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   Table of Contents - Current issue
Coverpage
April-June 2019
Volume 31 | Issue 2
Page Nos. 67-134

Online since Monday, March 25, 2019

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REVIEW ARTICLES  

Molecular basis for the association between depression and circadian rhythm p. 67
Peeraporn Varinthra, Ingrid Y Liu
DOI:10.4103/tcmj.tcmj_181_18  
Depression is a life-threatening psychiatric disorder and a major public health concern worldwide with an incidence of 5% and a lifetime prevalence of 15%–20%. It is related with the social disability, decreased quality of life, and a high incidence of suicide. Along with increased depressive cases, health care cost in treating patients suffering from depression has also surged. Previous evidence have reported that depressed patients often exhibit altered circadian rhythms. Circadian rhythm involves physical, mental, and behavioral changes in a daily cycle, and is controlled by the suprachiasmatic nucleus of the hypothalamus in responding to light and darkness in an environment. Circadian rhythm disturbance in depressive patients causes early morning waking, sleep disturbances, diurnal mood variation, changes of the mean core temperature, endocrine release, and metabolic functions. Many medical interventions have been used to treat depression; however, several adverse effects are noted. This article reviews the types, causes of depression, mechanism of circadian rhythm, and the relationship between circadian rhythm disturbance with depression. Pharmaceutical and alternative interventions used to treat depressed patients are also discussed.
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Improving the assessment of medication adherence: Challenges and considerations with a focus on low-resource settings p. 73
Saurav Basu, Suneela Garg, Nandini Sharma, M Meghachandra Singh
DOI:10.4103/tcmj.tcmj_177_18  
Improving patient survival and quality of life in chronic diseases requires prolonged and often lifelong medication intake. Less than half of patients with chronic diseases globally are adherent to their prescribed medications which preclude the full benefit of treatment, worsens therapeutic outcomes, accelerates disease progression, and causes enormous economic losses. The accurate assessment of medication adherence is pivotal for both researchers and clinicians. Medication adherence can be assessed through both direct and indirect measures. Indirect measures include both subjective (self-report measures such as questionnaire and interview) and objective (pill count and secondary database analysis) measures and constitute the mainstay of assessing medication adherence. However, the lack of an inexpensive, ubiquitous, universal gold standard for assessment of medication adherence emphasizes the need to utilize a combination of measures to differentiate adherent and nonadherent patients. The global heterogeneity in health systems precludes the development of a universal guideline for evaluating medication adherence. Methods based on the secondary database analysis are mostly ineffectual in low-resource settings lacking electronic pharmacy and insurance databases and allowing refills without updated, valid prescriptions from private pharmacies. This significantly restricts the choices for assessing adherence until digitization of medical data takes root in much of the developing world. Nevertheless, there is ample scope for improving self-report measures of adherence. Effective interview techniques, especially accounting for suboptimal patient health literacy, validation of adherence questionnaires, and avoiding conceptual fallacies in reporting adherence can improve the assessment of medication adherence and promote understanding of its causal factors.
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ORIGINAL ARTICLES - BASIC Top

Antinociceptive and anti-inflammatory effects of the citrus flavanone naringenin p. 81
Ting-Wen Chung, Shiming Li, Chi-Chien Lin, Sen-Wei Tsai
DOI:10.4103/tcmj.tcmj_103_18  
Objective: Naringenin, a flavonoid found in citrus fruits, has notably diverse pharmacological properties. In the present study, we investigated the antinociceptive and anti-inflammatory effects of naringenin. Materials and Methods: The antinociceptive effects were evaluated using hot-plate, acetic acid-induced writhing, and tail-flick assays in mice and rats. The anti-inflammatory effects were examined by a carrageenan-induced paw edema test in rats. Results: Naringenin (100 or 200 mg/kg, oral administration) significantly delayed the reaction time of mice to thermal stimulation generated by a hot plate and a tail-flick unit and reduced the acetic acid-induced writhing response in mice. In addition, naringenin significantly decreased paw edema induced by carrageenan in rats, showing its anti-inflammatory effect. Conclusion: Our results show that naringenin has therapeutic potential with antinociceptive and anti-inflammatory properties and can further be exploited for the development of drugs for pain and inflammatory-related diseases.
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HLA-A*29:01-B*07:05-C*15:29*DRB1*10:01-DQB1*05:01, a deduced probable human leukocyte antigen haplotype in association with a human leukocyte antigen-C low-incidence allele C*15:29 in Taiwanese individuals p. 86
Kuo-Liang Yang, Zheng-Zhong Zheng
DOI:10.4103/tcmj.tcmj_111_18  
Objective: HLA-C*15:29 is a low-frequency allele in the human leukocyte antigen (HLA)-C locus. The aim of this study is to confirm the ethnicity of C*15:29 and to deduce a probable HLA haplotype in association with C*15:29 in Taiwanese population. Materials and Methods: A total of 12,534 healthy unrelated Taiwanese individuals were tested for HLA using a sequence-based typing method. The DNA material was subjected to HLA genotyping for the HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci using a commercial polymerase chain reaction–sequencing-based typing kit as per the manufacturer's protocols. Results: The DNA sequence of C*15:29 is identical to C*15:02:01:01 in exons 1, 2, 3, 4, 5, and 6 except for residues 420 and 1034 where A and G of C*15:02:01:01 are substituted by C and A in C*15:29, respectively. The nucleotide substitutions introduce two amino acid replacements at residues 116 and 321 where leucine (L) and cysteine (C) of C*15:02:01:01 are replaced by phenylalanine (F) and tyrosine (Y) in C*15:29, respectively. A probable HLA haplotype associated with C*15:29 in Taiwanese was deduced as A*29:01-B*07:05-C*15:29-DRB1*10:01-DQB1*05:01. The frequency of C*15:29 is estimated at about 0.064%. Conclusion: Information on the ethnicity and distribution of C*15:29 and its deduced probable HLA haplotype is of value for HLA testing laboratories for reference purposes and can help bone marrow donor registries find compatible donors for patients with this uncommon HLA allele.
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ORIGINAL ARTICLES - CLINICAL RESEARCH Top

Bertolotti's syndrome in low-backache population: Classification and imaging findings p. 90
Reddy Ravikanth, Pooja Majumdar
DOI:10.4103/tcmj.tcmj_209_17  
Objective: Lumbosacral transition vertebrae (LSTVs) are associated with alterations in biomechanics and anatomy of spinal and paraspinal structures, which have important implications on surgical approaches and techniques. LSTVs are often inaccurately detected and classified on standard anteroposterior radiographs and magnetic resonance imaging. The use of whole-spine images as well as geometric relationships between the sacrum and lumbar vertebra increases accuracy. The diagnosis of symptomatic LSTV is considered with appropriate patient history and imaging studies. This study aimed to classify the anatomical variations in LSTV and determine, by plain radiography, if there exists a relationship between sacralization and low backache (LBP). Materials and Methods: Five hundred lumbosacral radiographs of LBP patients were examined after obtaining prior consent from the patient and approval from the “institutional ethics committee.” Data collection consisted of the patient's age at the time of imaging gender and number of lumbar vertebral bodies. Dysplastic transverse processes were classified according to the Castellvi radiographic classification system. The incidence of sacralization in patients and the control groups was reported, and the anomaly was compared according to the groups. Results: Of these patient groups, 134 were classified as positive for sacralization, which resulted in an incidence of 26.8%. The most common anatomical variant was Castellvi Type IA (7.6%). There were no statistically significant differences between men and women who had anomaly (P = 0.9256). Higher incidences of Type IB and Type IIB were found in men, but those results were not statistically significant (P = 0.133 and P = 0.581, respectively) when compared with the female group. Daily frequency and intensity of LBP were assessed in patients using visual analog scale (VAS) scores. The patients with LBP and no malformation reported an average pain level on the VAS for pain of 2.2 versus 5.2 in patients with LBP and a transitional vertebra, respectively. Conclusion: Based on our data, we conclude that lumbosacral transitional segments are a common cause in the low-backache population. However, no relationship was found between age and genders in this study. However, in comparison with the nonspecific low-backache group, the VAS scores were significantly higher and the pain duration was significantly longer in the LSTV group.
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Treatment of moderate-to-severe otosclerosis with simultaneous piston surgery and incus vibroplasty p. 96
Chan-Jung Chang, Yu-Hsuan Wen, Chuan-Hung Sun, Millo Achille Beltrame, Hung-Pin Wu
DOI:10.4103/tcmj.tcmj_176_17  
Objective: Whereas the nature of otosclerosis has been extensively investigated, treatment modalities in advanced otosclerosis with the sensorineural hearing loss (SNHL) are relatively unexplored. Materials and Methods: This article presents a retrospective case series study of nine patients who received a one-stage piston coupled with Vibrant Soundbridge® vibroplasty in treating otosclerosis with moderate-to-severe SNHL. Results: The findings suggest that hearing loss could be restored across frequencies and no significant change in the bone-conduction threshold were measured. Conclusion: One-stage piston surgery coupled with incus vibroplasty is a safe procedure and has sufficient efficacy to restore hearing loss in patients with otosclerosis with moderate-to-severe SNHL.
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The serum sclerostin level is positively associated with the aortic augmentation index in patients on peritoneal dialysis p. 102
Lin Lin, Yu-Hsien Lai, Liang-Te Chiu, Jen-Pi Tsai, Chih-Hsien Wang, Bang-Gee Hsu
DOI:10.4103/tcmj.tcmj_90_18  
Objective: Sclerostin is a canonical Wingless (Wnt)/β-catenin signaling pathway inhibitor and had been associated with high arterial stiffness in patients with chronic kidney disease. The aortic augmentation index (AIx), a noninvasive method of assessing central hemodynamics/wave reflections, has been widely used as a clinical index of arterial stiffness. The aim of this study was to evaluate the relationship between fasting serum sclerostin levels and AIx values in peritoneal dialysis (PD) patients. Materials and Methods: Fasting blood samples were obtained from 75 PD patients. The aortic AIx value was measured using a validated tonometry system (SphygmoCor, AtCor Medical, Sydney, New South Wales, Australia). Serum sclerostin and dickkopf-1 (DKK1) levels were quantified using commercial enzyme-linked immunosorbent assay kits. Results: Women PD patients had higher aortic AIx values than men (P = 0.039), while lower aortic AIx values were found in PD patients who used statins (P = 0.004). Univariate linear analysis of the aortic AIx values in PD patients showed that systolic blood pressure (P = 0.001), diastolic blood pressure (P = 0.018), and serum sclerostin levels (P = 0.001) were positively correlated, while height (P = 0.018), body weight (P = 0.001), body mass index (P = 0.043), and weekly total creatinine clearance (P = 0.015) were negatively correlated with aortic AIx values in PD patients. Multivariate linear regression analysis of the factors significantly associated with the aortic AIx values showed that serum sclerostin levels (adjusted R2 = 0.057, P = 0.011) and systolic blood pressure (adjusted R2 = 0.125, P = 0.004) were positively associated, while body weight (adjusted R2 = 0.113, P = 0.002) was inversely associated with aortic AIx values in PD patients. Conclusion: In this study, the serum sclerostin level, but not DKK1, was positively associated with aortic AIx values in PD patients.
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Quality of life in patients with Parkinson's disease after subthalamic stimulation: An observational cohort study for outcome prediction p. 107
Jiin-Ling Jiang, Shin-Yuan Chen, Sheng-Tzung Tsai
DOI:10.4103/tcmj.tcmj_92_18  
Objective: The objective of this study was to investigate the changes in health-related quality of life (HRQoL) and motor and depressive symptoms in patients with Parkinson's disease (PD) from baseline to 12 months following subthalamic nucleus deep brain stimulation (STN-DBS). Materials and Methods: The study utilized a prospective observational cohort design. Thirty-three PD patients with a good levodopa response but drug-related morbidity were included. PD Questionnaire-39 (PDQ-39) scores, unified PD rating scale (UPDRS) scores, Hoehn and Yahr stages, Beck Depression Inventory-II scores, and levodopa equivalent daily doses (LEDD) were obtained at baseline and 1 year after surgery. Results: The enrolled patients showed a significant HRQoL improvement of 21.43% at 12 months after STN-DBS as assessed by the PDQ-39 total score. There was a 34.92% improvement in UPDRS scores after STN-DBS at 1 year follow-up. Subitem analysis revealed significant improvement in UPDRS part II, III, and IV scores. The LEDD was significantly reduced by up to 27.36% 12 months after surgery. The preoperative PDQ-39 total score and LEDD predicted postoperative HRQoL in PD following STN-DBS. Conclusions: The current study demonstrated that STN-DBS surgery significantly improved HRQoL and motor outcomes of patients with PD. The preoperative PDQ-39 score and LEDD were predictors of the efficacy of postoperative HRQoL following surgery.
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Is prone sleeping dangerous for neonates? Polysomnographic characteristics and NDN gene analysis p. 113
Shi-Bing Wong, Lu-Lu Zhao, Shu-Hua Chuang, Wen-Hsin Tsai, Chun-Hsien Yu, Li-Ping Tsai
DOI:10.4103/tcmj.tcmj_29_18  
Objective: Prone sleep is an identified risk factor for sudden infant death syndrome, possibly due to reduced blood pressure, cerebral oxygenation, and impaired cerebral vascular control. Cardiac and respiratory responses in neonates during supine and prone sleep have not been reported. Materials and Methods: In this study, daytime polysomnography (PSG) data from 17 neonates aged 2–3 days during supine and prone sleep were reported and the NDN gene, an important gene for neonatal respiratory control, was sequenced for correlation with neonatal respiratory parameters. Heart rate (HR), oxygen saturation, carbon dioxide concentration, sleep stages, central apnea index (CAI), obstructive apnea/hypopnea index (OAHI), and oxygen nadir were compared between supine and prone sleep and between participants with different single-nucleotide polymorphisms (SNPs) in the NDN gene. Results: During prone sleep, neonates had a faster HR, decreased oxygen saturation, and a longer duration of oxygen saturation <90% than during supine sleep, suggesting that cardiopulmonary responsiveness was impaired. Sleep efficiency, sleep stages, oxygen nadir, and carbon dioxide tension were not different during supine and prone sleep. Central apnea occurred more significantly than obstructive apnea. During supine and prone sleep, the CAI was 3.3 ± 2.9/h and 2.3 ± 2.6/h and the OAHI was 0.6 ± 0.7/h and 0.6 ± 0.8/h, respectively. We found one SNP rs3743340 in the NDN gene that had no effect on the sleep and respiratory parameters of PSG. Conclusion: Tachycardia and respiratory instability were recorded in neonates during prone sleep, suggesting that neonates are vulnerable to cardiopulmonary events during prone sleep. Therefore, young neonates should be kept in the supine sleep position unless there are contraindications.
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Evaluation of mandibular anterior nutrient canals in hypertensive and diabetes mellitus patients: A comparative radiographic study p. 118
Sukhleen Kaur, Pradhuman Verma, Anjali Saigal
DOI:10.4103/tcmj.tcmj_43_18  
Objective: Radiographic evaluation of nutrient canals (NCs) in the mandibular anterior region using intraoral periapical radiographs (IOPARs) and to determine whether they can be used as a potential marker for hypertension (HT) and diabetes mellitus (DM). Materials and Methods: Randomly selected 600 patients of 21-60 years age group (Group I: 200 HT; Group II: 200 DM; Group III: Healthy subjects) were considered. The case history was recorded including details for DM and HT (duration, type, and medication). Blood pressure was measured, followed by blood examination for blood sugar levels. Selected patients were subjected to IOPARs using CS-2100C machine by the paralleling technique. Selected radiographs were evaluated by two observers independently for the presence/absence, number, and location of NCs between #33 and #43. Data obtained were tabulated and subjected to statistical analysis using SPSS 20.0 statistical software and intergroup reliability was checked using Cohen's kappa test. Results: Evaluation of various parameters of NCs showed an insignificant interobserver bias. The incidence of NCs presence was noted maximum in Group II (93.5%), followed by Group I (88.5%) and III (44.5%). Of total 888 NCs found, maximum were found in Group I, followed by II and III. On comparing the incidence of NCs present among both genders and location in study groups, no statistical correlation was found. Conclusion: Statistically significant increase in the incidence and number of NCs in Group I and II compared to controls can act as an adjunct diagnostic marker for the detection of DM and HT; although, no significant correlation was obtained between gender and location of NCs in different study groups. Furthermore, there was no significant correlation was found between the severity of disease and incidence of the presence of NCs.
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CASE REPORTS Top

A rare case of cefepime-induced cholestatic liver injury p. 124
Pei-Fei Liao, Yao-Kuang Wu, Kuo-Liang Huang, Hsin-Yi Chen
DOI:10.4103/tcmj.tcmj_151_18  
Cefepime is widely used in the hospital setting, and only a few studies have reported neurotoxicity and nephrotoxicity as side effects of this drug. Herein, we present a 93-year-old man who exhibited features of cholestatic hepatitis including elevated blood transaminases and direct-form predominant bilirubin levels after administration of cefepime. Blood liver tests showed total recovery after discontinuing the offending agent. Cefepime was probable to cause drug-induced cholestatic hepatitis in our patient since the Roussel Uclaf Causality Assessment Method score for cefepime was 7. No drug interactions were likely according to the Drug Interaction Probability Scale for this patient. No similar cases of cholestatic drug-induced liver injury related to cefepime have been reported previously. Hence, this rare condition requires a high degree of clinical suspicion for prompt diagnosis and treatment.
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Anaplastic sarcoma of the kidney: Case report and literature review p. 129
Chien-Chin Chen, Kai-Sheng Liao
DOI:10.4103/tcmj.tcmj_194_18  
We present a case of a 22-year-old female with gross hematuria for 1 month. A 9.5-cm tumor was found at her left kidney. On suspicion of a renal cancer, she received left nephrectomy. Histologically, it was a hypercellular tumor with undifferentiated anaplastic neoplastic cells in fascicular sheets intermixed with chondroid nodules. The differential diagnoses included anaplastic sarcoma of the kidney (ASK), anaplastic Wilms tumor, mesenchymal chondrosarcoma, sarcomatoid renal cell carcinoma, clear cell sarcoma of the kidney, rhabdoid tumor of the kidney, congenital mesoblastic nephroma, and synovial sarcoma. Based on the results of the work-up and literature review, ASK was diagnosed. The postoperative recovery was uneventful, and the patient began adjuvant chemotherapy (Ifosfamide [1800 mg/m2] and Epirubicin [60 mg/m2]) 5 weeks after the operation. Herein, we present this case to share the experience on an extremely rare entity.
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PATHOLOGY PAGE Top

High-grade fetal adenocarcinoma of the lung p. 133
Chiu-Hsuan Cheng
DOI:10.4103/tcmj.tcmj_179_18  
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