Utilizing online reviews for analyzing digital healthcare consultation services: Examining perspectives of both healthcare customers and healthcare professionals.

INTRODUCTION: Digital healthcare consultation services, also known as telemedicine, have seen a surge in their usage, especially after the COVID-19 pandemic. The purpose of this study is to investigate the satisfaction determinants of healthcare customers (patients) and healthcare professionals (doctors), providing digital healthcare consultation services. METHODS: The analysis involved scraping online reviews of 11 telemedicine apps meant for patients and 7 telemedicine apps meant for doctors, yielding a total of 44,440 patient reviews and 4748 doctor reviews. A structural topic modeling analysis followed by regression, dominance, correspondence, and emotion analysis was conducted to derive insights. RESULTS: The study identified ten determinants of satisfaction from patients' and eight from doctors' perspectives. For patients, 'service variety and quality' (ß = 0.5527) was the top positive determinant, while 'payment disputes' (ß = -0.1173) and 'in-app membership' (ß = -0.031) negatively impacted satisfaction. For doctors, 'patient consultation management' (ß = 0.2009) was the leading positive determinant, with 'profile management' (ß = -0.1843), 'subscription' (ß = -0.183), and 'customer care support' (ß = -0.0908) being the negative ones. The most influential negative emotion for patients, anger, was closely associated with 'customer care service' and 'in-app memberships,' while joy was tied to 'service variety and quality' and 'offers and discounts.' For doctors, anger was associated with 'cost-effectiveness,' and joy with 'app responsiveness.' CONCLUSION: This study offers new insights by examining patient and doctor determinants at a granular level which can be used by telemedicine app developers and managers to build customer-centric services.

A Need to Preserve Ejection Fraction during Heart Failure.

Heart failure (HF) is a significant global healthcare burden with increasing prevalence and high morbidity and mortality rates. The diagnosis and management of HF are closely tied to ejection fraction (EF), a crucial parameter for evaluating disease severity and determining treatment plans. This paper emphasizes the urgent need to maintain EF during heart failure, highlighting the distinct phenotypes of HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). It discusses the complexities of HFrEF pathophysiology and its negative impact on patient outcomes, stressing the importance of ongoing research and the development of effective therapeutic interventions to slow down the progression from preserved to reduced ejection fraction. Additionally, it explores the potential role of renal denervation in preserving ejection fraction and its implications for HFrEF management. This comprehensive review aims to offer valuable insights into the critical role of EF preservation in enhancing outcomes for patients with heart failure.

The voltage-gated sodium channel pore exhibits conformational flexibility during slow inactivation.

Slow inactivation in voltage-gated sodium channels (NaVs) directly regulates the excitability of neurons, cardiac myocytes, and skeletal muscles. Although NaV slow inactivation appears to be conserved across phylogenies-from bacteria to humans-the structural basis for this mechanism remains unclear. Here, using site-directed labeling and EPR spectroscopic measurements of membrane-reconstituted prokaryotic NaV homologues, we characterize the conformational dynamics of the selectivity filter region in the conductive and slow-inactivated states to determine the molecular events underlying NaV gating. Our findings reveal profound conformational flexibility of the pore in the slow-inactivated state. We find that the P1 and P2 pore helices undergo opposing movements with respect to the pore axis. These movements result in changes in volume of both the central and intersubunit cavities, which form pathways for lipophilic drugs that modulate slow inactivation. Our findings therefore provide novel insight into the molecular basis for state-dependent effects of lipophilic drugs on channel function.

Design and fabrication of surface trimmed silicon-on-insulator waveguide with adiabatic spot-size converters.

Theoretical and experimental studies reveal that a predefined single-mode rib waveguide fabricated in silicon-on-insulator (SOI) substrate with a device layer thickness of 2 µm can be adiabatically trimmed down to submicron waveguide dimensions (<1 µm), resulting in regional modification of waveguide properties. The fabrication process involves physical trimming/removal of a waveguide surface by plasma etchants that is spatially filtered by a shadow mask with a rectangular aperture inside a reactive ion etching system. The exact position of a shadow mask above a sample surface has been optimized (∼500 µm) to obtain the desired adiabatic spot-size converters of length up to 1 mm at both ends of the trimmed waveguides. For experimental demonstration, three different sets of 15-mm-long single-mode waveguides fabricated in 2-µm SOI were adiabatically trimmed in the middle for three different lengths of 3, 5, and 7 mm, respectively. Excess propagation loss and group index of a trimmed submicron waveguide section were extracted by analyzing the wavelength-dependent Fabry-Perot transmission characteristics of the device with polished input/output end facets. The insertion loss of a typical spot-size converter designed for the guidance of TE-like polarization has been recorded to be ∼0.25 dB for a wide range of wavelengths (1500 nm≤λ≤1600 nm). As predicted by numerical simulation, no polarization rotation has been observed in all the trimmed submicron waveguides. The proposed surface trimming technique can be potentially used to tune the waveguide cross-section/geometry for phase error correction and/or to avail stronger light-matter interactions at a desired location of an integrated optical circuit.

Right heart in septic shock: prospective observational study.

BACKGROUND: The right heart often receives less attention during echocardiography. The situation is no different in septic shock. We prospectively investigated the echocardiographic indices of the right heart in septic shock adult patients. METHODS: Septic shock ICU patients within 24 h of admission were subjected to transthoracic echocardiography (TTE) as per the 2005 guidelines from the American Society of Echocardiography. RESULTS: Eighty-eight septic shock patients (M:F = 52:36) underwent TTE. Thirty-six patients survived. Significant differences in demographic and biochemical (laboratory and metabolic) parameters, severity scores, life-support therapies (vasopressors, ventilation), and length of ICU stay were observed between survivors and non-survivors. Right heart abnormalities of chamber dimension and systolic and diastolic function existed in 79, 25, and 86 % of patients, respectively. Right ventricle subcostal wall thickness (91 %), pulse Doppler myocardial performance index (73 %), and E/E' (63 %) were the predominant abnormalities in chamber dimension, systolic function, and diastolic function of the right heart, respectively. However, the presence of these abnormalities did not signify poor survival in our study. CONCLUSIONS: Right heart dimensional and functional abnormalities exist in high proportions in septic shock. However, their predictability of poor outcomes remains questionable.

The Efficacy, Safety, and Cost Benefit of Olanzapine versus Aprepitant in Highly Emetogenic Chemotherapy: A Pilot Study from South India.

Background. The efficacy, safety, and cost benefit of olanzapine (OLN) when compared to aprepitant (APR) in the prevention of chemotherapy induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC) were evaluated. Methods. A prospective pilot study was done in chemotherapy-naive patients receiving HEC to compare OLN versus APR along with palonosetron and dexamethasone. 100 patients consented to the protocol and were randomized and evaluated for Complete Response (CR) (no emesis, no rescue). Results. CR was 86% for the acute period, 86% for the delayed period, and 80% for the overall period in 50 patients receiving the APD regimen. CR was 84% for the acute period, 88% for the delayed period, and 78% for the overall period for 50 patients receiving the OPD regimen. Patients without nausea were APD: 88% acute, 84% delayed, and 84% overall, and OPD: 84% acute, 88% delayed, and 84% overall. There were no significant grade 3 or 4 toxicities. OPD was comparable to APD in the control of CINV. Conclusion. In this study, there was no significant difference between olanzapine and aprepitant in preventing CINV with highly emetogenic chemotherapy. Olanzapine may thus be used as a potential, safe, and cost beneficial alternative to prevent nausea and vomiting in HEC.

Hyperleukocytosis, an unusual paraneoplastic manifestation of lung cancer: Case report and review of literature.

Leukocytosis may be found in patients with lung cancer either at time of diagnosis or during the course of the disease. Though mild leukocytosis is common in lung cancer, hyperleukocytosis defined as total leukocyte count more than 100,000 is uncommon. We describe a 68-year-old chronic smoker who presented with osteolytic pelvic bone lesion and hyperleukocytosis, who on evaluation was found to have a primary lung cancer. Bone marrow aspiration and biopsy showed marked myeloid hyperplasia. Myeloid series comprised predominantly mature neutrophils and stab forms. Cytogenetic investigation showed a normal chromosome set (46, XY). Repeated cultures from blood, urine, and sputum were sterile. He was started on chemotherapy but had a progressive downhill course. In patient with lung cancer, leukocytosis can be due to infection, use of corticosteroid or hematopoetic growth factors, bone marrow involvement, or paraneoplastic manifestation. Paraneoplastic leukocytosis is associated with poor prognosis and aggressive disease.

A chimeric prokaryotic pentameric ligand-gated channel reveals distinct pathways of activation.

Recent high resolution structures of several pentameric ligand-gated ion channels have provided unprecedented details of their molecular architecture. However, the conformational dynamics and structural rearrangements that underlie gating and allosteric modulation remain poorly understood. We used a combination of electrophysiology, double electron-electron resonance (DEER) spectroscopy, and x-ray crystallography to investigate activation mechanisms in a novel functional chimera with the extracellular domain (ECD) of amine-gated Erwinia chrysanthemi ligand-gated ion channel, which is activated by primary amines, and the transmembrane domain of Gloeobacter violaceus ligand-gated ion channel, which is activated by protons. We found that the chimera was independently gated by primary amines and by protons. The crystal structure of the chimera in its resting state, at pH 7.0 and in the absence of primary amines, revealed a closed-pore conformation and an ECD that is twisted with respect to the transmembrane region. Amine- and pH-induced conformational changes measured by DEER spectroscopy showed that the chimera exhibits a dual mode of gating that preserves the distinct conformational changes of the parent channels. Collectively, our findings shed light on both conserved and divergent features of gating mechanisms in this class of channels, and will facilitate the design of better allosteric modulators.

Methotrexate-induced chemical meningitis in patients with acute lymphoblastic leukemia/lymphoma.

BACKGROUND: Intrathecal methotrexate (ITMTX) is an important component in the treatment as well as prophylaxis of leukemia/lymphoma. ITMTX can cause chemical meningitis characterized by vomiting, headache, and fever lasting 2-5 days with spontaneous resolution of symptoms which differentiates this syndrome from bacterial meningitis. OBJECTIVE: This prospective observational study was carried out to determine incidence of post-ITMTX syndrome in patients receiving prophylactic ITMTX as part of Berlin-Frankfurt-Munster (BFM) protocol. MATERIALS AND METHODS: Patients aged 15-50 years receiving BFM 90 or BFM 95 protocol for acute lymphoblastic leukemia or lymphoblastic lymphoma were followed up for post-ITMTX syndrome, defined as vomiting, headache and fever between 38° and 39°C following ITMTX. RESULTS: Thirty-three patients received a total of 297 courses of ITMTX. Of the 297 doses of ITMTX, 20 episodes (6.7%) of post-ITMTX syndrome were observed. The incidence of post-ITMTX syndrome was highest after the second dose of ITMTX (24%). The most common symptom of post-ITMTX syndrome was headache which was seen in 17 (85%) patients. Seventeen (85%) patients had vomiting, 10 (50%) patients had fever, and 4 (20%) patients had backache. Meningeal signs were present in 2 (10%) patients. CONCLUSIONS: Post-ITMTX syndrome is not uncommon in adult patients receiving prophylactic ITMTX for treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma. Patients develop a toxic syndrome closely mimicking acute bacterial meningitis but spontaneous recovery is seen without any neurological sequelae.

Structural basis for allosteric coupling at the membrane-protein interface in Gloeobacter violaceus ligand-gated ion channel (GLIC).

Ligand binding at the extracellular domain of pentameric ligand-gated ion channels initiates a relay of conformational changes that culminates at the gate within the transmembrane domain. The interface between the two domains is a key structural entity that governs gating. Molecular events in signal transduction at the interface are poorly defined because of its intrinsically dynamic nature combined with functional modulation by membrane lipid and water vestibules. Here we used electron paramagnetic resonance spectroscopy to delineate protein motions underlying Gloeobacter violaceus ligand-gated ion channel gating in a membrane environment and report the interface conformation in the closed and the desensitized states. Extensive intrasubunit interactions were observed in the closed state that are weakened upon desensitization and replaced by newer intersubunit contacts. Gating involves major rearrangements of the interfacial loops, accompanied by reorganization of the protein-lipid-water interface. These structural changes may serve as targets for modulation of gating by lipids, alcohols, and amphipathic drug molecules.

Conformational transitions underlying pore opening and desensitization in membrane-embedded Gloeobacter violaceus ligand-gated ion channel (GLIC).

Direct structural insight into the mechanisms underlying activation and desensitization remain unavailable for the pentameric ligand-gated channel family. Here, we report the structural rearrangements underlying gating transitions in membrane-embedded GLIC, a prokaryotic homologue, using site-directed spin labeling and electron paramagnetic resonance (EPR) spectroscopy. We particularly probed the conformation of pore-lining second transmembrane segment (M2) under conditions that favor the closed and the ligand-bound desensitized states. The spin label mobility, intersubunit spin-spin proximity, and the solvent-accessibility parameters in the two states clearly delineate the underlying protein motions within M2. Our results show that during activation the extracellular hydrophobic region undergoes major changes involving an outward translational movement, away from the pore axis, leading to an increase in the pore diameter, whereas the lower end of M2 remains relatively immobile. Most notably, during desensitization, the intervening polar residues in the middle of M2 move closer to form a solvent-occluded barrier and thereby reveal the location of a distinct desensitization gate. In comparison with the crystal structure of GLIC, the structural dynamics of the channel in a membrane environment suggest a more loosely packed conformation with water-accessible intrasubunit vestibules penetrating from the extracellular end all the way to the middle of M2 in the closed state. These regions have been implicated to play a major role in alcohol and drug modulation. Overall, these findings represent a key step toward understanding the fundamentals of gating mechanisms in this class of channels.

Three cases of vagal nerve schwannoma and review of literature.

Schwannoma arising from the vagus is an uncommon (2-5%) benign nerve tumour. This tumour most often presents as a slow growing asymptomatic solitary neck mass which rarely undergoes malignant transformation. Definitive pre-operative diagnosis may be difficult and investigations such as FNAC have low specificity. The carotid artery and internal jugular vein may be displaced antero-laterally. Diagnosis is based on clinical suspicion and confirmation is obtained by means of surgical pathology. Surgical excision is the treatment of choice for this tumour, with recurrence being rare. We describe three cases of schwannoma involving the vagus who presented differently to our unit during past 5 years.

Characterization of microbial flora of leprous ulcers infested with maggots.

Swabs from 64 maggot infested leprosy ulcers before and after treatment for maggots and 100 non-infested leprosy ulcers were studied for the bacterial flora. From maggot infested ulcers (before treatment), the cultures usually showed mixed growth. Among the Gram positive isolates, Staphylococcus aureus (37%), S. albus (18%) and Streptococcus pyogenes (36%) were frequently isolated. Gram negative bacteria isolated were Proteus spp. (21%) and Escherichia coli (7%). Anaerobic bacteria isolated were Micrococcus (3%) and Bacteroides (4%). After treatment of maggot infested ulcers, S. aureus (36%) continued to be isolated with almost the same frequency. The isolates of other Gram negative organisms were slightly reduced. Among the Gram negatives the Proteus spp. (10%) were also less in number. In few cases Neisseria (3%) was found. Anaerobic isolates were M. luteus (2%) and B. necrophorus (3%). From the cases without maggot infestation, a single organism was isolated from 16 cases and 84 mixed cultures were obtained. Isolates included the aerobic Gram positives S. aureus (46%), S. albus (21%) and S. pyogenes (38%), and the Gram negative Proteus spp. (19%) and E. coli (7%). The anaerobic isolate was M. luteus (3%). From this study no apparent association between the type of bacterial flora and maggot infestation could be observed.

Evaluation of multiple regimens in leprosy

Assessment of bacteraemia has been made at weekly intervals in 36 lepromatous leprosy patients who were put on different antileprosy drug under four regimens, viz., DDS alone, DDS in combination with rifampicin (DDS + RIF), clofazimine (DDS + CLF) and thiacetazone (DDS + TCT). In general, with the continuation of treatment the bacillary load in the blood decreased considerably while bacteriological index (BI) of the skin remained constant during the study. No significant difference was noted in M. leprae clearance from blood between the groups treated with DDS alone and groups treated in combination with CLF and TCT. However, DDS + RIF treatment was most efficient in clearing acid-fast bacilli (AFB) from blood as compared to those noted with other drug regimens.