Accumulation of alkyl-lysophosphatidylcholines in Niemann-Pick disease type C1.

Lysosomal function is impaired in Niemann-Pick disease type C1 (NPC1), a rare and inherited neurodegenerative disorder, resulting in late endosomal/lysosomal accumulation of unesterified cholesterol. The precise pathogenic mechanism of NPC1 remains incompletely understood. In this study, we employed metabolomics to uncover secondary accumulated substances in NPC1. Our findings unveiled a substantial elevation in the levels of three alkyl-lysophosphatidylcholine [alkyl-LPC, also known as lyso-platelet activating factor (PAF)] species in NPC1 compared to controls across various tissues, including brain tissue from individuals with NPC1, liver, spleen, cerebrum, cerebellum, and brain stem from NPC1 mice, as well as in both brain and liver tissue from NPC1 cats. The three elevated alkyl-LPC species were as follows: LPC O-16:0, LPC O-18:1, and LPC O-18:0. However, the levels of PAF 16:0, PAF 18:1, and PAF 18:0 were not altered in NPC1. In the NPC1 feline model, the brain and liver alkyl-LPC levels were reduced following 2-hydroxypropyl-ß-cyclodextrin (HPßCD) treatment, suggesting that alkyl-LPCs are secondary storage metabolites in NPC1 disease. Unexpectedly, cerebrospinal fluid (CSF) levels of LPC O-16:0 and LPC O-18:1 were decreased in individuals with NPC1 compared to age-appropriate comparison samples, and their levels were increased in 80% of participants 2 years after intrathecal HPßCD treatment. The fold increases in CSF LPC O-16:0 and LPC O-18:1 levels were more pronounced in responders compared to nonresponders. This study identified alkyl-LPC species as secondary storage metabolites in NPC1 and indicates that LPC O-16:0 and LPC O-18:1, in particular, could serve as potential biomarkers for tracking treatment response in NPC1 patients.

"Eavesdropping": An Information Source for Inpatients.

Healthcare providers in the hospital setting must discuss patient information to ensure continuity of care and patient safety. This study explores how patients perceive the information they hear discussed between healthcare providers and how the concept of "eavesdropping" can be addressed by healthcare providers and in the field of medical informatics. Using an inductive analysis of interviews with 14 adult inpatients, research findings indicate that patients value receiving information in the hospital setting, including information received through eavesdropping. Patient eavesdropping opportunities include "eavesdropping by design" events, such as during bedside shift changes and handoffs, as well as unintended "unintended eavesdropping" events, such as listening to healthcare provider conversations outside of the patient's room. Healthcare providers and medical informaticists have opportunities to address eavesdropping in the inpatient setting. Informatics systems that address "eavesdropping by design" and "unintended eavesdropping opportunities" can improve patient-provider communication and satisfy patient preferences for receiving medical information.

Controlling pathogenesis in Candida albicans by targeting Efg1 and Glyoxylate pathway through naturally occurring polyphenols.

Candida albicans has frequently shown resistance to azoles, the commonly used antifungal drugs. Efg1 has dual role under normoxia and hypoxia supporting infection. It is the major regulator of morphogenesis in C. albicans requisite for its pathogenesis. Targeting this protein is expected to render Candida ineffective to undergo filamentation causing virulence. Further the glyoxylate pathway supports the stress resistance and pathogenesis. In the present study an in silico approach and in vitro validation has been performed to find the potential role of polyphenols in controlling hyphal growth in C. albicans. The aspect of changes biome which may provide required niche to the pathogen has been checked which certainly opens the doors towards safe natural polyphenol-based drugs as potent antifungals.

In-silico designing, chemical synthesis, characterization and in-vitro assessment of antibacterial properties of some analogues of curcumin.

In the present work two key regulator proteins, monomeric MipZ of Caulobacter vibrioides (similar to Pseudomonas aeruginosa) and Pyruvate kinase of Staphylococcus aureus were docked with curcumin, the wonder molecule from the spice turmeric and structures of its twelve analogues were designed, synthesized and tested in-vitro for antibacterial activity. Based on the test results a comparative account of the probable mechanism has been given Two major alternative targets are possible for antibacterial activity of drug molecules. These may be bacterial cell wall lipids or the proteins responsible for smooth functioning of bacterial cells. In the former case, due to significant difference in the structural components of the cell walls of Gram positive and Gram negative bacteria, it is improbable that same ligand will affect both equally. Majority of commercial drugs are anti-Gram negative bacteria while in the present work we have found most effective drugs against Gram positive bacteria. Based on the test results a comparative account of the probable mechanism has been given. Evidently along with the cell wall damaging mechanism other parallel mechanisms are also operative.

Prevention of IcaA regulated poly N-acetyl glucosamine formation in Staphylococcus aureus biofilm through new-drug like inhibitors: In silico approach and MD simulation study.

OBJECTIVES: The effectiveness of various ligands against the protein structure of IcaA of the IcaABCD gene locus of Staphylococcus aureus were examined using the approach of structure based drug designing in reference with the protein's efficiency to form biofilms. RESULTS: Four compounds CID42738592, CID90468752, CID24277882, and CID6435208 were secluded from a database of 31,242 inhibitory ligands on the justification of the evaluated values falling under the four - tier structure based virtual screening. Under this principle value of least binding energy, human oral absorption and ADME properties were taken into consideration. Using the Glide module of Schrödinger, the above mentioned ligands showed an effective action against the protein IcaA which showed reduced activity as a glucosaminyl transferase. The complex of protein and ligand with best docking score was chosen for simulation studies. CONCLUSIONS: Structure based drug designing for the protein IcaA has given us potential leads as anti - biofilm agents. These screened out ligands might enable the development of new therapeutic strategies aimed at disrupting Staphylococcus aureus biofilms. The complex was showing stability towards the end of time for which it has been put for simulation. Thus molecule could be considered for making of biofilms.

Restraining Pathogenicity in Candida albicans by Taxifolin as an Inhibitor of Ras1-pka Pathway.

Candida albicans is one of the most virulent and opportunistic fungal strains. In the present scenario, majority metabolic imbalances and unsuccessful treatments of some severe diseases including cancer, diabetes, HIV, psoriasis are because of invasive Candida emergence. Being a beneficial integral part of human biome, its elimination is not possible. The major pathogenicity characteristics in Candida involve hyphal growth, biofilm formation, HSP90 down regulation and genetic modifications. Ras1-pka pathway initiated by HSP90 down regulation is important for hyphal growth and has been focused in the present study. The principle transcriptional factors that induce hyphal growth causing invasiveness and virulence through this pathway have been identified as Tec1 and Rfg1. In the present study, taxifolin, a naturally occurring polyphenol, has been identified as inhibitor for both the transcriptional factors in parallel.

Resin related enterocolitis: An underreported co-occurrence.

ABSTRACT: Medication resins are often encountered in gastrointestinal biopsy specimens of patients being treated for renal compromise. As important as they are for the electrolyte equilibrium of the patients, they often come with a cost of fatal but reversible damage to the gastrointestinal tract. This often manifests as inflammatory bowel disease in the affected individuals. This misleading manifestation coupled with the lack of patient history further masks resin-related colitis from a pathologist's eyes. Through this report, we convey how meticulous history-taking, representative endoscopic sampling, and recognition under the microscope are vital for timely reporting in conditions like this.

Trends in antimicrobial susceptibility pattern of Salmonella species isolated from bacteremia patients at a tertiary care center in Northern India.

The study was done to assess the antimicrobial susceptibility pattern among Salmonella enterica serovars causing bacteremia in Northern India. In this observational study, blood samples positive for Salmonella enterica serovars from January 2021 to April 2023 were studied. Species identification was done using MALDI-ToF MS. Serotyping was done using slide agglutination method. Antimicrobial susceptibility was interpreted as per the CLSI guidelines. During the study period, 32 Salmonella enterica serovars were isolated. Salmonella enterica serovar Typhi was the predominant serovar, followed by Salmonella enterica serovar Paratyphi A. All isolates were susceptible to ceftriaxone, chloramphenicol, co-trimoxazole and cefotaxime. Pefloxacin showed 100% resistance. Resistance to nalidixic acid was found in 81.2% isolates. Of the isolates resistant to nalidixic acid, 19(73.08%) isolates were resistant to ciprofloxacin also. This changing susceptibility pattern necessitates continuous surveillance of antibiogram of Salmonella isolates to rationalize the treatment protocols for invasive salmonellosis and prevent emergence of resistant strains.

Engagement in mHealth-Prompted Self-Measured Blood Pressure Monitoring Among Participants Recruited From a Safety-Net Emergency Department: Secondary Analysis of the Reach Out Trial.

Background: Hypertension, a key modifiable risk factor for cardiovascular disease, is more prevalent among Black and low-income individuals. To address this health disparity, leveraging safety-net emergency departments for scalable mobile health (mHealth) interventions, specifically using text messaging for self-measured blood pressure (SMBP) monitoring, presents a promising strategy. This study investigates patterns of engagement, associated factors, and the impact of engagement on lowering blood pressure (BP) in an underserved population. Objective: We aimed to identify patterns of engagement with prompted SMBP monitoring with feedback, factors associated with engagement, and the association of engagement with lowered BP. Methods: This is a secondary analysis of data from Reach Out, an mHealth, factorial trial among 488 hypertensive patients recruited from a safety-net emergency department in Flint, Michigan. Reach Out participants were randomized to weekly or daily text message prompts to measure their BP and text in their responses. Engagement was defined as a BP response to the prompt. The k-means clustering algorithm and visualization were used to determine the pattern of SMBP engagement by SMBP prompt frequency-weekly or daily. BP was remotely measured at 12 months. For each prompt frequency group, logistic regression models were used to assess the univariate association of demographics, access to care, and comorbidities with high engagement. We then used linear mixed-effects models to explore the association between engagement and systolic BP at 12 months, estimated using average marginal effects. Results: For both SMBP prompt groups, the optimal number of engagement clusters was 2, which we defined as high and low engagement. Of the 241 weekly participants, 189 (78.4%) were low (response rate: mean 20%, SD 23.4) engagers, and 52 (21.6%) were high (response rate: mean 86%, SD 14.7) engagers. Of the 247 daily participants, 221 (89.5%) were low engagers (response rate: mean 9%, SD 12.2), and 26 (10.5%) were high (response rate: mean 67%, SD 8.7) engagers. Among weekly participants, those who were older (>65 years of age), attended some college (vs no college), married or lived with someone, had Medicare (vs Medicaid), were under the care of a primary care doctor, and took antihypertensive medication in the last 6 months had higher odds of high engagement. Participants who lacked transportation to appointments had lower odds of high engagement. In both prompt frequency groups, participants who were high engagers had a greater decline in BP compared to low engagers. Conclusions: Participants randomized to weekly SMBP monitoring prompts responded more frequently overall and were more likely to be classed as high engagers compared to participants who received daily prompts. High engagement was associated with a larger decrease in BP. New strategies to encourage engagement are needed for participants with lower access to care.

Acceptability of a Text Message-Based Mobile Health Intervention to Promote Physical Activity in Cardiac Rehabilitation Enrollees: A Qualitative Substudy of Participant Perspectives.

BACKGROUND: Mobile health (mHealth) interventions have the potential to deliver longitudinal support to users outside of episodic clinical encounters. We performed a qualitative substudy to assess the acceptability of a text message-based mHealth intervention designed to increase and sustain physical activity in cardiac rehabilitation enrollees. METHODS AND RESULTS: Semistructured interviews were conducted with intervention arm participants of a randomized controlled trial delivered to low- and moderate-risk cardiac rehabilitation enrollees. Interviews explored participants' interaction with the mobile application, reflections on tailored text messages, integration with cardiac rehabilitation, and opportunities for improvement. Transcripts were thematically analyzed using an iteratively developed codebook. Sample size consisted of 17 participants with mean age of 65.7 (SD 8.2) years; 29% were women, 29% had low functional capacity, and 12% were non-White. Four themes emerged from interviews: engagement, health impact, personalization, and future directions. Participants engaged meaningfully with the mHealth intervention, finding it beneficial in promoting increased physical activity. However, participants desired greater personalization to their individual health goals, fitness levels, and real-time environment. Generally, those with lower functional capacity and less experience with exercise were more likely to view the intervention positively. Finally, participants identified future directions for the intervention including better incorporation of exercise physiologists and social support systems. CONCLUSIONS: Cardiac rehabilitation enrollees viewed a text message-based mHealth intervention favorably, suggesting the potentially high usefulness of mHealth technologies in this population. Addressing participant-identified needs on increased user customization and inclusion of clinical and social support is crucial to enhancing the effectiveness of future mHealth interventions. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04587882.

A Text Messaging Intervention for Priming the Affective Rewards of Exercise in Adults: Protocol for a Microrandomized Trial.

BACKGROUND: Physical activity is a critical target for health interventions, but effective interventions remain elusive. A growing body of work suggests that interventions targeting affective attitudes toward physical activity may be more effective for sustaining activity long term than those that rely on cognitive constructs alone, such as goal setting and self-monitoring. Anticipated affective response in particular is a promising target for intervention. OBJECTIVE: We will evaluate the efficacy of an SMS text messaging intervention that manipulates anticipated affective response to exercise to promote physical activity. We hypothesize that reminding users of a positive postexercise affective state before their planned exercise sessions will increase their calories burned during this exercise session. We will deploy 2 forms of affective SMS text messages to explore the design space: low-reflection messages written by participants for themselves and high-reflection prompts that require users to reflect and respond. We will also explore the effect of the intervention on affective attitudes toward exercise. METHODS: A total of 120 individuals will be enrolled in a 9-week microrandomized trial testing affective messages that remind users about feeling good after exercise (40% probability), control reminders (30% probability), or no message (30% probability). Two types of affective SMS text messages will be deployed: one requiring a response and the other in a read-only format. Participants will write the read-only messages themselves to ensure that the messages accurately reflect the participants' anticipated postexercise affective state. Affective attitudes toward exercise and intrinsic motivation for exercise will be measured at the beginning and end of the study. The weighted and centered least squares method will be used to analyze the effect of delivering the intervention versus not on calories burned over 4 hours around the time of the planned activity, measured by the Apple Watch. Secondary analyses will include the effect of the intervention on step count and active minutes, as well as an investigation of the effects of the intervention on affective attitudes toward exercise and intrinsic motivation for exercise. Participants will be interviewed to gain qualitative insights into intervention impact and acceptability. RESULTS: Enrollment began in May 2023, with 57 participants enrolled at the end of July 2023. We anticipate enrolling 120 participants. CONCLUSIONS: This study will provide early evidence about the effect of a repeated manipulation of anticipated affective response to exercise. The use of 2 different types of messages will yield insight into optimal design strategies for improving affective attitudes toward exercise. TRIAL REGISTRATION: ClinicalTrials.gov NCT05582369; https://classic.clinicaltrials.gov/ct2/show/NCT05582369. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/46560.

Improving the Usability of Written Exposure Therapy for Therapists in the Department of Veterans Affairs Telemental Health: Formative Study Using Qualitative and User-Centered Design Methods.

BACKGROUND: User modifications are common in evidence-based psychosocial interventions (EBPIs) for mental health disorders. Often, EBPIs fit poorly into clinical workflows, require extensive resources, or pose considerable burden to patients and therapists. Implementation science is increasingly researching ways to improve the usability of EBPIs before implementation. A user-centered design can be used to support implementation methods to prioritize user needs and solutions to improve EBPI usability. OBJECTIVE: Trauma-focused EBPIs are a first-line treatment for patients with posttraumatic stress disorder (PTSD) in the Department of Veterans Affairs. Written exposure therapy (WET) is a brief, trauma-focused EBPI wherein patients handwrite about trauma associated with their PTSD. Initially developed for in-person delivery, WET is increasingly being delivered remotely, and outcomes appear to be equivalent to in-person delivery. However, there are logistical issues in delivering WET via video. In this evaluation, we explored usability issues related to WET telehealth delivery via videoconferencing software and designed a solution for therapist-facing challenges to systematize WET telehealth delivery. METHODS: The Discover, Design and Build, and Test framework guided this formative evaluation and served to inform a larger Virtual Care Quality Enhancement Research Initiative. We used qualitative descriptive methods in the Discover phase to understand the experiences and needs of 2 groups of users providing care within the Department of Veterans Affairs: in-person therapists delivering WET via video because of the COVID-19 pandemic and telehealth therapists who regularly deliver PTSD therapies. We then used user-centered design methods in the Design and Build phase to brainstorm, develop, and iteratively refine potential workflows to address identified usability issues. All procedures were conducted remotely. RESULTS: In the Discover phase, both groups had challenges delivering WET and other PTSD therapies via telehealth because of technology issues with videoconferencing software, environmental distractions, and workflow disruptions. Narrative transfer (ie, patients sending handwritten trauma accounts to therapists) was the first target for design solution development as it was deemed most critical to WET delivery. In the Design and Build phase, we identified design constraints and brainstormed solution ideas. This led to the development of 3 solution workflows that were presented to a subgroup of therapist users through cognitive walkthroughs. Meetings with this subgroup allowed workflow refinement to improve narrative transfers. Finally, to facilitate using these workflows, we developed PDF manuals that are being refined in subsequent phases of the implementation project (not mentioned in this paper). CONCLUSIONS: The Discover, Design and Build, and Test framework can be a useful tool for understanding user needs in complex EBPI interventions and designing solutions to user-identified usability issues. Building on this work, an iterative evaluation of the 3 solution workflows and accompanying manuals with therapists and patients is underway as part of a nationwide WET implementation in telehealth settings.

Quebrachitol from Putranjiva roxburghii Wall. (Putranjivaceae) a potent antimalarial: Pre-clinical efficacy and its interaction with PfLDH.

Researchers are exploring natural resources in search of a new and effective anti-malarial compound to address the challenges in malarial treatment due to emerging incidences of drug-resistant strains. Following background knowledge of traditional medicine, we evaluated the in-vitro and in-vivo anti-malarial efficacy of Putranjiva P. roxburghii (Putranjivaceae) twigs ethanol extracts and fraction (PRT). In-vitro parasite-specific lactate dehydrogenase (pLDH) assay was performed using a chloroquine-sensitive Plasmodium falciparum strain. The results of the in-vitro study were further validated by in-vivo anti-malarial studies on P. berghei Keyberg 173 (K173) infected mice. The crude ethanol extract of the PRT showed the most moderate antiparasitic activity (IC50 = 15.51 µg/mL). In contrast, its butanol fraction extract showed potent activity (IC50 = 5.14 µg/mL) with a selectivity index (SI) of 28.87. Two phytochemicals, viz. 2, 4 dihydroxy-5-(hydroxymethyl) benzoic acid (DHMBA), and quebrachitol (QBC), were identified with anti-parasitic activity (IC50 = 5.01 µg/mL and 0.87 µg/mL) and selectivity index (SI) of 45 and 158. The in-vivo studies confirmed the significant anti-malarial activity of QBC at the dose of 30 and 60 mg/kg body weight with chemo-suppression values of 73.26% and 61.88%, respectively. The present study demonstrates the bioactive marker-based standardization of P. roxburghii twig, the antiplasmodial potential of PRT, and the role of QBC in suppressing parasitemia. The findings of the study support QBC as a prospective lead for a natural product-based adjunct remedy to conventional antiparasitic agents for malarial infectious.

A pentasaccharide for monitoring pharmacodynamic response to gene therapy in GM1 gangliosidosis.

BACKGROUND: GM1 gangliosidosis is a rare, fatal, neurodegenerative disease caused by mutations in the GLB1 gene and deficiency in ß-galactosidase. Delay of symptom onset and increase in lifespan in a GM1 gangliosidosis cat model after adeno-associated viral (AAV) gene therapy treatment provide the basis for AAV gene therapy trials. The availability of validated biomarkers would greatly improve assessment of therapeutic efficacy. METHODS: The liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to screen oligosaccharides as potential biomarkers for GM1 gangliosidosis. The structures of pentasaccharide biomarkers were determined with mass spectrometry, as well as chemical and enzymatic degradations. Comparison of LC-MS/MS data of endogenous and synthetic compounds confirmed the identification. The study samples were analyzed with fully validated LC-MS/MS methods. FINDINGS: We identified two pentasaccharide biomarkers, H3N2a and H3N2b, that were elevated more than 18-fold in patient plasma, cerebrospinal fluid (CSF), and urine. Only H3N2b was detectable in the cat model, and it was negatively correlated with ß-galactosidase activity. Following intravenous (IV) AAV9 gene therapy treatment, reduction of H3N2b was observed in central nervous system, urine, plasma, and CSF samples from the cat model and in urine, plasma, and CSF samples from a patient. Reduction of H3N2b accurately reflected normalization of neuropathology in the cat model and improvement of clinical outcomes in the patient. INTERPRETATIONS: These results demonstrate that H3N2b is a useful pharmacodynamic biomarker to evaluate the efficacy of gene therapy for GM1 gangliosidosis. H3N2b will facilitate the translation of gene therapy from animal models to patients. FUNDING: This work was supported by grants U01NS114156, R01HD060576, ZIAHG200409, and P30 DK020579 from the National Institutes of Health (NIH) and a grant from National Tay-Sachs and Allied Diseases Association Inc.

Primary Malignant Melanoma of the Oral Cavity: A Retrospective Study From a Tertiary Care Centre of North India.

BACKGROUND: Mucosal melanoma is a rare but aggressive tumor associated with a poor prognosis arising from pigmented cells called melanocytes. They are usually asymptomatic and present in an advanced stage. It has an aggressive clinical outcome and is proven to be of poor prognosis. MATERIALS AND METHODS: This is a retrospective review of the computer database and clinical records at the All India Institute of Medical Sciences, Rishikesh, India. The data between 2018-2022 were reviewed for all small biopsy or excision specimen-proven cases of oral mucosal melanoma. RESULTS: The most common site of involvement in the head and neck region is the nasal cavity and paranasal sinuses. In this retrospective study from our institute, all three cases presented involved oral cavities. The median age of presentation was 51 years. Some literature specifies male preponderance. Our patients presented clinically with a black nodule in the oral cavity, which was increasing in size and associated with bleeding. A biopsy performed confirmed the diagnosis of melanoma based on the morphology and immunohistochemical profile of the tumor cells. CONCLUSION: Surgical resection is the mainstay treatment, followed by radiation postoperatively to reduce local and regional recurrence. Mucosal melanoma has a poor prognosis, and the majority of patients develop incurable metastatic disease.

Novel bioactive compound from the bark of Putranjiva roxburghii Wall.

Putranjivah (Putranjiva roxburghii Wall, family - Putranjivaceae) is an Indian native medicinal plant used to treat many diseases such as treatment of mouth and stomach ulcers, hot swellings, smallpox, burning sensation and ophthalmopathy. The study of chemical constituents in the bark of P. roxburghii resulted in a new triterpene (6) along with five known triterpenoids (1-5). The chemical characterisation was based on 1H, 13C, 2D-NMR experimentation, and ESI-MS data. The anti-plasmodial activity was investigated by measuring parasite-specific lactate dehydrogenase (pLDH) based in vitro assay. The IC50 value results showed that friedlein (2.40 ± 0.70) and roxburghonol (4.10 ± 1.7 µg/ml) possess better anti-plasmodial activity than other isolated triterpenes (2-5) but not as potent as chloroquine (0.023 ± 0.002 µg/ml) against chloroquine-sensitive Plasmodium falciparum (3D7) strain.

Standardization of Kaempferia galanga L. rhizome and vasorelaxation effect of its key metabolite ethyl p-methoxycinnamate.

ETHNOPHARMACOLOGICAL RELEVANCE: Kaempferia galanga L. rhizome (KGR) is part of more than sixty-one Ayurvedic formulations and commonly known as 'Chandramula'. KGR is widely used in traditional Indian medicines to treat fever (jwar), rheumatism (Amavata), respiratory (Shwasa), hypertension (Vyanabala vaishamya) and cardiovascular disorders (Vyanavayu Dushtijanya Hrudrog). Although ethnomedicinal properties have extensively been demonstrated in traditional medicines of south-east countries i.e. China, India, Indonesia, and Malaysia, the chemico-biological validation are still lacking. AIM OF THE STUDY: Chemico-biological standardization with respect to its vasorelaxation potential is the main objective of the present study. To investigate the vasorelaxation potential of key phytochemical of KGR, i.e., ethyl-p-methoxycinnamate (EPMC) and to study it's the mechanism of action. MATERIALS AND METHODS: A HPLC method was developed and validated for the quality assessment of KGR using its two major phytochemicals i.e. ethyl-p-methoxycinnamate (EPMC) and ethyl cinnamate (EC) in KGR. The vasorelaxation effect of major phytochemicals of KGR was evaluated on the main mesenteric arteries isolated from male Wistar rats. Specific BKca channel blocker tetraethylammonium (TEA), receptor antagonist, nitric oxide scavenging capacity, and antioxidant potential were also evaluated for its plausible mechanism. RESULTS: Present validated HPLC method facilitates simultaneous quantitation of EPMC and EC faster than classical GC techniques. EPMC has shown a dose-dependent relaxation in rat main mesenteric arteries (MMA) contracted by U46619 with an Emax of 58.68 ± 3.31%. Similarly, in endothelium-denuded MMA rings, relaxation was also observed (Emax of 61.83 ± 3.38%). Moreover, relaxation response to EPMC has strongly inhibited (Emax 14.76 ± 2.29%) when the tissue exposed to depolarizing high K+ containing buffer for the contraction. The point correlation dimension (pD2) values were also significantly decreased in high K+ treated arterial rings compared to control. Interestingly, when MMA rings incubated with a specific BKca channel blocker (TEA, 1 mM), the relaxation response to EPMC was also significantly blocked. CONCLUSIONS: The first time this study demonstrated the chemical standardization of K. galanga rhizome and EPMC is responsible for its vasorelaxation potential as demonstrated by the endothelium-independent response mediated by Ca2+ dependent potassium channels.

Different roles with different goals: Designing to support shared situational awareness between patients and clinicians in the hospital.

OBJECTIVE: Team situational awareness helps to ensure high-quality care and prevent errors in the complex hospital environment. Although extensive work has examined factors that contribute to breakdowns in situational awareness among clinicians, patients' and caregivers' roles have been neglected. To address this gap, we studied team-based situational awareness from the perspective of patients and their caregivers. MATERIALS AND METHODS: We utilized a mixed-methods approach, including card sorting and semi-structured interviews with hospitalized patients and their caregivers at a pediatric hospital and an adult hospital. We analyzed the results utilizing the situational awareness (SA) theoretical framework, which identifies 3 distinct stages: (1) perception of a signal, (2) comprehension of what the signal means, and (3) projection of what will happen as a result of the signal. RESULTS: A total of 28 patients and 19 caregivers across the 2 sites participated in the study. Our analysis uncovered how team SA helps patients and caregivers ensure that their values are heard, their autonomy is supported, and their clinical outcomes are the best possible. In addition, our participants described both barriers-such as challenges with communication-and enablers to facilitating shared SA in the hospital. DISCUSSION: Patients and caregivers possess critical knowledge, expertise, and values required to ensure successful and accurate team SA. Therefore, hospitals need to incorporate tools that facilitate patients and caregivers as key team members for effective SA. CONCLUSIONS: Elevating patients and caregivers from passive recipients to equal contributors and members of the healthcare team will improve SA and ensure the best possible outcomes.

Informatics opportunities to involve patients in hospital safety: a conceptual model.

OBJECTIVE: Inpatients could play an important role in identifying, preventing, and reporting problems in the quality and safety of their care. To support them effectively in that role, informatics solutions must align with their experiences. Thus, we set out to understand how inpatients experience undesirable events (UEs) and to surface opportunities for those informatics solutions. MATERIALS AND METHODS: We conducted a survey with 242 patients and caregivers during their hospital stay, asking open-ended questions about their experiences with UEs. Based on our qualitative analysis, we developed a conceptual model representing their experiences and identified informatics opportunities to support patients. RESULTS: Our 4-stage conceptual model illustrates inpatient experiences, from when they first encounter UEs, when they could intervene, when harms emerge, what types of harms they experience, and what they do in response to harms. DISCUSSION: Existing informatics solutions address the first stage of inpatients' experiences by increasing their awareness of potential UEs. However, future researchers can explore new opportunities to fill gaps in support that patients experience in subsequent stages, especially at critical decision points such as intervening in UEs and responding to harms that occur. CONCLUSIONS: Our conceptual model reveals the complex inpatient experiences with UEs, and opportunities for new informatics solutions to support them at all stages of their experience. Investigating these new opportunities could promote inpatients' participation and engagement in the quality and safety of their care, help healthcare systems learn from inpatients' experience, and reduce these harmful events.

Use and impact of an online community for hospital patients.

OBJECTIVE: Although patient-peer support technologies have demonstrated effectiveness in a variety of health contexts-including diabetes, weight loss, and cancer-less is known about how hospitalized patients can benefit from this support. We investigated the nature of peer support in the hospital and the impact this support had on patients' hospital stays. MATERIALS AND METHODS: We created a technology, resembling an online health community, in which patients could exchange advice about their hospitalization. We deployed it at 1 pediatric hospital and 1 adult hospital. With 30 participants, we conducted bedside interviews, observed how they used the technology during their hospitalization, and completed follow-up phone interviews. RESULTS: Participants shared advice about several topics, including adjusting to the hospital and building relationships with providers. Contrary to concerns that such a system would primarily serve as a place for patients to "complain," sentiment analysis showed that 23 of 36 (64%) of the shared advice reflected positive sentiment. Patients also reported positive impacts to their quality, safety, and hospital experience due to the inpatient peer support community. DISCUSSION: Participants benefited from peer support that transcended diagnoses and individual health conditions. The shared experience of being in the hospital was sufficient to yield valuable and practical peer support. Participants who did not contribute their own advice still experienced benefits from reading their peers' advice. CONCLUSIONS: Our study demonstrated the positive nature of peer advice exchanged, and the benefits of this advice on patients' hospital stays. Inpatient peer support technologies could be an additional resource for patients to engage in their care.