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   Table of Contents - Current issue
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July-September 2021
Volume 33 | Issue 3
Page Nos. 203-316

Online since Monday, June 28, 2021

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REVIEW ARTICLES - BASIC  

Interleukin-10: A double-edged sword in breast cancer p. 203
Chun-Ming Chang, Ho Yin Pekkle Lam, Hao-Jen Hsu, Shinn-Jong Jiang
DOI:10.4103/tcmj.tcmj_162_20  
Breast cancer (BC) is a frequently diagnosed cancer among women worldwide. Currently, BC can be divided into different subgroups according to the presence of the following hormone receptors: estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Each of these subgroups has different treatment strategies. However, the presence of new metastatic lesions and patient deterioration suggest resistance to a given treatment. Various lines of evidence had shown that cytokines are one of the important mediators of tumor growth, invasion, metastasis, and treatment resistance. Interleukin-10 (IL-10) is an immunoregulatory cytokine, and acts as a poor prognostic marker in many cancers. The anti-inflammatory IL-10 blocks certain effects of inflammatory cytokines. It also antagonizes the co-stimulatory molecules on the antigen-presenting cells. Here, we review the current knowledge on the function and molecular mechanism of IL-10, and recent findings on how IL-10 contributes to the progression of BC.
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The molecular etiology and treatment of glucocorticoid-induced osteoporosis p. 212
Cheng-Huan Peng, Wen-Ying Lin, Kuang-Ting Yeh, Ing-Ho Chen, Wen-Tien Wu, Ming-Der Lin
DOI:10.4103/tcmj.tcmj_233_20  
Glucocorticoid-induced osteoporosis (GIOP) is the most common form of secondary osteoporosis, accounting for 20% of osteoporosis diagnoses. Using glucocorticoids for >6 months leads to osteoporosis in 50% of patients, resulting in an increased risk of fracture and death. Osteoblasts, osteocytes, and osteoclasts work together to maintain bone homeostasis. When bone formation and resorption are out of balance, abnormalities in bone structure or function may occur. Excess glucocorticoids disrupt the bone homeostasis by promoting osteoclast formation and prolonging osteoclasts' lifespan, leading to an increase in bone resorption. On the other hand, glucocorticoids inhibit osteoblasts' formation and facilitate apoptosis of osteoblasts and osteocytes, resulting in a reduction of bone formation. Several signaling pathways, signaling modulators, endocrines, and cytokines are involved in the molecular etiology of GIOP. Clinically, adults ≥40 years of age using glucocorticoids chronically with a high fracture risk are considered to have medical intervention. In addition to vitamin D and calcium tablet supplementations, the major therapeutic options approved for GIOP treatment include antiresorption drug bisphosphonates, parathyroid hormone N-terminal fragment teriparatide, and the monoclonal antibody denosumab. The selective estrogen receptor modulator can only be used under specific condition for postmenopausal women who have GIOP but fail to the regular GIOP treatment or have specific therapeutic contraindications. In this review, we focus on the molecular etiology of GIOP and the molecular pharmacology of the therapeutic drugs used for GIOP treatment.
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Current advances of targeting epigenetic modifications in neuroendocrine prostate cancer p. 224
Wen-Chi Cheng, Hung-Jung Wang
DOI:10.4103/tcmj.tcmj_220_20  
Neuroendocrine prostate cancer (NEPC) is the most lethal malignancy of prostate cancer (PCa). Treatment with next-generation androgen receptor (AR) pathway inhibitors (ARPIs) has successfully extended patients' lifespan. However, with the emergence of drug resistance, PCa tumors increasingly adapt to potent ARPI therapies by transitioning to alternative cellular lineage. Such therapy-induced drug resistance is largely driven from the cellular plasticity of PCa cells to alter their phenotypes of AR independence for cell growth and survival. Some of the resistant PCa cells undergo cellular reprogramming to form neuroendocrine phenotypes. Recent evidences suggest that this cellular reprogramming or the lineage plasticity is driven by dysregulation of the epigenome and transcriptional networks. Aberrant DNA methylation and altered expression of epigenetic modifiers, such as enhancer of zeste-homolog 2, transcription factors, histone demethylases, are hallmarks of NEPC. In this review, we discuss the nature of the epigenetic and transcriptional landscapes of PCa cells which lose their AR independence and transition to the neuroendocrine lineage. We also discuss how oncogenic signaling and metabolic reprogramming fuel epigenetic and transcriptional alterations. In addition, the current state of epigenetic therapies for NEPC is addressed.
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REVIEW ARTICLES - CLINICAL Top

Sudden onset of olfactory and gustatory dysfunctions in coronavirus disease 2019 (COVID-19) is momentous marker p. 233
Himani Tiwari Chaturvedi, Chandrashekher Chaturvedi
DOI:10.4103/tcmj.tcmj_238_20  
Coronavirus disease 2019 (COVID-19) presenting as global pandemic left no boundaries untouched worldwide. There are conglomerates of clinical and pathological presentation depending on population and geographic distribution. However amidst of such variable presentations, the sudden onset of olfactory and gustatory dysfunctions, if present, remains the most consistent and reliable symptoms of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection. Olfactory and gustatory dysfunctions can be present either isolated or as a part of the spectrum of common symptoms such as fever, cough, dyspnea, and fatigue in COVID-19. The pathophysiology of olfactory and gustatory loss is thought to be due to the neural and cytopathic effect of SARS CoV-2 on nasal and tongue mucosa and olfactory neuroepithelium. This review intends to provide a concise description of recent evidence for structure, pathophysiology, prognosis, and treatment for smell and taste dysfunction in SARS CoV-2-infected patients, subjected to further studies and research. Vigilant screening of anosmia and ageusia could probably be an important tool in the fight against the COVID-19 pandemic.
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Stroke and diets – A review p. 238
Chin-Lon Lin
DOI:DOI: 10.4103/tcmj.tcmj_168_20  
Stroke was one of the most common causes of death and disability worldwide. In addition, there was a significant increase in the disease burden of stroke in the world over the past 25 years, especially in developing countries. We searched PubMed (National Library of Medicine, USA) and Embase (Elsevier) databases using “Stroke and diets” as strategy, and additional references were obtained from the selected articles. The risk factors of stroke include age, sex, and modifiable factors such as hypertension, smoking, diet, physical activity, diabetes mellitus, alcohol consumption, psychological factors, and cardiac causes.–together account for >90% of the population attributable risk for stroke. They were discussed individually (Hypertension, Diabetes, Dyslipidemia, Gut microbiota, Nutrition), and the dietary modifications to reduce these risks were also presented. In conclusion, besides low salt intake, plant-based dietary patterns (especially vegetarian diets) that are rich in fruit, vegetables, whole grains, legumes, seeds, nuts, and dairy and low in meat, sweets, and alcohol significantly improved risk factors for stroke, and observational studies clearly demonstrated the stroke morbidity and mortality benefits. Thus, dietary intervention should be considered as an important strategy in the prevention and management of stroke.
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Current treatment concepts for osteochondral lesions of the talus p. 243
Chen-Chie Wang, Kai-Chiang Yang, Ing-Ho Chen
DOI:10.4103/tcmj.tcmj_106_20  
Osteochondral lesions of the talus (OLT) are a well-known cause of ankle joint pain and can sometimes lead to instability. These lesions are not only confined to articular hyaline cartilage, they can also affect the subchondral bone at the weight-bearing aspect of the talar dome. Nonoperative treatment is the preferred option for small lesions, however surgical intervention is recommended for large lesions or those for which conservative treatment has failed. Microfracture, abrasion arthroplasty and multiple drilling are all classified as bone marrow stimulation procedures; they are used to try to recruit precursor cells for cartilage regeneration and are especially suitable for small OLT lesions. For large lesions, osteochondral autografting and allografting are better options to reconstruct the articular defect, as they have better contours and mechanical strength. When there is limited subchondral bone involvement in large lesions, cell-based therapies such as autogenous chondrocyte implantation, potentially combined with a biomaterial matrix, are a promising option and acceptable functional outcomes have been reported. To provide evidence-based recommendations for clinicians, this article evaluates the currently available treatment strategies for OLT and their evolution over the past few decades.
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Dual targeting of TAM receptors Tyro3, Axl, and MerTK: Role in tumors and the tumor immune microenvironment p. 250
Kai-Hung Wang, Dah-Ching Ding
DOI:10.4103/tcmj.tcmj_129_20  
In both normal and tumor tissues, receptor tyrosine kinases (RTKs) may be pleiotropically expressed. The RTKs not only regulate ordinary cellular processes, including proliferation, survival, adhesion, and migration, but also have a critical role in the development of many types of cancer. The Tyro3, Axl, and MerTK (TAM) family of RTKs (Tyro3, Axl, and MerTK) plays a pleiotropic role in phagocytosis, inflammation, and normal cellular processes. In this article, we highlight the cellular activities of TAM receptors and discuss their roles in cancer and immune cells. We also discuss cancer therapies that target TAM receptors. Further research is needed to elucidate the function of TAM receptors in immune cells toward the development of new targeted immunotherapies for cancer.
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The perspectives of interleukin-10 in the pathogenesis and therapeutics of multiple myeloma p. 257
Cheng-Der Liu, Chun-Chun Chang, Wei-Han Huang
DOI:10.4103/tcmj.tcmj_141_20  
Multiple myeloma (MM) is typically featured by the increased levels of inflammatory cytokines in the neoplastic plasma cells (PCs) producing monoclonal immunoglobulin. PCs proliferate in the bone marrow, which will lead to extensive skeletal destruction with osteolytic lesions, osteopenia, or pathologic fractures. The diagnostic biology of MM has progressed from morphology and low-sensitivity protein analysis into multiomics-based high-throughput readout, whereas therapeutics has evolved from single active agent to potential active drug combinations underlying precision medicine. Many studies have focused on the cytokine networks that control growth, progression, and dissemination of the disease. The complexity of cytokines in MM development remains to be elucidated comprehensively. Apart from knowing that interleukin (IL)-6 is important in the pathogenesis of MM, it has been shown that IL-6 is a paracrine factor supplied by the microenvironment comprising of those cells from the myeloid compartment. Due to IL-10 was considered an immunosuppressive cytokine to promote cancer escape from immune surveillance, the role of IL-10 in this regard has been underestimated although recent advances have reported that IL-10 induces both PC proliferation and angiogenesis in MM. In addition, cumulative studies have suggested that IL-10 plays an important role in the induction of chemoresistance in many cancers; a virtual requirement of autocrine IL-10 for MM cells to escape from an IL-6-dependent proliferation loop was implicated. In this review, we summarize the available information to elucidate a new understanding of the molecular and functional roles of IL-10 in MM.
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ORIGINAL ARTICLE - BASIC RESEARCH Top

Anxiolytic effect of minocycline in posttraumatic stress disorder model of Syrian hamsters p. 263
Panini Shrikant Patankar, Shirish Joshi, Abhishek Mane, PS Manjesh, Dhananjay Kokate
DOI:10.4103/tcmj.tcmj_243_20  
Objective: The objective was to study the anxiolytic effect of minocycline in resident–intruder social conflict in submissive hamsters post resident intrusion model using open field test (OFT) and elevated plus maze (EPM) and serum cortisol levels. Materials and Methods: Fifty-two singly housed male Syrian hamsters were used, post standardization of an animal model. Resident intrusion was done (5 min), in which smaller hamsters were placed in the cage of larger hamster, and the behavior of smaller hamster was noted. Eight submissive hamsters per group (disease control, lorazepam group as a positive control, and the test drug was minocycline) were used, and the drug was administered immediately post resident intrusion, intraperitoneally. Behavioral tests, namely OFT and EPM, were done followed by retro-orbital blood collection for serum cortisol estimation. The level of significance was set at P < 0.05. Results: The minocycline group showed a statistically significant decrease in serum cortisol levels compared to the disease control group. Among all the variables pertaining to both the behavioral tests, namely EPM and OFT, the results indicated an anxiolytic effect, which was statistically significant compared to the disease control group. Conclusion: As per the biochemical test using serum cortisol levels and behavioral tests in the form of EPM and OFT, the study concluded that the anxiolytic effect of minocycline is at least comparable to the positive control, lorazepam.
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ORIGINAL ARTICLES - CLINICAL RESEARCH Top

Evaluation of the effect of shift cycle time on chest compression quality during cardiopulmonary resuscitation p. 270
Farhad Heydari, Kourosh Eghdami, Majid Zamani, Keihan Golshani, Babak Masoumi
DOI:10.4103/tcmj.tcmj_228_20  
Objective: Considering the potential role of shift cycle time on chest compression quality during cardiopulmonary resuscitation (CPR) and the available contradictory results in this regard, the present study aimed at evaluating the effect of 1-min versus 2-min shift cycle time on the quality of CPR. Materials and Methods: In this randomized crossover study, 80 rescuers performed CPR on a manikin in two scenarios with a rotation of 1 and 2-min cycles. The quality of CPR was evaluated and compared based on the information obtained regarding the chest compression depth, recoil, and rate of chest compression. In addition, rescuer fatigue was recorded in 1-min versus 2-min shift cycles. Results: In the 1-min group, the number of chest compressions per minute, complete recoil, and good rate with the mean of 114.89 ± 3.62, 54.34 ± 3.86, and 76.06 ± 8.00 were significantly higher than those of the 2-min group with the mean of 113.78 ± 4.94, 53.49 ± 5.27, and 73.98 ± 7.87 (P < 0.05), respectively. In addition, the quality of CPR provided by males was significantly higher than females in both groups. The score of rescuer fatigue was higher in the 2-min group as compared with the 1-min group (P < 0.001). Conclusion: According to the results of the present study, the difference in the quality of CPR in terms of the number of chest compressions, complete recoil, and good rate was higher in the 1-min group as compared with the 2-min group. In addition, the quality of CPR in terms of chest compression depth and number in both 1-and 2-min rotation cycles was higher for male rescuers than females. Furthermore, rescuer fatigue was higher in the 2-min group as compared with the 1-min group. The mentioned finding may be a factor in reducing, albeit slightly, the quality of CPR in the group with a longer time.
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Detection rate of breast malignancy of needle localization biopsy of breast microcalcification p. 275
Kian-Hwee Chong, Kuo-Feng Huang, Hsiu-Wen Kuo, I-Shiang Tzeng, Jia-Hui Chen
DOI:10.4103/tcmj.tcmj_191_20  
Objective: The current study aimed to retrospectively assess the cancer detection rate of needle localization biopsy of breast microcalcifications undetectable on sonography. Materials and Methods: Patients who underwent mammography-guided needle localization biopsy of breast microcalcifications undetectable on sonography from January 2005 to December 2017 were included in the study. Patients with incomplete medical records were excluded from the study. Patient mammograms were categorized using the Breast Imaging-Reporting and Data System (BI-RADS) assessment criteria. The percentages of benign and malignant lesions were determined by pathological examination of surgically recovered specimens. Correlation between preoperative imaging assessment and final diagnosis was investigated, and the complications associated with the procedures were recorded. Results: A total of 301 needle-localized biopsies were performed under mammographic guidance. The mean age of the patients was 58.18 ± 7.73 years. The overall ductal carcinoma in situ (DCIS) and cancer detection rate was 23.3%. The proportion of patients with BI-RADS 0 category and undergoing second mammography was higher in the DCIS and cancer group. A total of 227 patients did not undergo second mammography. Of these patients, 70 demonstrated BI-RADS 4 category, 34 were diagnosed with DCIS, and 5 were diagnosed with breast cancer during subsequent follow-up. Conclusion: Needle-localized excision of microcalcifications undetectable on sonography has high detection rate for early stage of breast cancer with low risk of associated complications. Regular mammography is a satisfactory follow-up tool for female patients with microcalcifications in the breasts. Additional studies should be performed to compare between needle-localized excision and vacuum-assisted breast biopsy.
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Surgical management of abdominal tuberculosis: A prospective single-center study p. 282
Mithun Barot, Vipul D Yagnik, Kirankumar Patel, Sushil Dawka
DOI:10.4103/tcmj.tcmj_206_20  
Objective: Tuberculosis (TB) can affect any part of the gastrointestinal tract. It is estimated that in 2018, 10 million people were affected with TB worldwide and there were 1.2 million TB deaths among human immunodeficiency virus-negative people. India has the highest TB burden in the world (27%), a significant proportion of which are of intestinal TB. The aims of this study were to assess clinical features and investigations for the diagnosis of abdominal TB and to analyze its various surgical manifestations and its management. Materials and Methods: From October 1, 2014, to October 30, 2016, a total of 50 patients meeting the inclusion criteria for the study, age between 15 and 65 years and diagnosis of symptomatic intestinal TB requiring surgery, were enrolled in the study. We used descriptive statistics to analyze the data. Results: Abdominal TB was most commonly seen in young adults. Intestinal obstruction was the most frequent presentation. The most common site of involvement in the present study was the ileum. Ultrasonography (USG) and X-ray were an integral part of the diagnosis, with computed tomography (CT) scan being rarely required. Although both anemia and erythrocyte sedimentation rate (ESR) are nonspecific, they may help in supporting the clinical and pathological findings. Most operations were elective, with intestinal obstruction being the most common indication and resection and end-to-end anastomosis performed most often. Histopathological examination was performed in all patients and showed caseating granuloma in 90% of cases, while 10% of cases had chronic noncaseating granulomas with ill-defined aggregates of epithelioid histiocytes. Conclusion: Abdominal TB causes a significant problem in diagnosis due to nonspecific symptomatology and lack of specific laboratory tests. USG and X-ray were an integral part of the diagnosis. CT scan is rarely required. Although anemia and ESR are both nonspecific features, they may help in supporting the clinical and pathological findings. The most common site of involvement in the present study was the ileum. Intestinal obstruction was the most common indication for operation, with resection and end-to-end anastomosis being the most common operation. The mainstay of treatment is medical therapy and timely surgical intervention is required in a sizable number of patients.
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Evaluating the benefit of adjuvant radiotherapy after extensive lymph node dissection for gastric cancer: a single-institute retrospective study p. 288
Yu-Nong Wang, Shou-Yi Chang, Jing-Min Hwang, You-Kang Chang, Woei-Yau Kao, Hsiang-Lin Wan, I-Shiang Tzeng, Chao-Chuan Wu
DOI:10.4103/tcmj.tcmj_230_20  
Objective: This study aimed to evaluate whether adjuvant radiotherapy (RT) can improve the treatment outcome of patients with locally advanced gastric cancer who underwent extensive lymph node dissection (ELND). Materials and Methods: This retrospective study included patients with gastric cancer pathological stages IIA–IIIC at Taipei Tzu Chi Hospital between 2008 and 2015. Patients (a) aged >80 years, (b) with distant metastasis at diagnosis, (c) with coexisting malignancies, (d) who did not complete the prescribed RT course, and (e) who died 1 month after surgery were excluded. Among 420 patients diagnosed with gastric cancer, 98 were included. Results: The median follow-up was 24.5 months. Of 39 patients who underwent adjuvant RT, 38 also received adjuvant chemotherapy (CT). Of 59 patients who did not receive adjuvant RT, only 34 received adjuvant CT. ELND was performed in 67.3% of the patients. The 5-year overall survival (OS) rate was 40%. In the univariate analyses, adjuvant CT regimen, 5-fluorouracil + leucovorin, was associated with worst outcome, while TS-1 was associated with better survival outcome (P = 0.018). The number of involved lymph nodes was strongly related to the OS and disease-free survival (DFS) (P < 0.001). We tried using different numbers of involved lymph nodes as a cutoff point and found that adjuvant RT significantly improved both OS and DFS in patients whose involved lymph nodes were ≥4 (OS, P = 0.017; DFS, P = 0.015). In multivariate analyses, better DFS was associated with negative surgical margin (P = 0.04), earlier disease stage (P = 0.001), adjuvant radiotherapy (P = 0.045), and adjuvant CT regimen TS-1 (P = 0.001). Conclusion: Adjuvant RT could improve DFS of patients with locally advanced gastric cancer with or without ELND. When the number of involved lymph nodes is ≥4, adjuvant RT is strongly suggested.
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Test-retest reliability of subjective visual vertical measurements with lateral head tilt in virtual reality goggles p. 294
Chia-Han Wang, Ariel A Winnick, Yu-Hung Ko, Zheyu Wang, Tzu-Pu Chang
DOI:10.4103/tcmj.tcmj_207_20  
Objective: The objective is to investigate the test-retest reliability of subjective visual vertical (SVV) in the upright position and with lateral head tilts through a computerized SVV measuring system using virtual reality (VR) goggles. Materials and Methods: Thirty healthy controls underwent SVV test in upright position, with the head tilted to the right 30°, and with the head tilted to the left 30°. Subjects wore SVV VR goggles, which contained a gyroscope for monitoring the angle of head tilt. Each subject completed 10 adjustments in each head position. The mean value of SVV deviations and SVV imprecision (the intra-individual variability of SVV deviations from the 10 adjustments) were recorded and compared across different head positions. The participants then repeated the same SVV protocol at least 1 week later. The test-retest reliability of SVV deviation and SVV imprecision were analyzed. Results: The SVV deviation (mean ± standard deviation) was 0.22° ± 1.56° in upright position, −9.64° ± 5.91° in right head tilt, and 7.20° ± 6.36° in left head tilt. The test-retest reliability of SVV deviation was excellent in upright position (intra-class correlation coefficient [ICC] = 0.77, P < 0.001), right head tilt (ICC = 0.83, P < 0.001) and left head tilt (ICC = 0.84, P < 0.001). The SVV values from the 10 adjustments made during right and left head tilts were less precise than when measured at upright (P < 0.001). The test-retest reliability of SVV imprecision was poor at upright (ICC = 0.21, P = 0.26) but fair-to-good in right head tilt (ICC = 0.72, P < 0.001) and left head tilt (ICC = 0.44, P = 0.04). Conclusion: The test-retest reliability of SVV deviation during lateral head tilts via VR goggles is excellent, which supports further research into the diagnostic value of head-tilt SVV in various vestibular disorders. In addition, the degree of SVV imprecision during head tilt has fair-to-good test-retest reliability, which suggests SVV imprecision may have clinical applicability.
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Role of social capital and self-efficacy as determinants of stress in pregnancy p. 301
Hajar Pasha, Mahbobeh Faramarzi, Mohammad Chehrazi, Maria Esfandyari, Shiva Shafierizi
DOI:10.4103/tcmj.tcmj_156_20  
Objectives: The study investigated the role of social capital, self-efficacy, and depression as determinants of stress during pregnancy. Materials and Methods: In a cross-sectional study, 200 low-risk pregnant women with at least 5 years of education and ages 18 or more were enrolled in public obstetric clinics of Babol University of Medical Sciences. The participants completed four questionnaires including Social Capital, Revised Prenatal Distress Questionnaire (NuPDQ), Perceived Stress, and General Self-efficacy. Results: Women at late phase of pregnancy had lower mean scores of total social capital (61.5 ± 17.1 vs. 47.1 ± 18.1) and self-efficacy (60.1 ± 9.7 vs. 55.1 ± 15.2) compared to those at early pregnancy. Social capital was the negative independent variable associated with pregnancy-specific stress in the adjusted model (β = −0.418, P = 0.020). Both social capital (β = −0.563, P ≤ 0.001) and self-efficacy (β = −0.330, P ≤ 0.001) were negative independent variables associated with general stress. Conclusions: Our findings suggest that health professionals should note the benefits of social capital in stress management and encourage women in establishing stronger relations and neighborhood environments during pregnancy.
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Research trends in trabecular bone score: A bibliometric review from 2008 to 2019 p. 307
Malcolm Koo, Tzyy-Ling Chuang, Yuh-Feng Wang
DOI:10.4103/tcmj.tcmj_256_20  
Objective: Trabecular bone score (TBS) is a novel index for assessing bone microarchitecture quality. No bibliometric reviews to date have yet explored the literature of TBS. Therefore, this study aimed to provide a bibliometric review on the trends of research publications on TBS indexed in the Science Citation Index Expanded and the Social Sciences Citation Index from 2008 to 2019. Materials and Methods: Using the Science Citation Index Expanded and the Social Sciences Citation Index, articles designated as original articles or review articles were searched using the keyword “trabecular bone score.” The retrieved articles were analyzed using Histcite 12.03.17 and VOSviewer v. 1.6.15 to identify top authors, journals, countries, and occurrence of keywords. Results: A total of 430 original and review articles on TBS published between 2008 and 2019 were identified. The number of articles increased steadily from 2008 to 2019, reaching 80 articles in 2019 alone. The United States of America, Switzerland, and France were the countries with the highest output of publications. The journal Osteoporosis International published the largest number of articles on TBS. Analysis of co-occurrence of author-supplied keywords revealed four clusters, with TBS, bone mineral density, and osteoporosis as the most prominent keywords. Conclusion: This bibliometric study on TBS published between 2008 and 2019 revealed the collaborative network of countries and the highly published journals and authors. Co-occurrence of keywords also revealed clusters of research hotspots, which could contribute to the understanding of the current state of TBS research and the identification of research gap.
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CASE REPORT Top

Recurrent Tolosa–Hunt syndrome p. 314
Phyo-Wai Thu, Yu-Ming Chen, Weng-Ming Liu
DOI:10.4103/tcmj.tcmj_137_20  
The Tolosa–Hunt syndrome (THS) is caused by granulomatous inflammation in the cavernous sinus, superior orbital fissure, or orbit characterized by painful ophthalmoplegia. Here, we report a case of recurrent THS in a 48-year-old female, who initially showed a poor response to low-dose steroids. Each episode involved different cranial nerves and painful ophthalmoplegia. Neuroimaging showed enhancement in the right cavernous sinus. The patient was treated with glucocorticoid pulse therapy and azathioprine. THS was previously considered to be responsive to glucocorticoids. This report demonstrates a case of THS with poor response to steroids and unique presentation of frequent recurrence with different cranial nerve involvement.
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