Challenges faced by teachers of postgraduate health professions blended learning programs: a qualitative analysis.

INTRODUCTION: Blended learning, which integrates classroom face-to-face teaching with both asynchronous and synchronous online learning elements, has swiftly gained acceptance in educational environments. However, the implementation of blended learning presents challenges that impact all stakeholders, necessitating thoughtful consideration. Teachers play a central role in shaping the instructional experience among these stakeholders. To fully realize the potential of comprehensive blended learning, it is imperative to identify the challenges faced by these teachers and develop strategies that sensibly address and overcome them. METHODOLOGY: A qualitative exploratory study was conducted with twelve teachers involved in the postgraduate blended learning health professions program at Khyber Medical University, Peshawar in 2022. One-on-one semi-structured Interviews were conducted via WhatsApp/ZOOM, transcribed by Otter AI, coded on NVivo & analyzed using Braun/Clarke's Thematic Analysis. RESULTS: Three themes of challenges faced by teachers of postgraduate blended learning programs were constructed namely (1) Skills, such as (i) digital, (ii) instructional, and (iii) online class management, and (2) Administrative barriers in terms of (iv) resources (iv) training, and (3) Faculty resistance. CONCLUSION: This study provides profound insights into the daunting challenges that postgraduate blended learning program teachers encounter in terms of skills, administrative barriers, and faculty resistance. These findings offer a valuable opportunity for program directors to identify the critical requirements of these faculties in their pursuit of effective teaching and learning, ultimately transforming the landscape of blended education. This study emphasizes the need for ongoing faculty development and institutional support to address the identified challenges and improve the quality of postgraduate blended-learning programs.

A brief insight into the etiology, genetics, and immunology of polycystic ovarian syndrome (PCOS).

Polycystic ovarian syndrome (PCOS) is a prevailing endocrine and metabolic disorder occurring in about 6-20% of females in reproductive age. Most symptoms of PCOS arise early during puberty. Since PCOS involves a combination of signs and symptoms, thus it is considered as a heterogeneous disorderliness. The most accepted diagnostic criteria is Rotterdam criteria which involves two of the latter three features: (a) hyperandrogenism, (b) oligo- or an-ovulation, and (c) polycystic ovaries. The persistent hormonal imbalance leads to multiple small antral follicles formation and irregular menstrual cycle, ultimately causing infertility among females. Insulin resistance, cardiovascular diseases, abdominal obesity, psychological disorders, infertility, and cancer are also related to PCOS. These pathophysiologies associated with PCOS are interrelated with each other. Hyperandrogenism causes insulin resistance and hyperglycemia, leading to ROS formation, oxidative stress, and abdominal adiposity. In consequence, inflammation, ROS production, insulin resistance, and hyperandrogenemia also increase. Elevation of AGEs in the body either produced endogenously or consumed from diet exaggerates PCOS symptoms and is also related to ovarian dysfunction. This review summarizes how AGE formation, inflammation, and oxidative stress are significantly essential in PCOS progression. Alterations during prenatal development like exposure to excess AMH, androgens, or toxins (bisphenol-A, endocrine disruptors, etc.) may also be the etiologic mechanism behind PCOS. Although the etiology of this disorder is unclear, environmental and genetic factors are primarily involved. Physical inactivity, as well as unhealthy eating habits, has a vital role in the progression of PCOS. This review outlines a collection of specific genes phenotypically linked with PCOS. Furthermore, beneficial effect of metformin in maintaining endocrine abnormalities and ovarian function is also mentioned. Kisspeptin is a protein which helps in onset of puberty and increases GnRH pulsatile release during ovulation as well as role of KNDy neurons in GnRH pulsatile signal required for reproduction are also elaborated. This review also focuses on the immunology related to PCOS involving chronic low-grade inflammation, and how the alterations within the follicular microenvironment are intricated in the development of infertility in PCOS patients. How PCOS develops following antiepileptic and psychiatric medication is also expanded in this review. Initiation of antiandrogen treatment in early age (≤ 25 years) might be helpful in spontaneous conception in PCOS women. The role of BMP (bone morphogenetic proteins) in folliculogenesis and their expression in oocytes and granulosa cells are also explained. GDF8 and SERPINE1 expression in PCOS is given in detail.

Formulation development of directly compressible mebevarine tablets using superdisintegrant: A way to investigate quality atributes, in vitro release kinetics and stability profile.

In order for preparing a solid oral dosage form, tablet quality is of significant concern. Compressibility behavior of different powders and mixtures of formulations and release pattern of any tablets are characteristic measures to define prerequisite quality attributes of any compressed formulations. There are basically two major methods that can be adopted for the preparation of tablets including granulation and direct compression. Later process offer fewer processing steps and agreeable release profile with acceptable quality parameters and hence preferred over granulation method. In this investigation Mebeverine hydrochloride an anti-muscarinic drug is studied for compression and release behavior using various concentrations of filler binders and disintegrants via rotatable central composite design (CCRD) option of design expert (software). Nine formulations were developed from F1 to F9 with Crospovidone (superdisintegrant) as (X1) (-α=1.17% to ± α=6.83%) and microcrystalline cellulose (Avicel 102, Filler/binder) as X2 (-α = 29.82% to ± α = 65.18%). Disintegration Time (DT) as (R1) and Hardness in (kg) as (R2) were determined as two dependent response variables. The performance of powder blends and formulations was analyzed by micromeritic and physico-chemical and assessments. Dissolution comparisons were statistically analyzed by ANOVA and model dependent and in-dependent methods. Best fit model was found to be Hixon-crowell's model (r2 = 0.995) followed by Weibull's model (r2 = 0.985). The Trial formulations F2, F4, F6 and F8 were also studied on accelerated conditions (40±5ºC 75%±5% RH) for stability tests and validity of the formulations in months were also determined between 35-39 months.

Efficient RNP-directed Human Gene Targeting Reveals SPDEF Is Required for IL-13-induced Mucostasis.

Primary human bronchial epithelial cell (HBEC) cultures are a useful model for studies of lung health and major airway diseases. However, mechanistic studies have been limited by our ability to selectively disrupt specific genes in these cells. Here we optimize methods for gene targeting in HBECs by direct delivery of single guide RNA (sgRNA) and rCas9 (recombinant Cas9) complexes by electroporation, without a requirement for plasmids, viruses, or antibiotic selection. Variations in the method of delivery, sgRNA and rCas9 concentrations, and sgRNA sequences all had effects on targeting efficiency, allowing for predictable control of the extent of gene targeting and for near-complete disruption of gene expression. To demonstrate the value of this system, we targeted SPDEF, which encodes a transcription factor previously shown to be essential for the differentiation of MUC5AC-producing goblet cells in mouse models of asthma. Targeting SPDEF led to proportional decreases in MUC5AC expression in HBECs stimulated with IL-13, a central mediator of allergic asthma. Near-complete targeting of SPDEF abolished IL-13-induced MUC5AC expression and goblet cell differentiation. In addition, targeting of SPDEF prevented IL-13-induced impairment of mucociliary clearance, which is likely to be an important contributor to airway obstruction, morbidity, and mortality in asthma. We conclude that direct delivery of sgRNA and rCas9 complexes allows for predictable and efficient gene targeting and enables mechanistic studies of disease-relevant pathways in primary HBECs.

Biotechnological applications of microbial bioconversions.

Modern research has focused on the microbial transformation of a huge variety of organic compounds to obtain compounds of therapeutic and/or industrial interest. Microbial transformation is a useful tool for producing new compounds, as a consequence of the variety of reactions for natural products. This article describes the production of many important compounds by biotransformation. Emphasis is placed on reporting the metabolites that may be of special interest to the pharmaceutical and biotechnological industries, as well as the practical aspects of this work in the field of microbial transformations.

The mitochondrial uncoupler DNP triggers brain cell mTOR signaling network reprogramming and CREB pathway up-regulation.

Mitochondrial metabolism is highly responsive to nutrient availability and ongoing activity in neuronal circuits. The molecular mechanisms by which brain cells respond to an increase in cellular energy expenditure are largely unknown. Mild mitochondrial uncoupling enhances cellular energy expenditure in mitochondria and can be induced with 2,4-dinitrophenol (DNP), a proton ionophore previously used for weight loss. We found that DNP treatment reduces mitochondrial membrane potential, increases intracellular Ca(2+) levels and reduces oxidative stress in cerebral cortical neurons. Gene expression profiling of the cerebral cortex of DNP-treated mice revealed reprogramming of signaling cascades that included suppression of the mammalian target of rapamycin (mTOR) and insulin--PI3K - MAPK pathways, and up-regulation of tuberous sclerosis complex 2, a negative regulator of mTOR. Genes encoding proteins involved in autophagy processes were up-regulated in response to DNP. CREB (cAMP-response element-binding protein) signaling, Arc and brain-derived neurotrophic factor, which play important roles in synaptic plasticity and adaptive cellular stress responses, were up-regulated in response to DNP, and DNP-treated mice exhibited improved performance in a test of learning and memory. Immunoblot analysis verified that key DNP-induced changes in gene expression resulted in corresponding changes at the protein level. Our findings suggest that mild mitochondrial uncoupling triggers an integrated signaling response in brain cells characterized by reprogramming of mTOR and insulin signaling, and up-regulation of pathways involved in adaptive stress responses, molecular waste disposal, and synaptic plasticity. Physiological bioenergetic challenges such as exercise and fasting can enhance neuroplasticity and protect neurons against injury and neurodegeneration. Here, we show that the mitochondrial uncoupling agent 2,4-dinitrophenol (DNP) elicits adaptive signaling responses in the cerebral cortex involving activation of Ca(2+) -CREB and autophagy pathways, and inhibition of mTOR and insulin signaling pathways. The molecular reprogramming induced by DNP, which is similar to that of exercise and fasting, is associated with improved learning and memory, suggesting potential therapeutic applications for DNP.

Inhibitory effect of baicalein against glycation in HSA: an in vitro approach.

Hyperglycaemia accelerates the aging process significantly. Diabetes problems can be mitigated by inhibiting glycation. To learn more about glycation and antiglycation mediated by methyl glyoxal and baicalein, we studied human serum albumin as a model protein. A Methylglyoxal (MGO) incubation period of seven days at 37 degrees Celsius induced glycation of Human Serum Albumin.s Hyperchromicity, decreased tryptophan and intrinsic fluorescence, increased AGE-specific fluorescence, and reduced mobility were all seen in glycated human serum albumin (MGO-HSA) in sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Fourier transform infrared spectroscopy (FT-IR) and then far ultraviolet dichroism were used to detect secondary and tertiary structural perturbations (CD). The Congo red assay (CR), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) all verified the presence of amyloid-like clumps. Structure (carbonyl groups on ketoamine moieties) (CO), physiological problems including diabetes mellitus, and cardiovascular disease, etc. are linked to the structural and functional changes in glycated HSA, as proven by these studies.Communicated by Ramaswamy H. Sarma.

Vocal Fold Medialization Procedures in Previously Radiated Patients: A Survey of Practice Patterns.

BACKGROUND/OBJECTIVES: Head and neck radiation therapy (HNRT) has traditionally been considered a contraindication to vocal fold medialization procedures. Although safety has been demonstrated, we hypothesize that actual management varies. This study evaluates practice patterns of otolaryngologists regarding vocal fold medialization in patients after HNRT. METHODS: A 25-question survey evaluating respondents' management of patients status post HNRT with vocal fold paresis/paralysis was distributed to 357 otolaryngologists. Practice patterns regarding injection laryngoplasty (IL), medialization thyroplasty (MT), and arytenoid adduction (AA) were queried. RESULTS: Eight-two clinicians (23%) completed the survey. Ninety-one percent of respondents were laryngologists, 9% head and neck surgeons, 3% comprehensive otolaryngologists, and 3% "other." Eleven (15%) had been in practice <5 years, 19 (25%) for 5-10 years, and 46 (61%) for >10 years. No respondents considered HNRT a contraindication to IL, and 11 (14%) reported complications from the procedure. Hyaluronic acid (58, 75%) was most commonly injected. Twenty percent considered HNRT a contraindication to MT, and 37% considered it a contraindication to AA. Gore-Tex was used most commonly (65%). Twenty-seven percent reported major complications after MT. All complications occurred in the >10-year practice group, and this group was more likely to delay surgery after HNRT (p = 0.022). Respondents with complications were more likely to perform MT in HNRT patients (p = 0.0191). CONCLUSIONS: Otolaryngologists generally do not consider HNRT to be a contraindication to IL, but some consider it a contraindication to MT/AA. Previous complications do not appear to deter surgeons from performing MT. LEVEL OF EVIDENCE: N/A (Survey Study) Laryngoscope, 2024.

Biophysical insight into the binding mechanism of epigallocatechin-3-gallate and cholecalciferol to albumin and its preventive effect against AGEs formation: An in vitro and in silico approach.

Advanced glycation end products (AGEs) are produced non-enzymatically through the process of glycation. Increased AGEs production has been linked to several diseases including polycystic ovary syndrome (PCOS). PCOS contributes to the development of secondary comorbidities, such as diabetes, cardiovascular complications, infertility, etc. Consequently, research is going on AGEs-inhibiting phytochemicals for their potential to remediate and impede the progression of hyperglycaemia associated disorders. In this study human serum albumin is used as a model protein, as albumin is predominantly present in follicular fluid. This article focusses on the interaction and antiglycating potential of (-)-Epigallocatechin-3-gallate (EGCG) and vitamin D in combination using various techniques. The formation of the HSA-EGCG and HSA-vitamin D complex was confirmed by UV and fluorescence spectroscopy. Thermodynamic analysis verified the spontaneity of reaction, and presence of hydrogen bonds and van der Waals interactions. FRET confirms high possibility of energy transfer. Cumulative antiglycation resulted in almost 60 % prevention in AGEs formation, decreased alterations at lysine and arginine, and reduced protein carbonylation. Secondary and tertiary structural changes were analysed by circular dichroism, Raman spectroscopy and ANS binding assay. Type and size of aggregates were confirmed by Rayleigh and dynamic light scattering, ThT fluorescence, SEM and SDS-PAGE. Effect on cellular redox status, DNA integrity and cytotoxicity was analysed in lymphocytes using dichlorofluorescein (DCFH-DA), DAPI and MTT assay which depicted an enhancement in antioxidant level by cumulative treatment. These findings indicate that EGCG and vitamin D binds strongly to HSA and have antiglycation ability which enhances upon synergism.

Comparing cadaveric and 3D-printed laryngeal models in transcutaneous injection laryngoplasty.

Background: There is increasing focus on the development of high-quality simulation models for medical education. Cadaveric models, although considered more realistic, may be difficult to obtain and costly. The advent of three-dimensional (3D) printing has offered a low-cost, reliable, and reproducible alternative. This study sought to compare the utility of 3D-printed to cadaveric models for training in transcutaneous injection laryngoplasty (TIL). Methods: A simulation course with a cross-over design was employed. Video laryngoscopes were utilized for both the 3D and cadaveric models to assess the accuracy of injection into the vocal fold. Pre-procedure and post-procedure surveys were administered to evaluate understanding and comfort level on a Likert scale of 1-10. Each model was also rated on a 1-5 Likert scale for self-efficacy, fidelity, and educational value. Results: Pre- and post-survey data were completed by 15 otolaryngology residents and medical students. Mean pre-seminar understanding and comfort level were 3.7 and 2.2, respectively, compared to 6.9 and 5.9 (p < .05) following use of the 3D model and 6.4 and 4.7 (p < .05) following use of the cadaver model. When comparing 3D and cadaveric models, no significant differences were observed regarding self-efficacy, fidelity, and educational value. Conclusion: There was a similar mean increase in understanding and comfort following use of the 3D and cadaveric models. 3D-printing can provide an excellent adjunct to, and eventually a potential replacement for hands-on cadaveric training in medical education, particularly for TIL. Level of Evidence: Level III.

T cell-induced airway smooth muscle cell proliferation via the epidermal growth factor receptor.

Allergic asthma is a heterogeneous disease with no curative therapies. T cells infiltrate the airway smooth muscle (ASM) layer and may be implicated in airway remodeling and the increase of ASM mass, a cardinal feature of asthma. The mechanism by which CD4(+) T cells drive airway remodeling remains unknown. This study sought to determine the T cell-mediated mechanism of ASM cell proliferation. We hypothesized that CD4(+) T cells adhere to ASM cells via CD44, and induce ASM cell proliferation through the activation of the epidermal growth factor receptor (EGFR). A coculture model showed that the contact of antigen-stimulated CD4(+) T cells with ASM cells induced high levels of EGFR ligand expression in CD4(+) T cells and the activation of matrix metalloproteinase (MMP)-9, required for the shedding of EGFR ligands. The inhibition of EGFR and MMP-9 prevented the increase of ASM cell proliferation after coculture. The hyaluronan receptor CD44 is the dominant mediator of the tight adherence of T cells to ASM and is colocalized with MMP-9 on the cell surface. Moreover, the neutralization of CD44 prevents ASM cell hyperplasia. These data provide a novel mechanism by which antigen-stimulated CD4(+) T cells induce the remodeling indicative of a direct trophic role for CD4(+) T cells.

Airway contractility and remodeling: links to asthma symptoms.

Respiratory symptoms are largely caused by obstruction of the airways. In asthma, airway narrowing mediated by airway smooth muscle (ASM) contraction contributes significantly to obstruction. The spasmogens produced following exposure to environmental triggers, such as viruses or allergens, are initially responsible for ASM activation. However, the extent of narrowing of the airway lumen due to ASM shortening can be influenced by many factors and it remains a real challenge to decipher the exact role of ASM in causing asthmatic symptoms. Innovative tools, such as the forced oscillation technique, continue to develop and have been proven useful to assess some features of ASM function in vivo. Despite these technologic advances, it is still not clear whether excessive narrowing in asthma is driven by ASM abnormalities, by other alterations in non-muscle factors or simply because of the overexpression of spasmogens. This is because a multitude of forces are acting on the airway wall, and because not only are these forces constantly changing but they are also intricately interconnected. To counteract these limitations, investigators have utilized in vitro and ex vivo systems to assess and compare asthmatic and non-asthmatic ASM contractility. This review describes: 1- some muscle and non-muscle factors that are altered in asthma that may lead to airway narrowing and asthma symptoms; 2- some technologies such as the forced oscillation technique that have the potential to unveil the role of ASM in airway narrowing in vivo; and 3- some data from ex vivo and in vitro methods that probe the possibility that airway hyperresponsiveness is due to the altered environment surrounding the ASM or, alternatively, to a hypercontractile ASM phenotype that can be either innate or acquired.

Emerging airway smooth muscle targets to treat asthma.

Asthma is characterized in part by variable airflow obstruction and non-specific hyperresponsiveness to a variety of bronchoconstrictors, both of which are mediated by the airway smooth muscle (ASM). The ASM is also involved in the airway inflammation and airway wall remodeling observed in asthma. For all these reasons, the ASM provides an important target for the treatment of asthma. Several classes of drugs were developed decades ago which targeted the ASM - including ß-agonists, anti-cholinergics, anti-histamines and anti-leukotrienes - but no substantially new class of drug has appeared recently. In this review, we summarize the on-going work of several laboratories aimed at producing novel targets and/or tools for the treatment of asthma. These range from receptors and ion channels on the ASM plasmalemma, to intracellular effectors (particularly those related to cyclic nucleotide signaling, calcium-homeostasis and phosphorylation cascades), to anti-IgE therapy and outright destruction of the ASM itself.

Phenotype modulation of airway smooth muscle in asthma.

The biological responses of airway smooth muscle (ASM) are diverse, in part due to ASM phenotype plasticity. ASM phenotype plasticity refers to the ability of ASM cells to change the degree of a variety of functions, including contractility, proliferation, migration and secretion of inflammatory mediators. This plasticity occurs due to intrinsic or acquired abnormalities in ASM cells, and these abnormalities or predisposition of the ASM cell may alter the ASM response and in some cases recapitulate disease hallmarks of asthma. These phenotypic changes are ultimately determined by multiple stimuli and occur due to alterations in the intricate balance or reversible state that maintains ASM cells in either a contractile or synthetic state, through processes termed maturation or modulation, respectively. To elucidate the role of ASM phenotype in disease states, numerous in vitro studies have suggested a phenotypic switch in ASM primary cell cultures as an explanation for the plethora of responses mediated by ASM cells. Moreover, there is overwhelming evidence suggesting that the immunomodulatory response of ASM is due to the acquisition of a synthetic phenotype; however, whether this degree of plasticity is present in vivo as opposed to cell culture-based models remains speculative. Nonetheless, this review will give an overall scope of ASM phenotypic markers, triggers of ASM phenotype modulation and novel therapeutic approaches to control ASM phenotype plasticity.

Functional phenotype of airway myocytes from asthmatic airways.

In asthma, the airway smooth muscle (ASM) cell plays a central role in disease pathogenesis through cellular changes which may impact on its microenvironment and alter ASM response and function. The answer to the long debated question of what makes a 'healthy' ASM cell become 'asthmatic' still remains speculative. What is known of an 'asthmatic' ASM cell, is its ability to contribute to the hallmarks of asthma such as bronchoconstriction (contractile phenotype), inflammation (synthetic phenotype) and ASM hyperplasia (proliferative phenotype). The phenotype of healthy or diseased ASM cells or tissue for the most part is determined by expression of key phenotypic markers. ASM is commonly accepted to have different phenotypes: the contractile (differentiated) state versus the synthetic (dedifferentiated) state (with the capacity to synthesize mediators, proliferate and migrate). There is now accumulating evidence that the synthetic functions of ASM in culture derived from asthmatic and non-asthmatic donors differ. Some of these differences include an altered profile and increased production of extracellular matrix proteins, pro-inflammatory mediators and adhesion receptors, collectively suggesting that ASM cells from asthmatic subjects have the capacity to alter their environment, actively participate in repair processes and functionally respond to changes in their microenvironment.

Retrograde Cricopharyngeus Dysfunction: The Jefferson Experience.

OBJECTIVES: To describe our center's experience with the identification and treatment of retrograde cricopharyngeus dysfunction (R-CPD), a syndrome involving the inability to belch previously described by only one institution. Additionally, because all patients initially learned of their condition and sought treatment as a result of social media posts, we queried their source and comfort with this form of medical referral. METHODS: Retrospective chart review of patients who underwent botulism toxin injection into the cricopharyngeus muscle for treatment of R-CPD from 2019 to 2022. Demographic data, most common symptoms at presentation, and response to treatment and complications were documented. Post-treatment questionnaires were reviewed. RESULTS: A total of 85 patients were identified. Mean age at surgery was 27 years. There were 54 (63.5%) females and 31 (36.5%) males. The inability to burp (98.8%), bloating (92.9%), gurgling noises (31.8%), and excessive flatulence (21.2%) were the most common symptoms. The minimum units of botox utilized were 25, whereas the maximum was 100. The majority of patients (88.2%) had a successful response at initial follow-up visit. The most common complication was mild dysphagia (30.6%), which was transient for all patients. Most patients learned of our practice through social media, with only one patient being referred by a medical provider. CONCLUSIONS: The majority of patients in our cohort were young and female. The inability to burp and bloating were the most common presenting symptoms. Social media was the primary source of referral. Our institution favors 80-100 units for an effective response. Laryngoscope, 133:1081-1085, 2023.

Personalized Palliative and Survivorship Care for Patients With Metastatic Cancer Treated With Radiation Therapy.

While the benefits of early palliative care for patients with metastatic cancer are well established, cancer survivorship remains inadequately integrated into the care of patients with distant metastases. Moreover, the optimal model of care delivery is poorly defined. A prognostic model previously developed and validated at Good Samaritan University Hospital identified four groups of patients with metastatic solid tumor malignancy having very favorable, favorable, standard or unfavorable prognoses with median survival of 31, 14, 4 and 1 month, respectively. This framework holds promise for the personalized delivery of supportive, palliative and survivorship care services in the context of radiation therapy. We review the published literature providing the rationale for a novel multidisciplinary care model where the radiation oncology Clinical Nurse Specialist identifies and coordinates interventions to address unmet physical and emotional issues faced by survivors with metastatic cancer with the goal of improving quality of life and overall survival.