Low respiratory quotient correlates with high mortality in patients undergoing mechanical ventilation.

OBJECTIVE: Oxygen consumption (VO2), carbon dioxide generation (VCO2), and respiratory quotient (RQ), which is the ratio of VO2 to VCO2, are critical indicators of human metabolism. To seek a link between the patient's metabolism and pathophysiology of critical illness, we investigated the correlation of these values with mortality in critical care patients. METHODS: This was a prospective, observational study conducted at a suburban, quaternary care teaching hospital. Age 18 years or older healthy volunteers and patients who underwent mechanical ventilation were enrolled. A high-fidelity automation device, which accuracy is equivalent to the gold standard Douglas Bag technique, was used to measure VO2, VCO2, and RQ at a wide range of fraction of inspired oxygen (FIO2). RESULTS: We included a total of 21 subjects including 8 post-cardiothoracic surgery patients, 7 intensive care patients, 3 patients from the emergency room, and 3 healthy volunteers. This study included 10 critical care patients, whose metabolic measurements were performed in the ER and ICU, and 6 died. VO2, VCO2, and RQ of survivors were 282 +/- 95 mL/min, 202 +/- 81 mL/min, and 0.70 +/- 0.10, and those of non-survivors were 240 +/- 87 mL/min, 140 +/- 66 mL/min, and 0.57 +/- 0.08 (p = 0.34, p = 0.10, and p < 0.01), respectively. The difference of RQ was statistically significant (p < 0.01) and it remained significant when the subjects with FIO2 < 0.5 were excluded (p < 0.05). CONCLUSIONS: Low RQ correlated with high mortality, which may potentially indicate a decompensation of the oxygen metabolism in critically ill patients.

Efficient Adsorptive Removal of Methylene Blue Dye from Aqueous Solution Using Eragrostis Teff Biomass-Derived Nitrogen and Phosphorus-Codoped Carbon Quantum Dots.

Carbon quantum dots have a great application potential in environmental protection via adsorption technology due to their large specific surface area and negative zeta potential. In this work, nitrogen and phosphorus-codoped carbon quantum dots (NP-CQDs) with a large specific surface area and negative zeta potential were successfully synthesized by a single-step hydrothermal synthesis. Batch adsorption studies were utilized to assess the adsorbent's capacity to remove common methylene blue (MB) dye contaminants from an aqueous solution. The experiment showed that MB dye could be removed in 30 min under optimum experimental conditions, with a removal efficiency of 93.73%. The adsorbent's large surface area of 526.063 m2/g and negative zeta potential of -12.3 mV contribute to the high removal efficiency. The Freundlich isotherm model fits the adsorption process well at 298 K, with R2 and n values of 0.99678 and 4.564, respectively, indicating its applicability. A kinetic study demonstrated that the pseudo-second-order model, rather than the pseudo-first-order model, is more suited to represent the process of MB dye adsorption onto NP-CQDs. This research established a simple and cost-effective method for developing a highly efficient NP-CQD adsorbent for organic dye degradation by adsorption.

Continuous and repeat metabolic measurements compared between post-cardiothoracic surgery and critical care patients.

OBJECTIVE: Using a system, which accuracy is equivalent to the gold standard Douglas Bag (DB) technique for measuring oxygen consumption (VO2), carbon dioxide generation (VCO2), and respiratory quotient (RQ), we aimed to continuously measure these metabolic indicators and compare the values between post-cardiothoracic surgery and critical care patients. METHODS: This was a prospective, observational study conducted at a suburban, quaternary care teaching hospital. Age 18 years or older patients who underwent mechanical ventilation were enrolled. RESULTS: We included 4 post-surgery and 6 critical care patients. Of those, 3 critical care patients died. The longest measurement reached to 12 h and 15 min and 50 cycles of repeat measurements were performed. VO2 of the post-surgery patients were 234 ± 14, 262 ± 27, 212 ± 16, and 192 ± 20 mL/min, and those of critical care patients were 122 ± 20, 189 ± 9, 191 ± 7, 191 ± 24, 212 ± 12, and 135 ± 21 mL/min, respectively. The value of VO2 was more variable in the post-surgery patients and the range of each patient was 44, 126, 71, and 67, respectively. SOFA scores were higher in non-survivors and there were negative correlations of RQ with SOFA. CONCLUSIONS: We developed an accurate system that enables continuous and repeat measurements of VO2, VCO2, and RQ. Critical care patients may have less activity in metabolism represented by less variable values of VO2 and VCO2 over time as compared to those of post-cardiothoracic surgery patients. Additionally, an alteration of these values may mean a systemic distinction of the metabolism of critically ill patients.

Hydrogenation and dehydrogenation of N-heterocycles under Cp*Co(III)-catalysis.

To realize the goal of a carbon-free energy economy, it is crucial to discover reactions that utilize sustainable resources as alternatives to fossil feedstocks. In this study, a well-defined, air-stable Cp*Co(III)-catalyst for transfer hydrogenation of quinoline derivatives and oxidative dehydrogenation of cyclic amines in water is developed. While the former reaction is promoted by formic acid as a transfer hydrogenation reagent, the latter is mediated by molecular oxygen as the sole oxidant. These processes provide new avenues for the investigation of air-stable cobalt catalysts for environmentally benign hydrogenation and dehydrogenation reactions.

Antiviral Drugs and Vaccines for Omicron Variant: A Focused Review.

The Omicron variant of concern (VOC) replaced the delta variant rapidly and became the predominant strain due to more mutations in spike protein and receptor-binding domain (RBD) enhancing its infectivity and binding affinity. The severity of the illness is less than that of the delta variant. Omicron is nonsusceptible to REGEN-COV™ and bamlanivimab with etesevimab. Drugs that are effective against the Omicron variant are oral antiviral drugs such as Paxlovid (nirmatrelvir/ritonavir), remdesivir, sotrovimab, and molnupiravir. The potency of sotrovimab is reduced to 3-fold against Omicron, and 8-fold reduction in potency with sotrovimab is found in a particular variant of Omicron with a R346K substitution in spike protein. There are neither clinical trials comparing the efficacy of these 4 therapies with each other nor any data on a combination of two or more therapies. The current recommendation for mild-moderate, nonhospitalized patients who are at a high risk of disease progression is to use Paxlovid as the first-line option. If Paxlovid is not available or cannot be administered due to drug interactions, then the next best choice is sotrovimab. The third choice is remdesivir if sotrovimab is also not available and molnupiravir is to be given if the other three options are not available or cannot be administered. For prevention, 2130 (cilgavimab) in combination with COV2-2196 (tixagevimab) has been effective against BA.2 only. LY-CoV1404 (bebtelovimab) is recently authorized as it is effective against all sublineages of the Omicron variant. Regarding vaccine efficacy (VE), the 3-dose VE with mRNA vaccines at 14-60 days was found to be 71.6%, and after 60 days, it is 47.4%. There is a 34-38-fold reduction of neutralizing activity with prebooster sera and a 19-fold reduction with booster sera for the Omicron variant. This probably explains the reason for worldwide breakthrough infections with the Omicron variant with waning immunity. The neutralizing antibody response against Omicron elicited by the bivalent vaccine is superior to that of the ancestral Wuhan strain, without any safety concerns. For future advances, the ribosome display technology can be applied for the generation of human single-chain fragment variable (scFv) antibodies from B cells of recovered patients against Omicron and other Coronavirus variants as they are easier and faster to produce and have high affinity and high specificity.

An Automation System Equivalent to the Douglas Bag Technique Enables Continuous and Repeat Metabolic Measurements in Patients Undergoing Mechanical Ventilation.

PURPOSE: To develop a system that is equivalent to the gold standard Douglas Bag (DB) technique for measuring oxygen consumption (V̇o2), carbon dioxide generation (V̇co2), and respiratory quotient (RQ) and to validate its use in clinical settings. METHODS: This was a prospective, observational study conducted at a suburban, quaternary care teaching hospital. Healthy volunteers and patients 18 years or older who received mechanical ventilation were enrolled. FINDINGS: Data from 3 healthy volunteers and 7 patients were analyzed in this study. The interrater reliability between the automation device and DB methods were 0.999, 0.993, and 0.993 for V̇o2, V̇co2, and RQ, respectively. In healthy volunteers, mean (SD) V̇o2, V̇co2, and RQ measured by DB were 411 (100) mL/min, 288 (79) mL/min, and 0.70 (0.03) at high fraction of inspired oxygen (Fio2) and 323 (46) mL/min, 280 (45) mL/min, and 0.85 (0.05) at normal Fio2, respectively. V̇o2 was significantly higher (P < 0.05) and RQ was lower (P < 0.01) in the high Fio2 group as compared to those in the normal Fio2 group. Values measured by the automation system were 227 (31) mL/min, 141 (18) mL/min, and 0.62 (0.04) at high Fio2 and 209 (25) mL/min, 147 (18) mL/min, and 0.70 (0.06) at normal Fio2, respectively. RQ was significantly lower (P < 0.05) in the high Fio2 group as compared to the normal Fio2 group. We also successfully performed continuous and repeat measurements by using the device. The longest measurement reached 12 hours 15 minutes, including 50 cycles of repeat measurements that are equivalent to the DB technique as described above. IMPLICATIONS: We developed an automation system that enables repeat measurements of V̇o2, V̇co2, and RQ, and the accuracy was equivalent to the DB technique. High Fio2 may decrease RQ because of an increase in V̇o2.

Prevalence of chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy in two regions of Australia.

INTRODUCTION/AIMS: Immune-mediated neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) produce significant disability and often require maintenance treatment. There is a paucity of epidemiological data on these conditions in Australia. METHODS: We undertook a prevalence study of CIDP and MMN in North Queensland and Tasmania, coinciding with a national census. Diagnoses were classified against the diagnostic criteria of the European Federation of Neurological Societies/Peripheral Nerve Society. Case ascertainment was undertaken via multiple methods, including survey of local neurologists across public and private clinics, search of neurophysiology, neurology and hospital databases, search of admitted hospital database collections using ICD codes and through immunoglobulin therapy prescription lists. RESULTS: The crude prevalence of CIDP was 5.00 per 100,000 (95% confidence interval [CI] 3.79-6.62) and the crude prevalence of MMN was 1.33 per 100,000 (95% CI 0.78-2.27). Prevalence was also investigated using National Blood Authority numbers of cases prescribed immunoglobulin therapy, indicating a CIDP prevalence of 5.72 per 100,000 (95% CI 4.41-7.43) and MMN prevalence of 1.94 per 100,000 (95% CI 1.24-3.03). There was no significant difference between these numbers and those calculated through access of patient records locally. There was no significant difference in prevalence between Tasmania and North Queensland for any category. DISCUSSION: This study updates the prevalence of CIDP and MMN in Australia. Understanding the distribution of CIDP and MMN patients and their need for treatment is essential for future resource planning and to enable monitoring and coordination of therapies such as immunoglobulin.

Methanol as a hydrogen source: room-temperature highly-selective transfer hydrogenation of α,ß-unsaturated ketones.

The described system offers an ideal, user-friendly protocol for the chemoselective homogeneous hydrogenation of α,ß-unsaturated ketones at room temperature using methanol as a liquid organic hydrogen carrier. Excellent yields were achieved with an in situ-prepared phosphine-free Cp*Ir(III)/bipyridonate complex. Chemoselective reduction with other reducible functionalities and late-stage functionalization were also explored.

Exploring the Immunomodulatory Aspect of Mesenchymal Stem Cells for Treatment of Severe Coronavirus Disease 19.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is an enveloped, positive sense, single stranded RNA (+ssRNA) virus, belonging to the genus Betacoronavirus and family Coronaviridae. It is primarily transmitted from infected persons to healthy ones through inhalation of virus-laden respiratory droplets. After an average incubation period of 2-14 days, the majority of infected individuals remain asymptomatic and/or mildly symptomatic, whereas the remaining individuals manifest a myriad of clinical symptoms, including fever, sore throat, dry cough, fatigue, chest pain, and breathlessness. SARS-CoV-2 exploits the angiotensin converting enzyme 2 (ACE-2) receptor for cellular invasion, and lungs are amongst the most adversely affected organs in the body. Thereupon, immune responses are elicited, which may devolve into a cytokine storm characterized by enhanced secretion of multitude of inflammatory cytokines/chemokines and growth factors, such as interleukin (IL)-2, IL-6, IL-7, IL-8, IL-9, tumor necrosis factor alpha (TNF-α), granulocyte colony-stimulating factor (GCSF), basic fibroblast growth factor 2 (bFGF2), monocyte chemotactic protein-1 (MCP1), interferon-inducible protein 10 (IP10), macrophage inflammatory protein 1A (MIP1A), platelet-derived growth factor subunit B (PDGFB), and vascular endothelial factor (VEGF)-A. The systemic persistence of inflammatory molecules causes widespread histological injury, leading to functional deterioration of the infected organ(s). Although multiple treatment modalities with varying effectiveness are being employed, nevertheless, there is no curative COVID-19 therapy available to date. In this regard, one plausible supportive therapeutic modality may involve administration of mesenchymal stem cells (MSCs) and/or MSC-derived bioactive factors-based secretome to critically ill COVID-19 patients with the intention of accomplishing better clinical outcome owing to their empirically established beneficial effects. MSCs are well established adult stem cells (ASCs) with respect to their immunomodulatory, anti-inflammatory, anti-oxidative, anti-apoptotic, pro-angiogenic, and pro-regenerative properties. The immunomodulatory capabilities of MSCs are not constitutive but rather are highly dependent on a holistic niche. Following intravenous infusion, MSCs are known to undergo considerable histological trapping in the lungs and, therefore, become well positioned to directly engage with lung infiltrating immune cells, and thereby mitigate excessive inflammation and reverse/regenerate damaged alveolar epithelial cells and associated tissue post SARS-CoV-2 infection. Considering the myriad of abovementioned biologically beneficial properties and emerging translational insights, MSCs may be used as potential supportive therapy to counteract cytokine storms and reduce disease severity, thereby facilitating speedy recovery and health restoration.

"Could You Work in My Team?": Exploring How Professional Clinical Role Expectations Influence Decision-Making of Assessors During Exit-Level Medical School OSCEs.

Decision-making in clinical assessment, such as exit-level medical school Objective Structured Clinical Examinations (OSCEs), is complex. This study utilized an empirical phenomenological qualitative approach with thematic analysis to explore OSCE assessors' perceptions of the concept of a "prototypical intern" expressed during focus group discussions. Topics discussed included the concept of a prototypical intern, qualities to be assessed, and approaches to clinical assessment decision-making. The thematic analysis was then applied to a theoretical framework (Cultural Historical Activity Theory-CHAT) that explored the complexity of making assessment decisions amidst potentially contradicting pressures from academic and clinical perspectives. Ten Australasian medical schools were involved with 15 experienced and five less experienced assessors participating. Thematic analysis of the data revealed four major themes in relation to how the prototypical intern concept influences clinical assessors' judgements: (a) Suitability of marking rubric based on assessor characteristics and expectations; (b) Competence as final year student vs. performance as a prototypical intern; (c) Safety, trustworthiness and reliability as constructs requiring assessment and (d) Contradictions in decision making process due to assessor differences. These themes mapped well within the interaction between two proposed activity systems in the CHAT model: academic and clinical. More clinically engaged and more experienced assessors tend to fall back on a heuristic, mental construct of a "prototypical intern," to calibrate judgements, particularly, in difficult situations. Further research is needed to explore whether consensus on desirable intern qualities and their inclusion into OSCE marksheets decreases the cognitive load and increases the validity of assessor decision making.

Impact of COVID-19 on Emergency Medicine Residency Programs: A Cross-Sectional Study in New York State.

INTRODUCTION: The 2019 novel coronavirus pandemic has caused significant disruptions in the clinical operations of hospitals as well as clinical education, training, and research at academic centers. New York State was among the first and largest epicenters of the pandemic, resulting in significant disruptions across its 29 emergency medicine (EM) residency programs. We conducted a cross-sectional observational study of EM residency programs in New York State to assess the impact of the pandemic on resident education and training programs. METHODS: We surveyed a cross-sectional sample of residency programs throughout New York State in June 2020, in the timeframe immediately after the state's first "wave" of the pandemic. The survey was distributed to program leadership and elicited information on pandemic-prompted curricular modifications and other educational changes. The survey covered topics related to disruptions in medical education and sought details on solutions to educational issues encountered by programs. RESULTS: Of the 29 accredited EM residency programs in New York State, leadership from 22 (76%) responded. Of these participating programs, 11 (50%) experienced high pandemic impact on clinical services, 21 (95%) canceled their own trainees' off-service rotations, 22 (100%) canceled or postponed visiting medical student rotations, 22 (100%) adopted virtual conference formats (most within the first week of the pandemic wave), and 11 (50%) stopped all prospective research (excluding COVID-19 research), while most programs continued retrospective research. CONCLUSION: This study highlights the profound educational impact of the pandemic on residency programs in one of the hardest- and earliest-hit regions in the United States. Specifically, it highlights the ubiquity of virtual conferencing, the significant impact on research, and the concerns about canceled rotations and missed training opportunities for residents, as well as prehospital and non-physician practitioner trainees. This data should be used to prompt discussion regarding the necessity of alternate educational modalities for pandemic times and the sequelae of implementing these plans.

Application of Mobile Technology for Disease and Treatment Monitoring of Gestational Diabetes Mellitus Among Pregnant Women: A Systematic Review.

BACKGROUND: Gestational diabetes mellitus (GDM) is an increasing health issue among pregnant women worldwide. Treatment of hyperglycemia during pregnancy improves outcomes for both mothers and infants. Effectively performing and reviewing self-monitoring of blood glucose is time-consuming for patients and care providers. In the modern era, most people having access to smartphones create opportunities for use of phone-based technologies to improve patient care in chronic diseases. This review aims to investigate the awareness and use of the smartphone application (app) with respect to management of GDM among pregnant women. MATERIALS AND METHODS: Various relevant studies (n = 522) from 3 databases named Pub Med, Cochrane Library, and Google Scholar were included. For this, the study involved designing of a 5-stage review framework, which included research question identification, identification of articles, article selection, data collection, and result reporting. RESULTS: Initial search criteria used a combination of keywords, by which we found out 522 literatures from 3 databases. After screening the titles and abstracts, 249 articles were excluded due to duplicate literatures and 252 articles were excluded due to the following reasons: not relevant (n = 172), editorial (n = 43), not in English (n = 7), and abstract only (n = 30). Furthermore, 10 articles were excluded because apps such as MobiGuide, pregnant + app, and GDm health were not mentioned in these articles. A total of 11 articles were included for the final analysis. CONCLUSION: The mobile apps described in the present study (pregnant +, MobiGuide, and GDm health) provided personalized health care services, patient care improvement, and enhanced patient's compliance toward blood glucose monitoring and treatment.

Coomb's negative cold agglutinin disease: A rare report of an incidentally detected case.

Cold agglutinin disease (CAD) is a rare type of autoimmune hemolytic anemia which usually results due to production of immunoglobulin M-type autoantibody against the I/i and H antigens on red blood cell membrane. They can be idiopathic or may be due to underlying lymphoproliferative disorders or atypical infections. It can have a varied presentation ranging from being incidentally detected to being totally transfusion dependent for a longer or shorter duration. Several factors play a role in determining the ability of cold agglutinins in inducing hemolysis such as antibody concentration and temperature. Here, we present a 54-year-old patient, a known case of chronic obstructive pulmonary disease who was admitted to our hospital in the winter months as a case of alcohol withdrawal syndrome. During the course of the stay, the patient developed respiratory insufficiency and went into Type II respiratory failure and hematological investigations revealed features of CAD.

Angiotensin-Receptor Blockade Improves Inflammation and Endothelial Dysfunction in Ankylosing Spondylitis: ARB-AS Study.

Cardiovascular (CV) disease is the leading cause of premature death in ankylosing spondylitis (AS). Atherosclerosis and AS share similar pathogenic mechanisms. The proven benefits of angiotensin-receptor blockers (ARBs) in atherosclerotic cardiovascular disease and their role in immune mediation provide strong rationale to investigate its impact with olmesartan on inflammation and endothelial dysfunction in AS. To investigate the effect of olmesartan on inflammation and endothelial dysfunction in AS. 40 AS patients were randomized to receive 24 weeks of treatment with olmesartan (10 mg/day, n = 20) and placebo ( n = 20) as an adjunct to existing stable antirheumatic drugs. Markers of endothelial function included the following: flow-mediated dilation (FMD) assessed by AngioDefender, endothelial progenitor cells (EPCs) estimated by flow cytometry, nitrite (nitric oxide surrogate), intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and inflammatory measures including Bath ankylosing spondylitis disease activity index (BASDAI), ankylosing spondylitis disease activity score (ASDAS) and bath ankylosing spondylitis functional index (BASFI); erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); proinflammatory cytokines (interleukin-1 [IL-1], IL-6, tumor necrosis factor-α [TNF-α]) and marker of oxidative stress- thiobarbituric acid reactive substances (TBARS) estimated at baseline and after treatment. Health assessment questionnaire disability index (HAQDI), 36-item short form survey (SF-36), and systematic coronary risk evaluation (SCORE) were estimated using standard tools. FMD improved significantly in the olmesartan group (5.83 ± 0.31% to 7.68 ± 0.27%, p ≤ 0.05) as compared with placebo (5.89 ± 0.35% to 6.04 ± 0.32%, p = 0.33). EPC population, nitrite, VCAM-1, and TBARS levels improved significantly in olmesartan group as compared with placebo ( p ≤ 0.05). Olmesartan significantly decreased ASDAS, BASDAI, BASFI, ESR, CRP, IL-6, TNF-α, and SCORE as compared with placebo. HAQDI and SF-36 (PH) scores improved significantly in olmesartan group as compared with placebo. Olmesartan reduces inflammatory disease activity, improves quality of life (QOL), and decreases CV risk demonstrating the immunomodulatory, vasculoprotective, and cardioprotective potential of this drug in AS.

An Insight into the Dermatological Applications of Neem: A Review on Traditional and Modern Aspect.

BACKGROUND: Dermatological disorders are cutaneous infirmities which are frequently occurring and increasing at an alarming rate. These range from mild itching/redness (dermatitis) to fatal skin cancers and has posed a major health concern. Azadirachta indica A. Juss (commonly known as neem), a member of Meliaceae family, is an Indian medicinal plant which has been known for its health promoting effects since ancient times. OBJECTIVE: The review highlights the traditional practices, pharmacological aspects, and formulatory approach of neem for the treatment of dermatological disorders. Further, recent patents and novel delivery systems (developed and in pipeline) improving skin delivery and therapeutic profile of neem are discussed. RESULTS: Neem is a traditional medicinal plant that has been employed for the prevention and treatment of numerous ailments covering systemic and topical disorders. Scientific studies have validated the traditional claims of neem and attributed these health benefits to the presence of more than 300 structurally diverse and complex compounds. It possesses anti-inflammatory, antibacterial, analgesic, antiviral, antifungal, immunomodulatory and antioxidant activities which substantiate its use as skin therapy. Various novel formulations and associated patents that improved the permeability of neem based products across skin could be found in literature. CONCLUSION: Critical appraisal of available literature revealed that neem possesses anti-microbial, anti-inflammatory, antioxidant and antiseptic properties. Thus it has the potential to be developed as a single effective therapy for the management of multimodal skin disorders. Further, pharmaceutical tailoring of neem by implication of novel carriers could enhance its penetrability across skin.