Symptomatic post COVID patients have impaired alveolar capillary membrane function and high VE/VCO2.

BACKGROUND: Post COVID-19 syndrome is characterized by several cardiorespiratory symptoms but the origin of patients' reported symptomatology is still unclear. METHODS: Consecutive post COVID-19 patients were included. Patients underwent full clinical evaluation, symptoms dedicated questionnaires, blood tests, echocardiography, thoracic computer tomography (CT), spirometry including alveolar capillary membrane diffusion (DM) and capillary volume (Vcap) assessment by combined carbon dioxide and nitric oxide lung diffusion (DLCO/DLNO) and cardiopulmonary exercise test. We measured surfactant derive protein B (immature form) as blood marker of alveolar cell function. RESULTS: We evaluated 204 consecutive post COVID-19 patients (56.5 ± 14.5 years, 89 females) 171 ± 85 days after the end of acute COVID-19 infection. We measured: forced expiratory volume (FEV1) 99 ± 17%pred, FVC 99 ± 17%pred, DLCO 82 ± 19%, DM 47.6 ± 14.8 mL/min/mmHg, Vcap 59 ± 17 mL, residual parenchymal damage at CT 7.2 ± 3.2% of lung tissue, peakVO2 84 ± 18%pred, VE/VCO2 slope 112 [102-123]%pred. Major reported symptoms were: dyspnea 45% of cases, tiredness 60% and fatigability 77%. Low FEV1, Vcap and high VE/VCO2 slope were associated with persistence of dyspnea. Tiredness was associated with high VE/VCO2 slope and low PeakVO2 and FEV1 while fatigability with high VE/VCO2 slope. SPB was fivefold higher in post COVID-19 than in normal subjects, but not associated to any of the referred symptoms. SPB was negatively associated to Vcap. CONCLUSIONS: In patients with post COVID-19, cardiorespiratory symptoms are linked to VE/VCO2 slope. In these patients the alveolar cells are dysregulated as shown by the very high SPB. The Vcap is low likely due to post COVID-19 pulmonary endothelial/vasculature damage but DLCO is only minimally impaired being DM preserved.

Association between patient activation and adherence to a colorectal enhanced recovery pathway: a prospective cohort study.

BACKGROUND: Low adherence to enhanced recovery pathways (ERPs) may negatively affect postoperative outcomes. The objective of this study was to assess the extent to which patient activation (PA, i.e., knowledge, skills, and confidence to participate in care) is associated with adherence to an ERP for colorectal surgery. METHODS AND PROCEDURES: This cohort study included adult patients (≥ 18 yo) undergoing in-patient elective colorectal surgery at two university-affiliated hospitals in Montreal, Canada. Preoperatively, patients completed the Patient Activation Measure (PAM) questionnaire (score 0-100, categorized into low PA [≤ 55.1] vs. high PA [≥ 55.2]). All patients were managed with an ERP including 15 interventions classified into 2 groups: those requiring active patient participation (5 active ERP interventions, including early oral intake and mobilization) and those directed by the clinical team (10 passive ERP interventions, including early termination of IV fluids and urinary drainage). The adjusted association between PA and ERP adherence was evaluated using linear regression. RESULTS: A total of 286 patients were included (mean age 59 ± 15 years, 45% female, 62% laparoscopic, 33% rectal, median length of stay 4 days [IQR 2-6]). Most patients had high levels of PA (74%). Mean adherence was 90% (95% CI 88-91%) for passive ERP interventions and 72% (95% CI 70-75%) for active interventions. On regression analysis, high PA was associated with increased adherence to active ERP interventions (+ 6.8% [95% CI + 1.1 to + 12.5%]), but not to passive interventions (+ 2.5% [95% CI - 0.3 to + 5.3%]). Increased active ERP adherence was associated with reduced length of stay, 30-day complications, and hospital readmissions. CONCLUSION: This study supports that high PA is associated with increased adherence to ERP interventions, particularly those requiring active patient participation. Preoperative identification of patients with low activation may inform interventions to optimize patient involvement with ERPs and improve postoperative outcomes.

Surface hardness and wear resistance of prefabricated and CAD-CAM milled artificial teeth: A cross-over clinical study.

PURPOSE: To clinically evaluate the surface roughness and wear resistance of prefabricated and CAD-CAM milled acrylic resin teeth for complete dentures. MATERIALS AND METHODS: In a cross-over study design, 10 completely edentulous patients were randomly included in this study and given two complete dentures. The first complete denture was made using prefabricated teeth, while the second was constructed using CAD-CAM milled teeth. Following insertion (T0), 3 months (T3), and 6 months (T6), the complete dentures were scanned. Utilizing 3D surface super-imposition techniques, the vertical (2D wear), and volumetric (3D wear) material loss were measured. The hardness of the teeth was evaluated at the time of denture insertion (T0) and then after 6 months (T6) of denture insertion by digital Vickers hardness tester. Statistical analysis was done using SPSS software. Paired groups were compared by paired t-test. Also, a repeated measure test was used. The significant difference was considered if p ≤ 0.05. RESULTS: The time of denture function was linearly correlated with the wear of the prefabricated and CAD-CAM milled denture tooth. Prefabricated acrylic teeth had significantly more vertical and volumetric wear after 3 and 6 months, compared to CAD-CAM milled denture teeth where p-values were 0.01, 0.009, 0.003, and 0.024, respectively. Additionally, CAD-CAM milled teeth displayed significantly higher hardness values than prefabricated teeth both before and after 6 months of use where p-values were 0.001. After 6 months, all studied teeth showed a decrease in their hardness. CONCLUSIONS: In terms of wear resistance and surface hardness, CAD-CAM milled acrylic resin teeth were superior to prefabricated acrylic resin artificial teeth once the complete denture functions.

Species-Based Differences in Mechanical Properties, Cytocompatibility, and Printability of Methacrylated Collagen Hydrogels.

Collagen methacrylation is a promising approach to generate photo-cross-linkable cell-laden hydrogels with improved mechanical properties. However, the impact of species-based variations in amino acid composition and collagen isolation method on methacrylation degree (MD) and its subsequent effects on the physical properties of methacrylated collagen (CMA) hydrogels and cell response are unknown. Herein, we compared the effects of three collagen species (bovine, human, and rat), two collagen extraction methods (pepsin digestion and acid extraction), and two photoinitiators (lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) and Irgacure-2959 (I-2959)) on the physical properties of CMA hydrogels, printability and mesenchymal stem cell (MSC) response. Human collagen showed the highest MD. LAP was more cytocompatible than I-2959. The compressive modulus and cell viability of rat CMA were significantly higher (p < 0.05) than bovine CMA. Human CMA yielded constructs with superior print fidelity. Together, these results suggest that careful selection of collagen source and cross-linking conditions is essential for biomimetic design of CMA hydrogels for tissue engineering applications.

Remotely Monitoring COVID-19 Patient Health Condition Using Metaheuristics Convolute Networks from IoT-Based Wearable Device Health Data.

Today, COVID-19-patient health monitoring and management are major public health challenges for technologies. This research monitored COVID-19 patients by using the Internet of Things. IoT-based collected real-time GPS helps alert the patient automatically to reduce risk factors. Wearable IoT devices are attached to the human body, interconnected with edge nodes, to investigate data for making health-condition decisions. This system uses the wearable IoT sensor, cloud, and web layers to explore the patient's health condition remotely. Every layer has specific functionality in the COVID-19 symptoms' monitoring process. The first layer collects the patient health information, which is transferred to the second layer that stores that data in the cloud. The network examines health data and alerts the patients, thus helping users take immediate actions. Finally, the web layer notifies family members to take appropriate steps. This optimized deep-learning model allows for the management and monitoring for further analysis.

Pharmacological management of South Asians with type 2 diabetes: Consensus recommendations from the South Asian Health Foundation.

South Asians constitute approximately 1.6 billion people from the Indian subcontinent, comprising Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan and Sri Lanka; and make up the largest diaspora globally. Compared to the White European population, this group is at a higher risk of developing type 2 diabetes along with cardiovascular, renal and eye complications. Over the recent years, a number of new therapies for type 2 diabetes have become available for which cardiovascular outcome trials (CVOTs) have been published. The recent ADA/EASD consensus guidelines on diabetes, pre-diabetes and cardiovascular diseases' offer a transitional shift in type 2 diabetes management. The new consensus recommendations are based on recent CVOTs, many of which had a representation of South Asian cohorts. In light of this new evidence, there is urgent need for an integrated, evidence-based, cost-effective and individualised approach specific for South Asians. This review takes into consideration the evidence from these CVOTs and provides best practice recommendations for optimal management of South Asian people with type 2 diabetes, alongside the previously published consensus report from South Asian Health Foundation in 2014 [1].

Why do students skip classroom lectures: A single dental school report.

BACKGROUND: Conventional classroom lectures continue to represent a major component of the dental education system to ensure optimum delivery of knowledge. Certain number of students are less compliant and likely to skip classes which may impact the overall academic performance. The aim of this study was to investigate dental students' attitude towards classroom attendance and potential reasons for absenteeism at King Abdulaziz University-Faculty of Dentistry (KAU-FD). METHODS: This was a cross-sectional survey of all dental students actively enrolled at KAU-FD from January to June 2019. The survey included questions on demographics, average travel time to school, current dental year, most recent GPA, student's perspective toward classroom lectures. The survey was validated and distributed to all students at a pre-selected time frame. Data were analysed and presented as frequencies and percentages; chi-square test was used to explore parameters association. RESULTS: A total of 678 students consented and completed the survey. Overall, 44.3% of students were more likely to skip two classes or less per month. Second year dental students were more likely to be absent from classroom lectures (31.3%), while 3rd year dental students were less likely to do so (15.4%). Reported students' justifications for missing classes included early morning classes (47.9%), exams preparation (42%), and lecturer's weak presentation skills (41.9%). CONCLUSION: Compliance of dental students with classroom attendance has been an ongoing challenge for most programs. The current data suggests a multifactorial module for students' attitude toward classroom attendance. Future studies focusing on reasons behind classroom attendance behavior and addressing students' concerns are needed.

Setting Agenda for Medical Education Research in Pakistan.

OBJECTIVE: To justify the allocation of human and financial resources, this study aims to identify multiple stakeholders' views of medical education research priorities in Pakistan for the next five years. METHODS: This two-stage exploratory mixed-method study was conducted from Jan 2018 to Jun 2019. A purposively selected sample of 250 faculty members, research supervisors, postgraduate students, undergraduate students and policymakers actively involved in improving Medical Education were included. In Stage-I: An exploratory open-ended questionnaire asking about Medical Education Research (MER) priorities in Pakistan for the next five years was emailed. Data were thematically analyzed to identify MER areas. In Stage-II: Another questionnaire was developed based on MER areas. The participants were asked to rate their importance on a scale of one to five. Descriptive statistics were calculated using SPSS.v.24. RESULTS: In Stage-I, 140 participants and in Stage-II, 130 participants from different stakeholder groups responded. We identified 20 research priorities grouped under eight themes: curriculum organization, content, delivery, assessment, workplace, students, faculty and educational management. Top three research priorities were identifying needs and developing effective provisions for continuous professional development of the faculty, improving assessment and communication skills. CONCLUSION: The study identified top MER priority areas as continuous professional development, assessment and communication skills. Some areas unique to the current study include admissions, fostering critical thinking, Islamic values in professionalism and ethics. The study provides evidence-base for decision-making about allocating time and funds for MER in Pakistan.

Brain and Brown Adipose Tissue Metabolism in Transgenic Tg2576 Mice Models of Alzheimer Disease Assessed Using 18F-FDG PET Imaging.

OBJECTIVE: Imaging animal models of Alzheimer disease (AD) is useful for the development of therapeutic drugs and understanding AD. Transgenic Swedish hAPPswe Tg2576 mice are a good model of ß-amyloid plaques. We report 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET) imaging of brain and intrascapular brown adipose tissue (IBAT) in transgenic mice 2576 (Tg2576) and wild-type (WT) mice. METHODS: Transgenic Tg2576 mice and WT mice, >18 months were injected intraperitonally with ≈ 25 to 30 MBq 18F-FDG while awake. After 60 minutes, they were anesthetized with isoflurane (2.5%) and imaged with Inveon MicroPET. Select mice were killed, imaged ex vivo, and 20 µm sections cut for autoradiography. 18F-FDG uptake in brain and IBAT PET and brain autoradiographs were analyzed. RESULTS: Fasting blood glucose levels averaged 120 mg/dL for WT and 100 mg/dL for Tg2576. Compared to WT, Tg2576 mice exhibited a decrease in SUVglc in the various brain regions. Average reductions in the cerebrum regions were as high as -20%, while changes in cerebellum were -3%. Uptake of 18F-FDG in IBAT decreased by -60% in Tg2576 mice and was found to be significant. Intrascapular brown adipose tissue findings in Tg2576 mice are new and not previously reported. Use of blood glucose for PET data analysis and corpus callosum as reference region for autoradiographic analysis were important to detect change in Tg2576 mice. CONCLUSION: Our results suggest that 18F-FDG uptake in the Tg2576 mice brain show 18F-FDG deficits only when blood glucose is taken into consideration.

Unravelling the role of SNM1 in the DNA repair system of Trypanosoma brucei.

All living cells are subject to agents that promote DNA damage. A particularly lethal lesion are interstrand cross-links (ICL), a property exploited by several anti-cancer chemotherapies. In yeast and humans, an enzyme that plays a key role in repairing such damage are the PSO2/SNM1 nucleases. Here, we report that Trypanosoma brucei, the causative agent of African trypanosomiasis, possesses a bona fide member of this family (called TbSNM1) with expression of the parasite enzyme able to suppress the sensitivity yeast pso2Δ mutants display towards mechlorethamine, an ICL-inducing compound. By disrupting the Tbsnm1 gene, we demonstrate that TbSNM1 activity is non-essential to the medically relevant T. brucei life cycle stage. However, trypanosomes lacking this enzyme are more susceptible to bi- and tri-functional DNA alkylating agents with this phenotype readily complemented by ectopic expression of Tbsnm1. Genetically modified variants of the null mutant line were subsequently used to establish the anti-parasitic mechanism of action of nitrobenzylphosphoramide mustard and aziridinyl nitrobenzamide prodrugs, compounds previously shown to possess potent trypanocidal properties while exhibiting limited toxicity to mammalian cells. This established that these agents, following activation by a parasite specific type I nitroreductase, produce metabolites that promote formation of ICLs leading to inhibition of trypanosomal growth.

Quantitative Imaging Reveals Steatosis and Fibroinflammation in Multiple Organs in People With Type 2 Diabetes: A Real-World Study.

We aimed to determine the extent of multiorgan fat accumulation and fibroinflammation in individuals living with type 2 diabetes. We deeply phenotyped individuals with type 2 diabetes (134 from secondary care, 69 from primary care) with multiorgan, quantitative, multiparametric MRI and compared with 134 matched control individuals without diabetes and 92 control individuals with normal weight. We examined the impact of diabetes duration, obesity status, and glycemic control. Ninety-three of the individuals with type 2 diabetes were reevaluated at 7 months (median). Multiorgan abnormalities were more common in individuals with type 2 diabetes (94%) than in age- and BMI-matched healthy individuals or healthy individuals with normal weight. We demonstrated a high burden of combined steatosis and fibroinflammation within the liver, pancreas, and kidneys (41%, 17%, and 10%) associated with visceral adiposity (73%) and poor vascular health (82%). Obesity was most closely associated with advanced liver disease, renal and visceral steatosis, and multiorgan abnormalities, while poor glycemic control was associated with pancreatic fibroinflammation. Pharmacological therapies with proven cardiorenal protection improved liver and vascular health unlike conventional glucose-lowering treatments, while weight loss or improved glycemic control reduced multiorgan adiposity (P ≤ 0.01). Quantitative imaging in people with type 2 diabetes highlights widespread organ abnormalities and may provide useful risk and treatment stratification.

PPAR agonists as add-on treatment with metformin in management of type 2 diabetes: a systematic review and meta-analysis.

The combination of metformin and the peroxisome proliferator-activated receptors (PPAR) agonists offers a promising avenue for managing type 2 diabetes (T2D) through their potential complementary mechanisms of action. The results from randomized controlled trials (RCT) assessing the efficacy of PPAR agonists plus metformin versus metformin alone in T2D are inconsistent, which prompted the conduct of the systematic review and meta-analysis. We searched MEDLINE and EMBASE from inception (1966) to March 2023 to identify all RCTs comparing any PPAR agonists plus metformin versus metformin alone in T2D. Categorical variables were summarized as relative risk along with 95% confidence interval (CI). Twenty RCTs enrolling a total of 6058 patients met the inclusion criteria. The certainty of evidence ranged from moderate to very low. Pooled results show that using PPAR agonist plus metformin, as compared to metformin alone, results in lower concentrations of fasting glucose [MD = - 22.07 mg/dl (95% CI - 27.17, - 16.97), HbA1c [MD = - 0.53% (95% CI - 0.67, - 0.38)], HOMA-IR [MD = - 1.26 (95% CI - 2.16, - 0.37)], and fasting insulin [MD = - 19.83 pmol/L (95% CI - 29.54, - 10.13)] without significant increase in any adverse events. Thus, synthesized evidence from RCTs demonstrates the beneficial effects of PPAR agonist add-on treatment versus metformin alone in T2D patients. In particular, novel dual PPARα/γ agonist (tesaglitazar) demonstrate efficacy in improving glycaemic and lipid concentrations, so further RCTs should be performed to elucidate the long-term outcomes and safety profile of these novel combined and personalized therapeutic strategies in the management of T2D.PROSPERO registration no. CRD42023412603.

Role of advanced CMR features in identifying a positive genotype of hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. Cardiac magnetic resonance (CMR) imaging has emerged as a powerful tool for the non-invasive assessment of HCM. CMR can accurately quantify the extent and distribution of hypertrophy, assess the presence and severity of myocardial fibrosis, and detect associated abnormalities. We will study basic and advanced features of CMR in 2 groups of HCM patients with negative and positive genotype, respectively. MATERIALS AND METHODS: The study population consisted in consecutive HCM patients referred to Centro Cardiologico Monzino who performed both CMR and genetic testing. Clinical CMR images were acquired at 1.5 T Discovery MR450 scanner (GE Healthcare, Milwaukee, Wisconsin)) using standardized protocols T1 mapping, T2 mapping and late gadolinium enhancement (LGE). Population was divided in 2 groups: group 1 with HCM patients with a negative genotype and group 2 with a positive genotype. RESULTS: The analytic population consisted of 110 patients: 75 in group 1 and 35 patients in group 2. At CMR evaluation, patients with a positive genotype had higher LV mass (136 vs. 116 g, p = 0.02), LV thickness (17.5 vs. 16.9 mm), right ventricle ejection fraction (63 % vs. 58 %, p = 0.002). Regarding the LGE patients with positive genotype have a higher absolute (33.8 vs 16.7 g, p = 0.0003) and relative LGE mass (31.6 % vs 14.6 %, p = 0.0007). On a segmental analysis all the septum (segments 2, 8, 9, and 14) had a significantly increased native T1 compared to others segments. ECV in the mid antero and infero-septum (segments 8 and 9) have lower values in positive genotype HCM. Interestingly the mean T2 was lower in positive genotype HCM as compared to negative genotype HCM (50,1 ms vs 52,4). CONCLUSIONS: Our paper identifies the mid septum (segments 8 and 9) as a key to diagnose a positive genotype HCM.

Abdominal peer learning: advantages and lessons learned.

In 2017, our tertiary hospital-based imaging practice transitioned from score-based peer review to the peer learning methodology for learning and improvement. In our subspecialized practice, peer learning submissions are reviewed by domain experts, who then provide feedback to individual radiologists, curate cases for group learning sessions, and develop associated improvement initiatives. In this paper, we share lessons learned from our abdominal imaging peer learning submissions with the assumption that trends in our practice likely mimic others', and hope that other practices can avoid future errors and elevate the level of the quality of their own performance. Adoption of a nonjudgmental and efficient method to share peer "learning opportunities" and "great calls" has increased participation in this activity and increased transparency into our practice, thus allowing for visualization of trends in performance. Peer learning allows us to bring our own individual knowledge and practices together for group review in a collegial and safe environment. We learn from each other and decide how to improve together.