In this Review, we discuss the key features of type 2 inflammation in asthma, summarize the clinical trial evidence of monoclonal antibody asthma treatments, and explore future avenues for targeted asthma treatment. The field of asthma has undergone a dramatic change in recent years. Advances in our understanding of type 2 airway inflammation have driven the discovery of monoclonal antibodies targeting specific aspects of the immune pathway. In landmark trials, these drugs have shown efficacy in reducing asthma attacks and exposure to oral corticosteroids, important causes of morbidity in people with asthma. Our review explores the key features of type 2 inflammation in asthma and summarizes the clinical trial evidence of the novel monoclonal antibody treatments and future avenues for treatment. Asthma is characterized by variable symptoms of breathlessness, cough, chest tightness, and wheeze. Diagnosis is supported by evidence of reversible airflow obstruction on spirometry or airway hyperresponsiveness through bronchial provocation testing . Asthma For over 30 yr, the cornerstone of asthma treatment has been inhaled corticosteroids (ICSs). ICSs reduce eosinophilic airway inflammation and are proven to improve symptoms and reduce asthma attacks . HoweverOur understanding of type 2 immunity has matured from simply a tool to regulate type 1 immunity to a more complex role including host defense and tissue repair . The keyThe asthmatic airway is characterized by chronic inflammation of the airway wall due to a complex infiltration and interplay of immune cells including eosinophils, neutrophils, lymphocytes, dendritic cells (DCs), innate lymphoid cells (ILCs), and mast cells. The inflammation leads to narrowing of the airway, airway hyperresponsiveness, airway mucous plugging, and airway remodeling. This pathology underpins the typical asthma symptoms as well as the airflow obstruction seen on spirometry . See FigAirway epithelial cells are the interface between the external environment and internal structures. They act as the primary line of defense against pathogens and other inhaled insults such as allergens or chemical irritants . This deTSLP, IL-33, and IL-25 stimulate ILC2 and Th2 cells to produce type 2 cytokines . ILC2 ce+ T cells to become effector Th2 cells, which then produce type 2 cytokines  and CD18 and suppressing L-selectin . TSLP, Iytokines .Th2 cells formed in the draining lymph nodes also stimulate B cells to mature into plasma cells and produce antibodies . IL-4 anAllergic asthma is typically early onset but can persist into adulthood. DCs present inhaled aeroallergens, such as house dust mite, animal dander, or pollen, to tissue-resident memory Th2 lymphocytes, expressing antigen-specific TCRs . IgE croIL-4 and IL-13 play a powerful and intricate role in the type 2 cytokine response due to their effect on nearly every cell relevant to asthma. There are four receptor chains that compose the IL-4R complexes: IL-4Rα, γ chain, IL-13Rα1, and IL-13Rα2 . On naivOn airway epithelial and smooth muscle cells, IL-4 and IL-13 bind to the heterodimer IL-4Rα and IL-13Rα1 , ICAM-1, and the generation of eosinophil-attracting chemokines, such as eotaxins . In thisAll the IL-4R signaling pathways operate in a JAK-STAT6-dependent manner . The rol+ stem cells. Expression of certain transcription factors induces eosinophil differentiation . IL-5, GM-CSF, and IL-3 synergistically continue this process of differentiation and maturation in the bone marrow  that bind to the CCR3 receptors on eosinophils and induce chemotaxis . PGD2 anOnce in the airway tissue, eosinophils can generate inflammation in a variety of ways. By degranulating, akin to detonating a bomb, eosinophils damage lung structural cells through the release of cytotoxic proteins including major basic protein (MBP), eosinophil peroxidase (EPO), eosinophil-derived neurotoxin (EDN), and eosinophil cationic protein ECP; . ProinflAnother cause of persistent airflow obstruction is mucous plugging. Eosinophils can form extracellular traps (EETs) made from extracellular DNA fibers . FunctioIn 1956, OCSs were shown to be effective in treating asthma attacks . Trials ICSs have a much wider therapeutic index and are an important part of modern asthma treatment. They downregulate transcription of a wide range of cytokines, resulting in a reduction in Th2 cells, mast cells, macrophages, and DCs. Eosinophils are reduced in the airway epithelium because of apoptosis and by decreased chemotactic pull by chemokines such as eotaxin, which are also downregulated by ICSs. This effect is reflected by a reduction in FeNO . HoweverBiological therapies offer a reprieve by targeting specific parts of the type 2 inflammatory pathway. They have also proved safe and effective at reducing asthma attacks and oral steroid use. For clinical relevance and brevity, we will mainly focus on the mechanisms and efficacy of treatments that are currently licensed in adults. The key classes of monoclonal antibody are anti-IgE , anti-IL5/anti-IL5R , anti-IL4R (dupilumab), and anti-TSLP  on mast cells and basophils. This reduces cellular activation and inflammatory mediator release, particularly in the context of an allergic asthmatic response . OmalizuThe efficacy of omalizumab is extensively studied in allergic asthma. A recent systematic review and meta-analysis of five adult studies found a 37% (CI 21–50%) absolute risk reduction in the annual exacerbation rate AER; . This waDue to the inconsistent clinical evidence and unpredictable real-world data, omalizumab is best suited to a small, specific group of young asthmatics where allergy is the primary factor in their exacerbations. IgE appears to be the product of type 2-high inflammatory activation, rather than a key mediator.9 cells per liter.IL-5 plays a more central role in the pathogenesis of type 2-high asthma. Mepolizumab and reslizumab bind to IL-5, while benralizumab binds to IL-5Rα. All three treatments result in a marked reduction in blood eosinophils and are licensed for patients with severe eosinophilic asthma with a blood eosinophil count of at least 0.15 × 10The path to success for anti-IL5 biologics was not straightforward . Early cThe subsequent phase 3 trials of mepolizumab  confirme9 per liter (SIROCCO and CALIMA) decreased the annualized exacerbation rate by up to 50% and increased forced expiratory volume in 1 s (FEV1) by 110–160 ml  in uncontrolled moderate to severe asthmatics demonstrated a 48% reduction in exacerbations and 130 ml improvement in FEV1 compared with a placebo . Dupilum placebo .Additionally, dupilumab is efficacious and licensed for atopic dermatitis and chronic rhinosinusitis with nasal polyposis . ClinicaThe alarmins offer the potential to have more wide-ranging effects on downstream cytokines and hematopoietic cells.9 per liter. Similarly, there was a 73% reduction in exacerbations in patients with FeNO > 50 ppb. Tezepelumab showed clinical efficacy, albeit less pronounced, in the type 2-low phenotype. There was a 41% reduction in exacerbations in patients with baseline blood eosinophils <0.3 × 109, and a 32% exacerbation reduction in patients with FeNO < 25 ppb. However, the SOURCE study did not show a significant reduction in maintenance OCS between tezepelumab and placebo  in patients aged 12–80 yr showed a 56% reduction in exacerbations and 130 ml improvement in FEV1 compared with a placebo . Tezepel placebo . The DES placebo . Additio placebo . An ongo placebo .There are also drugs targeting IL-33 (itepekimab) and the IL-33 ST2 receptor (astegolimab). A phase 2 comparing dupilumab, itepekimab, itepekimab/dupilumab, and placebo study showed that itepekimab prevented loss of asthma control compared with a placebo when LABA and then ICS were removed sequentially . HoweverAstegolimab was tested in a phase 2 trial with no minimum threshold for blood eosinophils. Astegolimab reduced exacerbations by 43% compared with placebo at the 490 mg dose . There w9 per liter was noted in 1.2% of dupilumab recipients, but these patients were asymptomatic  and a very low risk of hypersensitivity reaction (<0.5%). The most notable side effect of dupilumab was blood hypereosinophilia of unknown significance. This occurs because the transport of eosinophils from the bloodstream is impeded. A blood eosinophil count of 3 × 10ptomatic . There aptomatic . The mosNippostrongylus brasiliensis  and offers a potential novel treatment for asthma. OX40L is expressed on antigen-presenting cells, such as DCs, endothelial cells, macrophages, and activated B cells . OX40 isBruton’s tyrosine kinase inhibitors (BTKi) are another class of small molecules already in use for B cell malignancies and are being explored in allergic asthma. BTK is an important kinase for FcεRI signaling in mast cells and basophils, therefore mediating allergic-driven inflammation . An inhaAtuliflapon is a FLAP inhibitor that reduces 5-lipoxygenase (5-LO) pathway activity and the production of proinflammatory leukotrienes. Following an inflammatory stimulus, 5-LO interacts with 5-lipoxygenase-activating protein (FLAP) on the nuclear membrane, which mediates arachidonic acid transfer to the active site of 5-LO . AtuliflCurrently, licensed monoclonal antibodies in asthma are all injected, so there is scope to deliver treatment less invasively. Dexpramipexole is an oral medication originally developed for amyotrophic lateral sclerosis but was incidentally found to significantly reduce the blood eosinophil count. The mechanism of action is thought to be by inhibiting the maturation of promyelocytes into eosinophils in the bone marrow. In the phase 2 EXHALE study, there was an 80% reduction in asthma exacerbations and a non-significant 172-ml increase in pre-bronchodilator FEV1 by week 12 . AdditioFurthermore, combining biologics targeting different type 2 pathways is being explored by drug companies. This could offer the benefit of having a portfolio of options that could target the mechanisms driving an individual person’s disease—a goal of precision medicine. However, this approach could also potentiate the side effects outlined above.Haemophilus influenzae  are formed when neutrophils shape a web of DNA and protein-rich fibers to immobilize pathogens . Evidencfluenzae . Targetifluenzae .2+-triggered membrane fusion in the production of mucin are a promising opportunity to reduce mucous production and have demonstrated efficacy in mice (Mucous plugging is an important patient symptom and there is emerging longitudinal computerised tomography evidence that persistent small mucous plugs lead to an increase in air trapping and airway obstruction . Finding in mice .Finally, obesity is a major driver of asthma symptoms and healthcare utilization. Part of the symptom burden is from changes to lung physiology. But mouse models also suggest that obesity alters inflammatory mechanisms by switching type 2 T helper–predominant disease to more severe, less responsive type 17 T helper–predominant disease. This may be related to decreased activity of nuclear receptor peroxisome proliferator-activated receptor-γ PPARγ; . TreatmeAsthma is fraught with misdiagnosis and mistreatment by attributing non-specific symptoms to the label of asthma . Given tThere is emerging evidence that blood eosinophils and FeNO are additive prognostic markers for the risk of future exacerbations . SymptomFuture research should also delve into the causes and mechanisms of asthma attacks. We know that viral infection is often implicated, but why they do not always lead to an attack and the impact of viral infections on the lower airway immunopathology in type 2-high asthma are not well understood. The MUPPITS-1 study observed heterogeneous nasal transcription modules in viral positive and viral negative asthma attacks in children . The MUPThe field of asthma has undergone a radical transformation over the past 20 yr. Patients with significant unmet needs now have access to highly effective and safe treatments in the form of biological therapies. These treatments yielded from our heightened understanding of type 2 inflammation and its interplay with pathophysiology in asthma. But the early failures of treatments in all-comer asthma patients underscores the important narrative that asthma should be diagnosed and treated in a targeted manner. As new treatments emerge for type 2-high or type 2-low asthma, it is imperative that we persist with the principle of precision medicine.


One of the main causes of proximal bowel obstruction in neonates is congenital duodenal obstruction. It can be grouped by intrinsic and extrinsic factors and the presentation may differ depending on whether the obstruction is complete or partial. The intrinsic factors include duodenal atresia, duodenal stenosis, or duodenal web. The extrinsic factors include malrotation with Ladd’s band, annular pancreas, anterior portal vein, and duodenal duplication. Malrotation may present with or without midgut volvulus.We are sharing a rare presentation of congenital duodenal obstruction with combined intrinsic and extrinsic causes, namely, duodenal stenosis with gastrointestinal malrotation in a neonate. The patient underwent successful exploratory laparotomy, corrective Kimura’s procedure (duodenostomy), Ladd's procedure, and appendicectomy.Early recognition of signs and symptoms, prompt corrective surgery, and adequate optimization of metabolic components post-operatively are important to determine the decreased morbidity and mortality of neonates. Congenital duodenal obstruction can be attributed as the main cause of intestinal obstruction in the neonatal age group . It can 9/L, haemoglobin of 5.7 g/dL, and platelet counts of 214 x 109/L. The patient developed respiratory distress syndrome and was intubated upon delivery. The initial blood gas revealed metabolic acidosis with a pH of 7.135 and a bicarbonate level of 14 mEq/litre. In view of haemodynamic instability, feeding was not started until after seven days of life. The patient was noted to pass meconium within 24 hours after delivery and minimal yellowish stool till the day of referral. Bedside echocardiography performed on day two of life showed levocardia with small patent ductus arteriosus, intact interventricular septum, and normal four heart chambers. The patient showed improvement and responded to antibiotics therapy and other supportive measures. Once the condition stabilized, feeding was commenced after day six of life but the patient developed feeding intolerance, where the patient started to have bilious drainage from the feeding tube and a grossly distended abdomen.A 10-day-old premature baby girl born at 32 weeks of gestation, with a birth weight of 2.42 kg, was referred to the paediatric surgery unit for feeding intolerance, associated with bilious drainage from the feeding tube. The patient's antenatal history was uneventful up till the 32 weeks of gestation when the mother developed chorioamnionitis and preterm premature rupture of the membrane of more than 12 hours, recording a temperature of 38.2°C prior to delivery. The mother had one previous emergency lower segment caesarean section (EMLSCS) in 2018 for late-onset pregnancy-induced hypertension, over-diabetes (glycosylated haemoglobin of 11.1%), and neonatal abruption. There was no other family history of congenital disease in the immediate family members. The patient was delivered via EMLSCS after two doses of dexamethasone were given together with intravenous antibiotics cefuroxime and metronidazole coverage for chorioamnionitis. The baseline blood work upon delivery recorded the total white count at 27.06 x 10Upon review of the serial imaging from birth, the imaging Figures , 2 showeAn earlier referral was deferred in view of haemodynamic instability and delay in the commencement of feeding at that time. The paediatric team then referred the patient to the paediatric surgical unit for proximal duodenal obstruction. Ultrasound abdomen study performed showed normal relation of superior mesenteric artery and vein; however, intestinal malrotation cannot be excluded. The horizontal segment of the third part of the duodenum was not visualized while the liver was seen on the right side of the abdomen and the spleen on the left. With these findings, the baby was subjected to an upper GI contrast study Figure .The patient then underwent exploratory laparotomy where we found that the patient has two pathologies, duodenal stricture at D2-D3, and gastrointestinal malrotation, as shown in intraoperative pictures Figures -6. We haIntraoperatively, the liver is located to the right of the abdomen, the spleen to the left, while there are no annular pancreas and no congenital band. The gallbladder is located to the right of the abdomen behind the liver but the extrahepatic bile duct is located in front of the first part of the duodenum. The stomach is on the right side, the duodenal-jejunal flexure is located to the right of the abdomen with short mesentery, the caecum is centrally located, and the rest of the large bowel is to the left of the abdomen. We performed corrective Kimura’s procedure (duodenoduodenostomy) for the duodenal stenosis and Ladd's procedure for the gastrointestinal malrotation.The patient was nursed in the neonatal intensive care unit (NICU) optimizing the patient’s post-operative parameters. The NICU team managed to commence feeding the baby, approximately within a week after surgery. The patient was also diagnosed with a nosocomial lung infection, presumed sepsis from chorioamnionitis, and hypothyroidism on top of delays in establishing optimal feeding. Despite a turbulent four-month stay due to prematurity and battling nosocomial infections, the patient was discharged home with bottle feeding 60cc every three hours and weighing 3.20 kg. A genetic study for this patient was not performed, as it was not routinely done in our setting in view of the high cost and limited testing capability.Congenital duodenal obstruction affects approximately one in 2,500-10,000 live births and almost half of the neonatal cases. The causes can be divided into two broad congenital factors: intrinsic and extrinsic. The intrinsic causes include duodenal atresia, duodenal stenosis, or duodenal web, whereas the extrinsic causes comprise malrotation with Ladd’s band, annular pancreas, anterior portal vein, and duodenal duplication. This case presentation has the unfortunate combination of duodenal stenosis (intrinsic) and gastrointestinal malrotation (extrinsic).Due to the nature of duodenal stenosis, it poses a challenge in terms of diagnosis, as the presentation may vary depending on the degree of obstruction , compareGastrointestinal malrotation on the other hand is a result of the failure of the midgut to rotate around the axis of the superior mesenteric artery. The patient may present with intestinal obstruction due to volvulus. It is usually diagnosed early and rare in adulthood . AccordiThe imaging modality of choice for both conditions can either be a contrast study or ultrasound, either prenatal ultrasound or postnatal ultrasound . A gastrPlain radiographs on the other hand can give rise to suspicions based on the presence of double bubble signs or multiple dilated bowel loops with or without transition zones. The location of the feeding tube in the plain radiographs may also be suggestive of malrotation as well as defining the normal location of the heart and liver.Surgery remains the mainstay in the treatment of duodenal stenosis and malrotation, with or without volvulus. Duodenoduodenostomy or Kimura’s procedure is often described as the surgery of choice for duodenal stenosis, introduced in 1977. Kimura described a method to bypass the stenosis by applying a diamond-shaped side-to-side duodenoduodenostomy  with gooOur case presentation was compounded with gastrointestinal malrotation, and more often than not, the surgical approach is Ladd’s procedure . In thisThe surgical approach has to be supported with post-operative optimization of fluid and electrolytes with parenteral nutrition to have a better overall outcome. The advancement in neonatal post-operative surgical care dramatically improved the outcome in recent years . The expIt is imperative to diagnose this condition as early as possible with the help of imaging and clinical suspicion. It is important to recognize that due to the partial or complete obstruction, the presentation may not be typical. Prompt corrective surgery with good post-operative care in a controlled environment is important to achieve a good outcome in general.


Understanding the correlation of work ability (WA) and anthropometric indices with cardiovascular diseases (CVDs) risk factors among public sector employees (PSE) is vital for policy direction. This study examined the correlation between work ability, anthropometric indices, and cardiovascular risk factors among PSEs.The cross‐sectional study had 254 (mean age = 37.18 ± 10.34) PSE. A self‐reported WA index was used to measure WA. Blood pressure (BP), body mass index (BMI), waist circumference (WC), hip circumference (HC), waist to hip ratio (WHR), and visceral fat were measured. Lifestyle CVDs risk history was also obtained.3.9% had moderate, 51.2% good, and 44.9% excellent WA. 37.4% overweight, 20.1% obese, 19.7% hypertension history, 67.7% no physical activity history. WA correlates with increased systolic BP, BMI, WC, WHR, weight to height ratio, and visceral fat significantly. Age 24−29 (aOR = 26.38), 30‐39 (aOR = 7.52), and 40‐49 (aOR = 4.94) independently predict excellent WA. Overweight (aOR = 0.44) independently predict decreased excellent WA.Participants were hypertension‐prone, had increased WC, WHR, physically inactive, overweight, and obese. WA and anthropometric indices of the participants predict CVDs risks. Workplace health care strategy should be put in place to control BP, BMI, WC, WHR, weight to height ratio, and visceral fat as CVDs risk factors. KMA is one of the 260 metropolitan, municipal, and district assemblies in Ghana. KMA is one of the 43 districts in Ashanti Region in Ghana, with Kumasi as its administrative capital. The study was conducted in line with the STrengthening the Reporting of Observational studies in Epidemiology (STROBE) for observational studies.n = (Z2 x PQ)/e2, where: Z is the standard normal variate at a confidence interval of 95% = 1.96. p is the prevalence = 7% of CVD in Ghana, e is the margin of error = 0.05, and Q = 1−p. n (minimum number of participants) = 1.962 x 0.07 x (1−0.07)/0.052 = 100. Hence, a minimum of 100 participants was required for the study.The study participants were recruited through a random sampling technique. The random sampling technique ensured that each participant has equal opportunity to be selected as established the literature.2.1Full time employees of public institutions within the KMA were included in the study. The study used PSE who experience high level of bureaucratic practise, tend to avoid unpaid overtime work, whose remunerations are often disbursed early and rarely delayed, more likely to be absent from work, tend to experience less stringent oversight responsibilities, and have job security when compared to private sector employees who were excluded. Employees of private and part time employees of public sectors are habitually dedicated to their job, rarely go to work late and often endure any challenge encountered for the sake of not losing one's job.2.2Demographic data on age, educational level, marital status, number of children, residence, religion, work experience (years), and working section was obtained. Lifestyle related information  was also obtained. Omron body composition analyzer and nonelastic tape measure were used to measure anthropometric indices. An Omron sphygmomanometer was used to measure blood pressure (BP) and heart rate of the study participants.The WA Index (WAI), a self‐assessment instrument, was administered to measure the work ability of the participants.2.32 (m). Data obtained were categorized according to standard.The height and weight were measured to the nearest 0.5 cm and 0.1 kg, respectively, while wearing light apparel and without shoes. The BMI formula was (weight [kg])/height2.4As CVD risk factor components, BP, heart rate, BMI, and visceral fat were measured and recorded. After each participant had sat for at least 10 min, two consecutive BP readings were taken from the participant's right arm. The systolic and diastolic BPs were recorded to the closest mmHg. If the difference between the two readings is greater than 4 mmHg, a third reading is taken. The subsequent analysis used the average of the two BP measurements. As the onset and disappearance of Korotkoff sounds, systolic and diastolic BP  were determined. Visceral adiposity was determined and recorded. The questionnaire on knowledge of cardiovascular risk factors (Q‐FARCS)Before data collection, the participants were given a thorough explanation of the study protocol and assurances of anonymity. Also, ethical approval was obtained from the Committee on Human Research, Publication, and Ethics, School of Medical Sciences, Kwame Nkrumah University of Science and Technology (Ref: CHRPE/AP/024/22). Authors declare that the work has been done in accordance with the declaration of Helsinki statement of ethical principles for medical research involving human subjects, including research on identifiable human material and data.2.4.1www.graphpad.com). Means and standard deviations served as the representations of parametric variables while medians and interquartile ranges served as those of nonparametric continuous variables. Variables of a categorical nature were represented as frequencies and percentages. Utilizing a Pearson χ2 test statistic and logistic regression analysis, correlation of cardiovascular risk factors as independent variables and WA as dependent were determined. A confidence interval of 95% and a p‐value deemed statistically significant at the 0.01 and 0.05 levels (2‐tailed).Microsoft Excel 2019 was used to enter, cleanse, and code the collected data. All statistical analyses were conducted using Statistical Package for the Social Sciences (SPSS) Version 26.0 and GraphPad Prism Version 8.0  significantly increased systolic BP, weight ; p = 0.041), and BMI ; p = 0.027) by 5% and 10% respectively. Also, increased WC; p = 0.003), and WHR ; p = 0.002) were significantly associated with 5%, 3%, 100% and 100% respectively of reduced WA. On the other hand, visceral fat ; p = 0.002) were associated with decreased excellent WA.According to Table From Table 4This study examined the correlation between WA, anthropometric indices, and cardiovascular risk factors among PSE. Findings showed that 57.5% were at least overweight, 38.6% had a history of hypertension, and 67.7% had never taken part in any physical activity, which reflects sedentary living  have been explained.


The students’ academic performance was also evaluated to look for quantitative differences between cohorts. We found similar overall academic scores for the Physiology course between cohorts. Interestingly, when we compared the academic scores obtained in the theoretical content from each cohort, we found a significant improvement (p < 0.05) in cohort 2 where the students achieved better results as compared to cohort 1. A subset of students was asked to fill a questionnaire assessment on their experience and found that 78.9% of them preferred integrated laboratory classes over laboratory classes alone. They consistently reported a better understanding of the theoretical content and the value they gave to ILCs for learning. In conclusion, our pilot study suggests that integrating laboratory classes into PBL-oriented clinical contexts help to retain core physiology contents and it can be considered as an engaging learning activity worth implementing in Psychology teaching.Physiology is a fundamental discipline to be studied in most Health Science studies including Psychology. Physiology content is perceived by students as rather difficult, who may lack vision on how to relate it with their professional training. Therefore, identifying novel active and more engaging pedagogical strategies for teaching physiology to psychology students may help to fill this gap. In this pilot study, we used the PBL methodology developed around a clinical case to evaluate psychology students’ experience and learning in two laboratory classes modalities. The aim of this study was to compare the undergraduates’ preference for laboratory classes taught either independently (cohort 1,  Physiology is considered a challenging discipline in most Health Science studies. Psychology students in particular usually consider physiology as a less relevant part of their professional training even though it provides an essential scientific understanding of the biological processes underlying human behavior and cognition . UnderstThe ability to make predictions about how external and internal changes affect the state of a biological system is central to physiology . Active All this suggest that students would be better able to handle with difficulties if they actively engage in the cognitive processes required to build connections amongst separate information pieces . This wiIn recent decades, the importance of teaching basic sciences such as Physiology in an integrated manner has been emphasized . This adUsing PBL methodologies can thus help to better engage Psychology students in learning physiology concepts, especially in relation to more real case scenarios. Integration of laboratory classes into the PBL framework has been shown to significantly improve understanding, leading to the development of critical thinking and other major competences . By provHere, we investigate the effectiveness of integrating Physiology teaching with PBL-based laboratory classes by evaluating the impact on academic performance and students’ perception in the first year of the Psychology undergraduate program. Our hypothesis is that students in which the laboratory classes are contextualized into PBL develop a better knowledge as compared to those who did not have the experience. To address this hypothesis, we developed a pilot study using a PBL-oriented clinical case on Parkinson’s disease using WSLA as an example. We compare a first group (academic year 2018–2019) in which laboratory classes were taught separately from the clinical case with an experimental group (year 2019–2020) for which laboratory classes were contextualized into the PBL and transformed into Integrated Laboratory Classes (ILCs) . Our stun = 87) from 2018/19, which was considered the control group, and cohort (n = 92) during 2019/2020 as the experimental group. Cohort 1 was organized in three homogeneous group of students each of 25–30 students. Cohort 2 was organized in four heterogeneous group of students, two of them composed by 30 students and the other two of less than 30 students. The students of both cohorts aged between 18 and 25 years. In both cohorts there were similar distribution per gender, with 69–77% women and 23–31% men.In this pilot study, we aimed to assess the impact of academic performance and student’s experience of teaching laboratory classes contextualized within the PBL applied to Physiology teaching in the first-year degree of Psychology. Two cohorts from consecutive academic years were selected: cohort 1 (The methodology used to teach the subject’s content consisted in lectures (theory block), laboratory classes , and problem-based learning (PBL block). The PBL block was taught through a clinical case that integrates different learning activities using WSLA. The theoretical block was delivered in the same way in both cohorts. The main difference between cohort 1 and cohort 2, was that in the first one (2018/19), the laboratory classes were conducted independently of the PBL block. As for the second cohort (2019/20), the practices were contextualized with PBL as an additional workstation and named Integrated Laboratory Classes (ILCs) in order to provide a meaningful context.Five clinical cases were completed in PBL blocks throughout the course. The cases consisted of a clinical scenario, a description of the patients, and various situations that students must solve in groups. Students had to rotate through different workstation learning activities. In each workstation, they worked with different aspects of the clinical case through learning activities such as bibliographic research, audiovisual material production, visiting external institutions, etc.To illustrate our approach, we here describe the example associated to the clinical case named ‘Practical Case: Parkinson’s disease’ . After tThe clinical case considered a protagonist, Peter, who suffered uncontrollable motor symptoms, such as shaking, stiffness, and difficulty with balance and coordination. He was worried and decided to talk to his nephew who was a Ph.D. student. Peter was about to visit a Parkinson’s disease association. Understanding the case required students to integrate information from different activities conducted across different workstation:Station 1: Students performed two external visits associated activities. In activity 1, they interviewed a neuropsychologist and a Parkinson’s patient (PD), both from the PD Association of Madrid. Previously, the students had worked on designing the interview questions. In activity 2, students visited an animal research laboratory at the Brain Mapping Center of Universidad Complutense de Madrid (UCM) where microPET imaging is used for translational research. They also visited the ‘Affective Neurolinguistics and Cognition Group’ of the UCM working with electroencephalography on human experimental subjects. Students solved problems through neuroimaging analysis, based on the training they received during these visits.Station 2: Students were exposed to theoretical explanations relevant to the clinical case.Station 3: For evaluation, students produced audiovisual material (video recordings), integrating all the learning activities worked on in the clinical case.In cohort 1, the motor reflexes were practiced as independent laboratory classes  with 4 options each, for which correct answers to each question were maximally scored and a penalty applied for incorrect answers, giving a partial score from 0 to 8 points. Exams also included two additional short-answers questions, which were scored from o to 2 points. The final score (10 points) resulted from the summation of the two parts.For quantitative analysis, academic scores from each of the different blocks in both cohorts were compared using an inferential non-parametric statistical study. As the two independent cohorts did not follow a normal distribution, a study was conducted using the Mann-Whitney non-parametric test. Academic scores were ranked from 0 to 10.n = 19). The rationale behind this decision was to be able to inform comparisons between the two academic experiences. To this purpose, we used a survey comprised of several questions scored with a Likert scale from 1 to 5 . To know more about what aspects the students remembered the most we also asked them to associate a particular concept learnt in different activities with each clinical case (question 8). Concepts included academic contents  as well as some particular characteristics of the clinical case .Internal validation was conducted by two experts who reviewed the coherence and consistency of the questionnaire. Additional validation was certified by an expert professor external to the project . ResultsWe analyzed the academic results of the theoretical block, common to both cohorts. To compare performance in the two different academic experiences, we looked for differences in the scores of the PBL block (cohort 1) vs. the PBL block in which ILCs were added as a workstation (cohort 2), as well as in laboratory classes (cohort 1) vs. ILCs (cohort 2). We also assessed the overall score of the Physiology course for both cohorts.p < 0.05) was found in cohort 2 , where the students achieved better results as compared to Cohort 1 . This trend was also reflected in the scores obtained in PBL+ILCs by cohort 2 (median 6.5) vs. PBL in cohort 1 (median 5.2), although it did not reach significance (p = 0.18).As shown in p < 0.05, Mann-Whitney U-test), suggesting that any improvement in understanding the relevant concepts may not be resulting from a single factor but at a more integrative level. These differences cannot be explained by external variables such as the temporality of the content explained, different teachers or type of assessment. The content was taught in the same semester (S1) and by the same teacher and even the same internship support teachers in Cohort 1 and 2. Exams in both cohorts were also similar. Moreover, as detailed in methods, both cohorts had similar profile of the students, and we did not face exceptional situations that contribute external variables.Regarding academic results from ILCs , we found them significantly lower than those obtained in laboratory classes alone  , more than half did not score them highly ; 60%. ReWe next assessed what methodology the students valued the most for learning and found that 78.9% of them preferred PBL+ILC over laboratory classes alone (question 5). Actually, 94.7% rated their opinion of ILCs between 4 and 5 of the Likert scale , we found 60% rated between 4 and 5 of the Likert scale, confirming the idea that the integrated PBL block added value to learning.Finally, we evaluated whether some concepts and ideas were able to trigger recalling of aspects of interest that were learnt over the course (question 8). With this we wanted to clarify the possible strategies used by students to build connections amongst separate information pieces. Consistent with a constructive perspective of learning, we found this to be strongly dependent on the case under study. For example, for the Clinical Case Parkinson’s disease, there was a notable higher percentage of students that answered appropriately to the questions related to the personal characteristics of the case protagonists, such as their names (73%) or the destination of their trip (68%). Regarding theoretical concepts, 56% of students correctly retrieved the clinical case in association with evoked potentials and only 25% with the concepts of neuroinflammation.In this work, we evaluated quantitatively if ILCs impact positively the academic performance of Physiology in first year students of psychology. Our findings show that no significant differences were obtained in the final grade for the subject. However, there was significant improvement of the score of the theoretical block of Cohort 2 students, where laboratory physiology classes were integrated and contextualized into the clinical case. Interestingly, we also found that academic results of the ILCs were significantly lower than for non-integrated laboratory classes. These results may suggest that ILCs are more challenging for students to accomplish than the non-integrated practical lesson. In spite of this difficulty, analysis of the students’ perception on questionnaires confirmed the value they give to ILCs for learning and highlight their strategies for knowledge integration of theoretical concepts.Experimental psychologist Robert Bjork, advocates for the so-called “desirable difficulties” as learning strategies which require learners to exert an appropriate effort when learning something new. It has been demonstrated that these activities tend to result in enhanced learning . In currStrategies to incorporate ‘desirable difficulty’ in health education include retrieval practice, spaced practice, and interleaved practice . In addiThe counterintuitive idea that more difficult learning processes can enhance learning outcomes supports our results. The ILCs is a learning activity where retrieval practice is included through questions for learners to probe their knowledge. These results suggest that students learn more significantly and are able to recall better the information they learnt through ILCs. Our results add to previous reports demonstrating that retrieval practice enhances the ability to evaluate complex physiology information .In this experience we use five clinical cases each based on a clinical scenario, a description of the patients, and various situations that students must solve in groups, working in an integrated manner through different learning activities. Health Science professionals are expected to integrate content that is traditionally taught in isolation, and this may be particularly challenging in the context of psychology. When combined, active and integrated learning approaches result in an enriched learning environment which encourages students to apply knowledge to real-world scenarios and develop critical thinking skills. By doing so, students are better equipped to understand complex problems, to analyze clinical situations, and to make informed decisions in their future practice . This isContextualization of the clinical case for Psychology students is crucial. All the clinical cases the students had to work with, were real. The protagonist of each case develops an illness related to the psychological and emotional domain, which naturally attracted the interest of psychology students. By feeling that the content they are studying comes close to their professional world, students gain motivation and engagement . ConsistAs for any pilot study, there may be some potential limitation. Our study focused on a particular cohort with a limited sample. Studies in education are usually limited by factors such as the teaching load, institutional policies and logistical constrains. Future studies would include the implementation and evaluation of integrated laboratory classes in other programs and courses with a longitudinal design. Active learning methodologies seldom reach the laboratory component of basic science courses losing an important chance to provide a better learning experience for students that may be less inclined toward laboratory work.In summary, our study supports that using active learning methodologies to teach laboratory classes within an attractive clinical context has a positive impact on learning and on the overall student’s experience. Moreover, ILCs are perceived as a motivating strategy by students which facilitates the understanding of complex physiological concepts. Using real clinical scenarios make students feel the content closer to their professional future and enhances engagement in their own learning process. This pilot study suggests that the ILCs help to retain core physiology content and it can be considered as a learning activity worth implementing in the Health curricula and in particularly in Psychology teaching.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee from the European University of Madrid (CIPI/18/060). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.BG: Conceptualization, Investigation, Supervision, Writing – original draft, Writing – review and editing. JS: Formal analysis, Investigation, Methodology, Writing – review and editing. BN-G: Data curation, Investigation, Writing – review and editing. ML: Investigation, Methodology, Writing – review and editing. MR: Formal analysis, Investigation, Methodology, Writing – review and editing.


Acremonium terricola is used in the feed of dairy animals to promote growth and control diseases. However, the effects of dietary supplementation with A. terricola on the gut microbial structure of weaning piglets remain poorly understood. Therefore, in this study, we investigated the effects of dietary supplementation with A. terricola culture (ATC) on the growth performance, antioxidant status, immunity, and gut environment of weaning piglets. Sixty piglets were fed a basal diet supplemented with 1 g ATC/kg of basal diet . Another 60 piglets did not receive ATC (control group). The intervention lasted for 20 days.P = 0.0018), insulin-like growth factor (P = 0.0018), triiodothyronine (P = 0.0031), immunoglobulin A (P < 0.0001), immunoglobulin M (P = 0.001), immunoglobulin G (P = 0.0001), and interferon γ (P < 0.0001) in the experimental group compared with the levels in the control group. Furthermore, ATC supplementation significantly reduced (P < 0.05) the relative abundance of Shuttleworthia, Succinivibrio, Roseburia, Ruminococcus, and Paludibacter but increased that of Phascolarctobacterium, Megasphaera, Faecalibacterium, and Prevotella in the experimental group compared with that in the control group. Notably, ATC supplementation significantly increased the relative abundance of Faecalibacterium prausnitzii (P < 0.05), which is involved in anti-inflammatory activities, gut barrier enhancement, and butyrate production.The experimental group had higher daily weight gain and feed efficiency than did the control group. Significant increases were noted in the levels of serum insulin (Dietary supplementation with ATC may improve the growth performance, antioxidant status, immunity, and fecal microflora of weaning pigs. In pig farming, postweaning is a crucial and challenging life stage because pigs are highly susceptible to nutritional, social, and environmental stress and gastrointestinal disorders, which result in growth retardation and even death . Over thBacillus, Cordyceps, and yeast, is an effective strategy for the prevention of various diseases and the improvement of weight gain and immunity in animals  were weaned at 42 days of age . The piglets were randomly and blinded assigned to two groups ; three replicate pens (20 piglets per pen) were used per group . Piglets were assigned individually (within litters) to the treatment groups. At admission, the animals were ear tagged as they came to hand and were allocated with the use of a computer-generated randomisation list (only known to BH) to one of the two treatment groups, until the required number of piglets had been reached. Animal feeding was conducted in a commercial pig farm . During the 20-day-long experimental period, the control group was fed a basal diet, whereas the experimental group was fed the same basal diet supplemented with 1 g ATC/kg of basal diet according to a previously described method . Table 2g for 10 min. The samples were prepared following a previously described method [On Day 20, blood samples were collected from the piglets after they had fasted for 12 h. For blood collection, 10 piglets were randomly selected from each group. The samples were collected in 10-mL evacuated blood collection tubes containing heparin sodium and then centrifuged at 2000 ×d method . The plad method . The prod method . All assAt the end of the intervention, fecal samples were collected from four piglets selected randomly from each group. The samples were collected through rectal dilation in plastic containers . Genomic DNA was isolated from the eight fecal samples by using a DNA extraction kit  according to the manufacturer’s instructions. The samples were treated with RNase to degrade RNA, and the quality and quantity (concentration) of DNA were evaluated through agarose gel electrophoresis and NanoDrop spectrophotometry. Sequencing libraries were established for the 16 S rRNA gene (V3 to V4 region) according to the relevant Illumina protocol. Paired-end shotgun sequencing was performed on the Illumina Hi-Seq 2000 platform. After the elimination of low-quality sequences, the remaining sequences were clustered into OTUs on the basis of ≥ 97% similarity assessed using Vsearch (version 2.3.4). Representative sequences were selected for each OTU, and taxonomic data were assigned to each representative sequence by using the Ribosomal Database Project Classifier, as described in a relevant study . OTU abuP < 0.05 indicated statistical significance.The pig was the statistical unit and the level of significance was set at 0.05. Sample size calculations were based on expected prevalence parameters, an expected coefficient of correlation of 0.5, α-value of 0.05, and power of 0.80. Data were analyzed using generalized linear models . A randomized complete block design was used with “pen” as the experimental unit for the evaluation of growth performance. Each pig was used as an experimental unit for the analysis of blood parameters and microbial counts. The significance of between-group differences was determined using Duncan’s multiple range test (SAS). All data are presented as mean ± standard error values.