Temperature trajectories and mortality in hypothermic sepsis patients.

OBJECTIVES: Hypothermia is associated with poor outcomes in sepsis patients, and hypothermic sepsis patients exhibit temperature alterations during initial treatment. The objective of this study was to classify hypothermic sepsis patients based on body temperature trajectories and investigate the associations of these patients with 28-day mortality. METHODS: This was a retrospective analysis of prospectively collected data from adult sepsis or septic shock patients who visited three emergency departments between August 2014 and December 2019. Hypothermic sepsis was defined as an initial body temperature <36 °C. delta temperature was calculated by subtracting the 0 h body temperature from the 6 h body temperature. We divided the patients into three groups according to delta temperature: Group A (delta temperature ≤ 0), Group B (0 < delta temperature ≤ 1) and Group C (delta temperature > 1). The primary outcome was 28-day mortality, and a multivariable Cox proportional hazards regression model was generated. RESULTS: Among 7344 patients with sepsis or septic shock, 325 hypothermic patients were included in the analysis, and the overall mortality rate was 36%. While initial body temperature was not different between survivors and nonsurvivors, survivors exhibited a higher body temperature at 6 h. The 28-day mortality rates for Groups A, B and C were 53.1%, 36.0%, and 30.0%, respectively, and Group A had significantly higher mortality than Group C did (p < 0.05). Group C demonstrated a 44.2% decrease in 28-day mortality compared to Group A (adjusted hazard ratio of 0.558; 95% confidence interval of 0.330-0.941). CONCLUSIONS: In hypothermic sepsis patients, an increase of 1 °C or more in body temperature after the initial 6 h is associated with a reduced risk of 28-day mortality.

Effect of Intravenous Push and Piggyback Administration of Ceftriaxone on Mortality in Sepsis.

BACKGROUND: There is a lack of evidence-based guidelines for the administration methods of ceftriaxone in emergency departments (EDs), resulting in the reliance on individual institutional protocols for decision-making. OBJECTIVE: This study was performed to compare the effects of administering ceftriaxone via intravenous push (IVP) and intravenous piggyback (IVPB) on 28-day mortality in patients with sepsis. METHODS: This was a retrospective study of patients aged 18 years or older with sepsis or septic shock who visited an ED and were treated with ceftriaxone as an initial antibiotic between March 2010 and February 2019. Patients were divided into the IVP group and the IVPB group based on the administration method. The primary outcome was 28-day mortality, and multivariable Cox proportional hazards regression analysis was performed to evaluate the relationship between antibiotic administration methods and 28-day mortality. RESULTS: During the study period, a total of 939 patients were included in the final analysis, and the overall mortality rate was 12.2%. The antibiotic administration time was significantly lower in the IVP group than in the IVPB group, and the rates of antibiotic administration within 1 h and within 3 h were higher in the IVP group than in the IVPB group (p < 0.05). However, there was no significant difference in 28-day mortality between the two groups (hazard ratio 1.07, 95% confidence interval 0.69-1.65). CONCLUSIONS: IVP administration of ceftriaxone reduced the time of antibiotic administration compared with IVPB, but there was no difference in 28-day mortality.

Successful management of feline CD4+ CD8+ T-cell mediastinal lymphoma with pericardial effusion.

A 2-year-old, castrated, male Russian blue cat presented with acute dyspnoea, cyanosis, and lethargy. A thoracic radiography revealed a large cranial mediastinal mass; the computed tomography revealed caudal lobe atelectasis of the right lung with pericardial and pleural effusions. The cytodiagnostic tests revealed high-grade CD4+ CD8+ T-cell mediastinal lymphoma as clinical stage Vb; l-asparaginase-cyclophosphamide-doxorubicin-vincristine-prednisolone (l-CHOP)-based chemotherapy was initiated, following which the mass shrunk rapidly; 1 week after the initiation of chemotherapy, the appetite-related and respiratory symptoms improved dramatically, and the pleural and pericardial effusion resolved. The patient remains in complete remission three years after the initiation of the l-CHOP chemotherapy. Therefore, the accurate diagnosis and instantaneous initiation of chemotherapy may resolve life-threatening pleural and pericardial effusions in cats with high-grade aberrant T-cell mediastinal lymphoma.

Different outcomes of multiple sialadenitis involving the submandibular and zygomatic salivary glands in a Welsh Corgi dog.

A ten-year-old indoor, castrated male Cardigan Welsh Corgi (Canis familiaris) presented with the chief complaints of chronic vomiting, retching, hypersalivation, and bilateral submandibular masses for two months. The systemic examinations, including serum chemistry, radiography, ultrasonography, and fluoroscopy, were unremarkable. A fine-needle aspiration revealed bilateral submandibular sialadenitis. Broad-spectrum antibiotics with phenobarbital were prescribed to alleviate the ptyalism. Thereafter, the left submandibular glands were normalised, and the right submandibular glands decreased to half their size. Three weeks later, the animal had an emergency visit because of a sudden left exophthalmos. Computed tomography and magnetic resonance imaging revealed enlarged left zygomatic and right mandibular salivary glands. The affected glands were surgically removed; the histopathologic examination confirmed non-septic sialadenitis, and the patient was finally diagnosed with idiopathic sialadenitis. Vomiting continued after the gland removal and the dog required a gradual increase in the phenobarbital dosage and an additional antiepileptic drug (potassium bromide) to manage the symptoms. The patient died eight months later from an unknown cause. This case report of bilateral submandibular sialadenitis concurrent with unilateral zygomatic sialadenitis in a Welsh Corgi dog suggests that when multiple salivary glands are involved, the response to anti-epileptic drugs and the prognosis is poor compared to that involving a single salivary gland.

Influence of a novel pH-cycling model using dental microcosm biofilm on the remineralizing efficacy of fluoride in early carious lesions.

OBJECTIVES: To evaluate the remineralizing efficacy of fluoride in early carious lesions using a novel microbial pH-cycling model that combines the chemical pH-cycling model with dental microcosm biofilms. MATERIALS AND METHODS: Artificial carious lesions were formed in 48 bovine incisors. The chemical and microbial pH-cycling models were applied to 24 specimens, respectively; the latter was applied after formation of dental microcosm biofilms for 6 days, based on the human saliva inoculation. The pH-cycling schedule was repeated for 12 days. All specimens were evaluated for fluorescence loss (ΔF) using quantitative light-induced fluorescence-digital before and after the pH-cycling. Specimen biofilms were further analyzed for red/green values (R/G ratios) and colony-forming units (CFUs). One-way analysis of variance and Tukey's post hoc analysis were used to analyze change in fluorescence loss (ΔΔF) according to the pH-cycling model and treatment. RESULTS: When the chemical pH-cycling and microbial pH-cycling models were used, ΔΔF was 1.36 (p = 0.008) and 1.17 (p > 0.05) times higher, respectively, in the fluoride-treated group than that in the distilled water-treated group. In the microbial pH-cycling model, R/G ratios and CFU counts of biofilms were not significantly different between treatments (p > 0.05). CONCLUSIONS: No significant difference was observed in the remineralizing efficacy of fluoride according to the presence of dental biofilms covering early carious lesions. CLINICAL RELEVANCE: The remineralizing efficacy of fluoride could be overestimated in the absence of dental biofilms. Therefore, for accurate evaluation of the clinical value of remineralizing agents, dental biofilms should be included in in vitro tests.

miR-106b-5p and miR-17-5p could predict recurrence and progression in breast ductal carcinoma in situ based on the transforming growth factor-beta pathway.

PURPOSE: Ductal carcinoma in situ (DCIS) is well-known precursor of invasive ductal carcinoma (IDC). Parts of patients show recurrence as DCIS or IDC after local treatment, but there are no established markers predicting relapse. We analyzed changes in miRNA and oncogene expression during DCIS progression/evolution to identify potential markers predicting recurrence. METHODS: Forty archival tissues diagnosed as primary or recurrent DCIS and DCIS adjacent to IDC were analyzed. MiRNA hierarchical clustering showed up-regulation of miR-17-5p and miR-106b-5p in recurrent DCIS and DCIS adjacent to IDC. Target genes were predicted based on pre-formed miRNA databases and PanCancer Pathway panel. MiRNAs were transfected into MCF-10A and MCF-7 cells; western blot analysis was performed with MCF-7 cell line to evaluate the effects on TGF-ß downstream pathway. RESULTS: miRNA hierarchical clustering showed 17 dysregulated miRNAs, including miR-17-5p and miR-106b-5p. Based on miRNA database and nCounter Pancancer pathway analysis, TGFßRII was selected as target of miR-106b-5p and miR-17-5p. MiR-106b-5p- and miR-17-5p-transfected MCF-7 cells showed decreased expression of TGFßRII, especially in cells transfected with both miRNAs. CONCLUSION: miR-106b-5p and miR-17-5p might have a role in breast cancer recurrence and progression by suppressing TGF-ß activity, leading to early breast cancer carcinogenesis.

Base-pair opening dynamics of primary miR156a using NMR elucidates structural determinants important for its processing level and leaf number phenotype in Arabidopsis.

MicroRNAs originate from primary transcripts containing hairpin structures. The levels of mature miR156 influence the leaf number prior to flowering in the life cycle of plants. To understand the molecular mechanism of biogenesis of primary miR156a (pri-miR156a) to mature miR156, a base-pair opening dynamics study was performed using model RNAs mimicking the cleavage site of wild type and B5 bulge-stabilizing mutant pri-miR156a constructs. We also determined the mature miR156 levels and measured leaf numbers at flowering of plants overexpressing the wild type and mutant constructs. Our results suggest that the stabilities and/or opening dynamics of the C15·G98 and U16·A97 base-pairs at the cleavage site are essential for formation of the active conformation and for efficient processing of pri-miR156a, and that mutations of the B5 bulge can modulate mature miR156 levels as well as miR156-driven leaf number phenotypes via changes in the base-pair stability of the cleavage site.

Investigation of the Support Effect in Atomically Dispersed Pt on WO3-x for Utilization of Pt in the Hydrogen Evolution Reaction.

Single-atom catalysts (SACs) have attracted growing attention because they maximize the number of active sites, with unpredictable catalytic activity. Despite numerous studies on SACs, there is little research on the support, which is essential to understanding SAC. Herein, we systematically investigated the influence of the support on the performance of the SAC by comparing with single-atom Pt supported on carbon (Pt SA/C) and Pt nanoparticles supported on WO3-x (Pt NP/WO3-x ). The results revealed that the support effect was maximized for atomically dispersed Pt supported on WO3-x (Pt SA/WO3-x ). The Pt SA/WO3-x exhibited a higher degree of hydrogen spillover from Pt atoms to WO3-x at the interface, compared with Pt NP/WO3-x , which drastically enhanced Pt mass activity for hydrogen evolution (up to 10 times). This strategy provides a new framework for enhancing catalytic activity for HER, by reducing noble metal usage in the field of SACs.

A Generalizable Top-Down Nanostructuring Method of Bulk Oxides: Sequential Oxygen-Nitrogen Exchange Reaction.

A thermal reaction route that induces grain fracture instead of grain growth is devised and developed as a top-down approach to prepare nanostructured oxides from bulk solids. This novel synthesis approach, referred to as the sequential oxygen-nitrogen exchange (SONE) reaction, exploits the reversible anion exchange between oxygen and nitrogen in oxides that is driven by a simple two-step thermal treatment in ammonia and air. Internal stress developed by significant structural rearrangement via the formation of (oxy)nitride and the creation of oxygen vacancies and their subsequent combination into nanopores transforms bulk solid oxides into nanostructured oxides. The SONE reaction can be applicable to most transition metal oxides, and when utilized in a lithium-ion battery, the produced nanostructured materials are superior to their bulk counterparts and even comparable to those produced by conventional bottom-up approaches. Given its simplicity and scalability, this synthesis method could open a new avenue to the development of high-performance nanostructured electrode materials that can meet the industrial demand of cost-effectiveness for mass production.

Structural features of influenza A virus panhandle RNA enabling the activation of RIG-I independently of 5'-triphosphate.

Retinoic acid-inducible gene I (RIG-I) recognizes specific molecular patterns of viral RNAs for inducing type I interferon. The C-terminal domain (CTD) of RIG-I binds to double-stranded RNA (dsRNA) with the 5'-triphosphate (5'-PPP), which induces a conformational change in RIG-I to an active form. It has been suggested that RIG-I detects infection of influenza A virus by recognizing the 5'-triphosphorylated panhandle structure of the viral RNA genome. Influenza panhandle RNA has a unique structure with a sharp helical bending. In spite of extensive studies of how viral RNAs activate RIG-I, whether the structural elements of the influenza panhandle RNA confer the ability to activate RIG-I signaling has been poorly explored. Here, we investigated the dynamics of the influenza panhandle RNA in complex with RIG-I CTD using NMR spectroscopy and showed that the bending structure of the panhandle RNA negates the requirement of a 5'-PPP moiety for RIG-I activation.

Unilateral Chewing as a Risk Factor for Hearing Loss: Association between Chewing Habits and Hearing Acuity.

Hearing loss is a common disease in older adults. In order to lower the prevalence of hearing loss, it is important to identify its risk factors. Although some studies have found a relationship between dental status and hearing acuity, few studies have investigated the relationship between unilateral chewing and hearing acuity. This study aimed to assess the effects of unilateral chewing on hearing acuity, with a focus on the risk of hearing loss. Eighty-one participants (aged 51-87 years) were included in the present study. Their chewing habits were determined by visual inspection. The participants were divided into two groups: the Unilateral Chewing Group (UCG; n = 43) and the Bilateral Chewing Group (BCG; n = 38). The preferred chewing side was identified for the UCG. Hearing acuity was determined using pure tone audiometry in a noise-free chamber, conducted at frequencies of 500, 1,000, 2,000, and 4,000 Hz. Hearing loss was defined as a lower hearing threshold greater than 50 dB in either ear at any frequency. Mean hearing thresholds at frequencies of 2,000 and 4,000 Hz were significantly higher, by 5.12 and 15.75 dB, respectively, for the UCG compared to the BCG (P < 0.05). The UCG had a 3.78-fold higher likelihood of suffering from hearing loss (95% confidence interval [CI]: 1.81-7.88). The results suggest that bilateral chewing could be beneficial for preventing hearing loss. This study may provide evidence to support clinical interventions aimed at reducing the risk of hearing loss in patients with unilateral chewing habits.

Simplified Prediction Model for Accurate Assessment of Dental Caries Risk among Participants Aged 10-18 Years.

Dental caries assessment needs to be targeted at specific age groups, as many risk factors are related to patient age. Pre-teen and teenage patients, who are still at risk of occurrence of new carious lesions, need more individualized caries management strategies. Therefore, this study aimed to identify caries-related risk factors and develop a simplified risk prediction model for dental caries. Risk factors for caries were assessed in 171 participants aged 10-18 years, based on a questionnaire survey, previous history of caries, oral hygiene, microorganism colonization, saliva secretion, saliva buffer capacity examinations, and the acidogenicity of dental biofilms. These risk factors were entered into a computer-based risk assessment program (the Cariogram), and correlations between these factors and Cariogram scores were investigated. Significant risk predictors were used to develop a simplified risk prediction model. The performance of this model in predicting dental caries incidence was evaluated using receiver operating characteristic analysis, to determine its applicability to the management of caries. Our simplified prediction model included three predictors that were significantly associated with caries incidence: use of fluoride-containing toothpaste, the acidogenicity of dental biofilms, and saliva secretion (p < 0.001). The resulting model had a sensitivity and specificity of 60.5 and 85.0%, respectively, with a cut-off value of 69.41 as the threshold. The area under the curve of this model was 0.782 (95% confidence interval = 0.681-0.884, p < 0.001). Our new caries risk prediction model is expected to allow clinicians to accurately and easily predict patients' risk of occurrence of new caries.

Relationship between salivary haemoglobin and number of remaining teeth in older Koreans.

OBJECTIVE: We investigated the relationship between saliva and dental biofilm characteristics, oral hygiene behaviours and the number of remaining teeth in a sample of older Koreans. MATERIALS AND METHODS: This cross-sectional study included 133 participants, aged 65 years and older, recruited from senior welfare facilities in Incheon, South Korea. The outcome variable was the number of remaining teeth, and its associations with the independent variables of participants' general characteristics, salivary haemoglobin level, dental biofilm acidogenicity, salivary flow rate and oral hygiene behaviours were assessed. For statistical analyses, chi-squared test and step-wise multiple linear regression were used. RESULTS: The multiple linear regression model, which included all related factors identified in the bivariate analyses, showed that older adults who had high salivary haemoglobin levels (P < .05), brushed their teeth using the horizontal scrub method (P< .001), and did not use an interproximal cleaning device (P < .01) were more likely to have fewer remaining teeth. However, dental biofilm acidogenicity was not associated with the number of remaining teeth. CONCLUSION: The number of remaining teeth was associated with salivary haemoglobin level, appropriate toothbrushing technique and interdental cleaning. These findings suggest that the monitoring of salivary haemoglobin may contribute to the prevention of tooth loss caused by periodontal disease.

Masticatory efficiency contributing to the improved dynamic postural balance: A cross-sectional study.

OBJECTIVE: To evaluate whether masticatory efficiency is associated with dynamic postural balance. BACKGROUND: Masticatory dysfunction can cause deterioration of general health due to nutritional imbalances, thereby negatively affecting postural balance. However, few studies have investigated the association between masticatory efficiency and postural balance. MATERIALS AND METHODS: The masticatory efficiency of 74 participants was evaluated by calculating mixing ability index (MAI) using a wax cube. The timed up and go test (TUGT) was used to measure dynamic balance. Participants with an MAI above or below the median value of 1.05 were defined as having high or low masticatory efficiency, respectively. An independent samples t-test was used to identify significant differences in TUGT, according to masticatory efficiency. Analysis of covariance was performed to adjust for confounding factors. Logistic regression analysis was used to assess the correlation between masticatory efficiency and postural balance. RESULTS: The high masticatory efficiency group could complete the TUGT exercise approximately 1.67 seconds faster while maintaining the postural balance, compared to the low masticatory efficiency group (P = .005). Furthermore, the postural imbalance odds of the group with high mastication efficiency decreased by 0.14-fold, relative to the group with low mastication efficiency (95% confidence interval: 0.04-0.46). CONCLUSION: With some reservations about statistical power, the association found between masticatory efficiency and postural balance justifies further investigations to confirm the strength of the associations, and possibly to identify causal relationships between mastication and posture in old age.

Base-pair opening dynamics of the microRNA precursor pri-miR156a affect temperature-responsive flowering in Arabidopsis.

Internal and environmental cues, including ambient temperature changes, regulate the timing of flowering in plants. Arabidopsis miR156 represses flowering and plays an important role in the regulation of temperature-responsive flowering. However, the molecular basis of miR156 processing at lower temperatures remains largely unknown. Here, we performed nuclear magnetic resonance studies to investigate the base-pair opening dynamics of model RNAs at 16 °C and investigated the in vivo effects of the mutant RNAs on temperature-responsive flowering. The A9C and A10CG mutations in the B5 bulge of the lower stem of pri-miR156a stabilized the C15∙G98 and U16∙A97 base-pairs at the cleavage site of pri-miR156a at 16 °C. Consistent with this, production of mature miR156 was severely affected in plants overexpressing the A9C and A10CG constructs and these plants exhibited almost no delay in flowering at 16 °C. The A10G and A9AC mutations did not strongly affect C15∙G98 and U16∙A97 base-pairs at 16 °C, and plants overexpressing A10G and A9AC mutants of miR156 produced more mature miR156 than plants overexpressing the A9C and A10CG mutants and showed a strong delay in flowering at 16 °C. Interestingly, the A9AC mutation had distinct effects on the opening dynamics of the C15∙G98 and U16∙A97 base-pairs between 16 °C and 23 °C, and plants expressing the A9AC mutant miR156 showed only a moderate delay in flowering at 16 °C. Based on these results, we propose that fine-tuning of the base-pair stability at the cleavage site is essential for efficient processing of pri-miR156a at a low temperature and for reduced flowering sensitivity to ambient temperature changes.

Effect of Coronary Artery Calcification Score by Lifestyle and Correlation With Coronary Artery Stenosis by Multidetector Computed Tomography.

OBJECTIVE: This study examined the effect of coronary artery calcification score by lifestyle and correlation with coronary artery stenosis in persons who underwent coronary artery computed tomography (CT) angiography among health examinees for heart diseases in Korea. METHODS AND MATERIALS: The study included 506 subjects (256 men and 250 women) who underwent coronary artery CT angiography among health examines for heart diseases at the Incheon Branch of the Korea Association of Health Promotion between January 2, 2014, and December 31, 2014. The demographical variables of the subjects were determined by frequency analysis, and the difference by sex was compared and analyzed using χ independence test. Independent 2-sample t test was performed to determine any difference in main factors by coronary artery calcification. RESULTS: According to the results, 175 (34.6%) had calcification, men showed statistically higher scores than women, and calcification seemed higher in those who were older, taller, heavier, and thicker in waist. Regarding blood pressure, calcification was shown if contraction phase and relaxation blood pressure was higher, blood sugar before meal was higher, and neutral fat was higher. By lifestyle, calcification seemed to be higher in those with more alcohol drinking per week, long past smoking years, and higher smoking amount per day in the past and present. In addition, coronary artery stenosis rate showed statistical correlation with calcification from the left anterior descending artery, right coronary artery, left circumflex artery, and left main coronary artery in sequence. CONCLUSIONS: In conclusion, coronary artery calcification score CT is deemed to be a suitable method for the estimation of coronary artery stenosis with short examination time, low radiation exposure, and noninvasive method.

Photodiagnosis of White Spot Lesions after Orthodontic Treatment with a Quantitative Light-induced Fluorescence-Digital System: A Pilot Study.

PURPOSE: To confirm that the quantitative light-induced fluorescence-digital (QLF-D) system is an adequate tool for monitoring changes in the mineral contents of white spot lesions. MATERIALS AND METHODS: Twenty-three anterior teeth from five orthodontic patients were selected for the samples. Initial fluorescent images were taken with the QLF-D system immediately after removing the fixed orthodontic appliances, and the white spot lesions were visualised in the fluorescent images that were selected. Subsequently, a fluoride varnish containing 0.1% fluoride was applied to all white spot lesions, and the final QLF-D images were taken two weeks after fluoride treatment. Finally, the following four parameters were compared between the images taken at baseline and two weeks after the treatment with paired t-tests: the mean fluorescence loss (∆F), maximum fluorescence loss (∆Fmax), lesion area (area), and lesion volume (∆Q). RESULTS: All the parameters obtained by QLF-D after two weeks had improved significantly when compared with baseline (p < 0.01). The recovery rates of the ∆F, ∆Fmax, area, and ∆Q were 11.4%, 17.1%, -37.5%, and 42.1%, respectively. Shallow lesions (∆Fi ≥ -15%) were better remineralized than deep lesions (∆Fi < -15%). The ratios of the ∆F, ∆Fmax, area, and ∆Q parameters between the shallow and deep lesions were 2.86, 3.30, 2.20, and 1.88, respectively. CONCLUSION: The QLF-D system is a sensitive tool for the assessment of small levels of mineral changes in carious lesions after the removal of orthodontic appliances.

Measures of Dynamic Chewing Function, Rather than the Number of Teeth, are a Better Predictors of the Elderly's Ability to Intake Food and Nutrients.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Dietary intake is associated with occlusal force rather than number of teeth in 80-y-old Japanese. Inomata C, Ikebe K, Okubo H et al. J Dent Res 2016;2(2):187-97. SOURCE OF FUNDING: The study was supported by a Grant-in-Aid for Scientific Research (Nos. 23390440 and 25293394) from the Japan Society for the Promotion of Science TYPE OF STUDY/DESIGN: Cross-sectional study.

Analysis of Orange/Red Fluorescence for Bacterial Activity in Initial Carious Lesions May Provide Accurate Lesion Activity Assessment for Caries Progression.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Orange/Red Fluorescence of Active Caries by Retrospective Quantitative Light-Induced Fluorescence Image Analysis. Gomez GF, Eckert GJ, Zandoná AF.Caries Res 2016; 50(3):295-302. SOURCE OF FUNDING: The study was partially supported by a grant from NIH/NIDCR (R01DE017890) TYPE OF STUDY/DESIGN: Retrospective case-control design using the data collected in a longitudinal study.

The New Marginal Plaque Index May Allow a More Valid Assessment of Gingival Plaque Level Than the Turesky Modification of the Quigley and Hein Index.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Establishment of a new marginal plaque index with high sensitivity for changes in oral hygiene. Deinzer R, Jahns S, Harnacke D. J Periodontol 2014; 85(12):1730-8. SOURCE OF FUNDING: The study was supported by a sponsorship from GABA International, Therwil, Switzerland. TYPE OF STUDY/DESIGN: Observational case-control study.