Interactive Journal Club: A Learning Method to Enhance Collaboration and Participation among Medical Students.

Objectives: This quality improvement study aimed to explore the viability of a learning pedagogy for medical students, the interactive journal club (IJC), in stimulating active learning and engagement among learners. The study intends to explore the benefits provided by the IJC when compared to traditional learning methods (e.g., traditional journal clubs). It attempts to highlight the importance of didactics which focus on active learning and interactive engagement between learners. Methods: The IJC was implemented as a course requirement in HI 201: Health Informatics, a midyear elective course at the College of Medicine, University of the Philippines Manila. A class of MD-PhD (Molecular Medicine) students was divided into two separate groups: the designated leaders who presented the article and moderated the discussion, and the audience who did not read the article beforehand yet were involved in its critical analysis. The IJC was conducted twice in two different sections of MD-PhD (Molecular Medicine) students, across two different midyear terms, Midyear Term 2021, and Midyear Term 2022. Reflection papers were collected and the responses through this requirement were collated before the primary takeaways were extrapolated. A survey was also sent out to the students of each class to itemize the consolidated feedback of students on the proposed didactic. Results: The overall process of IJC was deemed both exciting and stimulating. The learning pedagogy provided an alternative platform for active learning, fostering a student-centered approach that placed a heavy emphasis on critical thinking. One major challenge identified in the implementation of the educational design was the heavy reliance on student participation which was identified to, at times, be a difficult factor to overcome. In order to improve its implementation, expectations may be set at the beginning and assessed at the end of the session. In addition, a pre- and post-questionnaire may be given to assess the perceived usefulness of this new method for qualitative comparison. Conclusion: Interactive and student-centered modes of learning are empirical for the improvement of literature appraisal, journal presentation, and evidence-based critical thinking among medical students. IJCs may be utilized as an alternative and effective learning strategy in teaching pertinent skills expected of a proper physician. When compared to traditional pedagogies, IJCs provide a platform for deeper learning and enable the achievement of learning outcomes, with learner engagement as the focal point. Future attempts at executing IJCs may consider the implementation of learning outcomes setting, and the use of pre- and post- IJC surveys to assess the effectiveness of the modality.

The location of pain in cluster headache: Data from the International Cluster Headache Questionnaire.

OBJECTIVE: To identify the most common locations of cluster headache pain from an international, non-clinic-based survey of participants with cluster headache, and to compare these locations to other cluster headache features as well as to somatotopic maps of peripheral, brainstem, thalamic, and cortical areas. BACKGROUND: Official criteria for cluster headache state pain in the orbital, supraorbital, and/or temporal areas, yet studies have noted pain extending beyond these locations, and the occipital nerve appears relevant, given the effectiveness of suboccipital corticosteroid injections and occipital nerve stimulation. Furthermore, cranial autonomic features vary between patients, and it is not clear if the trigeminovascular reflex is dermatome specific (e.g., do patients with maxillary or V2 division pain have more rhinorrhea?). Finally, functional imaging studies show early activation of the posterior hypothalamus in a cluster headache attack. However, the first somatosensory area to be sensitized is unclear; the first area can be hypothesized based on the complete map of pain locations. METHODS: The International Cluster Headache Questionnaire was an internet-based cross-sectional survey that included a clickable pain map of the face. These data were compared to several other datasets: (1) a meta-analysis of 22 previous publications of pain location in cluster headache (consisting of 6074 patients); (2) four cephalic dermatome maps; (3) participants' survey responses for demographics, autonomic features, and effective medications; and (4) previously published somatotopic maps of the brainstem, thalamus, primary somatosensory cortex, and higher order somatosensory cortex. RESULTS: One thousand five hundred eighty-nine participants completed the pain map portion of the survey, and the primary locations of pain across all respondents was the orbital, periorbital, and temporal areas with a secondary location in the lower occiput; these primary and secondary locations were consistent with our meta-analysis of 22 previous publications. Of the four cephalic dermatomes (V1, V2, V3, and a combination of C2-3), our study found that most respondents had pain in two or more dermatomes (range 85.7% to 88.7%, or 1361-1410 of 1589 respondents, across the four dermatome maps). Dermatomes did not correlate with their respective autonomic features or with medication effectiveness. The first area to be sensitized in the canonical somatosensory pathway is either a subcortical (brainstem or thalamus) or higher order somatosensory area (parietal ventral or secondary somatosensory cortices) because the primary somatosensory cortex (area 3b) and somatosensory area 1 have discontinuous face and occipital regions. CONCLUSIONS: The primary pain locations in cluster headache are the orbital, supraorbital, and temporal areas, consistent with the official International Classification of Headache Disorders criteria. However, activation of the occiput in many participants suggests a role for the occipital nerve, and the pain locations suggest that somatosensory sensitization does not start in the primary somatosensory cortex.

Virgin Coconut Oil as Adjunctive Therapy for Hospitalized COVID-19 Patients in a Tertiary Referral Hospital: A Randomized Controlled Trial.

Background: Virgin coconut oil (VCO) has anti-viral and anti-inflammatory properties, making it a potential therapeutic candidate against COVID-19 infection. Objective: To determine the efficacy and safety of VCO as adjunctive therapy for hospitalized patients with COVID-19. Methods: We conducted a randomized, open-label controlled trial involving laboratory-confirmed COVID-19 patients admitted at the Philippine General Hospital. The study participants were randomized to the intervention group who received virgin coconut oil with local standard of care, or to the control group who received local standard of care alone. Results: We enrolled 39 participants into the VCO group and 38 participants into the control group. Significantly fewer participants in the VCO group had abnormal CRP levels at the end of treatment compared to control. (relative risk [RR] 0.75, 95% confidence interval [CI] 0.58 to 0.95; p=0.02) No significant difference was found in the duration of hospital stay (mean 9.33 days for VCO vs. 10.29 days for control; p=0.45) and time to symptom resolution (mean 6.8 days for VCO, vs. 6.74 days for control; p=0.91). Although the proportion of patients who developed the secondary outcomes of mortality, need for ICU admission, need for invasive ventilation, and negative viral conversion was lower in the VCO group, results did not reach statistical significance. The VCO group had larger reduction in the inflammatory markers ferritin, lactate dehydrogenase, TNF-alpha, IP-10 and IL-6, but results did not reach statistical significance. Adverse events were significantly higher in the VCO group (RR 4.87, 95% CI 1.14 to 20.79; p=0.03). Conclusion: This clinical trial on hospitalized patients showed significant benefit in CRP levels of participants given VCO compared to control. There was no significant benefit in the use of VCO as adjunctive therapy in reducing duration of hospital stay. Larger studies are needed to conclusively demonstrate the effect of VCO on other clinical outcomes and inflammatory markers.

Local exposure misclassification in national models: relationships with urban infrastructure and demographics.

BACKGROUND: National-scale linear regression-based modeling may mischaracterize localized patterns, including hyperlocal peaks and neighborhood- to regional-scale gradients. For studies focused on within-city differences, this mischaracterization poses a risk of exposure misclassification, affecting epidemiological and environmental justice conclusions. OBJECTIVE: Characterize the difference between intraurban pollution patterns predicted by national-scale land use regression modeling and observation-based estimates within a localized domain and examine the relationship between that difference and urban infrastructure and demographics. METHODS: We compare highly resolved (0.01 km2) observations of NO2 mixing ratio and ultrafine particle (UFP) count obtained via mobile monitoring with national model predictions in thirteen neighborhoods in the San Francisco Bay Area. Grid cell-level divergence between modeled and observed concentrations is termed "localized difference." We use a flexible machine learning modeling technique, Bayesian Additive Regression Trees, to investigate potentially nonlinear relationships between discrepancy between localized difference and known local emission sources as well as census block group racial/ethnic composition. RESULTS: We find that observed local pollution extremes are not represented by land use regression predictions and that observed UFP count significantly exceeds regression predictions. Machine learning models show significant nonlinear relationships among localized differences between predictions and observations and the density of several types of pollution-related infrastructure (roadways, commercial and industrial operations). In addition, localized difference was greater in areas with higher population density and a lower share of white non-Hispanic residents, indicating that exposure misclassification by national models differs among subpopulations. IMPACT: Comparing national-scale pollution predictions with hyperlocal observations in the San Francisco Bay Area, we find greater discrepancies near major roadways and food service locations and systematic underestimation of concentrations in neighborhoods with a lower share of non-Hispanic white residents. These findings carry implications for using national-scale models in intraurban epidemiological and environmental justice applications and establish the potential utility of supplementing large-scale estimates with publicly available urban infrastructure and pollution source information.

Evaluation of lateral flow devices for postmortem rabies diagnosis in animals in the Philippines: a multicenter study.

Expansion of the use of lateral flow devices (LFD) for animal rabies diagnosis can help mitigate the widespread underreporting of rabies. However, this has been hindered by the limited number and small sample size of previous studies. To overcome this limitation, we conducted a multicenter study with a larger sample size to assess the diagnostic accuracy of the ADTEC LFD for postmortem rabies diagnosis in animals. Thirteen governmental animal diagnostic laboratories in the Philippines were involved in this study, and 791 animals suspected of having rabies were tested using both the direct fluorescence antibody test (DFAT) and ADTEC LFD between August 2021 and October 2022. The LFD demonstrated a sensitivity of 96.3% [95% confidence interval (CI): 94.1%-97.9%] and a specificity of 99.7% (95% CI: 98.4%-100%). Notably, false-negative results were more likely to occur in laboratories with lower annual processing volumes of rabies samples in the previous years (adjusted odds ratio 4.97, 95% CI: 1.49-16.53). In this multicenter study, the high sensitivity and specificity of the LFD for the diagnosis of animal rabies, compared to that of the DFAT, was demonstrated, yet concerns regarding false-negative results remain. In areas with limited experience in processing rabies samples, it is essential to provide comprehensive training and careful attention during implementation.

Topical Finasteride: A Comprehensive Review of Androgenetic Alopecia Management for Men and Women.

The most prevalent kind of alopecia, androgenetic alopecia, commonly known as male or female pattern hair loss, affects both men and women, with the frequency rising with advancing years. Even though practicing dermatologists and hair experts frequently encounter it, it might be one of the most challenging disorders to treat since choosing a course of action frequently requires a comprehensive analysis of several variables and moral judgment. Effectiveness, side effect profiles, practicability, promoting compliance, and treatment cost are the most important factors to take into account, especially given the chronic nature of androgenetic alopecia. A clinician's ability to select the optimum course of treatment for each patient may be constrained and clouded by their knowledge base, experience, and financial compensation. A search was done to find research on the effectiveness of topical finasteride therapy, including clinically pertinent case reports and papers. Only topical minoxidil and oral finasteride are now approved by the Food and Drug Administration and the European Medicines Agency for the treatment of androgenetic alopecia. Despite being effective for hair regeneration, systemic use of finasteride is accompanied by adverse effects that prevent long-term use. Investigating topical finasteride as another possible treatment plan may be fruitful. Early research on the use of topical finasteride is safe and encouraging, despite its limitations. More research on drug distribution, ideal topical strength and usage regularity, adverse effects, and application for other alopecias would aid in elucidating the range of topical finasteride use.

The Philippines stingless bee propolis promotes hair growth through activation of Wnt/ß-catenin signaling pathway.

Although hair loss is not a horrible disease, it sometimes reduces the patients' quality of life (QOL) and increases their mental stress. Currently, there is no effective treatment for hair loss. It is known that honeybee propolis has various biological activities, including stimulating the proliferation of hair matrix keratinocytes. However, little is known with the hair promoting activity of stingless bee propolis. Hence, this study investigates the hair growth-promoting activity of Philippines stingless bee propolis extract and the underlying a molecular mechanism of promoting hair growth. For the evaluation of hair growth stimulating activity, 99.5% ethanolic extract of Philippines stingless bee propolis is examined using the simple shaving model in C57BL/6N mice. Melaninization of dorsal skin and histological analysis of hair follicles (HFs) revealed that propolis promotes hair growth by stimulating HFs development. The expression of mRNA (Wnt3a, Ctnnb1/ß-catenin, Lef1, and Bmp2) and protein (WNT3A and ß-catenin) of selected Wnt/ß-catenin associated genes explains Philippines stingless bee propolis promoting HFs development by activating Wnt/ß-catenin signaling pathway. These results suggest that the treatment of propolis strongly promotes hair growth by stimulating the development of HFs via activation of Wnt/ß-catenin signaling pathway. This further indicates the potential of Philippines stingless bee propolis as a novel promising agricultural product for hair growth.

Alcohol induced behavioral and immune perturbations are attenuated by activation of CB2 cannabinoid receptors.

The endocannabinoidome (eCBome) is the expanded endocannabinoid system (ECS) and studies show that there is a link between this system and how it modulates alcohol induced neuroinflammation. Using conditional knockout (cKO) mice with selective deletion of cannabinoid type 2 receptors (CB2Rs) in dopamine neurons (DAT-Cnr2) and in microglia (Cx3Cr1-Cnr2), we investigated how CB2Rs modulate behavioral and neuroinflammation induced by alcohol. Behavioral tests including locomotor and wheel running activity, rotarod performance test, and alcohol preference tests were used to evaluate behavioral changes induced by alcohol. Using ELISA assay, we investigated the level of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1α (IL-1α), and interleukin-1ß (IL-1ß) in the hippocampus of mice. The findings demonstrated that locomotor activity, wheel running, and rotarod performance activities were significantly affected by cell-type specific deletion of CB2Rs in dopamine neurons and microglia. The non-selective CB2R agonist, WIN 55,212-2, reduced alcohol preference in the wild type and cell-type specific CB2R cKO mice. In addition, the result showed that cell-type specific deletion of CB2Rs per se and administration of alcohol to CB2R cKO mice increased the expression of proinflammatory cytokines in the hippocampus. These findings suggest the involvement of CB2Rs in modulating behavioral and immune alterations induced by alcohol.

From Perpetual Wetness to Soil Chemistry: Enumerating Environmental and Physicochemical Factors Favoring Oncomelania hupensis quadrasi Snail Presence in the Municipality of Gonzaga, Cagayan, Philippines.

Snail control to complement mass drug administration is being promoted by the World Health Organization for schistosomiasis control. Oncomelania hupensis quadrasi, the snail intermediate host of Schistosoma japonicum in the Philippines, has a very focal distribution; thus, scrutinizing baseline data and parameters affecting this distribution is very crucial. In this study in Gonzaga, Cagayan, Philippines, snail habitats were surveyed, and the various factors affecting the existence of the snails were determined. Malacological surveys and the mapping of sites of perpetual wetness in five endemic and five neighboring non-endemic barangays were conducted. Environmental and physicochemical factors were also examined. Maps of both snail and non-snail sites were generated. Of the fifty sites surveyed, O. h. quadrasi were found in twelve sites, and two sites yielded snails that were infected with S. japonicum cercariae. Factors such as silty loam soil, proximity to a snail site, water ammonia, and soil attributes (organic matter, iron, and pH) are all significantly associated with the presence of snails. In contrast, types of habitats, temperatures, and soil aggregation have no established association with the existence of snails. Mapping snail sites and determining factors favoring snail presence are vital to eliminating snails. These approaches will significantly maximize control impact and minimize wasted efforts and resources, especially in resource-limited schistosomiasis endemic areas.

Establishing a Standardized Method for the Effective Intraoperative Collection and Biological Preservation of Brain Tumor Tissue Samples Using a Novel Tissue Preservation System: A Pilot Study.

BACKGROUND: Glioblastoma (GB) is an aggressive tumor showing extensive intertumoral and intratumoral heterogeneity. Several possible reasons contribute to the historical inability to develop effective therapeutic strategies for treatment of GB. One such challenge is the inability to consistently procure high-quality biologically preserved specimens for use in molecular research and patient-derived xenograft model development. No scientifically derived standardized method exists for intraoperative tissue collection specifically designed with the fragility of RNA in mind. METHODS: In this investigation, we set out to characterize matched specimens from 6 GB patients comparing the traditional handling and collection processes of intraoperative tissue used in most neurosurgical operating rooms versus an automated resection, collection, and biological preservation system (APS) which captures, preserves, and biologically maintains tissue in a prescribed and controlled microenvironment. Matched specimens were processed in parallel at various time points and temperatures, evaluating viability, RNA and protein concentrations, and isolation of GB cell lines. RESULTS: We found that APS-derived GB slices stored in an APS modified medium remained viable and maintained high-quality RNA and protein concentration for up to 24 hours. CONCLUSIONS: Our results showed that primary GB cell cultures derived in this manner had improved growth over widely used collection and preservation methods. By implementing an automated intraoperative system, we also eliminated inconsistencies in methodology of tissue collection, handling and biological preservation, establishing a repeatable and standardized practice that does not require additional staff or a laboratory technician to manage it.

Investigation of the Kinematic Upper-Limb Movement Assessment (KUMA): A Pilot Study.

Purpose: Upper limb movement disorders are common after stroke and can severely impact activities of daily living. Available clinical measures of these disorders are subjective and may lack the sensitivity needed to track a patient's progress and to compare different therapies. Kinematic analyses can provide clinicians with more objective measures for evaluating the effects of rehabilitation. We present a novel method to assess the quality of upper limb movement: the Kinematic Upper-limb Movement Assessment (KUMA). This assessment uses motion capture to provide three kinematic measures of upper limb movement: active range of motion, speed, and compensatory trunk movement. The researchers sought to evaluate the ability of the KUMA to distinguish motion in the affected versus unaffected limb. Method: We used the KUMA with three participants with stroke to assess three single-joint movements in: wrist flexion and extension, elbow flexion and extension, and shoulder flexion/extension and abduction/adduction. Participants also completed the Modified Ashworth Scale and the Chedoke-McMaster Stroke Assessment, two clinical measures of functional ability. Results: The KUMA distinguished between affected and unaffected upper limb motion. Conclusions: The KUMA provides clinicians with supplementary objective information for motion characterization that is not available through clinical measures alone. The KUMA can complement existing clinical measures such as the MAS and CMSA and can be helpful for monitoring patient progress.

Objectif : les troubles des mouvements de membres supérieurs sont courants après un accident vasculaire cérébral et peuvent nuire fortement aux activités de la vie quotidienne. Les mesures cliniques disponibles pour ces troubles sont subjectives et ne possèdent peut-être pas la sensibilité nécessaire pour suivre le progrès d'un patient et comparer les diverses thérapies. Les analyses de cinématique peuvent fournir aux cliniciens des mesures plus objectives pour évaluer les effets de la réadaptation. Les auteurs présentent une nouvelle méthode pour évaluer la qualité des mouvements des membres supérieurs : l'évaluation cinématique des mouvements des membres supérieurs (KUMA, pour Kinematic Upper-limb Movement Assessment ). Cette évaluation fait appel à la capture des mouvements pour fournir trois mesures cinématiques des mouvements des membres supérieurs : l'amplitude de mouvements actifs, la vitesse et le mouvement compensatoire du tronc. Les chercheurs ont cherché à évaluer la capacité de la KUMA à distinguer le mouvement du membre touché par rapport au membre non touché. Méthodologie : les chercheurs ont utilisé la KUMA auprès de trois participants ayant subi un accident vasculaire cérébral pour évaluer trois mouvements monoarticulaires : flexion et extension du poignet, flexion et extension du coude, et flexion et extension, abduction et adduction de l'épaule. Les participants ont également utilisé l'échelle modifiée d'Ashworth (MAS) et l'évaluation Chedoke-McMaster de l'accident vasculaire cérébral (AVC), deux mesures cliniques de la capacité fonctionnelle. Résultats : la KUMA distinguait le mouvement du membre supérieur atteint de celui qui ne l'était pas. Conclusions : La KUMA fournit aux cliniciens de l'information objective supplémentaires pour caractériser les mouvements d'une manière qui n'est pas disponible par les seules mesures cliniques. La KUMA peut compléter les mesures cliniques en place comme l'échelle modifiée d'Ashworth et l'évaluation Chedoke-McMaster de l'AVC et peut être utile pour surveiller le progrès des patients.

COX Inhibitory and Cytotoxic Naphthoketal-Bearing Polyketides from Sparticola junci.

Axenic fermentation on solid rice of the saprobic fungus Sparticola junci afforded two new highly oxidized naphthalenoid polyketide derivatives, sparticatechol A (1) and sparticolin H (2) along with sparticolin A (3). The structures of 1 and 2 were elucidated on the basis of their NMR and HR-ESIMS spectroscopic data. Assignment of absolute configurations was performed using electronic circular dichroism (ECD) experiments and Time-Dependent Density Functional Theory (TDDFT) calculations. Compounds 1-3 were evaluated for COX inhibitory, antiproliferative, cytotoxic and antimicrobial activities. Compounds 1 and 2 exhibited strong inhibitory activities against COX-1 and COX-2. Molecular docking analysis of 1 conferred favorable binding against COX-2. Sparticolin H (2) and A (3) showed a moderate antiproliferative effect against myelogenous leukemia K-562 cells and weak cytotoxicity against HeLa and mouse fibroblast cells.

Immunohistochemical detection of virus antigen in the nasal planum of rabid dogs.

The rabies virus is one of the most neurotropic of all viruses infecting mammals. During the terminal phases of infection, the virus spreads to peripheral tissues, including the skin. The external skin of the nose, called the nasal planum, is a sensory organ where numerous nerve bundles and terminal nerves are distributed. Therefore, the nasal planum is expected to serve as a postmortem diagnostic material. However, the distribution of rabies virus antigens in the nasal planum in rabid animals has not yet been studied. In this study, the nasal planum was obtained from 45 rabid dogs. In all rabid dogs, the viral antigen was detected in the peripheral nerve tissues, Merkel cells, and squamous cells. The viral antigen in the epidermis exhibited three patterns: first, a diffuse positive pattern from the basal layer to the squamous layer; second, a reticular positive pattern along the cell membrane in the squamous layer; and third, a basal layer pattern of the epidermis. In the dermis, viral antigens were detected more often in lamellated corpuscles just beneath the rete pegs. These results suggest that the nasal planum could serve as a useful alternative source for postmortem diagnosis in rabies endemic countries.

Effects of orally administered Euglena gracilis and its reserve polysaccharide, paramylon, on gastric dysplasia in A4gnt knockout mice.

Euglena gracilis is widely utilized as food or supplement to promote human and animal health, as it contains rich nutrients. In this study, we administered spray-dried powder of E. gracilis and paramylon, ß-glucan stored in E. gracilis cells, to A4gnt knockout (KO) mice. A4gnt KO mice are a mutant mouse model that spontaneously develops gastric cancer through hyperplasia-dysplasia-adenocarcinoma sequence in the antrum of the stomach, and we observed the effects of E. gracilis and paramylon on the early involvements of A4gnt KO mice. Male and female 10-week-old A4gnt KO mice and their age-matched wildtype C57BL/6J mice were orally administered with 50 mg of E. gracilis or paramylon suspended in saline or saline as a control. After 3-week administration, animals were euthanatized and the stomach was examined histopathologically and immunohistochemically. Gene expression patterns of the stomach, which have been reported to be altered with A4gnt KO, and IgA concentration in small intestine were also analyzed with real-time PCR and ELISA, respectively. Administration of Euglena significantly reduced the number of stimulated CD3-positive T-lymphocytes in pyloric mucosa of A4gnt KO mice and tend to reduce polymorphonuclear leukocytes infiltration. Euglena administration further downregulated the expression of Il11 and Cxcl1 of A4gnt KO mice. Euglena administration also affected IgA concentration in small intestinal contents of A4gnt KO mice. Paramylon administration reduced the number of CD3-positive lymphocytes in pyloric mucosa of A4gnt KO mice, and downregulated the expressions of Il11 and Ccl2 of A4gnt KO mice. Although we found no significant effects on gross and microscopic signs of gastric dysplasia and cell proliferation, the present study suggests that the administration of Euglena and paramylon may ameliorate the early involvements of A4gnt mice through the effects on inflammatory reactions in the gastric mucosa. The cancer-preventing effects should be studied with long-term experiments until actual gastric cancer formation.

Insights on the Functional Role of Beta-Glucans in Fungal Immunity Using Receptor-Deficient Mouse Models.

Understanding the host anti-fungal immunity induced by beta-glucan has been one of the most challenging conundrums in the field of biomedical research. During the last couple of decades, insights on the role of beta-glucan in fungal disease progression, susceptibility, and resistance have been greatly augmented through the utility of various beta-glucan cognate receptor-deficient mouse models. Analysis of dectin-1 knockout mice has clarified the downstream signaling pathways and adaptive effector responses triggered by beta-glucan in anti-fungal immunity. On the other hand, assessment of CR3-deficient mice has elucidated the compelling action of beta-glucans in neutrophil-mediated fungal clearance, and the investigation of EphA2-deficient mice has highlighted its novel involvement in host sensing and defense to oral mucosal fungal infection. Based on these accounts, this review focuses on the recent discoveries made by these gene-targeted mice in beta-glucan research with particular emphasis on the multifaceted aspects of fungal immunity.

Attenuation of carrageenan-induced hind paw edema and plasma TNF-α level by Philippine stingless bee (Tetragonula biroi Friese) propolis.

Despite decades-long existence of the Philippine stingless bee industry, the biological activity of propolis from this native bee species (Tetragonula biroi Friese) remains poorly understood and sparingly investigated. Herein, we examined the potential anti-inflammatory efficacy of Philippine stingless bee propolis using the lambda (λ)-carrageenan-induced mice model of hind paw edema. Thirty (30), six-week-old, male ICR mice were randomly assigned into three treatment groups (n=10/group) as follows: distilled water group, diclofenac sodium group (10 mg/kg), and propolis group (100 mg/kg). All treatment were administered an hour prior to the injection of the phlogistic agent. As observed at 3 h post-injection, λ-carrageenan remarkably evoked the classical signs of hind paw edema exemplified grossly by swelling and hyperemia. The ameliorative effect of propolis became apparent at the onset of 6 h post-injection with a statistically significant finding evident at the 24-h period. This gross attenuation histologically correlated to a considerable and specific reduction of the dermal edema, which mirrored those of the diclofenac sodium group. Furthermore, both propolis and diclofenac sodium significantly attenuated the λ-carrageenan-induced increase in the protein expression levels of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) depicting more than two-fold decrement relative to the distilled water group. Altogether, these suggest that Philippine stingless bee propolis also exhibited a promising in vivo anti-inflammatory property, which can be partly mediated through the inhibition of TNF-α.

Discovery of PEGylated 6-Benzhydryl-4-amino-quinazolines as Peripherally Restricted CB1R Inverse Agonists.

The 6-benzhydryl-4-amino-quinolin-2-ones are peripherally restricted CB1 receptor inverse agonists (CB1RIAs) that have been reported to attenuate obesity and improve insulin sensitivity in the diet-induced obese (DIO) mouse model. However, chronic dosing of select compounds from the series showed time-dependent brain accumulation despite a low brain/plasma exposure ratio. To address this issue, a PEGylation approach was employed to identify a novel series of homodimeric 6-benzhydryl-4-amino-quinazoline-PEG conjugates with an extended half-life. The lead compound 18 engaged peripheral CB1Rs in a gastrointestinal (GI) tract motility study and demonstrated a high level of peripheral restriction in a chronic DIO mouse pharmacokinetic study.

Toothpick in the porta: Recurrent liver abscesses secondary to transgastric migration of a toothpick with successful surgical exploration retrieval.

We present a rare case of a 72-year-old man with recurrent hepatic abscesses secondary to transgastric migration of a toothpick into the liver parenchyma and left portal venous branch. Prior to identification of the foreign body, the patient received multiple courses of antibiotics and underwent image-guided catheter placement without resolution of infection. Given his refractory abdominal pain, fevers, and chills, a repeat abdominal CT was obtained and demonstrated a radio-opaque object extending through the prepyloric gastric submucosa into the liver parenchyma and left portal vein. EGD confirmed a pre-pyloric fistula tract with purulent discharge. The patient subsequently underwent exploratory laparotomy, cholecystectomy, porta hepatis exploration, removal of foreign body, and ligation of porto-enteric fistula tract. A wooden toothpick was removed in its entirety. Interval CT demonstrated resolution of hepatic abscesses and no evidence of persistent porto-enteric fistula. This exceptional case demonstrates the value of multidisciplinary care, hypervigilance for patients with refractory pyogenic liver abscesses of unknown origin, and the importance of careful preoperative planning.

Build Your Own Eye: A Method for Teaching Ocular Anatomy and Pathophysiology.

Audience: Residents and medical students. Introduction: The eye is a critical, but often neglected, part of medical learning. This team-based learning (TBL) module was developed for emergency medicine residents and medical students; however, is applicable to any learner who should know basic eye anatomy and pathology. Emergency medicine teams, primary care providers, and ophthalmologists are most likely to encounter ocular emergencies.1-3 These emergencies are uncommon but quite dire when they occur and can result in permanent disability and life-changing morbidity.2, 4 It is critical that medical practitioners who are exposed to these types of emergencies are well prepared to evaluate and treat them.To fully understand how pathology affects the eye, it is critical that learners understand the anatomy and physiology of the eye.5, 6 Many diagnoses are associated with specific parts of ocular anatomy;5, 6 therefore, teaching pathology in an anatomy-based lesson will help learners understand the physiology. This lesson teaches learners about physiology and pathology in a systemic, anatomically oriented way. Educational Objectives: By the end of this session the participant will be able to:Describe basic anatomy of the eye.Build a basic model of the eye.Identify which diseases are associated with which parts of the eye.Identify the pathophysiology behind diseases of the eye.Name correct treatment for each disease. Educational Methods: The "build your own eye" lesson was taught as a classic team-based learning (cTBL) exercise. The modality of TBL with hands-on construction of an eye allow for social learning, competition and spatial learning related to anatomy. The creation of an eye allows residents to fully understand ocular anatomy which is not as evident when a two-dimensional paper image is used. Some learners need tactical stimuli for better understanding. This aspect of the exercise was focused on using alternative modalities to enhance spatial learning. These concepts are reinforced by the GRAT and IRAT portions of the exercise which tend to multiple choice learners. The fill-in the-blank aspect of the exercise requires recall and research to match the three-dimensional eye parts with pathology. Research Methods: Learners were given the opportunity to complete an anonymous survey. Verbal feedback was also obtained from learners during the lesson. The survey asked learners questions about the effectiveness and value of the exercise, whether the content was applicable to work in the emergency department, whether this exercise should be kept as a part of the curriculum, and whether there was any practice-changing information. Learners enjoyed the competitive aspects of the exercise and also noted that they felt much more comfortable with ocular anatomy and pathology after the lesson. Results: Learners felt that the ocular team-based learning module was effective in teaching more about the eye in an atypical way. Some learners felt that an explanation in advance of the eye building aspects of the project may have been helpful so they could have brought supplies from home. Other learners felt that they would not have brought supplies from home; thus no explanation was necessary. Discussion: Learners seemed to enjoy the experience. The competitive aspects of the TBL, where the eye models were judged for accuracy, creativity, and appearance as well as the correct answers on the worksheet, seemed to enhance learner enjoyment and engagement. Learners felt that enough time was provided for the exercise. While some learners would have preferred an explanation in advance of the project in order to bring supplies from home, others felt that this was not necessary. Educators should determine what would be preferred by their particular learning group for future implementations. Topics: Eye lid, tear duct, cornea, conjunctiva, pupil, iris, lens, anterior chamber, vitreous body, posterior chamber, retina, macula, choroid, optic disc, optic nerve, retinal artery, retinal vein, blepharitis, hordeolum, chalazion, canaliculus, dacryocystitis, corneal abrasion, corneal ulcer, ultraviolet keratitis, herpes keratitis, astigmatism, bacterial conjunctivitis, viral conjunctivitis, episcleritis, globe rupture, iritis, uveitis, anterior uveitis, posterior uveitis, hypopyon, hyphema, acute angle closure glaucoma, congenital pupillary deformity, coloboma, globe rupture, nevus, essential iris atrophy, cataracts, presbyopia, myopia, hyperopia, traumatic iritis, iridocyclitis, ciliary body melanoma, vitreous degeneration, vitreous hemorrhage, endophthalmitis, macular degeneration, retinal detachment, choroid nevus, choroid detachment, papilledema, optic nerve glioma, optic nerve meningioma, anterior ischemic optic neuropathy, retinal artery occlusion, retinal vein occlusion.

Tumor-suppressing potential of stingless bee propolis in in vitro and in vivo models of differentiated-type gastric adenocarcinoma.

The protective property of propolis across a wide spectrum of diseases has long been realized, yet the anti-tumor efficacy of this bioactive substance from Philippine stingless bees has remained poorly understood. Here, we showed the tumor-suppressing potential of crude ethanolic extract of Philippine stingless bee propolis (EEP) in in vitro models of gastric cancer highlighting the first indication of remarkable subtype specificity towards differentiated-type human gastric cancer cell lines but not the diffuse-type. Mechanistically, this involved the profound modulation of several cell cycle related gene transcripts, which correlated with the prominent cell cycle arrest at the G0/G1 phase. To reinforce our data, a unique differentiated-type gastric cancer model, A4gnt KO mice, together with age-matched 60 week-old C57BL/6 J mice were randomly assigned to treatment groups receiving distilled water or EEP for 30 consecutive days. EEP treatment induced significant regression of gross and histological lesions of gastric pyloric tumors that consistently corresponded with specific transcriptional regulation of cell cycle components. Also, the considerable p21 protein expression coupled with a marked reduction in rapidly dividing BrdU-labeled S-phase cells unequivocally supported our observation. Altogether, these findings support the role of Philippine stingless bee propolis as a promising adjunct treatment option in differentiated-type gastric cancer.