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.

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.

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.

"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.

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.

Microwave-assisted Single Step Cinnamic Acid Derivatization and Evaluation for Cytotoxic Potential.

BACKGROUND: Phenylpropylene biosynthesis pathway plays a crucial role in the vanillin and their derivative(s) production in the plants. The intermediate of vanillin synthesis i.e. cinnamic acid (CA) is converted into 2-Hydroxy 4-MethoxyBenzaldehyde (HMB) in Decalepis arayalpathra having a number of therapeutic value. OBJECTIVE: Microwave-assisted modifications in cinnamic acid were planned for potential anticancer properties with better yield and efficiency. The present study also confirms the presence of HMB and its precursor i.e. cinnamic acid in D. arayalpathra tubers. METHODS: We used a single step Microwave Assisted Synthesis (MAS) to modify cinnamic acid, and then examined the synthetic and natural cinnamic acid derivatives anticancer potential against six human cancer (K-562, WRL-68, A549, A431, MCF-7, and COLO-201) and two normal (L-132 and HEK-293) cell lines at 2, 10 and 50 µg/ml concentrations. RESULTS: ß-bromostyrene and ß -nitrostyrene have shown inhibition with IC50 values ranging 0.10-21 µM and 0.03-0.06 µM, respectively to the cancer cell lines. ß-bromostyrene was the most potent anticancer derivative of CA with better cellular safety and biocompatibility. CONCLUSION: The present study of microwave-assisted synthesis demonstrates a single-step modification in cinnamic acid. MAS is a fast, reliable, and robust method. The resultant compounds have shown in-vitro anticancer activity against human lung carcinoma and breast adenocarcinoma.

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.

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.

Amruthapala (Decalepis arayalpathra (J. Joseph and V. Chandras.) Venter): A Comprehensive Review on Diversity, Therapeutic Uses, and Valorization of Bioactive Constituents.

BACKGROUND: Decalepis arayalpathra (J. Joseph and V. Chandras.) Venter is used primarily for nutrition besides its therapeutic values. Traditional preparations/formulations from its tuber are used as a vitalizer and blood purifier drink. The folklore medicinal uses cover inflammation, cough, wound healing, antipyretic, and digestive system management. A comprehensive review of the current understanding of the plant is required due to emerging concerns over its safety and efficacy. OBJECTIVE: The systematic collection of the authentic information from different sources with the critical discussion is summarised in order to address various issues related to botanical identity, therapeutic medicine, nutritional usage, phytochemical, and pharmacological potentials of the D. arayalpathra. Current use of traditional systems of medicine can be used to expand future research opportunities. MATERIALS AND METHODS: Available scripted information was collected manually, from peered review research papers and international databases viz. Science Direct, Google Scholar, SciFinder, Scopus, etc. The unpublished resources which were not available in database were collected through the classical books of 'Ayurveda' and 'Siddha' published in regional languages. The information from books, Ph.D. and MSc dissertations, conference papers and government reports were also collected. We thoroughly screened the scripted information of classical books, titles, abstracts, reports, and full-texts of the journals to establish the reliability of the content. RESULTS: Tuber bearing vanilla like signature flavor is due to the presence of 2-hydroxy-4-methoxybenzaldehyde (HMB). Among five other species, Decalepis arayalpathra (DA) has come under the 'critically endangered' category, due to over-exploitation for traditional, therapeutic and cool drink use. The experimental studies proved that it possesses gastro-protective, anti-tumor, and antiinflammatory activities. Some efforts were also made to develop better therapeutics by logical modifications in 2-Hydroxy-4-methoxy-benzaldehyde, which is a major secondary metabolite of D. arayalpathra. 'Amruthapala' offers the enormous opportunity to develop herbal drink with health benefits like gastro-protective, anti-oxidant and anti-inflammatory actions. CONCLUSION: The plant has the potential to generate the investigational new lead (IND) based on its major secondary metabolite i.e. 2-Hydroxy-4-methoxy-benzaldehyde. The present mini-review summarizes the current knowledge on Decalepis arayalpathra, covering its phytochemical diversity, biological potentials, strategies for its conservation, and intellectual property rights (IPR) status. Chemical Compounds: 2-hydroxy-4-methoxybenzaldehyde (Pubchem CID: 69600), α-amyrin acetate (Pubchem CID: 293754), Magnificol (Pubchem CID: 44575983), ß-sitosterol (Pubchem CID: 222284), 3-hydroxy-p-anisaldehyde (Pubchem CID: 12127), Naringenin (Pubchem CID: 932), Kaempferol (Pubchem CID: 5280863), Aromadendrin (Pubchem CID: 122850), 3-methoxy-1,2-cyclopentanedione (Pubchem CID: 61209), p-anisaldehyde (Pubchem CID: 31244), Menthyl acetate (Pubchem CID: 27867), Benzaldehyde (Pubchem CID: 240), p-cymene (Pubchem CID: 7463), Salicylaldehyde (Pubchem CID: 6998), 10-epi-γ-eudesmol (Pubchem CID: 6430754), α -amyrin (Pubchem CID: 225688), 3-hydroxy-4-methoxy benzaldehyde (Pubchem CID: 12127).

The Value of Patient-Peer Support in Improving Hospital Safety.

Healthcare systems worldwide have dedicated several years, special attention, and action toward improving safety for their patients. Although many innovative technological solutions have helped providers reduce medical errors, hospitalized patients lack access to these solutions, and face difficulties in having a proactive role in their safety. In this paper, we examine how patient-peer support can be a valuable resource for patients in the context of hospital safety. Through semi-structured interviews with 30 patients and caregivers at a pediatric and an adult hospital, we identify the potential benefits of incorporating patient-peer support into patient-facing technologies. Facilitating such support can provide patients with new avenues for engaging in, and improving, the quality and safety of their hospital care.

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.

Exploring the Design of an Inpatient Peer Support Tool: Views of Adult Patients.

Despite wide recognition of the value, expertise, and support that patient-peers provide in a variety of health contexts, mechanisms to design and enable peer support in the inpatient setting have not been sufficiently explored. To better understand the opportunities for an inpatient peer support tool, we surveyed 100 adult patients and caregivers, and conducted follow-up, semi-structured interviews with 15 adult patients. In this paper, we describe five key peer support needs that our adult patient participants expressed: (1) adjusting to the hospital environment, (2) understanding and normalizing medical care, (3) communicating with providers, (4) reporting and preventing medical errors, and (5) empowering peers. In addition, we identify privacy concerns, situational impairments, and communication mode as barriers to, and preferences for, interacting with peers. Based on our findings, we discuss intelligent peer matching and aggregating peer data as design recommendations for future inpatient peer support tools.

Must We Bust the Trust?: Understanding How the Clinician-Patient Relationship Influences Patient Engagement in Safety.

Although patients desire safe care, they are reluctant to perform safety-related behaviors when they worry it could harm the relationships they have with clinicians. This influence of the clinician-patient relationship on patient engagement in safety is poorly understood, and most patient-facing safety interventions ignore its influence, focusing instead on helping patients access information about their care and report errors. We conducted semi-structured interviews with hospitalized patients to uncover their needs for patient-facing information systems that could help them prevent medical errors. We found that the clinician-patient relationship could either encourage or discourage patients and caregivers from engaging in patient safety actions. We describe our findings and discuss the implications for the design of patient-facing interventions to promote patient engagement in safety. Our findings shed light on how patient-facing safety interventions can be designed to effectively engage patients and caregivers.

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.

"Scared to go to the Hospital": Inpatient Experiences with Undesirable Events.

Involving patients in healthcare safety practices has long been an area of priority and importance. However, we still need to understand how patients perceive undesirable events during their hospital stay, and what role patients play in the prevention of these events. To address this gap, we surveyed pediatric inpatients and caregivers to understand their perspectives on undesirable events. By giving them an opportunity to use their own words to describe their experiences, we found a diverse array of undesirable events. Our qualitative analysis revealed four major types of events that patients and caregivers experienced: mismanagement, communication, policy, and lack of care coordination. We also examined the information needs that patients and caregivers experienced during these situations, and learned how they would prefer to receive this information. Based on these results, we provide recommendations for inpatient technologies that could enable patients to identify and prevent such undesirable events.