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   Table of Contents - Current issue
Coverpage
April-June 2020
Volume 32 | Issue 2
Page Nos. 101-222

Online since Tuesday, March 3, 2020

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REVIEW ARTICLES - BASIC  

Induced pluripotent stem cells and derivative photoreceptor precursors as therapeutic cells for retinal degenerations p. 101
Rupendra Shrestha, Yao-Tseng Wen, Rong-Kung Tsai
DOI:10.4103/tcmj.tcmj_147_19  
The visual impairment associated with inherited retinal degeneration and age-related degeneration of photoreceptors is causing substantial challenges in finding effective therapies. However, induced pluripotent stem cell (iPSC)-derived therapeutic cells such as photoreceptor and retinal pigment epithelium (RPE) cells provide the ultimate options in the rescue of lost photoreceptors to improve the visual function in end-stage degeneration. Retinal cells derived from iPSC are therapeutic cells that could be promising in the field of cell replacement therapy and regenerative medicine. This review presents an overview of the photoreceptor degeneration, methods of iPSC generation, iPSC in retinal disease modeling, summarizes the photoreceptor differentiation protocols, and challenges remained with photoreceptor cell replacement for the treatment of retinal diseases. Thus, the burden and increased incidence of visual impairment emphasizes the need of novel therapy, where iPSC-derived photoreceptor and RPE cells proved to be promising for curing the retinal dysfunction and act as renovation in approach to improve visual function.
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Exosomes in clinical trial and their production in compliance with good manufacturing practice p. 113
Yu-Shuan Chen, En-Yi Lin, Tzyy-Wen Chiou, Horng-Jyh Harn
DOI:10.4103/tcmj.tcmj_182_19  
Exosomes, 60-200-nm extracellular vesicles secreted from cells, have been used as an active pharmaceutical ingredient or drug carrier in disease treatment. Human- and plant-derived exosomes are registered in clinical trials, but more complete reports are available for human-derived exosomes. Because exosomes act as vesicles and carry cell secreting components, they have been used as drug or peptide vehicles to treat diseases. The dendritic cells (DCs) and mesenchymal stem cells (MSCs) are two popular cell sources for exosome preparation. Exosomes from DCs can initiate inflammation in patients, particularly in patients with cancer, as they contain the tumor antigen to induce specific inflammation response. A well-established cell bank of MSCs is available, and these cells can be used as an alternative source for exosome preparation. The major application of MSC-derived exosomes is in inflammation treatment. Exosomes in clinical trials need to comply with good manufacturing practice (GMP). Three important issues are prevalent in GMP for exosomes, i.e., upstream of cell cultivation process, downstream of the purification process, and exosome quality control. This paper concisely reviews exosome development, including exosome generation and clinical trial application.
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REVIEW ARTICLES - CLINICAL Top

Role of videourodynamic study in precision diagnosis and treatment for lower urinary tract dysfunction p. 121
Yuan-Hong Jiang, Sheng-Fu Chen, Hann-Chorng Kuo
DOI:10.4103/tcmj.tcmj_178_19  
Lower urinary tract symptoms (LUTS) are complicated and cannot be used alone to diagnose lower urinary tract dysfunctions (LUTDs) and guide treatment. Patients with bladder outlet obstruction (BOO), impaired detrusor contractility, and hypersensitive bladder might present with voiding predominant symptoms, whereas patients with detrusor overactivity (DO), dysfunctional voiding, or BOO might also present with storage symptoms. To clearly identify the pathophysiology of LUTD, a comprehensive urodynamic study (UDS) including pressure flow and image during the storage and emptying phases, naming videourodynamic study (VUDS), is necessary. This study is especially mandatory in the diagnosis of (1) male LUTS refractory to medical treatment for benign prostatic hyperplasia, (2) female voiding dysfunction and urinary retention, (3) diagnosis of overactive bladder syndrome refractory to first-line medication, (4) management of female stress urinary incontinence and postoperative LUTS, (5) diagnosis and management of neurogenic LUTD, (6) pediatric urinary incontinence and enuresis, (7) geriatric urinary incontinence, and (8) recurrent bacterial cystitis. Although VUDS should not be used as a screening test for any LUTS, it should be considered when the initial management cannot relieve LUTS, or when invasive surgical procedure is planning to undertake for patients with refractory LUTS. VUDS should be recommended as the second-line investigation when the initial diagnosis and treatment based on the symptoms alone or noninvasive tests fail to improve LUTS.
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Impact of new techniques on adenoma detection rate based on meta-analysis data p. 131
Chih-Wei Tseng, Felix W Leung, Yu-Hsi Hsieha
DOI:10.4103/tcmj.tcmj_148_19  
The high incidence of colorectal cancer and the occurrence of interval cancers after screening colonoscopy support the need to develop methods to increase adenoma detection rate (ADR). This review focuses on the importance of ADR and the impact of new techniques on ADR based on meta-analysis data. The low-cost interventions (such as water-aided colonoscopy, second observation, and dynamic position change) were effective in increasing ADR. So were enhanced imaging techniques and add-on devices. Increase with higher cost interventions such as newer scopes is uncertain. Water exchange (WE) has the highest ADR compared with water immersion, air insufflation, and carbon dioxide insufflation. Second observation with forward or retroflexed views improved the right colon ADR. Add-on devices result in only modest improvement in ADR, of particular help in low performing endoscopists. The second-generation narrow-band imaging (NBI) provided a two-fold brighter image than the previous system. The improvement in ADR with NBI required the “best” quality bowel preparation. New endoscopic techniques incur various additional costs, nil for WE, small for tip attachments but large for the newer scopes. In conclusion, one or more of the above methods to improve ADR may be applicable in Taiwan. A comparison of these approaches to determine which is the most cost-effective is warranted.
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Clinical characteristics and epilepsy in genomic imprinting disorders: Angelman syndrome and Prader–Willi syndrome p. 137
Tzong-Shi Wang, Wen-Hsin Tsai, Li-Ping Tsai, Shi-Bing Wong
DOI:10.4103/tcmj.tcmj_103_19  
Angelman syndrome (AS) and Prader–Willi syndrome (PWS) are considered sister imprinting disorders. Although both AS and PWS congenital neurodevelopmental disorders have chromosome 15q11.3-q13 dysfunction, their molecular mechanisms differ owing to genomic imprinting, which results in different parent-of-the-origin gene expressions. Recently, several randomized controlled trials have been proceeded to treat specific symptoms of AS and PWS. Due to the advance of clinical management, early diagnosis for patients with AS and PWS is important. PWS is induced by multiple paternal gene dysfunctions, including those in MKRN3, MAGEL2, NDN, SNURF-SNPRPN, NPAP1, and a cluster of small nucleolar RNA genes. PWS patients exhibit characteristic facial features, endocrinological, and behavioral phenotypes, including short and obese figures, hyperphagia, growth hormone deficiency, hypogonadism, autism, or obsessive–compulsive-like behaviors. In addition, hypotonia, poor feeding, failure to thrive, and typical facial features are major factors for early diagnosis of PWS. For PWS patients, epilepsy is not common and easy to treat. Conversely, AS is a single-gene disorder induced by ubiquitin-protein ligase E3A dysfunction, which only expresses from a maternal allele. AS patients develop epilepsy in their early lives and their seizures are difficult to control. The distinctive gait pattern, excessive laughter, and characteristic electroencephalography features, which contain anterior-dominated, high-voltage triphasic delta waves intermixed with epileptic spikes, result in early suspicion of AS. Often, polytherapy, including the combination of valproate, levetiracetam, lamotrigine, and benzodiazepines, is required for controlling seizures of AS patients. Notably, carbamazepine, oxcarbazepine, and vigabatrin should be avoided, since these may induce nonconvulsive status epilepticus. AS and PWS presented with distinct clinical manifestations according to specific molecular defects due to genomic imprinting. Early diagnosis and teamwork intervention, including geneticists, neurologists, rehabilitation physicians, and pulmonologists, are important. Epilepsy is common in patients with AS, and after proper treatment, seizures could be effectively controlled in late childhood or early adulthood for both AS and PWS patients.
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ORIGINAL ARTICLES - BASIC RESEARCH Top

Visualizing the effects of antibiotics on the mouse colonic mucus layer p. 145
Chun-Yao Chen, Kai-Chieh Hsu, Hsuan-Yu Yeh, Han-Chen Ho
DOI:10.4103/tcmj.tcmj_70_19  
Objective: Mucus provides a protective barrier separating sensitive epithelial surfaces from the outside world. The mouse colonic mucus is organized as a bacteria-free inner layer and a bacteria-colonized outer layer. Antibiotic treatments are known to disturb gut microbiota, but their effect on the mucosal barrier is rarely discussed. The aim was to evaluate and visualize the impact of antibiotics on the colonic mucus and the microbial community. Materials and Methods: Two sets of experiments were conducted. In the antibiotic experiment, mice orally ingested both streptomycin and bacitracin for 7 days. In the recovery experiment, mice were allowed to recover for 7 days without antibiotics after having received the 7-day antibiotic treatment. Mouse colons were isolated and divided into proximal, middle, and distal parts. Specimens were examined under a transmission electron microscope to identify morphological changes. The gut microbial community was evaluated by analyzing 16S rDNA sequences isolated from the different parts of the mouse colon. Results: The antibiotic-treated mice were physiologically normal. However, a significantly increased inner mucus layer in the proximal and middle colon and a dramatic decrease in bacterial numbers in the outer mucus layers were observed. The 16S rDNA compositions showed a similarity in the dominant taxa among different colon sections. While control mice had a diverse microbiota, antibiotic treatments effectively eliminated most of the bacteria, such that the community was dominated by only one genus (Turicibacter or Staphylococcus). Furthermore, following antibiotic withdrawal in treated mice, the thickness of the inner mucus layer returned to control levels, and the microbial community regained a more complex structure, dominated by Firmicutes, Bacteroidetes, and Proteobacteria. Conclusions: Our results indicated that antibiotic treatments not only disturbed the microbiota but also altered the structure of the mucus layer. After the withdrawal of antibiotics, the mucus layer was quickly regenerated within days, probably in response to microbial growth. The recolonization by gut inhabitants with diverse ecological roles, such as mucin-degraders and fermenters indicate that the gut ecosystem is functionally sound and highly resilient.
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Mechanisms of the antiplatelet and analgesic effects of dextromethorphan and its metabolites p. 154
Wen-Lin Su, Yu-Ya Weng, Wen-Hsin Huang, Hao-Ai Shui, Tz-Chong Chou
DOI:10.4103/tcmj.tcmj_48_19  
Objective: In the present study, we investigated the effects of dextromethorphan (DM) and its metabolites, including dextrorphan (LK2), 3-methoxymorphinan (LK3), and 3-hydroxymorphinan (LK4), on platelet aggregationin vitro and the inflammatory pain caused by carrageenan in rats, and their underlying mechanisms. Materials and Methods: Rabbit platelets were pretreated with DM or its metabolites to assess their effects on platelet aggregation and related target mediators. In addition, the analgesic activity and the underlying mechanisms of DM and LK3 were investigated in a carrageenan-evoked thermal hyperalgesia rat model. Results: The inhibitory potency of DM and its metabolites on platelet aggregation induced by arachidonic acid or collagen was LK3> DM > LK4>> LK2 as demonstrated by the half-maximal inhibitory concentration values. Moreover, the mechanisms of the antiplatelet effect of DM and LK3 may involve the inhibition of intracellular calcium mobilization, expression of platelet surface glycoprotein IIb/IIIa, the formation of thromboxane B2, and elevation of platelet membrane fluidity. DM and LK3 also exhibited analgesic effects on carrageenan-evoked thermal hyperalgesia by suppressing the production of pro-inflammatory cytokines, nitric oxide, prostaglandin E2, and neutrophil infiltration in inflammatory sites. Conclusion: DM and its metabolites, especially LK3, exhibit both antiplatelet and analgesic effects, and may, therefore, potentially ameliorate platelet hyperactivity and inflammatory-related diseases.
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Genomic investigation of emerging zoonotic pathogen Shewanella xiamenensis p. 162
Jui-Hsing Wang, Shu-Ying Tseng, Kwong-Chung Tung
DOI:10.4103/tcmj.tcmj_69_19  
Objective: Shewanella xiamenensis is an emerging zoonotic pathogen commonly found in aquatic ecosystem. Clustered regularly interspaced short palindromic repeats (CRISPR) and (CRISPR)-associated gene systems act as adaptive immune system of prokaryotes. Recently, growing evidence suggested their role in bacterial virulence and resistance. Despite its medical importance, little is known about the genomic characteristics of S. xiamenensis. Materials and Methods: Strain ZYW6 was isolated from Epinephelus awoara. We sequenced the 16S rRNA gene and blast against the GenBank bacterial database. Antibiotic susceptibility tests and interpretation were performed by automatic VITEK 2 system. We extracted the genomic DNA with QIAGEN Genomic-tip 100/G kit and QIAGEN Genomic DNA Buffer Set. Whole-genome shotgun sequencing was performed using the Illumina MiSeq sequencer. To identify the CRISPR-Cas System in the genome of S. xiamenensis ZYW6, the Integrated Microbial Genomes and Microbiomes and CRISPRFinder were used. Results: We characterized the genome of a S. xiamenensis strain. The genome is 4,765,190 bp in length and encodes 4262 open-reading frames. Type I CRISPR-Cas system and serine biosynthesis genes were identified. Conclusion: Our results demonstrate the genetic structure of CRISPR-Cas system, l-serine synthesis, and oxacillinase in S. xiamenensis. The report of antibiotics resistance genes in the study might indicate a possible reservoir of antimicrobial drug resistance determinants in food animal, resulting in potential infection source. The findings provide insights into the structure and composition of CRISPR-Cas system in S. xiamenensis and foundation for future biological validation.
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ORIGINAL ARTICLES - CLINICAL RESEARCH Top

Testing for weak D Antigen: Spectrum and its applied role in rhesus-negative transfusions in Andaman and Nicobar Islands p. 167
Rupinder Kaur Brar, PS Shaiji, Sahil Sehgal
DOI:10.4103/tcmj.tcmj_222_18  
Objectives: Rhesus (Rh) blood group with variable expression of D antigen is one of the complex systems in immunohematology. Weak D antigen is a phenotype where the D antigen is weakly expressed on red blood cells, and this antigen cannot be detected by routine methods. This study was conducted to determine the frequency of Rh D negativity and weak D antigen among healthy blood donors and to review the clinical significance of weak D antigen pertaining to Rh D-negative transfusions. Materials and Methods: This cross-sectional prospective study was conducted in G. B Pant Hospital from January 2016 to June 2017 in which all the blood donors from Port Blair and adjacent islands of Andaman and Nicobar were grouped for Rh D antigen and those who tested negative for the D antigen were further tested for weak D antigen by incubating for 30 min and subsequent addition of anti-human globulin sera. Results: Out of 6415 donors, 6085 (94.86%) were Rh D positive and 330 (05.14%) were Rh D negative. Among the Rh D-negative donors, 05 (01.51%) were positive for weak D antigen. The frequency of Rh D negativity was 25.76% in a blood group, 25.15% in B, 07.88% in AB and 41.21% in O blood group phenotype. Conclusion: Although the frequency of weak D antigen is low (01.51%), the strong immunogenicity of Rh D antigen discernates the need for appropriate testing for weak D antigen. This is of particular concern in Rh D-negative pregnant females as it can produce alloimmunization if accidentally given weak D antigen positive blood.
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Factors determining institutional delivery in eastern part of India p. 171
Madhumita Mukherjee, Manas Pratim Roy
DOI:10.4103/tcmj.tcmj_11_19  
Objective: Institutional delivery (ID) plays a vital role for determining the outcome of pregnancy and ensuring care to mother and newborn. The present study aims to find out the correlates of ID from the eastern part of India. Materials and Methods: Data from National Family Health Survey 4 were analyzed for three states – Bihar, West Bengal, and Jharkhand, keeping district as a unit of analysis. Correlation and regression were used for finding out the determinants of ID. Results: Overall, 67.8% of deliveries were conducted in hospitals. All the three states were able to improve performance on related health parameters like antenatal care. After adjusting for other variables, on multiple linear regression, female literacy was significantly related to ID. Conclusions: Social parameters need to be focused for encouraging ID.
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Younger tamoxifen-treated breast cancer patients also had higher risk of endometrial cancer and the risk could be reduced by sequenced aromatase inhibitor use: A population-based study in Taiwan p. 175
Sung-Chao Chu, Chia-Jung Hsieh, Tso-Fu Wang, Mun-Kun Hong, Tang-Yuan Chu
DOI:10.4103/tcmj.tcmj_17_19  
Objective: Previous Western studies reported that older (≥50 years) breast cancer survivors with tamoxifen treatment had higher risk of endometrial cancer. This study aims to disclose whether younger (<50 years) tamoxifen-treated breast cancer patients also had higher risk of endometrial cancer and to examine whether sequenced aromatase inhibitor (AI) use could reduce the risk. Materials and Methods: A population-based cohort of 39,216 newly diagnosed breast cancer patients was identified from Taiwan National Health Insurance Database from 1999 to 2012. The risk of endometrial cancer in nonusers (n = 14,588), tamoxifen-only (n = 19,302), and sequenced AI (n = 5326) users was compared with Cox regression analysis and was adjusted with age, diabetes, hypertension, and chemotherapy. Results: During the 14-year study period, 133 patients were diagnosed with subsequent endometrial cancers. Compared with nonusers, tamoxifen-only users had higher risk of endometrial cancer (14-year incidence 1.7% vs. 0.3%; adjusted hazard ratio [HR] 3.90; 95% confidence interval [CI], 2.37–6.42). This was observed in both older (≥50 years) and younger (40–50 years) age groups. Adjusted HR (95% CI) for the latter was 3.74 (1.65–8.48). This risk persisted after cessation of tamoxifen use. The risk of endometrial cancer was lower in sequenced AI when compared with tamoxifen-only users (adjusted HR 0.43; 95% CI, 0.25–0.72). Conclusions: Not only patients ≥50 years but also younger (40–49 years) patients with tamoxifen treatment had higher risk of subsequent endometrial cancer in this nation-wide cohort. We suggest regular gynecologic monitoring not only during active use but also during follow-up phase. Sequenced AI use may reduce the risk of endometrial cancer in tamoxifen-treated breast cancer patients.
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Parenting stress and depressive symptoms in the family caregivers of children with genetic or rare diseases: The mediation effects of coping strategies and self-esteem p. 181
Chin-Chen Wen, Shao-Yin Chu
DOI:10.4103/tcmj.tcmj_35_19  
Objective: To elucidate how parenting stress influence depressive symptoms in the family caregivers of children with genetic or rare diseases by examining the mediation effects of coping strategies (problem-focused, emotion-focused, and dysfunctional coping) and self-esteem. Materials and Methods: In total, 100 family caregivers were recruited and administered a questionnaire assessing demographics and study measures. We used the PROCESS for SPSS macro with 10,000 bootstrapped samples and a 95% confidence interval to test the proposed mediation models. Results: Increased parenting stress was associated with more depressive symptoms, partially via dysfunctional coping, but not problem- or emotion-focused coping strategies. The serial multiple mediation pathway (parenting stress → low self-esteem → dysfunctional coping → depressive symptoms) was not significant, whereas the indirect effect of via dysfunctional coping alone had a significantly partial mediation effect. Conclusions: Dysfunctional coping strategies may explain the parenting stress–depressive symptom relationship. The goals of psychosocial medical care for family caregivers were suggested.
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Adaptive immunoregulation of luteolin and chlorogenic acid in lipopolysaccharide-induced interleukin-10 expression p. 186
Chu-Yen Cheng, Chia-Chou Yeh
DOI:10.4103/tcmj.tcmj_23_19  
Objective: To investigate the mechanism of the adaptive effect of two compounds in Lonicerae japonica flos (LJF), luteolin (LUT) and chlorogenic acid (CGA), on the expression of interleukin (IL) IL-10 and IL-6. Materials and Methods: RAW264.7 cells receiving lipopolysaccharide (LPS) were pretreated with CGA and LJF. The expression of pro-inflammatory cytokines and IL-10 was evaluated by reverse transcription-polymerase chain reaction. Moreover, the concentrations of IL-10 and IL-6 were measured by enzyme-linked immunosorbent assay in the culture medium obtained 24 h after LPS treatment. Nuclear extracts of RAW264.7 cells, pretreated with CGA or LUT and LPS, were prepared after 6 h, and C/EBPβ and C/EBPδ were measured by Western blotting. Nuclear factor-κB (NF-κB) activity was measured by electrophoretic mobility shift assay. The phosphorylated form of IκB, ERK1/2, p38, JNK, and IκB, ERK2, p38, or JNK were also measured by Western blotting. Results: CGA enhanced the LPS-induced expression of IL-10 and IL-6, and increased NF-κB, Sp1, C/EBPβ and δ. The effect of CGA is interfered with Lut by suppressing the phosphorylation of IκB and p38, and NF-κB activity. In the event, IL-6 was suppressed and IL-10 was not influenced. Conclusion: LUT and CGA, which are abundant in LJF that is one of the ingredients in Gingyo-san, have adaptive immunoregulative effect on the expression of IL-10.
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Copy number alternations of the 17q23-rs6504950 locus are associated with advanced breast cancers in Taiwanese women p. 193
Chien-Yu Lin, Shu-Fen Yang, Yu-Ling Ho, Cheng-Mao Ho
DOI:10.4103/tcmj.tcmj_45_19  
Objective: Breast cancer is one of the most common malignancies and a leading cause of cancer-related death in women worldwide. Both hormone-related factors and genetic aberrations could cause breast cancer. We investigated copy number alternations (CNAs) on four breast cancer-susceptible loci, namely 2q35-rs13387042, 3p24-rs4973768, 17q23-rs6504950, and fibroblast growth factor receptor 2 (FGFR2)-rs2981578, in Taiwanese women. Patients and Methods: Breast cancer tissues and blood samples from 66 patients and their clinical data were collected from a human biobank. The copy numbers of the germline samples (from blood) and cancer tissues from each patient on the susceptible loci – 2q35, 3p24, 17q23, and FGFR2 – were obtained using TaqMan probes in the Applied Biosystems Inc., (ABI) StepOnePlus Real-Time Polymerase Chain Reaction instrument and CopyCaller® Software v1.0 (ABI, CA, USA). Results: The mean copy numbers output by CopyCaller® Software v1.0 of the cancer tissues on these susceptible loci (2q35, 3p24, 17q23, and FGFR2) from the 66 patients were higher than those of the blood samples (2.0 vs. 1.9); however, significantly higher copy numbers for cancer tissues compared with germline samples were discovered only on 2q35-rs13387042 (P = 0.035). In addition, patients with advanced breast cancers had relatively many CNAs between their cancer tissues and germline samples on 17q23-rs6504950 (P = 0.008). Multivariate analysis revealed that the risk factor for patients with advanced breast cancers was CNAs between cancer tissues and germline samples on 17q23-rs6504950 (odds ratio = 13.337, 95% confidence interval: 1.525–122.468). Conclusions: CNAs on 17q23-rs6504950 between cancer tissues and germline samples could affect cancer progression in Taiwanese women with breast cancer. Further investigations regarding the role of CNAs on 17q23-rs6504950 in cancer progression are necessary to elucidate the pathogenesis of breast cancer.
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The pattern of problematic internet use and mental health-related internet use among psychiatric outpatients at a tertiary care center p. 198
Yatan Pal Singh Balhara, Swarndeep Singh, Rachna Bhargava
DOI:10.4103/tcmj.tcmj_50_19  
Objective: There is scarce literature available on the pattern of problematic internet use (PIU) and use of internet for mental health help-seeking among adult patients with psychiatric disorders in South-East Asian countries. The present study aimed to understand the pattern of PIU among adult patients attending the outpatient psychiatry services at a tertiary care center in India. Further, it aimed to explore the use of internet for seeking mental health-related information or services among them. Materials and Methods: This cross-sectional study recruited adult outpatients attending the outpatient psychiatry services following purposive sampling between June 2018 and December 2018. A semi-structured questionnaire was used to collect information regarding sociodemographic characteristics and internet use pattern of participants, including use of internet for various mental health-related purposes. The Generalized Problematic Internet Use Scale 2 (GPIUS-2) was used to assess the PIU. Statistical analysis was performed using SPSS version 23.0 software. Results: Among 155 study participants, 45 (29.03%) scored above 60 on GPIUS-2. Those with PIU were significantly younger, reported higher duration of daily internet use, and spent greater proportion of time online on activities related to social networking or social media than those with and without PIU. More than half of the participants reported internet use for seeking mental health-related information at least once in the past 1 month. There was no significant difference in the mental health-related internet use among adult patients with different psychiatric diagnoses, except for two situations. There was lesser use of internet for seeking information related to the symptoms of illness and various treatment modalities available among participants diagnosed with psychotic disorder. On the other hand, a greater use of internet for seeking information related to the symptoms of illness was reported by participants diagnosed with anxiety disorder. Conclusion: This study suggested that PIU is a frequently cooccurring condition among adult patients with primary psychiatric disorder. The importance of internet as a medium for seeking mental health information and services was observed among most of the study participants.
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Assessment of prevalence and position of mandibular incisive canal: A cone beam computed tomography study p. 205
Reema Talat Ayesha, Balaji Pachipulusu, Poornima Govindaraju
DOI:10.4103/tcmj.tcmj_76_19  
Objectives: To avoid anatomical and functional damage to mandibular interforaminal region during surgeries, it is necessary to detect the existence of mandibular incisive canal (MIC) and its proximity to adjacent structures. This study was aimed to evaluate the prevalence of MIC and its proximity to adjacent structures among Indian population. Materials and Methods: The images of 80 subjects with the age range of 20–60 years who had undergone cone beam computed tomography examination of the mandible were retrieved from the archival records. There was equal distribution of males and females. Results: The prevalence of MIC in the current study sample was found to be 43.89% with a slightly higher prevalence on left side as compared to right side, and higher prevalence among females as compared to males. Among different age groups, there was an increased incidence in the age group of >50 years. The distance of MIC from labial and lingual cortical plates and lower border of mandible were 4.338 ± 1.478 mm, 4.34 ± 1.53 mm and 9.417 ± 1.832 mm respectively. Conclusions: To conclude, the prevalence of MIC among Indian population was lower as compared to the prevalence among other populations. There were variations in prevalence in terms of age, gender and laterality, which could be used as a reference for further studies conducted on larger sample size. Mapping the incisive nerve canal will enable oral radiologists, to plan safely and negotiate the interforaminal region.
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ORIGINAL ARTICLE - MEDICAL EDUCATION Top

An evaluation study on gamified online learning experiences and its acceptance among medical students p. 211
May Honey Ohn, Khin-Maung Ohn
DOI:10.4103/tcmj.tcmj_5_19  
Objective: The successful application of gamification in different educational settings shows that the use of gamification in medical education may be an effective solution. Even though many studies have been conducted to investigate the efficacy of the integration of gamification to different education curriculums, few studies have examined the reactions, behaviors, and attitudes of learners toward the use of gamification in medical education. Hence, this study aimed to evaluate the medical students' learning experience and acceptance of the use of gamification for the delivery of electrocardiogram lessons. Materials and Methods: A qualitative research method was used to generate findings in this study. The data collection methods included focus group discussions and interviews. Triangulation methods were used to ensure the validity and reliability of the qualitative data analyzed in this study. The thematic analysis of the data collected in this study helped to garner insights into the perception of participants and experts about the use of GaMed@ for the delivery of ECG lessons. Results: A total number of 32 medical students and four experts in the fields of user experience, communication, social psychology, and game design participated in this study. The findings showed that in spite of the negative reports about the user experience and application of GaMed@™, the participants and experts affirmed its positive impact on the increased motivation and engagement of users. Conclusions: The impact of this concept can be maximized by tailoring the game design to foster-positive learning attributes, behaviors, and outcomes in students. However, further research studies must be conducted to investigate the impact of gamification designs on specific learning outcomes in students.
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CASE REPORTS Top

An interesting case of Herlyn–Werner–Wunderlich syndrome p. 216
Maureen P Tigga
DOI:10.4103/tcmj.tcmj_13_19  
Herlyn–Werner–Wunderlich syndrome (HWWS) is a rare congenital anomaly characterized by uterus didelphys with blind hemivagina and ipsilateral renal agenesis. Usually, such patients present with dysmenorrhea shortly after menarche, increasing pelvic pain and a palpable mass due to the obstructed hemivagina. Interestingly in the present case, the patient had her menarche seven years ago, but dysmenorrhea started only 1-year back. She never sought medical help previously as she was mostly asymptomatic all through the years. It was only after she conceived and got investigated for antenatal concerns that she was found to have HWWS. A tortuous history and an unusual clinical presentation made this case an interesting one.
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Abdominal compartment syndrome secondary to myxedema ileus p. 219
Vishal Thakur, Jagdish Kumar Gupta, Archit Gupta
DOI:10.4103/tcmj.tcmj_31_19  
Acute pseudo-obstruction of the colon is known as Ogilvie syndrome (OS). There are varied causes of OS. Myxedema ileus (MI) as a cause of acute pseudo-obstruction is rare. Surgery in cases of MI is reserved only in cases of cecal distension of >12 cm, bowel ischemia, and perforated bowel. We present a rare case of a 71-year-old female who was operated for abdominal compartment syndrome secondary to MI.
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CORRIGENDUM Top

Corrigendum: An evaluation study on gamified online learning experiences and its acceptance among medical students p. 222

DOI:10.4103/1016-3190.266816  
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