Efficacy and safety of biological treatment for inflammatory bowel disease in elderly patients: Results from a GETECCU cohort.

INTRODUCTION: Biological therapies used for the treatment of inflammatory bowel disease (IBD) have shown to be effective and safe, although these results were obtained from studies involving mostly a young population, who are generally included in clinical trials. The aim of our study was to determine the efficacy and safety of the different biological treatments in the elderly population. METHODS: Multicenter study was carried out in the GETECCU group. Patients diagnosed with IBD and aged over 65 years at the time of initiating biological therapy (infliximab, adalimumab, golimumab, ustekinumab or vedolizumab) were retrospectively included. Among the patients included, clinical response was assessed after drug induction (12 weeks of treatment) and at 52 weeks. Patients' colonoscopy data in week 52 were assessment, where available. Regarding complications, development of oncological events during follow-up and infectious processes occurring during biological treatment were collected (excluding bowel infection by cytomegalovirus). RESULTS: A total of 1090 patients were included. After induction, at approximately 12-14 weeks of treatment, 419 patients (39.6%) were in clinical remission, 502 patients (47.4%) had responded without remission and 137 patients (12.9%) had no response. At 52 weeks of treatment 442 patients (57.1%) had achieved clinical remission, 249 patients had responded without remission (32.2%) and 53 patients had no response to the treatment (6.8%). Before 52 weeks, 129 patients (14.8%) had discontinued treatment due to inefficacy, this being significantly higher (p<0.0001) for Golimumab - 9 patients (37.5%) - compared to the other biological treatments analyzed. With respect to tumor development, an oncological event was observed in 74 patients (6.9%): 30 patients (8%) on infliximab, 23 (7.14%) on adalimumab, 3 (11.1%) on golimumab, 10 (6.4%) on ustekinumab, and 8 (3.8%) on vedolizumab. The incidence was significantly lower (p=0.04) for the vedolizumab group compared to other treatments. As regards infections, these occurred in 160 patients during treatment (14.9%), with no differences between the different biologicals used (p=0.61): 61 patients (19.4%) on infliximab, 39 (12.5%) on adalimumab, 5 (17.8%) on golimumab, 22 (14.1%) on ustekinumab, and 34 (16.5%) on vedolizumab. CONCLUSIONS: Biological drug therapies have response rates in elderly patients similar to those described in the general population, Golimumab was the drug that was discontinued most frequently due to inefficacy. In our experience, tumor development was more frequent in patients who used anti-TNF therapies compared to other targets, although its incidence was generally low and that this is in line with younger patients based on previous literature.

Delving into the Role of lncRNAs in Papillary Thyroid Cancer: Upregulation of LINC00887 Promotes Cell Proliferation, Growth and Invasion.

Papillary thyroid carcinoma (PTC) is the most common histological category of thyroid cancer. In recent years, there has been an increasing number of studies on lncRNAs in PTC. Long intergenic non-protein coding RNA 887 (LINC00887) is a critical oncogene in developing other cancers. LINC00887 is upregulated in PTC samples but its role in PTC is currently unclear. This study aimed to investigate the impact the disruption of LINC00887 expression has on PTC progression. We performed a CRISPR/Cas9 strategy for the truncation of LINC00887 in BCPAP and TPC1 cell lines. Functional assays showed that LINC00887 knockdown in both TPC1 and BCPAP cells reduced cell proliferation, colony formation and migration, delayed the cell cycle, and increased apoptosis. These results strengthened the role of LINC00887 in cancer and showed for the first time that this lncRNA could be a potential oncogene in PTC, acting as a tumor promoter. Modulation of the immune system may be one of the etiopathogenic mechanisms of LINC00887 in PTC, as shown by the observed influence of this lncRNA on PD-L1 expression. In addition, the biological pathways of LINC00887 identified to date, such as EMT, the Wnt/ß-catenin signaling pathway or the FRMD6-Hippo signaling pathway may also be relevant regulatory mechanisms operating in PTC.

Corrigendum: Study protocol for FIBROKIT: a new tool for fibromyalgia diagnosis and patient follow-up.

[This corrects the article DOI: 10.3389/fneur.2023.1286539.].

Implication of intestinal microbiota in the etiopathogenesis of fibromyalgia: A systematic review.

Fibromyalgia (FM) is a highly prevalent chronic disease. About 4.7% of the world's population suffers from generalized pain and hypersensitivity, in addition to a wide range of physical and psychological symptoms. The etiopathogenesis of this disease is multifactorial, which makes its diagnosis and treatment challenging. Recently, the increase in the number of studies on microbiota has provided new data that can help to understand the onset and development of FM. An updated systematic review of the causes of FM has been carried out in this work. Particularly in the last decade, research has focused on the gut-brain axis, which has emerged as a crucial mechanism for microbiota-host crosstalk. In FM patients, quantitative imbalances of the intestinal microbiota (dysbiosis) and bacterial metabolites with differential relative abundance have been found, especially short-chain fatty acids and lipopolysaccharides. Furthermore, the microbiota has been found to indirectly influence host neurotransmitter mechanisms, mainly through the serotonin precursor, glutamate, and gamma-aminobutyric acid. Thus, all these mechanisms and their influence on the etiopathogenesis of FM are discussed in this review.

Long-term results of the AptisTM total distal radioulnar joint prosthesis after previous failed surgical procedures.

We present a prospective study with the results of ten Aptis total distal radioulnar joint replacements in patients who had one to five previous operations. The mean postoperative follow-up was 9.7 years (range 3-14.7). The mean postoperative range of motion of the wrist improved by 9° for extension, 15° for flexion, 10° for pronation and 14° for supination, achieving values equivalent to 88%, 78%, 97% and 88% of those of the non-operated hand. There were minimal changes in radial and ulnar deviations. Grip strength improved by 7 kg, pain decreased by 8 points, QuickDASH and Mayo wrist scores improved by 51 and 53 points, respectively. Two implants had radiolucency less than 1 mm. Serum titanium ion levels were slightly elevated in two patients. Three prostheses required revision surgery for heterotopic ossification, a prominent radial screw and a periprosthetic fracture. No prostheses were removed. Six patients returned to their former professional activities and four patients adapted their jobs.Level of evidence: IV.

Study protocol for FIBROKIT: a new tool for fibromyalgia diagnosis and patient follow-up.

Fibromyalgia (FM) is a complex disease that is characterized by chronic musculoskeletal pain and has great economic impact. FM prevalence is about 2% to 4% worldwide, affecting mainly middle-aged women, and its complex pathophysiology complicates diagnosis, treatment and the findings of solid biomarkers. Previous studies have suggested an association between the disease and oxidative stress, mitochondrial metabolism, intestinal microbiota and inflammation, providing sufficient data to support the multifactorial origin of FM. Hence, the objective of this randomized, prospective, low-interventional, double-blinded and placebo-controlled clinical trial is the development of a specific panel of FM biomarkers and the evaluation of their response to a six-month nutritional intervention based on the Mediterranean diet supplemented with extra virgin olive oil (EVOO). For this purpose, the experimental design implies the recruitment of a large cohort of female Spanish patients. Middle-aged women who meet the diagnostic criteria for FM according to the American College of Rheumatology (ACR) will be eligible, along with age-matched healthy women. Both groups will be randomly divided into placebo (olive oil, OO) and treatment groups (extra virgin olive oil, EVOO), and will provide samples at the beginning (T0), after 3 months of nutritional intervention (T1), at the end of the nutritional intervention in 6 months (T2), and 6 months after the end of nutritional intervention (TF), being enrolled for 1 year. Data will be collected through health questionnaires, and whole blood and stool samples will be taken and analyzed. Blood will be used for western-blotting and proteomic analysis of mitochondrial homeostasis and plasma proteome, while stool will undergo metagenomic analysis, respectively. This study represents the first low-interventional investigation with more than 200 participants focused on exploring the association of oxidative stress, mitochondrial metabolism, intestinal microbiota and related pathways with a nutritional intervention in the context of FM. As a result, the outcomes of this study will significantly contribute to the development of a comprehensive and robust panel of diagnostic biomarkers, and will shed some light on their modulation with non-pharmacological therapies such as nutrition. Clinical trial registration: https://clinicaltrials.gov/study/NCT05921409, identifier: NCT05921409.

Comparison of Surgical Risk Scores in a European Cohort of Patients with Advanced Chronic Liver Disease.

Patients with advanced chronic liver disease (ACLD) or cirrhosis undergoing surgery have an increased risk of morbidity and mortality in contrast to the general population. This is a retrospective, observational study to evaluate the predictive capacity of surgical risk scores in European patients with ACLD. Cirrhosis was defined by the presence of thrombocytopenia with <150,000/uL and splenomegaly, and AST-to-Platelet Ratio Index >2, a nodular liver edge seen via ultrasound, transient elastography of >15 kPa, and/or signs of portal hypertension. We assessed variables related to 90-day mortality and the discrimination and calibration of current surgical scores (Child-Pugh, MELD-Na, MRS, NSQIP, and VOCAL-Penn). Only patients with ACLD and major surgeries included in VOCAL-Penn were considered (n = 512). The mortality rate at 90 days after surgery was 9.8%. Baseline disparities between the H. Mar and VOCAL-Penn cohorts were identified. Etiology, obesity, and platelet count were not associated with mortality. The VOCAL-Penn showed the best discrimination (C-statistic90D = 0.876) and overall predictive capacity (Brier90D = 0.054), but calibration was not excellent in our cohort. VOCAL-Penn was suboptimal in patients with diabetes (C-statistic30D = 0.770), without signs of portal hypertension (C-statistic30D = 0.555), or with abdominal wall (C-statistic30D = 0.608) or urgent (C-statistic180D = 0.692) surgeries. Our European cohort has shown a mortality rate after surgery similar to those described in American studies. However, some variables included in the VOCAL-Penn score were not associated with mortality, and VOCAL-Penn's discriminative ability decreases in patients with diabetes, without signs of portal hypertension, and with abdominal wall or urgent surgeries. These results should be validated in larger multicenter and prospective studies.

Inflammatory response to bacterial lipopolysaccharide drives iron accumulation in human adipocytes.

The association among increased inflammation, disrupted iron homeostasis, and adipose tissue dysfunction in obesity has been widely recognized. However, the specific impact of inflammation on iron homeostasis during human adipogenesis and in adipocytes remains poorly understood. In this study, we investigated the effects of bacterial lipopolysaccharide (LPS) on iron homeostasis during human adipocyte differentiation, in fully differentiated adipocytes, and in human adipose tissue. We found that LPS-induced inflammation hindered adipogenesis and led to a gene expression profile indicative of intracellular iron accumulation. This was accompanied by increased expression of iron importers (TFRC and SLC11A2), markers of intracellular iron accumulation (FTH, CYBA, FTL, and LCN2), and decreased expression of iron exporter-related genes (SLC40A1), concomitant with elevated intracellular iron levels. Mechanistically, RNA-seq analysis and gene knockdown experiments revealed the significant involvement of iron importers SLC39A14, SLC39A8, and STEAP4 in LPS-induced intracellular iron accumulation in human adipocytes. Notably, markers of LPS signaling pathway-related inflammation were also associated with a gene expression pattern indicative of intracellular iron accumulation in human adipose tissue, corroborating the link between LPS-induced inflammation and iron accumulation at the tissue level. In conclusion, our findings demonstrate that induction of adipocyte inflammation disrupts iron homeostasis, resulting in adipocyte iron overload.

Bone metastases from differentiated thyroid cancer: characteristics and prognostic factors in a multicenter series.

Objective: The aim of this study is to describe the characteristics, survival and prognostic factors of a cohort of patients with bone metastases (BMs) from differentiated thyroid carcinoma (DTC). Methods: This was a multicenter retrospective observational study including patients diagnosed with BMs from DTC between 1980 and 2021. A Cox regression was performed to study prognostic factors for 5- and 10-year survival. Kaplan-Meier and log-rank tests were performed for the survival analysis and comparison between groups. Results: Sixty-three patients were evaluated. Median follow-up from BM diagnosis was 35 (15-68) months. About 30 (48.4%) patients presented with synchronous BMs. Regarding histology, 38 (60.3%) had the papillary variant. BMs were multiple in 32 (50.8%) patients. The most frequent location was the spine (60.3%). Other metastases were present in 77.8%, mainly pulmonary (69.8%). Concerning treatment, 54 (85.9%) patients received I131, with BM uptake in 31 (49.2%) and 25 (39.7%) received treatment with multikinase inhibitors. Regarding complications, 34 (54%) patients had skeletal-related events, 34 (54%) died and 5- and 10-year overall survival was 42.4% and 20.4%, respectively. Significant prognostic factors in the multivariate analysis were the presence of lymph node involvement (hazard ratio (HR): 2.916; 95% confidence interval (CI): 1.013-8.391; P = 0.047) and treatment with I131 (HR 0.214 (95% CI 0.069-0.665); P = 0.008) at 5 years, the presence of other metastases (HR 6.844. 95% CI 1.017-46.05; P = 0.048) and treatment with I131 (HR 0.23 (95% CI 0.058-0.913); P = 0.037) at 10 years. Conclusions: Our study reflects the management of patients with bone metastases from differentiated thyroid carcinoma in real clinical practice in several centers in southern Spain. Overall survival at 5 and 10 years was lower in patients who were not treated with I131, had nodal involvement and/or had other metastases.

Microbiota and Mitochondrial Sex-Dependent Imbalance in Fibromyalgia: A Pilot Descriptive Study.

Fibromyalgia is a widespread chronic condition characterized by pain and fatigue. Among the long list of physiological disturbances linked to this syndrome, mitochondrial imbalance and oxidative stress stand out. Recently, the crosstalk between mitochondria and intestinal microbiota has caught the attention of biomedical researchers, who have found connections between this axis and several inflammatory and pain-related conditions. Hence, this pilot descriptive study focused on characterizing the mitochondrial mass/mitophagy ratio and total antioxidant capacity in PBMCs, as well as some microbiota components in feces, from a Peruvian cohort of 19 females and 7 males with FM. Through Western blotting, electrochemical oxidation, ELISA, and real-time qPCR, we determined VDAC1 and MALPLC3B protein levels; total antioxidant capacity; secretory immunoglobulin A (sIgA) levels; and Firmicutes/Bacteroidetes, Bacteroides/Prevotella, and Roseburia/Eubacterium ratios; as well as Ruminococcus spp., Pseudomonas spp., and Akkermansia muciniphila levels, respectively. We found statistically significant differences in Ruminococcus spp. and Pseudomonas spp. levels between females and males, as well as a marked polarization in mitochondrial mass in both groups. Taken together, our results point to a mitochondrial imbalance in FM patients, as well as a sex-dependent difference in intestinal microbiota composition.

Human genetics influences microbiome composition involved in asthma exacerbations despite inhaled corticosteroid treatment.

BACKGROUND: The upper-airway microbiome is involved in asthma exacerbations despite inhaled corticosteroid (ICS) treatment. Although human genetics regulates microbiome composition, its influence on asthma-related airway bacteria remains unknown. OBJECTIVE: We sought to identify genes and biological pathways regulating airway-microbiome traits involved in asthma exacerbations and ICS response. METHODS: Saliva, nasal, and pharyngeal samples from 257 European patients with asthma were analyzed. The association of 6,296,951 genetic variants with exacerbation-related microbiome traits despite ICS treatment was tested through microbiome genome-wide association studies. Variants with 1 × 10-4 

Sentinel Lymph Node Impact on the Quality of Life of Patients with Endometrial Cancer.

OBJECTIVE: Given the improvement in the surgical treatment of endometrial cancer with the inclusion of sentinel lymph node biopsy (SLNB), our aim was to evaluate the impact of this minimally invasive and tailored nodal assessment on patients' quality of life (QoL). METHODS: This was a cross-sectional study conducted in a single-centre, tertiary-level hospital. Patients diagnosed with preoperative early-stage endometrial cancer, who underwent primary surgical treatment between August 2015 and November 2021, were included. The enrolled patients were divided into two cohorts according to the nodal staging performed: the first group underwent only SLNB (SLNB group); the second group underwent pelvic and/or para-aortic lymphadenectomy (LND group). We evaluated the overall QoL using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life core 30-item questionnaire (EORTC QLQ-C30) and a sexual health questionnaire (EORTC SHQ-C20). The scores were compared between the groups. RESULTS: Ninety patients were enrolled in the study: 61 (67.8%) in the SLNB group and 29 (32.2%) in the LND group. In the LND group, 24 (82.7%) patients underwent pelvic and para-aortic LND, while 5 (17.3%) patients underwent pelvic LND. The assessment of the functional scales showed better results for the SLNB group than for the LND group, with a significantly lower impact on physical status (8.2% vs. 25%, respectively; p = 0.031). In terms of the symptom scales, the SLNB group reported a significantly lower negative impact on sleep quality (4.9% vs. 27.6%, respectively; p < 0.01), pain (1.6% vs. 13.8%, respectively; p = 0.019), and dyspnoea (0% vs. 10.3%, respectively; p = 0.011) than the LND group. The SLNB group had better results for all analysed items regarding sexual QoL. CONCLUSIONS: The implementation of a surgical technique with SLNB improved patients' overall QoL by increasing their well-being in the functional and symptom spheres.

Identification of Novel Candidate Genes for Familial Thyroid Cancer by Whole Exome Sequencing.

Thyroid carcinoma (TC) can be classified as medullary (MTC) and non-medullary (NMTC). While most TCs are sporadic, familial forms of MTC and NMTC also exist (less than 1% and 3-9% of all TC cases, respectively). Germline mutations in RET are found in more than 95% of familial MTC, whereas familial NMTC shows a high degree of genetic heterogeneity. Herein, we aimed to identify susceptibility genes for familial NMTC and non-RET MTC by whole exome sequencing in 58 individuals belonging to 18 Spanish families with these carcinomas. After data analysis, 53 rare candidate segregating variants were identified in 12 of the families, 7 of them located in previously TC-associated genes. Although no common mutated genes were detected, biological processes regulating functions such as cell proliferation, differentiation, survival and adhesion were enriched. The reported functions of the identified genes together with pathogenicity and structural predictions, reinforced the candidacy of 36 of them, suggesting new loci related to TC and novel genotype-phenotype correlations. Therefore, our strategy provides clues to possible molecular mechanisms underlying familial forms of MTC and NMTC. These new molecular findings and clinical data of patients may be helpful for the early detection, development of tailored therapies and optimizing patient management.

Electropolishing Stainless Steel Optimization Using Surface Quality, Dimensional Accuracy, and Electrical Consumption Criteria.

Electropolishing (EP) processes require high electrical consumption that must be optimized to minimize production costs without sacrificing the objectives of surface quality and dimensional accuracy. The aim of the present paper was to analyze the effects of the interelectrode gap, initial surface roughness, electrolyte temperature, current density, and EP time on aspects of the EP process applied to AISI 316L stainless steel, which have not been examined in the literature, such as polishing rate, final surface roughness, dimensional accuracy, and electrical consumption cost. In addition, the paper aimed to obtain optimum individual and multi-objective considering criteria of surface quality, dimensional accuracy, and electrical consumption cost. The results showed that the electrode gap was not significant on the surface finish or current density, and the EP time was the parameter having the greatest effect on all criteria analyzed, with a temperature of 35 °C showing the best electrolyte performance. The initial surface texture with the lowest roughness Ra10 (0.5 ≤ Ra ≤ 0.8 µm) obtained the best results with a maximum polishing rate of ~90% and minimum final roughness (Ra) of ~0.035 µm. The response surface methodology showed the EP parameter effects and the optimum individual objective. The desirability function obtained the best global multi-objective optimum, while the overlapping contour plot provided optimum individual and simultaneous per polishing range.

Clinical Guideline on Perioperative Management of Patients with Advanced Chronic Liver Disease.

(1) Background: Patients with advanced chronic liver disease (ACLD) are living longer with more comorbidities because of improved medical and surgical management. However, patients with ACLD are at increased risk of perioperative morbidity and mortality; (2) Methods: We conducted a comprehensive review of the literature to support a narrative clinical guideline about the assessment of mortality risk and management of perioperative morbidity in patients with ACLD undergoing surgical procedures; (3) Results: Slight data exist to guide the perioperative management of patients with ACLD, and most recommendations are based on case series and expert opinion. The severity of liver dysfunction, portal hypertension, cardiopulmonary and renal comorbidities, and complexity of surgery and type (elective versus emergent) are predictors of perioperative morbidity and mortality. Expert multidisciplinary teams are necessary to evaluate and manage ACLD before, during, and after surgical procedures; (4) Conclusions: This clinical practice document updates the available data and recommendations to optimize the management of patients with advanced chronic liver disease who undergo surgical procedures.

Effect of Liposuction on Body Weight and Serum Concentrations of Leptin, Lipids, Glucose, and Insulin: A Meta-Analysis.

BACKGROUND: Abdominal obesity has been associated with an increased risk of insulin resistance, metabolic syndrome, and diabetes. Central fat removal procedures such as liposuction, lipectomy, and abdominoplasty are among the most common surgical procedures. The impact of the latter on the former is controversial and understudied. The authors aimed to explore the effect of subcutaneous fat elimination procedures on insulin resistance measures and adipokine levels. METHODS: Relevant studies regarding the effects of surgical subcutaneous fat removal on glucose, insulin, adipokines, and lipid metabolism, as well as blood pressure, were identified by searching PubMed and Ovid-Cochrane without limits in date, type of publication, or language. After the selection process, 24 studies were obtained. The results of the articles were summarized using descriptive statistics. For the final analysis, a randomized effects model was used to evaluate heterogeneity; averages and meta-analytic differences were expressed with a confidence interval of 95%. RESULTS: All studies reported a reduction in weight (-2.64 kg; 95% CI, -4.32 to -0.96; P = 0.002; I 2 = 36%; P of I 2 < 0.001) and body mass index after liposuction. A significant improvement in triglycerides (-10.06 mg/dL; 95% CI, -14.03 to -6.09; P < 0.001; I 2 = 48%; P of I 2 = 0.05), serum glucose concentration (-4.25 mg/dL; 95% CI, -5.93 to -2.56; P < 0.001; I 2 = 68%; P of I 2 < 0.001), serum insulin concentration (-2.86 µIU/mL; 95% CI, -3.75 to -1.97; P < 0.001; I 2 = 59%; P of I 2 = 0.003), and serum leptin concentration (-7.70 ng/mL; 95% CI, -11.49 to -3.92; P = 0.0001; I 2 = 96%; P of I 2 < 0.001) was consistently observed. CONCLUSION: In addition to weight loss, there is a significant decrease in leptin, triglyceride, glucose, and insulin serum concentrations after liposuction, a fact that should be considered in future discussions.

Effectiveness of minimally invasive surgery using incomplete phalangeal osteotomy for symptomatic curly toe of adults with a trapezoidal phalanx: An observational study.

Background and aims: Digital deformity in flexion, varismus (external rotation), and adduction with the toe in both supraduction and infraduction are called clinocampodactyly or curly toe. All adult patients with symptoms and a diagnosis of semirigid/rigid curly toes underwent radiological examination to verify the presence of a trapezoidal phalanx. The purpose of this study was to quantitatively determine the degrees of improvement of a dysmetric phalanx after incomplete phalangeal osteotomy using minimally invasive surgery. The points of improvement were determined using the American Orthopedic Foot and Ankle Society (AOFAS) scale score. Methods: Between May 2021 and June 2022, 30 patients diagnosed with curly toes underwent unicortical osteotomy of the affected phalanx. The convergence angle was measured and the AOFAS scale scores were compared. Results: A total of 33 toes underwent surgery. The average reduction of the convergence angle was 9°. The average improvement in the AOFAS scale score was 53 points at 6 months and reached almost 90 points (89.9 ± 6.1 points). Conclusions: Incomplete phalangeal osteotomy performed with minimally invasive surgery of the trapezoidal phalanges of curly toes of adults can improve alignment and AOFAS scale scores.

Gamification on Instagram: Nursing students' degree of satisfaction with and perception of learning in an educational game.

BACKGROUND: Gamification has been shown to lead to greater motivation and participation among students. Currently, many teachers use social networks to share supplementary course materials and student work, but they have not incorporated gamified educational activities into social networking sites. OBJECTIVE: To determine nursing students' satisfaction with an Instagram-based educational game and their perceptions of its effects on their learning. DESIGN: We conducted a cross-sectional, descriptive, observational study. PARTICIPANTS: First-year nursing students in the subject "Dietetics and Nutrition". RESULTS: Of the total sample, 71.7 % agreed that gamification had helped them assimilate the content. Between 66 % and 70 % agreed that the experience had motivated them to keep up with the subject and learn more about the topic, that it had helped them to better understand certain concepts of the subject, that they would recommend the experience to other students, and that they enjoyed the experience of playing a game while learning. 71.7 % of them were in favour of increased use of gamification in other subjects. CONCLUSIONS: The use of an Instagram-based educational game as a complement to in-class teaching was useful, enjoyable, and motivating for the acquisition of new knowledge.