Glutamate-cysteine ligase (GCL) is a crucial enzyme involved in the synthesis of glutathione (GSH). Despite various studies on glutathione transferase, and its essential role in detoxification and resistance to oxidative stress, GSH synthesis has not been described in Bombyx mori (silkworms) to date. Silkworms form part of the lepidopterans that are considered as a model of agricultural pests. This study aimed to understand the GSH synthesis by GCL in silkworms, which may help in developing insecticides to tackle agricultural pests. Based on the amino acid sequence and phylogenetic tree, the B. mori GCL belongs to group 2, and is designated bmGCL. Recombinant bmGCL was overexpressed and purified to ensure homogeneity. Biochemical studies revealed that bmGCL uses ATP and Mg2+ to ligate glutamate and cysteine. High expression levels of bmgcl mRNA and GSH were observed in the silkworm fat body after exposure to insecticides and UV-B irradiation. Moreover, we found an increase in bmgcl mRNA and GSH content during pupation in the silkworm fat body. In this study, we characterized the B. mori GCL and analyzed its biochemical properties. These observations indicate that bmGCL might play an important role in the resistance to oxidative stress in the silkworms.

GLP-1 (Glucagon-like peptide-1) is a peptide that stimulates insulin secretion from the β-cell for glycemic control of the plasma blood glucose level. Its mimetic exenatide (synthetic Exendin-4) with a longer half-life of approximately 3.3-4 h is widely used in clinical application to treat diabetes. Currently, exenatide is chemically synthesized. In this study, we report that the GLP-1 analogue recombinant Exendin-4 (Exdn-4) can be produced at a high level in Nicotiana benthamiana, with an estimated yield of 50.0 µg/g fresh biomass. For high-level expression, we generated a recombinant gene, B:GB1:ddCBD1m:8xHis : Exendin-4 (BGC : Exdn-4), for the production of Exendin-4 using various domains such as the BiP signal peptide, the GB1 domain (B1 domain of streptococcal G protein), a double cellulose binding domain 1 (CBD1), and 8 His residues (8xHis) to the N-terminus of Exendin-4. GB1 was used to increase the expression, whereas double CBD1 and 8xHis were included as affinity tags for easy purification using MCC beads and Ni2+-NTA resin, respectively. BGC : Exdn-4 was purified by single-step purification to near homogeneity using both Ni2+-NTA resin and microcrystalline cellulose (MCC) beads. Moreover, Exdn-4 without any extra residues was produced from BGC : Exdn-4 bound onto MCC beads by treating with enterokinase. Plant-produced Exdn-4 (Exendin-4) was as effective as chemically synthesized Exendin-4 in glucose-induced insulin secretion (GIIS) from mouse MIN6m9 cells a pancreatic beta cell line.

Evaluation of the in vitro antibacterial activity of Chloroform extracts isolated from Henna (Lawsonia inermis) leaf against two food born & nosocomial infection causing pathogens, gram-positive Staphylococcus aureus and gram-negative Escherichia coli. This interventional study was carried out during the period of January 2021 to December 2021 in the Department of Pharmacology and Therapeutics in collaboration with the Department of Microbiology, Mymensingh Medical College, Mymensingh, Bangladesh. The antibacterial activity was tested at different concentrations of Chloroform Henna leaf extracts by using disc diffusion and broth dilution method. The extract was prepared by using solvents chloroform and 0.1% DMSO. The test microorganisms were also tested for their activity against a standard antibiotic Ciprofloxacin by broth dilution method and the result was compared with that of Chloroform extracts. Chloroform Henna Extracts (CHE) were used initially in nine different concentrations (2.5, 5, 10, 20, 50, 100, 200, 500 and 1000mg/ml) and later in selected concentrations as needed to confirm the more precise margin of antimicrobial sensitivity of the extracts. Among different concentrations of the CHE, 100mg/ml and above concentrations showed inhibitory effect against Staphylococcus aureus and 300mg/ml and above concentrations showed inhibitory effect against Escherichia coli. The MIC for Staphylococcus aureus and Escherichia coli were 100 and 350mg/ml in CHE respectively. The MIC of Ciprofloxacin was 1μg/ml against both Staphylococcus aureus and Escherichia coli. The MIC of Ciprofloxacin was the lowest in comparison to MICs of CHE for the test organisms. The present study showed that Chloroform Henna extracts demonstrated antibacterial effects against food borne pathogens. From this study, it is clearly observed that there is definite antibacterial effect of the chloroform extract of Henna leaves against Staphylococcus aureus and Escherichia coli.

Huntingtin-associated protein 1(HAP1) is an immunohistochemical marker of the stigmoid body (STB). Brain and spinal cord regions with lack of STB/HAP1 immunoreactivity are always neurodegenerative targets, whereas STB/HAP1 abundant regions are usually spared from neurodegeneration. In addition to the brain and spinal cord, HAP1 is abundantly expressed in the excitatory and inhibitory motor neurons in myenteric plexuses of the enteric nervous system (ENS). However, the detailed expression of HAP1 and its neurochemical characterization in submucosal plexuses of ENS are still unknown. In this study, we aimed to clarify the expression and neurochemical characterization of HAP1 in the submucosal plexuses of the small intestine in adult mice and rats. HAP1 was highly expressed in the submucosal plexuses of both rodents. The percentage of HAP1-immunoreactive submucosal neurons was not significantly varied between the intestinal segments of these rodents. Double immunofluorescence results revealed that almost all the cholinergic secretomotor neurons containing ChAT/ CGRP/ somatostatin/ calretinin, non-cholinergic secretomotor neurons containing VIP/NOS/TH/calretinin, and vasodilator neurons containing VIP/calretinin expressed HAP1. Our current study is the first to clarify that STB/HAP1 is expressed in secretomotor and vasodilator neurons of submucosal plexuses, suggesting that STB/HAP1 might modulate or protect the secretomotor and vasodilator functions of submucosal neurons in ENS.

The degree to which the media report a health emergency affects the seriousness with which the people respond to combat the health crisis. Engagement from local newspapers in the US has received scant scrutiny, even though there is a sizable body of scholarship on the analysis of COVID-19 news. We fill this void by focusing on the Rio Grande Valley area of the US-Mexico border. To understand the differences, we compared such local news coverage with the coverage of a national news outlet. After collecting the relevant news articles, we used sentiment analysis, rapid automatic keyword extraction (RAKE), and co-occurrence network analysis to examine the main themes and sentiments of COVID-19 news articles. The RAKE identified that county-specific news or local regulations are more prevalent among the key terms in The Monitor which are absent in USA Today. The co-occurrence network shows the coverage of the disruption of sports season in USA Today which is not present in The Monitor. The sentiment analysis presents fear emotion is more dominant in USA Today, but trust emotion becomes more prevalent in The Monitor news coverage. These findings show us that, although the subject of the health emergency is the same, local and national newspapers describe it in different ways, and the sentiments they convey are also not the same.

This study determined the food-safety situation of street food by analyzing the KAP of street food vendors (SFVs). A quantitative descriptive cross-sectional study was conducted among the 266 SFVs through structured questionnaire from October to December, 2020. Majority of the SFVs were male (92.86%), age between 35 to 44 years (34.21%), married (83.83%), had primary education (46.99%), experience of 5-9 years (32.71%), and monthly income was <10000 BDT (35.71%). Additionally, utmost had no any training on food-safety (93.61%), and food preparation-preservation (89.47%). The knowledge and practice score of "≥50 to <75" was for highest proportion of SFVs amounting 57.89% and 47.7% respectively. And the attitudes score "≥67 to <83" was recorded for the highest number of SFVs (70.3%). Moreover, the mean KAP score was 71.94 ± 10.21, 73.89 ± 7.37 and 55.37 ± 15.08 respectively. However, the knowledge score had a moderate-strength of positive correlation with attitudes score (r = 0.342, p < 0.01) and practice score (r = 0.389, p < 0.01); having the regression-equation, y = 0.25∗x + 56.12 and y = 0.57∗x + 14.01 respectively. Besides, the similar correlation was also observed between attitudes and practice score (r = 0.328, p < 0.01) with the regression, y = 0.67∗x + 5.81. In this regard, a regular basis training on basics of food-safety and cotemporary education on food-safety at initial stage of education could be imposed to improve the KAP on food-safety.

Restless Legs Syndrome (RLS) is characterized by bothersome leg discomfort accompanied by an urge to move to obtain relief and symptoms are worse at night and on lying down. There is at least partial and temporary relief with activity. It is also an opioid responsive disorder, often accompanied by iron deficiency with or without anemia, and inflammation may be a precipitating factor in some cases. We created two in-vivo opiate receptor knock out mouse models of RLS - a triple opiate receptor knock-out mouse and a mu opiate receptor knock-out mouse. Both sets of animals were restless during the sleep period as is also true of RLS. Both of our knockout models showed statistically significantly decreased Hemoglobin and Hematocrit indicating anemia and both models showed statistically significant decreases in serum iron suggestive of either iron deficiency anemia or inflammatory anemia. The rest of the hematologic studies were not consistent enough to determine which of these two types of anemia was present in either model. An additional experiment in normal wild type mice showed a statistically significant decrease in serum iron when an opiate receptor blocker was used. To our knowledge this is the first demonstration that deficiency of endogenous opioids might play a role in the production of anemia. Our hypothesis is that an intact endogenous opiate system is necessary for red cell homeostasis. The presence of opioid receptors both on red blood cells and on various immunologically based white blood cells suggest mechanisms by which deficiency in the endogenous opiate system could cause anemia of either the iron deficiency or inflammatory types. The administration of opioid agonists or antagonists to iron deficient cultures of red blood cell precursors is a next step in determining the role of the endogenous opiate system in the maintenance of red cell homeostasis and in the possible prevention of iron deficiency or inflammatory anemia where iron dysregulation is key.

Bachmann-Bupp syndrome (OMIM #619075) is a novel autosomal dominant disorder caused by variants in the c-terminus of the ornithine decarboxylase 1 gene, resulting in increased levels of ornithine decarboxylase. This case report includes two patients diagnosed with Bachmann-Bupp syndrome who were treated with difluoromethylornithine through compassionate use approval from the United States Food and Drug Administration. In both patients, treatment with difluoromethylornithine has resulted in improved dermatologic signs, including regrowth of eyebrow and scalp hair and cessation of recurrent follicular cyst development.

Monoamine oxidase inhibitors (MAOI) are a class of drugs that were originally developed for the treatment of depression but have since been expanded to be used in management of affective and neurological disorders, as well as stroke and aging-related neurocognitive changes. Ranging from irreversible to reversible and selective to non-selective, these drugs target the monoamine oxidase (MAO) enzyme and prevent the oxidative deamination of various monoamines and catecholamines such as serotonin and dopamine, respectively. Tyramine is a potent releaser of norepinephrine (NE) and is found in high concentrations in foods such as aged cheeses and meats. Under normal conditions, NE is unable to accumulate to toxic levels due to the presence of MAO-A, an enzyme that degrades neurotransmitters, including NE. When MAO-A is inhibited, the capacity to handle tyramine intake from the diet is significantly reduced causing the brain to be vulnerable to overstimulation of postsynaptic adrenergic receptors with as little as 8-10 mg of tyramine ingested and can result in life-threatening blood pressure elevations. In addition to adverse reactions with certain foods, both older and newer MAOIs can negatively interact with both sympathomimetic and serotonergic drugs. In general, patients on a MAOI want to avoid two types of medications: those that can elevate blood pressure via sympathomimetic actions (e.g., phenylephrine and oxymetazoline) and those that can increase serotonin levels via 5-HT reuptake inhibition (e.g., dextromethorphan, chlorpheniramine, and brompheniramine). Illicit drugs that stimulate the central nervous system such as ecstasy (MDMA, 3,4-methylenedioxymethamphetamine) act as serotonin releasers. Patient involvement is also crucial to ensure any interaction within the healthcare setting includes making other providers aware of a MAOI prescription as well as avoiding certain OTC medications that can interact adversely with MAOIs.

This study observed the cutaneous analgesic effect of adrenergic agonists when combined with lidocaine. We aimed at the usefulness of four adrenergic agonists and epinephrine as analgesics or as tools to prolong the effect of local anesthetics using a model of cutaneous trunci muscle reflex (pinprick pain) in rats. We showed that subcutaneous four adrenergic agonists and epinephrine, as well as the local anesthetic bupivacaine and lidocaine, developed a concentration-dependent cutaneous analgesia. The rank order of the efficacy of different compounds (ED50 ; median effective dose) was epinephrine [0.013 (0.012-0.014) μmol] > oxymetazoline [0.25 (0.22-0.28) μmol] > naphazoline [0.42 (0.34-0.53) μmol] = bupivacaine [0.43 (0.37-0.50) μmol] > xylometazoline [1.34 (1.25-1.45) μmol] > lidocaine [5.86 (5.11-6.72) μmol] > tetrahydrozoline [6.76 (6.21-7.36) μmol]. The duration of full recovery caused by tetrahydrozoline, oxymetazoline, or xylometazoline was greater (P < 0.01) than that induced via epinephrine, bupivacaine, lidocaine, or naphazoline at equianesthetic doses (ED25 , ED50 , and ED75). Co-administration of lidocaine (ED50) with four adrenergic agonists or epinephrine enhanced the cutaneous analgesic effect. We observed that four adrenergic agonists and epinephrine induce analgesia by themselves, and such an effect has a longer duration than local anesthetics. Co-administration of lidocaine with the adrenergic agonist enhances the analgesic effect, and the cutaneous analgesic effect of lidocaine plus naphazoline (or oxymetazoline) is greater than that of lidocaine plus epinephrine.

Although microplastic (MP) pollution of aquatic ecosystems is a high-priority study topic, the issue of terrestrial environment and textile manufacturing waste has received little attention. Thus, this study was carried out to investigate the presence of MPs in agricultural land near textile industries and textile sludge samples in Bangladesh. Thirty-two soil samples from four agricultural farmland and five sludge samples were collected and analyzed. We show that the MPs content from agricultural farmland soil and textile sludge samples was 2.13 × 104 ± 0.13 × 104 MPs/kg and 2.92 × 104 ± 0.14 × 104 MPs/kg, respectively. MPs with a size between 1.0 and 1.5 mm were the least frequent in both soil and textile sludge samples. Fibers were more prevalent in textile sludge and fragments in soil samples. In addition, the percentage of transparent/white MPs was higher in the soil samples, and those classified as "multicolor" and "others" were more frequent in the sludge samples. Nine types of polymers were identified in the soil samples: PS, EVA, latex, HDPE, PVC, ABS, CA, LDPE, and PP. Except for LDPE, all these polymers were also found in the textile sludge samples, in addition to PU, nylon, and FEP, totaling eleven polymer types. On the other hand, we did not find evidence to support the association between MP contamination in soil samples and MPs identified in textile sludge samples. As demonstrated in the principal components analysis (PCA), the analyzed samples were separated by PC1, which suggests that the MPs reported in the soil come from sources that are not directly related to the textile industries. Thus, further research is needed to fully reveal MPs' fate and ecological risks in the soil environment and textile sludge, and necessary action is required to control MP pollution in terrestrial ecosystems.

Over 19 million people worldwide were diagnosed with cancer in 2020. Informal caregivers of adults with cancer play an important role in helping their loved ones with cancer yet often receive little support in developing the necessary skills for caregiving. A systematic review of skill-building interventions for informal caregivers of adults with cancer was conducted across three electronic databases for academic articles published through February 2022. PRISMA reporting guidelines were followed throughout this review, the Mixed Methods Appraisal Tool was used to assess study quality, and results were summarized in a narrative synthesis. The main components of skill-building interventions examined include caregiving preparedness, communication, and self-care. Nine of the 11 included articles showed that interventions effectively built skills for informal caregivers. The articles reviewed had a wide variety of intervention strategies, outcome measures, and study designs. Two of the 11 articles mentioned vulnerable and key groups, and no studies were performed in low- and middle-income countries. Findings generally support implementing skill-building interventions for informal caregivers of adults with cancer; however, further research is necessary to determine the most effective approaches for improving caregiver skills and reaching vulnerable and key populations.

Rosacea is a chronic and relapsing facial dermatosis that encompasses a wide spectrum of clinical phenotypes (transient/persistent erythema, telangiectasias, papules/pustules, edema, phymatous changes, and ocular symptoms) often with uncomfortable symptoms such as flushing, pain, burning, edema, and dryness. Current pharmacological treatment includes topical agents, spanning from several conventional (azelaic acid, metronidazole, sodium sulfacetamide) to new ones (brimonidine, oxymetazoline, ivermectine, minocycline), and systemic agents (doxycycline 40 mg modified-release), all Food and Drug Administration approved.

Celebrities, athletes and even politicians are frequently identified as role models for most impressionable students. But the reality is, outside of their own home, one of the greatest role models in a student's life is standing in front of the classroom. Teachers are people to look up to and emulate. This paper attempts to discover some of the essential qualities and skills that would help teachers and the students they teach achieve their full potentials, and also some key characteristics that contribute to teachers and instruction effectiveness. This paper also attempts to highlight the features of 3H (Head, Heart and Hands) model in effective instructional approach and theorizes that the 3H attributes in combination with Bloom's Taxonomy will produce effective 21st century teachers. Hence, this article endeavors to create awareness and contribute to the transformation of teachers toward reflective and visionary; confident and competent teachers. After all, effective teachers will inspire their talented students to live up to their full potentials. Effective 21st century teachers are in the best position to shape and equip students with the desired 21st century skills.

Gene expression can serve as a powerful predictor for disease progression and other phenotypes. Consequently, microarrays, which capture gene expression genome-wide, have been used widely over the past two decades to derive biomarker signatures for tasks such as cancer grading, prognosticating the formation of metastases, survival, and others. Each of these signatures was selected and optimized for a very specific phenotype, tissue type, and experimental set-up. While all of these differences may naturally contribute to very heterogeneous and different biomarker signatures, all cancers share characteristics regardless of particular cell types or tissue as summarized in the hallmarks of cancer. These commonalities could give rise to biomarker signatures, which perform well across different phenotypes, cell and tissue types. Here, we explore this possibility by employing a network-based approach for pan-cancer biomarker discovery. We implement a random surfer model, which integrates interaction, expression, and phenotypic information to rank genes by their suitability for outcome prediction. To evaluate our approach, we assembled 105 high-quality microarray datasets sampled from around 13,000 patients and covering 13 cancer types. We applied our approach (NetRank) to each dataset and aggregated individual signatures into one compact signature of 50 genes. This signature stands out for two reasons. First, in contrast to other signatures of the 105 datasets, it is performant across nearly all cancer types and phenotypes. Second, It is interpretable, as the majority of genes are linked to the hallmarks of cancer in general and proliferation specifically. Many of the identified genes are cancer drivers with a known mutation burden linked to cancer. Overall, our work demonstrates the power of network-based approaches to compose robust, compact, and universal biomarker signatures for cancer outcome prediction.

Introduction In the current otorhinolaryngology practice, technology has always been an essential part. Therefore, diagnostic nasal endoscopy (DNE) has become a vital examination in today's practice. In order to visualize the nasal cavity in a systematic manner without any discomfort to both patient and doctor, the nose should be well anesthetized and decongested. Objective The study is to compare and evaluate the efficacy of 4% lignocaine-oxymetazoline cotton pledget packing versus topical sprays in the preparation of nasal cavities for DNE. Methodology The prospective, randomized, double-blind study was conducted among 246 patients and was divided into two groups. In the first group, the nose was packed with cotton pledgets containing 4% lignocaine-oxymetazoline and another group with 4% lignocaine-oxymetazoline spray. Following DNE, patients and surgeons were questioned on a pre-formed questionnaire to evaluate their experience during the procedure. Results It was observed that the time taken for the pre-endoscopic preparation of the packing group was more than the spray group. A total of 91.9% of the spray group had pain during the pre-endoscopic preparation and more burning and tingling sensation than in the nasal pack (75.6%). A total of 69.9% of the patients among the spray group participants compared to 32.5% of the packing group patients experienced more throat discomfort. In addition, 12% of the packing group had mucosal bleeding during the preparation. A total of 32.5% of the spray group experienced severe pain when compared to 12.2% of the packing group during the endoscopic procedure. Most of the participants from both groups had difficulty visualizing the superior turbinate and sphenoethmoidal recess during the procedure. There was a significant difference seen between both the groups with respect to pain during the pre-endoscopic procedure (p=0.0005), burning/tingling sensation (p<0.0001), throat pain (<0.0001), mucosal bleed (p=0.0003), pain during the procedure (p=0.0001), and discomfort after the procedure (p<0.0001). Conclusion Both methods of nasal preparation have merits and demerits in terms of discomfort, pain, and visualization of structures. Still, the packing of the nasal cavity with cotton pledgets is better when compared to spraying with 4% lignocaine-oxymetazoline. However, 4% lignocaine-oxymetazoline spray can be used during an emergency situation and with sensitive patients.

Viruses that induce pulmonary difficulties and auto-inflammation are more common in people with Down syndrome. They also have a higher number of comorbidities associated with a worse prognosis than the overall population. Adult patients with acute COVID-19 are increasingly being diagnosed with Long COVID. However, patients with Down syndrome with later long COVID-19 are the first example documented in Bangladesh.

Memory impairment is a serious problem that has a significant negative impact on survival and quality of life. When used for a long time, drugs used to treat memory loss become less effective and have more side effects, making therapy more difficult. Different medicinal plants are now being highlighted because of their valuable applications and low risk of adverse effects. Moringa oleifera is one of these plants that has gained much attention due to its diverse biological functions. The study aimed to determine the effects of Moringa oleifera on working memory in memory-impaired Wistar rats.

Snake venom is a valuable raw material for numerous therapeutic formulations because of its life-saving pharmacological potential. However, due to their high price, fake "snake venoms" have captured a significant portion of the global market, and there is currently no reliable reported DNA-based method available for quickly distinguishing between fakes and originals. Therefore, in this study, a set of newly designed snake-specific universal primers targeting mitochondrial D-loop fragments were employed to detect snake origins in commercial venom crystals by only simplex polymerase chain reaction analysis. Under the optimal thermal cycling conditions, only the 145-149 bp snake-specific mitochondrial D-loop fragments from pure and mixed backgrounds were amplified by the newly designed primers. Specificity was achieved by confirming no DNA amplification occurred in the DNA admixture of ten different chordates, and universality by individual DNA amplification of nine different snakes. The primers that efficiently amplified the minimum mitochondrial DNA contained in a total of 10-2 ng in a 10.0 μl reaction were also successfully able to detect the snake origin in commercial cobra venom crystals. These findings suggest that the newly designed primers can be used to differentiate the original and fake commercial snake venom crystals in order to achieve the highest standards of snake venom-based medications through amplifying the snake-specific mitochondrial D-loop fragments.

Obesity is a complex disorder associated with immense health consequences including high risk of cardiovascular diseases, diabetes, and cancer. Abnormality in the thyroid gland, genetics, less physical activity, uptake of excessive diet, and leptin resistance are critical factors in the development of obesity. To determine the treatment strategy, understanding the pathophysiology of obesity is crucial. For instances, leptin resistance mediated obesity defined by the presence of excessive leptin hormone (Lep) in the systemic circulation is very common in diet induced obesity. Therefore, our hypothesis is that quantitative measurement of Lep from blood can help to identify individuals with Lep resistant mediated obesity and thereby guide toward a proper treatment strategy. In this work, we aim to utilize an electrochemical immunosensing platform for diagnosis of obesity by measuring the Lep content in systemic circulation. A porous carbon confined FeNi bimetallic system was synthesized with three different ratios of Fe and Ni ions using high temperature pyrolysis technique. The suitability of the sensor for detecting Lep was studied using both CV and EIS techniques. The limit of detection (LOD) for GCE was recorded as 157.4 fg/mL with a wide linear concentration range of 500 fg/mL to 80 ng/mL, while for SPCE the LOD was 184.9 fg/mL with a linear range of 500 fg/mL to 50 ng/mL. Finally, the feasibility and applicability of the sensor for Lep detection was tested with serum collected from high fat diet induced obese rats. The selectivity, sensitivity, storage, and experimental stability and reproducibility tests showed potential for this biosensor platform as a point-of-care Lep detection device.

The emerging concept of planetary health needs to be discussed in a more organized and sustainable way within the global public health and healthcare disciplines. Therefore, planetary health should be considered a cardinal component of the global academic framework for healthcare professionals. The availability of related curricula and courses is crucial to equip health professionals in this relatively new discipline of planetary health. In this review article, we aimed to explore published articles and online databases of courses to summarize the available planetary health education opportunities and discussions for health professionals, to identify the gaps in resource allocation and to suggest future recommendations. We observed a visible resource inequity in the global south with the lack of a universal planetary health module for healthcare professionals. Additionally, there is minimal inclusion of allied health disciplines in this learning process. We therefore recommend a dedicated network of motivated healthcare professionals and regional hubs with an agenda to ensure a comprehensive, uniform, and inclusive planetary health education curriculum and practice.