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A prodrome is an early set of symptoms, which indicates the onset of a disease; these symptoms are often non-specific. Prodromal phases are now recognized in multiple central nervous system diseases. The depth of understanding of the prodromal phase varies across diseases, being more nascent for multiple sclerosis for example, than for Parkinson disease or Alzheimer's disease. Key challenges when identifying the prodromal phase of a disease include the lack of specificity of prodromal symptoms, and consequent need for accessible and informative biomarkers. Further, heterogeneity of the prodromal phase may be influenced by age, sex, genetics and other poorly understood factors. Nonetheless, recognition that an individual is in the prodromal phase of disease offers the opportunity for earlier diagnosis and with it the opportunity for earlier intervention.

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PURPOSE: The objective of this retrospective study was to assess safety and comparative clinical effectiveness of laparoscopic inguinal hernia repair (LIHR) and robot-assisted inguinal hernia repair (RIHR) from multi-institutional experience in Taiwan. METHODS: Medical records from a total of eight hospitals were retrospectively collected and analyzed. Patients primarily diagnosed of inguinal hernia, recurrent inguinal hernia or incarceration groin hernia patients who either underwent laparoscopic or robot-assisted inguinal hernia repair between January 2018 and December 2022 were included in the study. Baseline characteristics, intra-operative and post-operative results were analyzed. To compare two cohorts, overlap weighting was employed to balance the significant inter-group differences. We also conducted subgroup analyses by state of a hernia (primary or recurrent/incarceration) and laterality (unilateral or bilateral) that indicated complexity of surgery. RESULTS: A total of 1,080 patients who underwent minimally invasive inguinal hernia repair from 8 hospitals across Taiwan were collected. Following the application of inclusion criteria, there were 279 patients received RIHR and 763 patients received LIHR. In the baseline analysis, RIHR was more often performed in recurrent/incarceration (RIHR 18.6% vs LIHR 10.3%, p = 0.001) and bilateral cases (RIHR 81.4 vs LIHR 58.3, p < 0.001). Suturing was dominant mesh fixation method in RIHR (RIHR 81% vs LIHR 35.8%, p < 0.001). More overweight patients were treated with RIHR (RIHR 58.8% vs LIHR 48.9%, p = 0.006). After overlap weighting, there were no significant difference in intraoperative and post-operative complications between RIHR and LIHR. Reoperation and prescription rates of pain medication (opioid) were significantly lower in RIHR than LIHR in overall group comparison (reoperation: RIHR 0% vs. LIHR 2.9%, p = 0.016) (Opioid prescription: RIHR 3.34 mg vs LIHR 10.82 mg, p = 0.001) while operation time was significantly longer in RIHR (OR time: RIHR 155.27 min vs LIHR 95.30 min, p < 0.001). CONCLUSIONS: This real-world experience suggested that RIHR is a safe, and feasible option with comparable intra-operative and post-operative outcomes to LHIR. In our study, RIHR showed technical advantages in more complicated hernia cases with yielding to lower reoperation rates, and less opioid use.

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UNLABELLED: Temporomandibular disorders (TMD) are a significant public health problem, affecting approximately 5-12% of the population. OBJECTIVES: This retrospective cross-sectional study investigated the relationship between 8 AM serum cortisol levels (8ASC) and disc displacement disorders (DDD) of TMD. One hundred and forty patients with DDD were recruited. Among them, 60 patients comprised the case group of disc displacement without reduction with limited opening (DDWORWLO, age 37·7 ± 17·22), and 80 were 'other DDD' for the control group (age 36·4 ± 13·08). The independent variables included domains of demography, history, malocclusion, comorbid symptoms, comorbid TMD and 8ASC. Data were analysed with the chi-square test, logistic regression and receiver operating characteristic (ROC) curve. Results of multiple logistic regression showed that 8ASC was the only factor significantly related to DDWORWLO (P = 0·006). Receiver operating characteristic analysis of DDWORWLO and 8ASC indicated an area under the curve of 0·669, standard error of 0·049 and P value of 0·001. The adequate cut-off point of 8ASC was 12·45 (µg dL(-1) ), with sensitivity of 0·636, and specificity of 0·729. 8 AM serum cortisol level can be used as a clinical clue to differentiate DDWORWLO from other DDD.

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SETTING: Impaired immunity in patients with rheumatic diseases can increase the risk of pulmonary tuberculosis (PTB). However, it is less clear whether rheumatic diseases affect the risk of extra-pulmonary tuberculosis (EPTB). OBJECTIVE: To investigate the risk of PTB and EPTB in patients with rheumatic diseases using a population-based database. DESIGN: From Taiwan's National Health Insurance Research Database, 8536 patients with tuberculosis (TB) were frequency-matched with 42,680 controls for sex, 10-year age group and index year. Subjects were retrospectively traced back for their first diagnosis of rheumatic diseases. The association between TB and rheumatic diseases was assessed using multivariate logistic regression analyses. RESULTS: The risk of developing PTB was significantly higher in patients with systemic lupus erythematosus (adjusted odds ratio [aOR] 4.90, P < 0.001), rheumatoid arthritis (RA) (aOR 2.00, P < 0.001) and Sjögren's syndrome (aOR 6.11, P < 0.001). In addition, the risks of developing EPTB were significantly higher in RA patients (aOR 4.67, P < 0.001), those with Sjögren's syndrome (aOR 5.94, P < 0.001), and the group comprising progressive systemic sclerosis, polymyositis or dermatomyositis (aOR 8.31, P = 0.021). CONCLUSION: Elevated risks of PTB and EPTB were associated with various rheumatic diseases. Rheumatologists should be vigilant to the possibility of TB, and particularly EPTB, in their patients.

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BACKGROUND AND OBJECTIVE: The present study investigated the association between the RAGE G82S polymorphism, the plasma levels of sRAGE and chronic periodontitis in subjects with and without diabetes mellitus (DM). MATERIAL AND METHODS: A total of 230 patients with DM and 264 non-DM participants were recruited for this study. Genotyping of the RAGE G82S polymorphism was accomplished using polymerase chain reaction-restriction fragment length polymorphism, and associations were analyzed with the chi-squared test and logistic regression analysis. RESULTS: In the non-DM group, the chi-squared test showed that the frequency distributions of the G82S polymorphism were significantly different between chronic periodontitis and non-chronic periodontitis subjects (χ(2) = 8.39, p = 0.02). A multivariate logistic regression model showed that the (G82S + S82S) genotypes were associated with a significantly increased risk of chronic periodontitis development compared to the G82G genotype (adjusted odds ratio = 2.06, 95% confidence interval: 1.08-4.07). In the DM group, there was no association between the G82S polymorphism and chronic periodontitis development when a multivariate logistic regression was performed. Plasma levels of sRAGE were significantly higher in subjects with the G82G genotype compared to those with the (G82S + S82S) genotypes in both the non-DM (856.6 ± 332.0 vs. 720.4 ± 311.4 pg/mL, p = 0.003) and DM groups (915.3 ± 497.1 vs. 603.5 ± 298.3 pg/mL, p < 0.0001). However, there was no difference in plasma sRAGE levels between chronic periodontitis and non-chronic periodontitis subjects in both the DM and non-DM groups. Moreover, when the subjects were further sub-divided by the G82S polymorphism, the difference in plasma levels of sRAGE between chronic periodontitis and non-chronic periodontitis subjects in the DM and non-DM groups remained statistically insignificant. CONCLUSIONS: The present study revealed that the RAGE G82S polymorphism was associated with chronic periodontitis in the non-DM group but not in the DM group. Our results also showed that the plasma levels of sRAGE were significantly higher in subjects with the RAGE G82G genotype, and this correlation was not affected by the presence of chronic periodontitis in the DM and non-DM groups.

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STUDY DESIGN: Cross-sectional, correlational design. OBJECTIVES: To examine the effects of individual demographics, activities of daily living, social support, and self-concept on depressive symptoms in people with spinal cord injury (SCI). SETTING: A convenience sample of 135 adults with SCI was recruited from medical and rehabilitation centres in Taiwan. METHODS: Face-to-face, structured interviews were employed to collect information. Study questionnaires included a demographic sheet, the Barthel scale, the modified Social Support Inventory, the Huang self-concept scale and the Beck Depression Inventory. Data were analysed by structural equation modelling (SEM). RESULTS: The average age of the participants was 43.3 years (±11.98), the mean duration of injury was 114 months (±93.78), and most were males. Emotional support (r=-0.173, P<0.05) and appraisal support (r=-0.261, P<0.01) were negatively correlated with depressive symptoms. The best fitted SEM model included individual demographics and physical function, social support and self-concept as significant predictors of depressive symptoms, with self-concept acting as a mediator in this relationship. Participants' characteristics and social support both contributed substantial indirect effects on depressive symptoms via self-concept. Self-concept also mediated the relationship between education, income, physical functioning and participants' depressive symptoms. CONCLUSION: For this sample, the more negative that individuals perceived themselves, the more likely they were to report worsening depressive symptoms. The more social support that individuals have, the more likely they were to report less depressive symptoms. Further longitudinal research will help clarify the direction of these relationships.

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OBJECTIVE: The objective of this study was to optimize ultrasound-assisted extraction of phenolic compounds from Phyllanthus emblica. METHODS: Extracts obtained by UAE were evaluated for their antioxidant activities. Extraction experiments were carried out with three factors and three levels namely extraction time (varying from 15 to 60 min), ethanol concentration (varying from 50 to 90%) and frequency (varying from 28 to 56 kHz). RESULTS: The results showed that the UAE optimal conditions of extracting total phenol components were as follows: 15 min of extraction time, 60°C of extraction temperature, 70% of ethanol concentration, 56 kHz of ultrasonic frequency and a 1: 50 solid to solvent ratio. Under optimal conditions, the leaching-out rate of phenolic compounds was up to 55.34 mg g(-1) , and the yield of crude extract of P. emblica was up to 56.82%. The results reveal that the yield of phenolic compounds of UAE (56.82%) is higher than that of conventional solvent extraction (16.78%). Furthermore, the antioxidant activities of ethanol extracts obtained by UAE were evaluated in terms of activities of DPPH (1,1'-diphenyl-2-2'-picrylhydrazyl) radical scavenging activity, total antioxidant activity, metal chelating activity, and reducing power. P. emblica extracts obtained by UAE showed high antioxidant activity (26.00, 50.11 and 115.91 µg mL(-1) of IC50 values for DPPH radicals, total antioxidant ability and chelating ability of ferrous ion). CONCLUSION: The result of this study showed that UAE was a suitable method for the extraction of total phenolic compounds. Moreover, the author's main finding in this work is the fact that phenolic compounds from P. emblica show excellent antioxidant activity in multi-test systems.

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Although breast cancer is, unfortunately, not uncommon in women, a mere 0.04% of malignant breast tumours are primary angiosarcomas. Chemotherapy is advocated for treatment of breast angiosarcomas; however, no guidelines exist regarding optimal chemotherapeutics or protocols. Presently, the prognosis for breast angiosarcomas is poor. This case report describes a 24-year old woman diagnosed with primary breast angiosarcoma. She initially refused to receive treatment, but later returned to the hospital four years later with a haemopneumothorax. She was treated with rescue chemotherapy using a combination of high-dose tamoxifen plus ifosfamide and epirubicin (an anthracycline). She achieved a partial response, but died 16 months after therapy was initiated. More research is needed to devise novel chemotherapeutics and protocols to improve outcomes in women diagnosed with primary angiosarcomas ofthe breast.

Aunque el cáncer de mama, desafortunadamente, no es poco común en las mujeres, apenas 0.04% de los tumores malignos de mama son angiosarcomas primarios. La quimioterapia es el tratamiento de preferencia en los casos de angiosarcomas de mama. Sin embargo, no existen guías en relación con los protocolos o la quimioterapia óptima. En la actualidad, el pronóstico para los angiosarcomas de mama es pobre. Este informe del caso describe a una mujer de 24 años diagnosticada con angiosarcoma primario de mama. Inicialmente la paciente se negó a recibir tratamiento, pero volvió al hospital cuatro años más tarde con un hemoneumotórax. Fue tratada entonces con quimioterapia de rescate usando una combinación de alta dosis de tamoxifen con ifosfamida y epirrubicina (antraciclina). Llegó a responder parcialmente al tratamiento, pero falleció 16 meses después del inicio de la terapia. Se necesitan más investigaciones para elaborar nuevos quimioterápeuticos y protocolos que mejoren los resultados en los casos de mujeres diagnosticadas con angiosarcomas primarios de mama.

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Although breast cancer is, unfortunately, not uncommon in women, a mere 0.04% of malignant breast tumours are primary angiosarcomas. Chemotherapy is advocated for treatment of breast angiosarcomas; however, no guidelines exist regarding optimal chemotherapeutics or protocols. Presently, the prognosis for breast angiosarcomas is poor. This case report describes a 24-year old woman diagnosed with primary breast angiosarcoma. She initially refused to receive treatment, but later returned to the hospital four years later with a haemopneumothorax. She was treated with rescue chemotherapy using a combination of high-dose tamoxifen plus ifosfamide and epirubicin (an anthracycline). She achieved a partial response, but died 16 months after therapy was initiated. More research is needed to devise novel chemotherapeutics and protocols to improve outcomes in women diagnosed with primary angiosarcomas of the breast.

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BACKGROUND AND OBJECTIVE: The interleukin-13 (IL-13) -1112 C/T polymorphisms have been analyzed previously in a North European population of patients with aggressive periodontitis. The present study was carried out to investigate the association of polymorphisms in the IL-13 gene with susceptibility to periodontitis in a Taiwanese population. MATERIAL AND METHODS: The genotyping of IL-13 -1112 C/T polymorphisms in 60 patients with aggressive periodontitis, 204 patients with chronic periodontitis and 95 healthy controls was carried out using the polymerase chain reaction-restriction fragment length polymorphism technique. Genotypes and allele frequencies among study groups were compared using Fisher's exact test (p < 0.05). Pearson's chi-square test was used for analysis of the Hardy-Weinberg equilibrium. RESULTS: The distributions of CC genotypes and C alleles between patients with aggressive periodontitis and healthy controls were significantly different (p = 0.034 and 0.046). After adjustment for age, gender, betel nut chewing and smoking status using logistic regression analysis, the odds ratio (OR) was 6.45 [95% confidence interval (CI) = 1.99-23.72, p = 0.003] for aggressive periodontitis. However, the CC genotype was only significantly associated with the risk of aggressive periodontitis in the nonsmoking group (OR = 4.48, 95% CI = 1.31-16.93, p = 0.020). CONCLUSION: The CC genotype or C allele appears to increase the risk of developing aggressive periodontitis in Taiwanese subjects.

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PURPOSE: We investigated the oxidative stress in orbital fibroadipose tissues and cultured orbital fibroblasts from patients with Graves' ophthalmopathy (GO). METHODS: The content of 8-hydroxy 2'-deoxyguanosine (8-OHdG), an important biomarker of oxidative DNA damage, was measured in orbital fibroadipose tissues and cultured orbital fibroblasts from patients with GO and compared with age-matched normal controls. A product of lipid peroxidation, malondialdehyde (MDA), and intracellular reactive oxygen species (ROS) in cultured orbital fibroblasts was also determined. RESULTS: There was no significant difference in the 8-OHdG content of orbital fibroadipose tissues between patients with GO and age-matched normal controls (P=0.074). However, the levels of 8-OHdG and MDA in GO orbital fibroblasts were significantly higher than those of normal controls (P=0.0026 and P<0.001, respectively). In addition, GO orbital fibroblasts had higher contents of superoxide anions and hydrogen peroxide compared with those of normal controls (P=0.0133 and 0.0025, respectively). CONCLUSIONS: Orbital fibroblasts represent the most abundant cell type among orbital connective tissues and exhibit great differences in their phenotypes. Increased oxidative DNA damage and lipid peroxidation, as well as higher intracellular ROS levels in GO orbital fibroblasts may have a role in the pathogenesis of GO.

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BACKGROUND AND OBJECTIVE: The association between psychosocial factors and periodontal disease has been widely reported and might be modified by smoking status. This study investigated the association of periodontal status with psychosocial factors and smoking in a community population. MATERIAL AND METHODS: A structured questionnaire was administered to a total of 1,764 civilian noninstitutional (general population excluding from nursing homes, sanitariums and hospitals) Taiwanese individuals to assess the presence and severity of psychosocial factors [using the 12-item Chinese health questionnaire (CHQ-12)], smoking habits and other related factors. Periodontal status was established using the community periodontal index and by measuring clinical loss of attachment. RESULTS: Psychological factors and smoking were significantly associated with loss of attachment (odds ratio = 1.69, 95% confidence interval = 1.01-2.77, comparing the CHQ-12 score of >or= 6 with the CHQ-12 score of 0-2 and p = 0.032 for linear trend; odds ratio = 2.21, 95% confidence interval = 1.45-3.37, comparing smokers with nonsmokers) but not with community periodontal index. The association was found to be stronger among smokers than among nonsmokers. Smokers with a CHQ-12 score of >or= 6 had a higher odds ratio of loss of attachment (odds ratio = 2.49, 95% confidence interval = 0.91-6.49) than nonsmokers (odds ratio = 1.43, 95% confidence interval = 0.76-2.58). For periodontal health measured using the community periodontal index, married and divorced/widowed subjects tended to have poorer periodontal health (odds ratio = 3.38, 95% confidence interval = 1.26-10.81 and odds ratio = 3.83, 95% confidence interval = 1.21-13.83, respectively) than single subjects among nonsmokers but not among smokers. CONCLUSION: Poor mental health had a stronger association with periodontal disease among smokers than among nonsmokers, especially in accumulative attachment loss. Our findings suggest that mental health and smoking might have a synergistic effect on the risk of developing periodontal disease.

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BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is a major target for antiretroviral strategy to block or curtail HIV infection. A suitable RT-SHIV/macaque model is urgently needed for the evaluation of HIV/AIDS therapies and microbicides specifically targeting HIV-1 RT. METHODS: Fifteen cynomolgus macaques (Macaca fascicularis) were divided into three groups (n = 5) and intravaginally inoculated with 4800, 1200, or 300 TCID(50) of RT-SHIVtc. Systemic infections of RT-SHIVtc exposed macaques were determined by both virological and immunologic parameters during 24 weeks post-challenge. RESULTS: Within 2 weeks post-inoculation, 13 of 15 macaques became infected as confirmed by virus isolation, plasma viral RNA, proviral DNA, declined CD4(+)T cell counts in peripheral blood and seroconversion. CONCLUSIONS: Results serve to validate the infectivity and pathogenicity of RT-SHIVtc following vaginal exposure in M. fascicularis. This RT-SHIVtc/macaque model could be suitable for the pre-clinical evaluation of non-nucleoside RT inhibitor-based anti-HIV microbicides.

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SETTING: The W-Beijing strain of Mycobacterium tuberculosis is distributed globally, and is associated with high drug resistance rates in some areas. The effect of the W-Beijing strain on radiological features of pulmonary tuberculosis (PTB) remains unclear. OBJECTIVE: To compare the chest radiological presentation of PTB in patients infected with W-Beijing with that of patients infected with non-W-Beijing strains, and to explore factors affecting radiological patterns. DESIGN: Culture-proven PTB patients without previous anti-tuberculosis treatment were enrolled retrospectively. Chest radiographs were independently reviewed by two qualified chest physicians, and radiological presentation was classified into characteristic and unusual patterns. RESULTS: Of 233 patients studied, 123 (52.8%) were infected with the W-Beijing strain. Characteristic radiological patterns (91.1% vs. 76.4%, P = 0.002) and fibronodular lesions without cavity (57.7% vs. 43.6%, P = 0.032) were more common, while miliary lesions (0.0% vs. 3.8%, P = 0.048) were less frequent, in the W-Beijing group. After stepwise logistic regression analysis, the W-Beijing strain (P = 0.006) was found to be an independent factor for the characteristic radiological pattern for PTB. CONCLUSION: The characteristic radiological pattern for PTB was more common in patients infected with the W-Beijing strain. M. tuberculosis genotyping was an independent factor affecting the radiological presentation of pulmonary TB.

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BACKGROUND AND OBJECTIVE: Single nucleotide polymorphisms are assumed to be associated with the differential production of cytokines. We evaluated gene polymorphisms of interleukin-10 (-592C>A, -819C>T and -1082G>A) and interleukin-12B (+16974) in patients with chronic periodontitis (n = 145) and generalized aggressive periodontitis (n = 65) in comparison with healthy controls (n = 126). MATERIAL AND METHODS: Gene promoter polymorphisms were analyzed by polymerase chain reaction with sequence-specific primers. Genotype and allele frequencies were analyzed using the chi-square test and logistic regression analysis. RESULTS: The interleukin-10 -592 polymorphism showed significant differences among the three groups (p = 0.0330). The genotype frequencies of the -592 locus between the chronic periodontitis and healthy control groups were significantly different (AC vs. AA: odds ratio = 0.33). The combination ATA/ATA seemed to be associated with susceptibility to generalized aggressive periodontitis (p = 0.0276). Patients with the composite ATA/ACC were less likely to develop chronic periodontitis (p = 0.0248). The CC genotype of interleukin-12B (+16974) was related to chronic periodontitis (CC vs. AA, p = 0.0211; CC vs. AA+AC, p = 0.0187). The AC heterozygosity of interleukin-12B was significantly lower in chronic periodontitis vs. healthy controls (p = 0.0500). CONCLUSION: The interleukin-10 gene polymorphism at position -592C>A may be associated with a lower risk for development of chronic periodontitis. The interleukin-10 haplotype ATA is associated with generalized aggressive periodontitis. On the other hand, interleukin-12B genetic variants at position +16974 are associated with susceptibility to chronic periodontitis.

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