) had no periodontitis. Based on CAL measurement, 12 (26%) patients had mild periodontitis, 29 (63.0%) had moderate periodontitis and 5 (11%) had severe periodontitis. The mean (standard deviation [SD]) value of mild and moderate-to-severe periodontitis by PPD measurement were 4.26 (0.26) and 5.24 (0.36), respectively. The mean of mild and moderate-to-severe periodontitis by CAL measurement were 2.66 (0.62) and 4.98 (0.73), respectively. There was no correlation between the periodontal parameters and estimated glomerular filtration rate (PPD: r = -0.160, P = 0.914; CAL: r = -0.135, P = 0.372; plaque index: r = 0.005, P = 0.974). CONCLUSION: This study revealed a greater prevalence and severity of chronic periodontitis among CKD patients. Thus, the periodontal health of CKD patients' needs to be screened and monitored.

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BACKGROUND: Stroke is one of the leading causes of mortality and morbidity in Malaysia. Repetitive transcranial magnetic stimulation (rTMS) is one of the new non-invasive modality to enhance the motor recovery in stroke patients. OBJECTIVES: This pilot study compared the motor evoked potential (MEP) changes using different settings of rTMS in the post-ischemic stroke patient. The goal of the study is to identify effect sizes for a further trial and evaluate safety aspects. METHODS: Eight post-stroke patients with upper limb hemiparesis for at least six months duration were studied in a tertiary hospital in Northeast Malaysia. Quasi experimental design was applied and the participants were randomised into two groups using software generated random numbers. One of the two settings: i) inhibitory setting, or ii) facilitatory setting have been applied randomly during the first meeting. The motor evoked potential (MEP) were recorded before and after application of the rTMS setting. A week later, a similar procedure will be repeated but using different setting than the first intervention. Each patient will serve as their own control. Repeated measures ANOVA test was applied to determine the effect sizes for both intervention through the options of partial eta-squared (η2 p). RESULT: The study observed large effect sizes (η2 p > 0.14) for both rTMS settings in the lesion and non-lesion sides. For safety aspects, no minor or major side effects associated with the rTMS was reported by the participants. CONCLUSIONS: The partial eta square of MEP value for both rTMS settings (fascilitatory and inhibitory) in both lesion and non-lesion sides represents large effect sizes. We recommend further trial to increase number of sample in order to study the effectiveness of both settings in ischemic stroke patient. Our preliminary data showed both settings may improve the MEP of the upper extremity in the ischemic stroke patient. No significant improvement noted when comparing both settings.

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INTRODUCTION: Oral cancer is a life-threatening disease. Lack of public awareness is a potent barrier for the early detection of oral cancer, especially for high-risk populations. OBJECTIVE: This study aimed to determine the awareness and knowledge of the signs, symptoms and risk factors of oral cancer among a Siamese ethnic group in Tumpat, Kelantan. METHODS: A cross-sectional study was conducted, using a guided questionnaire on sociodemography, habits, awareness and knowledge of the signs, symptoms and risk factors of oral cancer. Individuals under 18 years old and who had been diagnosed with oral cancer were excluded from this study. RESULTS: A total of 195 respondents participated, 61.5% were female and the mean age was 46 (1.64). About 41% of the respondents had received secondary education and 35.4% were illiterate. Most respondents were self-employed (21.5%), followed by farmers (19.5%) and housewives (20%). The majority of them had a monthly income that fell below the poverty level of RM 830 (76.9%). Among the respondents, 22.6% had the habit of smoking, 25.6% consumed alcohol, 8.2% were betel quid chewers and 2.6% chewed tobacco. Out of 195 respondents, only 6.7% were aware of oral cancer. About 16.9% of the respondents correctly answered all of the questions regarding the signs and symptoms of oral cancer and only 4.1% knew the risk factors of oral cancer. CONCLUSION: The awareness and knowledge of oral cancer in this targeted population were unsatisfactory. Future effective health promotion programs and education should be emphasised.