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Most students in higher education at present are 'digital natives.' They use technology in every facet of their life, including their education. They learn from formally organised courses as well as from informal learning. Hence, informal learning has been identified as crucial for the sustainability of higher education in the current global context. Technology facilitates informal learning and, thus, has made substantial changes in how learning occurs in modern age learners. These changes that occurred in the learning process due to the influence of technology should be addressed by the educational approaches used in higher education to achieve the best outcomes in relation to the academic performance of students and students' satisfaction. This commentary presents an educational approach: 'Connective Alignment' for higher education in the digital age, which can fulfil the learning needs of the learners in this digital age.

Instructional design (ID) is a systematic process that is used to develop education and training programmes in a consistent and reliable way. A key challenge faced by educators is selecting an ID model by deciding which ID model will be more suitable in order to achieve an effective digital teaching and learning process. The objective of this scoping review was to present recommendations to select ID models for digital learning in higher education. Nine databases were searched for eligible publications. The search retrieved 643 records. Forty articles were included in this review. Results show that employing a systematic process in instructional design (an ID model) has produced an effective, consistent and reliable digital teaching and learning process in higher education. Selection of an ID model depends on the requirements of the course, timeline, resources available for the design and development of the course and the expertise in the ID process.

BACKGROUND: Treatment for fluoroquinolone-resistant multidrug-resistant/rifampicin-resistant tuberculosis (pre-XDR TB) often lasts longer than treatment for less resistant strains, yields worse efficacy results, and causes substantial toxicity. The newer anti-tuberculosis drugs, bedaquiline and delamanid, and repurposed drugs clofazimine and linezolid, show great promise for combination in shorter, less-toxic, and effective regimens. To date, there has been no randomized, internally and concurrently controlled trial of a shorter, all-oral regimen comprising these newer and repurposed drugs sufficiently powered to produce results for pre-XDR TB patients. METHODS: endTB-Q is a phase III, multi-country, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of a treatment strategy for patients with pre-XDR TB. Study participants are randomized 2:1 to experimental or control arms, respectively. The experimental arm contains bedaquiline, linezolid, clofazimine, and delamanid. The control comprises the contemporaneous WHO standard of care for pre-XDR TB. Experimental arm duration is determined by a composite of smear microscopy and chest radiographic imaging at baseline and re-evaluated at 6 months using sputum culture results: participants with less extensive disease receive 6 months and participants with more extensive disease receive 9 months of treatment. Randomization is stratified by country and by participant extent-of-TB-disease phenotype defined according to screening/baseline characteristics. Study participation lasts up to 104 weeks post randomization. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 324 participants across 2 arms affords at least 80% power to show the non-inferiority, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per-protocol populations. DISCUSSION: This internally controlled study of shortened treatment for pre-XDR TB will provide urgently needed data and evidence for clinical and policy decision-making around the treatment of pre-XDR TB with a four-drug, all-oral, shortened regimen. TRIAL REGISTRATION: ClinicalTrials.Gov NCT03896685. Registered on 1 April 2018; the record was last updated for study protocol version 4.3 on 17 March 2023.

Purpose – Green innovations (GI) is an emerging field that presents an opportunity to thrive in the competitive market. Nevertheless, in the field of green innovation, there is no clear and complete picture. To fill this gap the current study was conducted with the following objectives. (1) To identify existing knowledge on green innovation and offer bibliographic insights through a systematic literature review (SLR), (2) To comprehend the areas in which research is lacking within the territory of green innovation. Design/methodology/approach – The SLR methodology was employed in this study, following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A total of 381 articles published between 2015 and 2023 were extracted from Lens org. database for review. Additionally, a bibliometric analysis was conducted to fulfill the research objectives. Findings – The findings revealed that the field of green innovation lacks sufficient scholarly attention, despite being an emerging area. As a result, several gaps have been identified, encompassing various aspects of green innovation. These gaps include areas such as green innovation behavior, green finance, barriers to green innovation, green product innovation, green technological innovation and more. Originality/value – This study adds to the existing body of knowledge on green innovation by addressing identified knowledge gaps. In particular, this knowledge contributes to future researchers aiming to design and conduct studies that target these identified research gaps.

Abstract Background Anaemia is a global public health issue that impacts individuals of all ages in both developed and developing countries. Anaemia is common in patients with diabetes mellitus; however, it is often undiagnosed and untreated. The main aim of this study was to assess the prevalence and associated factors of anaemia in patients with type 2 diabetes mellitus admitting to a medical unit at National Hospital Kandy. Methods A descriptive, cross-sectional study was conducted in type 2 diabetes mellitus (T2DM) patients admitted to a medical ward at National Hospital Kandy (NHK). They were assessed with a pre-tested, interviewer-administered, structured questionnaire using consecutive sampling method. The data was entered and analyzed using SPSS 26. Results Total 252 patients with diabetes were included. The prevalence of anaemia in patients with T2DM was 31.3%. The corresponding values for males and females were 34.2% and 65.8% respectively. Independent predictors for anaemia among diabetic patients were older age, female gender, poor glycemic control, diabetes duration > 5 years, diabetic nephropathy, retinopathy, neuropathy, stage ≥ 3 chronic kidney disease (CKD), ischaemic heart disease (IHD), peripheral vascular disease (PVD), diabetic foot ulcers (DFU) and usage of aspirin. These were significantly associated with the prevalence anemia among patients with type 2 diabetes mellitus. Multivariate logistic regression analysis revealed that female gender, age ≥ 65 years, diabetic duration > 5 years, poor glycaemic control, stage ≥ 3 CKD, diabetic nephropathy and retinopathy were associated with greater odds for the presence of anaemia. Conclusion We found that 31.3% T2DM patients in a medical ward at NHK had previously undiagnosed anaemia. Anaemia screening during diabetes diagnosis, maintaining glycaemic control and raising patient awareness can reduce anaemia prevalence, improve patient quality of life and potentially reduce microvascular complications.

Abstract Background Hypocalcaemia is a rare, but reversible, cause of dilated cardiomyopathy causing heart failure. Several case reports have been reported on reversible cardiomyopathy secondary to hypocalcaemia. Case presentation We report a case of 54-year-old female Sri Lankan patient who presented with shortness of breath and was diagnosed with heart failure with reduced ejection fraction due to dilated cardiomyopathy. The etiology for dilated cardiomyopathy was identified as hypocalcemic cardiomyopathy, secondary to primary hypoparathyroidism, which was successfully treated with calcium and vitamin D replacement therapy. Conclusion This adds to literature of this rare cause of reversible cardiomyopathy secondary to hypocalcemia reported from the South Asian region of the world. This case highlights the impact of proper treatment improving the heart failure in patients with hypocalcemic cardiomyopathy.

Background: Phospholipids are significant constituents of bacterial membranes. Bacteria can alter their cytoplasmic membrane fatty acid composition in response to changing environmental stress conditions. Carvacrol, a mono-terpenoid phenol, has excellent antibacterial properties against Streptococcus pyogenes. Purpose: This study examined modifications of the membrane phospholipid composition in the presence of sublethal carvacrol concentrations using erythromycin-resistant S. pyogenes. Methods: The cell membrane isolates (CMIs) were prepared from S. pyogenes strain Spy 1558, erm. The ultrastructural morphology was studied using transmission electron microscopy (TEM). Carvacrol-treated CMIs were analyzed for fluidity changes using fluorescence-anisotropy. Changes in membrane lipid composition were assessed using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS/MS). Results: Fluidity of the bacterial membrane increased time-dependently when exposed to carvacrol. The CMI isolated from cells treated with carvacrol showed a change in cardiolipins (CL), phosphatidylglycerol (PG), and phosphatidylethanolamine (PE) percentages compared to the untreated control. Conclusion: Carvacrol induces modulation of specific membrane phospholipid and fatty acid composition of S. pyogenes. Further investigations are necessary to understand how fatty acid and phospholipid biosynthesis can be influenced by carvacrol.

Introduction: Use of multiple concomitant medications or ‘polypharmacy’ is linked to decreased medication adherence, adverse drug reactions and increased financial burden on patients and the economy. Deprescribing by experienced healthcare personnel can ensure safe and effective use of medications. Many medications, prescribed during hospital stay or at clinic level are continued for unnecessarily long periods, highlighting the necessity for deprescribing. The objectives of this audit were to identify and deprescribe inappropriate medications in patients, identify their comorbidities and explore reasons for the inappropriate medication use. Methods: This deprescribing audit was conducted by systematic sampling in selected adult patients >18 years, attending a medical clinic at National Hospital, Kandy over one month. The audit standard was the American Academy of Family Physicians (AAFP) ‘5-step process in deprescribing’. Our study was based only on the first 3 steps of the AAFP deprescribing process. Results: Out of a total of 402 patients, deprescribing was carried out in 135 (33.58%). In this deprescribed group, 59.3% of patients were female and the mean age was 62.3 (±10.9) years. Furthermore, of the deprescribed patients, 52.6% had hypertension, 44.4% had ischaemic heart disease, and 34.1% had diabetes mellitus. The most deprescribed medication was antiplatelets (37.8%), followed by analgesics (24.4%) and diuretics (20%). A clear indication for using the drug was lacking in 68.9%, while 31.1% of patients continued taking the medication for longer than recommended. Conclusions: In this audit, over one third of patients underwent deprescribing. It provides just a glimpse of the broader issue of inappropriate polypharmacy and the necessity of deprescribing. Future research involving multiple centres is recommended to enhance understanding of medication patterns necessitating deprescribing.

Due to the high embodied carbon of cement and limited availability of conventional supplementary cementitious materials (SCMs), calcined clay has gained numerous attentions worldwide as an alternative SCM. This study explores the potential of four kaolinic clay-rich soils from waste streams in Victoria, Australia, as SCMs. The clays are compared to three commercial calcined clay products from different countries after undergoing grinding and calcination processes. The research assesses physical, chemical, and mineralogical characteristics, as well as pozzolanic activity in ternary cement systems. Results highlight the importance of fineness and calcined kaolinite content in influencing performance. Overall, the study demonstrates the feasibility of Victorian clays as SCM, even from waste streams, with suitable calcination procedures, contributing to sustainable alternatives in cement production.

BACKGROUND: Non-Asian body mass index (BMI) classifications are commonly used as a risk factor for high fasting blood glucose (FBG). We investigated the incidence and factors associated with high FBG among people living with HIV in the Asia-Pacific region, using a World Health Organization BMI classification specific to Asian populations. METHODS: This study included people living with HIV enrolled in a longitudinal cohort study from 2003 to 2019, receiving antiretroviral therapy (ART), and without prior tuberculosis. BMI at ART initiation was categorized using Asian BMI classifications: underweight (25 kg/m2 were at increased risk of high FBG. This indicates that regular assessments should be performed in those with high BMI, irrespective of the classification used.

Annona fruit, leaves, seeds, roots, and bark have been conventionally used in many countries for medical treatments as they are considered ideal sources of pharmacologically active compounds, but Annona remains an underutilized fruit in many countries. The fruit of these plants is delicately flavored and is used in industrial products such as ready-to-serve beverages, wine, jellies, jam, and fruit-butter preserve, while the seeds generally go to waste. Annona seed oil contains numerous health-benefiting factors such as vitamins, minerals, bioactive compounds, fatty acids, antioxidants, and phenolic compounds, which are responsible for various biological activities, including antibacterial, antioxidant, and antitumor activities. Cancer is a worldwide major health problem that remains unresolved. Even though the current treatments can manage to reduce tumor growth, there is an urgent need to investigate more efficient but less expensive novel techniques to overcome some of the restrictions in treating tumors. Annona might offer an indispensable choice besides chemotherapy and radiotherapy, especially for terminally ill patients, as the Annona genus contains secondary metabolites in nearly every component of Annona plants. Research has shown that many Annona species contain promising components that could potentially exhibit anticancer activity, but the information available is scarce and inconsistent. Annona muricata (Soursop, “Katuanoda”), Annona squamosa (Sweetsop, “Seenianoda”), and Annona reticulata (Custard apple, “Welianoda”) are three commonly cultivated edible Annona species in Sri Lanka. The main objective of the review was to present an updated comprehensive literature analysis of the putative chemopreventive functions against cancer cell lines/the anticancer effect on cancers, phytochemical properties, and antioxidant properties possessed by the seed oils of three selected common Annona species. Although there are some in vitro and in vivo experimental investigations supporting the benefits of Annona seed oils, clinical investigations are still needed to explore concealed areas, determine the effects on the human body, determine the safest concentration, and determine health-contributing benefits before they are submitted to clinical trials.

Response Surface Methodology (RSM) and Artificial Neural Network (ANN) were employed to optimize saponin extraction from North Atlantic Sea cucumber (Cucumaria frondosa). Ultrasonication-assisted ethanol-based extractions were used in a second-order polynomial and 3n full factorial RSM interconnected with neural design ANN model. A 3-10-2 neural network architecture was constructed to predict the relationship between the independent variables and bioactive compounds adequately. The extracts with the highest frondoside A yield were characterized for different triterpene glycosides (saponins) by high-resolution mass spectrometry (HRMS). A total of ten saponins were detected and tentatively identified including fallaxoside, frondoside, cucumarioside, cercodemasoide, colochiroside, and lefevreioside, with two unknown saponins. Six of the saponins were detected in C. frondosa extracts for the first time. The extract of body walls have a higher concentration of frondoside A (0.73 mg/g DW) than internal organs and tentacles (flowers or aquapharyngeal bulb). The optimized extracts exhibit a significantly higher concentration of polyphenols and saponins when compared with extracts prepared from conventional methods. The ANN model demonstrated a low p and high f values to indicate a perfect good fit for RSM model. The advanced knowledge of saponins of C. frondosa can contribute to the development of novel functional foods and ingredients from C. frondosa and their processing byproducts.

The food packaging industry is seeking innovative ways to extend product shelf life and ensure food safety and quality through real-time monitoring. The bioactive properties and halochromic transitions of bioactive compounds make them suitable candidates for active and intelligent packaging, respectively. Starch is considered a potential matrix for developing food packaging materials. However, starch in its native form possesses poor mechanical stability and barrier properties. Thus, this review comprehends the conversion of native starch to a suitable matrix through plasticizing and composting. Furthermore, various film casting techniques are discussed and the suitability of such techniques for developing smart packaging is evaluated. Besides, the techno-functional changes in the starch matrix upon impregnating berry bioactive compounds are discussed in detail. In addition, the bioactive properties and epistemic values of the berry-impregnated starch-based films are elaborated. The feasibility of using berry-impregnated starch-based films in a micro-gravity environment is evaluated for space foods. The review concludes with a futuristic view of using these films for commercial applications.

Abstract BackgroundElectrocardiography (ECG) interpretation is a fundamental skill for medical students and practicing medical professionals. Recognizing ECG pathologies promptly allows for quick intervention, especially in acute settings where urgent care is needed. However, many medical students find ECG interpretation and understanding of the underlying pathology challenging, with teaching methods varying greatly. ObjectiveThis study involved the development of novel animations demonstrating the passage of electrical activity for well-described cardiac pathologies and showcased them alongside the corresponding live ECG traces during a web-based tutorial for final-year medical students. We aimed to assess whether the animations improved medical students’ confidence in visualizing cardiac electrical activity and ECG interpretation, compared to standard ECG teaching methods. MethodsFinal-year medical students at Imperial College London attended a web-based tutorial demonstrating the 7 animations depicting cardiac electrical activity and the corresponding ECG trace. Another tutorial without the animations was held to act as a control. Students completed a questionnaire assessing their confidence in interpreting ECGs and visualizing cardiovascular electrical transmission before and after the tutorial. Intervention-arm participants were also invited to a web-based focus group to explore their experiences of past ECG teaching and the tutorial, particularly on aspects they found helpful and what could be further improved in the tutorial and animations. Wilcoxon signed-rank tests and Mann-Whitney U ResultsOverall, 19 students attended the intervention arm, with 15 (79%) completing both the pre- and posttutorial questionnaires and 15 (79%) participating in focus groups, whereas 14 students attended the control arm, with 13 (93%) completing both questionnaires. Median confidence in interpreting ECGs in the intervention arm increased after the tutorial (2, IQR 1.5-3.0 vs 3, IQR 3-4.5; PP ConclusionsThis study highlights the value of providing concise explanations of the meaning and pathophysiology behind ECG traces, both visually and verbally. ECG teaching that incorporates relevant pathophysiology, alongside vignettes with discussions regarding investigations and management options, is likely more helpful to students than practices based solely on pattern recognition. Although the animations supported student learning, the key element was the tutor’s explanations. These animations may be more helpful as a supplement to teaching, for instance, as open-access videos.

Abstract Introduction Liver disease is a leading cause of morbidity and mortality among persons living with HIV (PLHIV). While chronic viral hepatitis has been extensively studied in low‐ and middle‐income countries (LMICs), there is limited information about the burden of metabolic disorders on liver disease in PLHIV. Methods We conducted a cross‐sectional analysis of baseline data collected between October 2020 and July 2022 from the IeDEA‐Sentinel Research Network, a prospective cohort enrolling PLHIV ≥40 years on antiretroviral treatment (ART) for ≥6 months from eight clinics in Asia, Americas, and central, East, southern and West Africa. Clinical assessments, laboratory testing on fasting blood samples and liver stiffness measurement (LSM)/controlled attenuation parameter (CAP) by vibration‐controlled transient elastography were performed. Multivariable logistic regression models assessed factors associated with liver fibrosis (LSM ≥7.1 kPa) and steatosis (CAP ≥248 dB/m). Population attributable fraction (PAF) of each variable associated with significant liver fibrosis was estimated using Levin's formula. Results Overall, 2120 PLHIV (56% female, median age 50 [interquartile range: 45−56] years) were included. The prevalence of obesity was 19%, 12% had type 2 diabetes mellitus (T2DM), 29% had hypertension and 53% had dyslipidaemia. The overall prevalence of liver fibrosis and steatosis was 7.6% (95% confidence interval [CI] 6.1−8.4) and 28.4% (95% CI 26.5−30.7), respectively, with regional variability. Male sex at birth (odds ratio [OR] 1.62, CI 1.10−2.40), overweight/obesity (OR = 2.50, 95% CI 1.69−3.75), T2DM (OR 2.26, 95% CI 1.46−3.47) and prolonged exposure to didanosine (OR 3.13, 95% CI 1.46−6.49) were associated with liver fibrosis. Overweight/obesity and T2DM accounted for 42% and 11% of the PAF for liver fibrosis, while HBsAg and anti‐HCV accounted for 3% and 1%, respectively. Factors associated with steatosis included overweight/obesity (OR 4.25, 95% CI 3.29−5.51), T2DM (OR 2.06, 95% CI 1.47−2.88), prolonged exposure to stavudine (OR 1.69, 95% CI 1.27−2.26) and dyslipidaemia (OR 1.68, 95% CI 1.31−2.16). Conclusions Metabolic disorders were significant risk factors for liver disease among PLHIV in LMICs. Early recognition of metabolic disorders risk factors might be helpful to guide clinical and lifestyle interventions. Further prospective studies are needed to determine the causative natures of these findings.

Abstract This study explores the sphingolipid class of oligohexosylceramides (OHCs), a rarely studied group, in barley (Hordeum vulgare L.) through a new lipidomics approach. Profiling identified 45 OHCs in barley (Hordeum vulgare L.), elucidating their fatty acid (FA), long-chain base (LCB) and sugar residue compositions; and was accomplished by monophasic extraction followed by reverse-phased high performance liquid chromatography electrospray ionisation quadrupole-time-of-flight tandem mass spectrometry (HPLC–ESI–QqTOF–MS/MS) employing parallel reaction monitoring (PRM). Results revealed unknown ceramide species and highlighted distinctive FA and LCB compositions when compared to other sphingolipid classes. Structurally, the OHCs featured predominantly trihydroxy LCBs associated with hydroxylated FAs and oligohexosyl residues consisting of two–five glucose units in a linear 1 → 4 linkage. A survey found OHCs in tissues of major cereal crops while noting their absence in conventional dicot model plants. This study found salinity stress had only minor effects on the OHC profile in barley roots, leaving questions about their precise functions in plant biology unanswered.

Abstract Background Treatment for fluoroquinolone-resistant multidrug-resistant/rifampicin-resistant tuberculosis (pre-XDR TB) often lasts longer than treatment for less resistant strains, yields worse efficacy results, and causes substantial toxicity. The newer anti-tuberculosis drugs, bedaquiline and delamanid, and repurposed drugs clofazimine and linezolid, show great promise for combination in shorter, less-toxic, and effective regimens. To date, there has been no randomized, internally and concurrently controlled trial of a shorter, all-oral regimen comprising these newer and repurposed drugs sufficiently powered to produce results for pre-XDR TB patients. Methods endTB-Q is a phase III, multi-country, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of a treatment strategy for patients with pre-XDR TB. Study participants are randomized 2:1 to experimental or control arms, respectively. The experimental arm contains bedaquiline, linezolid, clofazimine, and delamanid. The control comprises the contemporaneous WHO standard of care for pre-XDR TB. Experimental arm duration is determined by a composite of smear microscopy and chest radiographic imaging at baseline and re-evaluated at 6 months using sputum culture results: participants with less extensive disease receive 6 months and participants with more extensive disease receive 9 months of treatment. Randomization is stratified by country and by participant extent-of-TB-disease phenotype defined according to screening/baseline characteristics. Study participation lasts up to 104 weeks post randomization. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 324 participants across 2 arms affords at least 80% power to show the non-inferiority, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per-protocol populations. Discussion This internally controlled study of shortened treatment for pre-XDR TB will provide urgently needed data and evidence for clinical and policy decision-making around the treatment of pre-XDR TB with a four-drug, all-oral, shortened regimen. Trial registration ClinicalTrials.Gov NCT03896685. Registered on 1 April 2018; the record was last updated for study protocol version 4.3 on 17 March 2023.

Abstract Obesity is a state of metabolic dysfunction that can lead to dyslipidemia and impaired glucose homeostasis. Apple polyphenols have been shown to ameliorate dyslipidemia/metabolic dysfunction in humans. The influence of apple (poly)phenols on energy metabolism in high-fat (HF) diet-induced obese mice remains controversial. This study examined the effect of dietary supplementation of (poly)phenol-rich ‘Daux Belan’ apple (DB; 6.2 mg gallic acid equivalence (GAE)/mouse/day; 0.15% (poly)phenol) in the form of freeze-dried powder on glucose and lipid metabolism in male HF-fed C57BL/6NCrl mice, in comparison to low-(poly)phenol-containing ‘Zestar’ apple (Z; 0.4 mg GAE/mouse/day). Obesity, glucose intolerance, hypertriglyceridemia, and hepatic lipid vacuolation were induced by HF feeding while circulating cholesterol levels remained unchanged. DB apple supplementation did not protect against HF-induced body weight gain, hyperglycemia, hepatic triglyceride level elevation, and hepatic lipid vacuolation at the tested dosage. Future studies should be conducted with increased DB dosage and employ apple (poly)phenols supplemented in the form of extracts or sugar-free powder.

The family Carangidae is considered a markedly diverse, widespread taxon. Due to the characteristic “cryptic diversity” and “hybrid speciation” within the family, there is an exigency for taxonomic approaches that go beyond traditional phenotypic modus in identifying species. Mitochondrial cytochrome c oxidase subunit - I (COI) barcoding gene region plays a significant role over phenotypic characters in identifying species. This study evaluates the combination of the two molecular approaches: the COI DNA barcoding and PCR-RFLP for judicious species discrimination. The partial mitochondrial COI gene region of the selected Carangid fish species was amplified, sequenced and confirmed sequences with a mean length of 655 bp were submitted to the main databases; NCBI and BOLD. Intraspecific and interspecific nucleotide divergences were computed by the Kimura-2-Parameter (K2P) and they ranged between (0.00–2.96 %) and (6.46–21.83 %), respectively. The possibility of acquiring the same RFLP profiles given by the restriction enzymes HaeIII and MbOII was observed by the theoretical cleavage of 250 reference sequences of the corresponding gene. Hence, major and minority composite haplotypes of each species were obtained based on the fragment types derived by both HaeIII and MbOII. The resulting divergence values were compatible with the previously reported values for marine fish species. All the species were clearly differentiated by both RFLP banding patterns and the highest probability assumption of getting the same RFLP profile was compatible with the most abundant composite haplotype of each species. This reveals the practicability of the combination of two consolidated molecular approaches, COI barcoding and PCR-RFLP (COIBar-RFLP).

Most students in higher education at present are ‘digital natives.’ They use technology in every facet of their life, including their education. They learn from formally organised courses as well as from informal learning. Hence, informal learning has been identified as crucial for the sustainability of higher education in the current global context. Technology facilitates informal learning and, thus, has made substantial changes in how learning occurs in modern age learners. These changes that occurred in the learning process due to the influence of technology should be addressed by the educational approaches used in higher education to achieve the best outcomes in relation to the academic performance of students and students’ satisfaction. This commentary presents an educational approach: ‘Connective Alignment’ for higher education in the digital age, which can fulfil the learning needs of the learners in this digital age.

Instructional design (ID) is a systematic process that is used to develop education and training programmes in a consistent and reliable way. A key challenge faced by educators is selecting an ID model by deciding which ID model will be more suitable in order to achieve an effective digital teaching and learning process. The objective of this scoping review was to present recommendations to select ID models for digital learning in higher education. Nine databases were searched for eligible publications. The search retrieved 643 records. Forty articles were included in this review. Results show that employing a systematic process in instructional design (an ID model) has produced an effective, consistent and reliable digital teaching and learning process in higher education. Selection of an ID model depends on the requirements of the course, timeline, resources available for the design and development of the course and the expertise in the ID process.

ABSTRACTPrevious work reported unprecedented differences in the intrinsic in vitro susceptibility of the Mycobacterium tuberculosis complex (MTBC) to pretomanid (Pa) using the Mycobacteria Growth Indicator Tube (MGIT) system. We tested 125 phylogenetically diverse strains from all known MTBC lineages (1–9) without known Pa resistance mutations and four strains with known resistance mutations as controls. This confirmed that MTBC, unlike most bacteria-antimicrobial combinations, displayed substantial differences in the intrinsic susceptibility relative to the technical variation of Pa MIC testing. This was also the case for the Middlebrook 7H11 (7H11) medium, demonstrating that these differences were not specific to MGIT. Notably, lineage 1 was confirmed to have intrinsically elevated MICs compared with lineages 2, 3, 4, and 7 (L2–4/7), underlining the urgent need for WHO to publish its decision of whether lineage 1 should be deemed treatable by BPaL(M), the now preferred all-oral regimen for treating rifampin-resistant tuberculosis. Lineages 5 and 6, which are most frequent in West Africa, responded differently to Pa, with lineage 5 being more similar to L2–4/7 and lineage 6 being more susceptible. More data are needed to determine whether 7H11 MICs are systematically lower than those in MGIT.IMPORTANCEThis study confirmed that the Mycobacterium tuberculosis complex lineage 1, responsible for 28% of global tuberculosis cases, is less susceptible to pretomanid (Pa). It also refined the understanding of the intrinsic susceptibilities of lineages 5 and 6, most frequent in West Africa, and lineages 8 and 9. Regulators must review whether these in vitro differences affect the clinical efficacy of the WHO-recommended BPaL(M) regimen and set breakpoints for antimicrobial susceptibility testing accordingly. Notably, regulators should provide detailed justifications for their decisions to facilitate public scrutiny.

This study evaluated the use of endemic enteric coronaviruses polymerase chain reaction (PCR)-negative testing results as an alternative approach to detect the emergence of animal health threats with similar clinical diseases presentation. This retrospective study, conducted in the United States, used PCR-negative testing results from porcine samples tested at six veterinary diagnostic laboratories. As a proof of concept, the database was first searched for transmissible gastroenteritis virus (TGEV) negative submissions between January 1st, 2010, through April 29th, 2013, when the first porcine epidemic diarrhea virus (PEDV) case was diagnosed. Secondly, TGEV- and PEDV-negative submissions were used to detect the porcine delta coronavirus (PDCoV) emergence in 2014. Lastly, encountered best detection algorithms were implemented to prospectively monitor the 2023 enteric coronavirus-negative submissions. Time series (weekly TGEV-negative counts) and Seasonal Autoregressive-Integrated Moving-Average (SARIMA) were used to control for outliers, trends, and seasonality. The SARIMA's fitted and residuals were then subjected to anomaly detection algorithms (EARS, EWMA, CUSUM, Farrington) to identify alarms, defined as weeks of higher TGEV-negativity than what was predicted by models preceding the PEDV emergence. The best-performing detection algorithms had the lowest false alarms (number of alarms detected during the baseline) and highest time to detect (number of weeks between the first alarm and PEDV emergence). The best-performing detection algorithms were CUSUM, EWMA, and Farrington flexible using SARIMA fitted values, having a lower false alarm rate and identified alarms 4 to 17 weeks before PEDV and PDCoV emergences. No alarms were identified in the 2023 enteric negative testing results. The negative-based monitoring system functioned in the case of PEDV propagating epidemic and in the presence of a concurrent propagating epidemic with the PDCoV emergence. It demonstrated its applicability as an additional tool for diagnostic data monitoring of emergent pathogens having similar clinical disease as the monitored endemic pathogens.

Oligomeric and polymeric proanthocyanidins (PAC) were biotransformed with Saccharomyces cerevisiae to improve bioavailability and bioactivity. Biotransformation significantly increased the bioavailability of PAC in vitro and generated many metabolites, most notably, 3-aminophenol, pyrogallol, phloroglucinol, 4-hydroxyphenylacetamide, 2,4-dihydroxy-6-methylbenzaldehyde, 2,4,6-trihydroxyacetophenone, and 2-hydroxyphenylacetic, 3-aminosalicylic, dihydroxybenzoic, 2-hydroxycinnamic, 3-phenyllactic, and gallic acids. The bioactivity of biotransformed (BT)-PAC and non-BT-PAC was compared using palmitic acid (PA)-induced steatosis/nonalcoholic fatty liver disease (NAFLD) and PA + bacterial lipopolysaccharide-induced nonalcoholic steatohepatitis (NASH) models of AML12 hepatocytes. BT-PAC reduced the PA-induced cellular oxidative stress and lipid accumulation by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway and modulating key regulators of cellular lipid metabolism. BT-PAC reduced the progression of steatosis to NASH in vitro by suppressing toll-like receptor 4-mediated cellular inflammation. Non-BT-PAC was less potent in the reduction of cellular lipotoxicity and inflammation. S. cerevisiae-mediated biotransformation significantly enhances the bioavailability of PAC and the bioactivity against steatosis and NASH.

Introduction Tuberculosis (TB) is a leading infectious cause of death globally. It is the most common opportunistic infection in people living with HIV, and the most common cause of their morbidity and mortality. Following TB treatment, surviving individuals may be at risk for post-TB lung disease. The TB Sentinel Research Network (TB-SRN) provides a platform for coordinated observational TB research within the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium.Methods and analysis This prospective, observational cohort study will assess treatment and post-treatment outcomes of pulmonary TB (microbiologically confirmed or clinically diagnosed) among 2600 people aged ≥15 years, with and without HIV coinfection, consecutively enrolled at 16 sites in 11 countries, across 6 of IeDEA’s global regions. Data regarding clinical and sociodemographic factors, mental health, health-related quality of life, pulmonary function, and laboratory and radiographic findings will be collected using standardised questionnaires and data collection tools, beginning from the initiation of TB treatment and through 12 months after the end of treatment. Data will be aggregated for proposed analyses.Ethics and dissemination Ethics approval was obtained at all implementing study sites, including the Vanderbilt University Medical Center Human Research Protections Programme. Participants will provide informed consent; for minors, this includes both adolescent assent and the consent of their parent or primary caregiver. Protections for vulnerable groups are included, in alignment with local standards and considerations at sites. Procedures for requesting use and analysis of TB-SRN data are publicly available. Findings from TB-SRN analyses will be shared with national TB programmes to inform TB programming and policy, and disseminated at regional and global conferences and other venues.

Research on cancer in dogs and cats, among other diseases, finds an important source of information in registry data collected from hospitals. These sources have proved to be decisive in establishing incidences and identifying temporal patterns and risk factors. However, the attendance of patients is not random, so the correct delimitation of the hospital catchment area (CA) as well as the identification of the factors influencing its shape is relevant to prevent possible biases in posterior inferences. Despite this, there is a lack of data-driven approaches in veterinary epidemiology to establish CA. Therefore, our aim here was to apply a Bayesian method to estimate the CA of a hospital. We obtained cancer (n = 27,390) and visit (n = 232,014) registries of dogs and cats attending the Veterinary Medical Teaching Hospital of the University of California, Davis from 2000 to 2019 with 2,707 census tracts (CTs) of 40 neighboring counties. We ran hierarchical Bayesian models with different likelihood distributions to define CA for cancer cases and visits based on the exceedance probabilities for CT random effects, adjusting for species and period (2000-2004, 2005-2009, 2010-2014, and 2015-2019). The identified CAs of cancer cases and visits represented 75.4 and 83.1% of the records, respectively, including only 34.6 and 39.3% of the CT in the study area. The models detected variation by species (higher number of records in dogs) and period. We also found that distance to hospital and average household income were important predictors of the inclusion of a CT in the CA. Our results show that the application of this methodology is useful for obtaining data-driven CA and evaluating the factors that influence and predict data collection. Therefore, this could be useful to improve the accuracy of analysis and inferences based on registry data.

Abstract Road pavement maintenance and upgrades (RPU) need to be scheduled in a way that minimises congestion across the road network and matches the schedule with the availability of equipment and skilled labourers to ensure that they are completed on time. RPU should not introduce unbearable congestion around blocked lanes or roads, and increased traffic due to ongoing road upgrades needs to be transferred to alternative routes. In situations where multiple upgrades are planned together, the scheduled road closures should be coordinated to not block alternative routes. While extensive studies have been conducted separately on scheduling and routing, limited research has linked these processes together, and only in restricted scenarios. In this paper, we investigate how to minimise the disruption of a set of road maintenance tasks based on their interaction with other tasks. We propose a new approach for scheduling a set of road maintenance tasks, some at the same time and others at different times, to minimise overall disruption. The proposed approach has two phases: (1) identify the local area affected by the RPU, and (2) determine which upgrades can be planned together to minimise congestion. The comparison of the results shows how the novel optimized approach identifies a better schedule to minimise congestion.

BackgroundTreatment of multidrug- and rifampin-resistant tuberculosis (MDR/RR-TB) is expensive, labour-intensive, and associated with substantial adverse events and poor outcomes. While most MDR/RR-TB patients do not receive treatment, many who do are treated for 18 months or more. A shorter all-oral regimen is currently recommended for only a sub-set of MDR/RR-TB. Its use is only conditionally recommended because of very low-quality evidence underpinning the recommendation. Novel combinations of newer and repurposed drugs bring hope in the fight against MDR/RR-TB, but their use has not been optimized in all-oral, shorter regimens. This has greatly limited their impact on the burden of disease. There is, therefore, dire need for high-quality evidence on the performance of new, shortened, injectable-sparing regimens for MDR-TB which can be adapted to individual patients and different settings.MethodsendTB is a phase III, pragmatic, multi-country, adaptive, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of shorter treatment regimens containing new drugs for patients with fluoroquinolone-susceptible, rifampin-resistant tuberculosis. Study participants are randomized to either the control arm, based on the current standard of care for MDR/RR-TB, or to one of five 39-week multi-drug regimens containing newly approved and repurposed drugs. Study participation in all arms lasts at least 73 and up to 104 weeks post-randomization. Randomization is response-adapted using interim Bayesian analysis of efficacy endpoints. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 750 patients across 6 arms affords at least 80% power to detect the non-inferiority of at least 1 (and up to 3) experimental regimens, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per protocol populations.DiscussionThe lack of a safe and effective regimen that can be used in all patients is a major obstacle to delivering appropriate treatment to all patients with active MDR/RR-TB. Identifying multiple shorter, safe, and effective regimens has the potential to greatly reduce the burden of this deadly disease worldwide.Trial registrationClinicalTrials.gov Identifier NCT02754765. Registered on 28 April 2016; the record was last updated for study protocol version 3.3, on 27 August 2019.

Angiogenesis is a normal physiological process that also contributes to diabetic retinopathy-related complications and facilitates tumor metastasis by promoting the hematogenic dissemination of malignant cells from solid tumors. Here, we investigated the in vitro, ex vivo, and in vivo anti-angiogenic activity of phloridzin docosahexaenoate (PZ-DHA), a novel ω-3 fatty acid ester of a flavonoid precursor. Human umbilical vein endothelial cells (HUVEC) and human dermal microvascular endothelial cells (HMVEC) treated with a sub-cytotoxic concentration of PZ-DHA to assess in vitro anti-angiogenic activity showed impaired tubule formation on a Matrigel matrix. Ex vivo angiogenesis was measured using rat thoracic aortas, which exhibited reduced vessel sprouting and tubule formation in the presence of PZ-DHA. Female BALB/c mice bearing VEGF165- and basic fibroblast growth factor-containing Matrigel plugs showed a significant reduction in blood vessel development following PZ-DHA treatment. PZ-DHA inhibited HUVEC and HMVEC proliferation, as well as the migration of HUVECs in gap closure and trans-well cell migration assays. PZ-DHA inhibited upstream and downstream components of the Akt pathway and vascular endothelial growth factor (VEGF165)-induced overexpression of small molecular Rho GTPases in HUVECs, suggesting a decrease in actin cytoskeletal-mediated stress fiber formation and migration. Taken together, these findings reveal the potential of combined food biomolecules in PZ-DHA to inhibit angiogenesis.

Haskap berry (Lonicera caerulea L.) is a rich dietary source of anthocyanins with potent anti-inflammatory properties. In this study, isolated haskap berry anthocyanins were encapsulated in maltodextrin and inulin (3:1) by freeze-drying to improve stability and bioavailability. The structural properties of microcapsules, encapsulation yield, efficiency, recovery, and powder retention were evaluated. The microcapsules that exhibited the highest encapsulation efficiency (60%) and anthocyanin recovery (89%) were used in the dextran sulfate sodium (DSS)-induced acute colitis in mice. Thirty-five BALB/c male mice of seven weeks old were divided into seven dietary supplementation groups (n = 5) to receive either free anthocyanins, encapsulated anthocyanins (6.2 mg/day), or probiotics (1 × 109 CFU/day) alone or as combinations of anthocyanin and probiotics. As observed by clinical data, free anthocyanin and probiotic supplementation significantly reduced the severity of colitis. The supplementary diets suppressed the DSS-induced elevation of serum inflammatory (interleukin (IL)-6 and tumor necrosis factor) and apoptosis markers (B-cell lymphoma 2 and Bcl-2-associated X protein) in mice colon tissues. The free anthocyanins and probiotics significantly reduced the serum IL-6 levels. In conclusion, the dietary supplementation of haskap berry anthocyanins and probiotics protects against DSS-induced colitis possibly by attenuating mucosal inflammation, and this combination has the potential as a health-promoting dietary supplement and nutraceutical.

Eczema (atopic dermatitis, AD) is a skin disease characterized by skin barrier dysfunction due to various factors, including genetics, immune system abnormalities, and environmental triggers. Application of emollients and topical drugs such as corticosteroids and calcineurin inhibitors form the mainstay of treatments for this challenging condition. This review aims to summarize the recent advances made in phytochemical-based topical applications to treat AD and the different carriers that are being used. In this review, the clinical efficacy of several plant extracts and bioactive phytochemical compounds in treating AD are discussed. The anti-atopic effects of the herbs are evident through improvements in the Scoring Atopic Dermatitis (SCORAD) index, reduced epidermal thickness, decreased transepidermal water loss, and alleviated itching and dryness in individuals affected by AD as well as in AD mouse models. Histopathological studies and serum analyses conducted in AD mouse models demonstrated a reduction in key inflammatory factors, including thymic stromal lymphopoietin (TSLP), serum immunoglobulin E (IgE), and interleukins (IL). Additionally, there was an observed upregulation of the filaggrin (FLG) gene, which regulates the proteins constituting the stratum corneum, the outermost layer of the epidermis. Carriers play a crucial role in topical drug applications, influencing dose delivery, retention, and bioavailability. This discussion delves into the efficacy of various nanocarriers, including liposomes, ethosomes, nanoemulsions, micelles, nanocrystals, solid-lipid nanoparticles, and polymeric nanoparticles. Consequently, the potential long-term side effects such as atrophy, eruptions, lymphoma, pain, and allergic reactions that are associated with current topical treatments, including emollients, topical corticosteroids, topical calcineurin inhibitors, and crisaborole, can potentially be mitigated through the use of phytochemical-based natural topical treatments.

Minimally invasive alternatives to traditional prostate surgery are increasingly utilized to treat benign prostatic hyperplasia and localized prostate cancer in select patients. Advantages of these treatments over prostatectomy include lower risk of complication, shorter length of hospital stay, and a more favorable safety profile. Multiparametric magnetic resonance imaging (mpMRI) has become a widely accepted imaging modality for evaluation of the prostate gland and provides both anatomical and functional information. As prostate mpMRI and minimally invasive prostate procedure volumes increase, it is important for radiologists to be familiar with normal post-procedure imaging findings and potential complications. This paper reviews the indications, procedural concepts, common post-procedure imaging findings, and potential complications of prostatic artery embolization, prostatic urethral lift, irreversible electroporation, photodynamic therapy, high-intensity focused ultrasound, focal cryotherapy, and focal laser ablation.