HLA alleles, haplotypes frequencies, and their association with hematological disorders: a report from 1550 families whose patients underwent allogeneic bone marrow transplantation in Egypt.

HLA alleles are representative of ethnicities and may play important roles in predisposition to hematological disorders. We analyzed DNA samples for HLA-A, -B, -C, -DRB1, and -DQB1 loci, from 1550 patients and 4450 potential related donors by PCR-SSO (Polymerase chain reaction sequence-specific oligonucleotides) and estimated allele frequencies in donors and patients from 1550 families who underwent bone marrow transplantation (BMT) in Egypt. We also studied the association between HLA allele frequencies and incidence of acute myeloid leukemia, acute lymphoblastic leukemia, and severe aplastic anemia. The most frequently observed HLA class I alleles were HLA- A*01:01 (16.9%), A*02:01 (16.1%), B*41:01 (8.7%), B*49:01 (7.3%), C*06:02 (25.1%), and C*07:01 (25.1%), and the most frequently observed class II alleles were HLA-DRB1*11:01 (11.8%), DRB1*03:01 (11.6%), DQB1*03:01 (27.5%), and DQB1*05:01 (18.9%). The most frequently observed haplotypes were A*33:01~B*14:02 ~ DRB1*01:02 (2.35%) and A*01:01~B*52:01~DRB1*15:01 (2.11%). HLA-DRB1*07:01 was associated with higher AML odds (OR, 1.26; 95% CI, 1.02-1.55; p = 0.030). Only HLA-B38 antigen showed a trend towards increased odds of ALL (OR, 1.52; 95% CI, 1.00-2.30; p = 0.049) HLA-A*02:01, -B*14:02, and -DRB1*15:01 were associated with higher odds of SAA (A*02:01: OR, 1.35; 95% CI, 1.07-1.70; p = 0.010; B*14:02: OR, 1.43; 95% CI, 1.06-1.93; p = 0.020; DRB1*15:01: OR, 1.32; 95% CI, 1.07-1.64; p = 0.011). This study provides estimates of HLA allele and haplotype frequencies and their association with hematological disorders in an Egyptian population.

High volume, low volume, or pills, which way should we go? a review of bowel preparation for colonoscopy.

PURPOSE OF REVIEW: Colorectal cancer (CRC) is the second leading cause of adult cancer-related deaths in the United States. Colonoscopy is the gold standard for CRC screening. Adequate bowel preparation prior to colonoscopy is essential for good visualization, which results in higher polyp detection rates and shorter procedural times. Achieving adequate preparation prior to colonoscopy is accomplished approximately 75% of the time. This review covers current recommendations and recent updates in bowel preparation for colonoscopy. RECENT FINDINGS: Split-dose bowel preparation is recommended, but recent studies show that same day, low-volume preparations are noninferior. Low-volume polyethylene glycol with electrolytes + ascorbic acid can achieve high-quality bowel preparation and 1-day, low-residue diets prior to colonoscopy, particularly prepackaged low-residue diets, can lead to better outcomes. Utilizing visual aids and artificial intelligence in the form of smartphone applications and quality prediction systems can also lead to higher rates of bowel preparation adequacy. SUMMARY: An individualized approach should be used to decide on the best preparation option for patients. Lower volume, same day preparations are available and lead to better patient tolerability and compliance, along with less stringent precolonoscopy diets. Smartphone applications and artificial intelligence will allow us to better educate and guide patients with regards to following preparation instructions.

Impact of Artificial Intelligence on Colonoscopy Surveillance After Polyp Removal: A Pooled Analysis of Randomized Trials.

BACKGROUND AND AIMS: Artificial intelligence (AI) tools aimed at improving polyp detection have been shown to increase the adenoma detection rate during colonoscopy. However, it is unknown how increased polyp detection rates by AI affect the burden of patient surveillance after polyp removal. METHODS: We conducted a pooled analysis of 9 randomized controlled trials (5 in China, 2 in Italy, 1 in Japan, and 1 in the United States) comparing colonoscopy with or without AI detection aids. The primary outcome was the proportion of patients recommended to undergo intensive surveillance (ie, 3-year interval). We analyzed intervals for AI and non-AI colonoscopies for the U.S. and European recommendations separately. We estimated proportions by calculating relative risks using the Mantel-Haenszel method. RESULTS: A total of 5796 patients (51% male, mean 53 years of age) were included; 2894 underwent AI-assisted colonoscopy and 2902 non-AI colonoscopy. When following U.S. guidelines, the proportion of patients recommended intensive surveillance increased from 8.4% (95% CI, 7.4%-9.5%) in the non-AI group to 11.3% (95% CI, 10.2%-12.6%) in the AI group (absolute difference, 2.9% [95% CI, 1.4%-4.4%]; risk ratio, 1.35 [95% CI, 1.16-1.57]). When following European guidelines, it increased from 6.1% (95% CI, 5.3%-7.0%) to 7.4% (95% CI, 6.5%-8.4%) (absolute difference, 1.3% [95% CI, 0.01%-2.6%]; risk ratio, 1.22 [95% CI, 1.01-1.47]). CONCLUSIONS: The use of AI during colonoscopy increased the proportion of patients requiring intensive colonoscopy surveillance by approximately 35% in the United States and 20% in Europe (absolute increases of 2.9% and 1.3%, respectively). While this may contribute to improved cancer prevention, it significantly adds patient burden and healthcare costs.

Comparison of Noninvasive Mechanical Ventilation With High-Flow Nasal Cannula, Face-Mask, and Helmet in Hypoxemic Respiratory Failure in Patients With COVID-19: A Randomized Controlled Trial.

OBJECTIVES: For COVID-19-related respiratory failure, noninvasive respiratory assistance via a high-flow nasal cannula (HFNC), helmet, and face-mask noninvasive ventilation is used. However, which of these options is most effective is yet to be determined. This study aimed to compare the three techniques of noninvasive respiratory support and to determine the superior technique. DESIGN: A randomized control trial with permuted block randomization of nine cases per block for each parallel, open-labeled arm. SETTING AND PATIENTS: Adult patients with COVID-19 with a Pa o2 /F io2 ratio of less than 300, admitted between February 4, 2021, and August 9, 2021, to three tertiary centers in Oman, were studied. INTERVENTIONS: This study included three interventions: HFNC ( n = 47), helmet continuous positive airway pressure (CPAP; n = 52), and face-mask CPAP ( n = 52). MEASUREMENTS AND MAIN RESULTS: The endotracheal intubation rate and mortality at 28 and 90 days were measured as the primary and secondary outcomes, respectively. Of the 159 randomized patients, 151 were analyzed. The median age was 52 years, and 74% were men. The endotracheal intubation rates were 44%, 45%, and 46% ( p = 0.99), and the median intubation times were 7.0, 5.5, and 4.5 days ( p = 0.11) in the HFNC, face-mask CPAP, and helmet CPAP, respectively. In comparison to face-mask CPAP, the relative risk of intubation was 0.97 (95% CI, 0.63-1.49) for HFNC and 1.0 (95% CI 0.66-1.51) for helmet CPAP. The mortality rates were 23%, 32%, and 38% at 28 days ( p = 0.24) and 43%, 38%, and 40% ( p = 0.89) at 90 days for HFNC, face-mask CPAP, and helmet CPAP, respectively. The trial was stopped prematurely because of a decline in cases. CONCLUSIONS: This exploratory trial found no difference in intubation rate and mortality among the three intervention groups for the COVID-19 patients with hypoxemic respiratory failure; however, more evidence is needed to confirm these findings as the trial was aborted prematurely.

Targeting GBM with an Oncolytic Picornavirus SVV-001 alone and in combination with fractionated Radiation in a Novel Panel of Orthotopic PDX models.

BACKGROUND: Animal models representing different molecular subtypes of glioblastoma multiforme (GBM) is desired for developing new therapies. SVV-001 is an oncolytic virus selectively targeting cancer cells. It's capacity of passing through the blood brain barrier makes is an attractive novel approach for GBM. MATERIALS AND METHODS: 23 patient tumor samples were implanted into the brains of NOD/SCID mice (1 × 105 cells/mouse). Tumor histology, gene expression (RNAseq), and growth rate of the developed patient-derived orthotopic xenograft (PDOX) models were compared with the originating patient tumors during serial subtransplantations. Anti-tumor activities of SVV-001 were examined in vivo; and therapeutic efficacy validated in vivo via single i.v. injection (1 × 1011 viral particle) with or without fractionated (2 Gy/day x 5 days) radiation followed by analysis of animal survival times, viral infection, and DNA damage. RESULTS: PDOX formation was confirmed in 17/23 (73.9%) GBMs while maintaining key histopathological features and diffuse invasion of the patient tumors. Using differentially expressed genes, we subclassified PDOX models into proneural, classic and mesenchymal groups. Animal survival times were inversely correlated with the implanted tumor cells. SVV-001 was active in vitro by killing primary monolayer culture (4/13 models), 3D neurospheres (7/13 models) and glioma stem cells. In 2/2 models, SVV-001 infected PDOX cells in vivo without harming normal brain cells and significantly prolonged survival times in 2/2 models. When combined with radiation, SVV-001 enhanced DNA damages and further prolonged animal survival times. CONCLUSION: A panel of 17 clinically relevant and molecularly annotated PDOX modes of GBM is developed, and SVV-001 exhibited strong anti-tumor activities in vitro and in vivo.

Artificial Intelligence in Colonoscopy.

PURPOSE OF REVIEW: Artificial intelligence (AI) is a rapidly growing field in gastrointestinal endoscopy, and its potential applications are virtually endless, with studies demonstrating use of AI for early gastric cancer, inflammatory bowel disease, Barrett's esophagus, capsule endoscopy, as well as other areas in gastroenterology. Much of the early studies and applications of AI in gastroenterology have revolved around colonoscopy, particularly with regards to real-time polyp detection and characterization. This review will cover much of the existing data on computer-aided detection (CADe), computer-aided diagnosis (CADx), and briefly discuss some other interesting applications of AI for colonoscopy, while also considering some of the challenges and limitations that exist around the use of AI for colonoscopy. RECENT FINDINGS: Multiple randomized controlled trials have now been published which show a statistically significant improvement when using AI to improve adenoma detection and reduce adenoma miss rates during colonoscopy. There is also a growing pool of literature showing that AI can be helpful for characterizing/diagnosing colorectal polyps in real time. AI has also shown promise in other areas of colonoscopy, including polyp sizing and automated measurement and monitoring of quality metrics during colonoscopy. AI is a promising tool that has the ability to shape the future of gastrointestinal endoscopy, with much of the early data showing significant benefits to use of AI during colonoscopy. However, there remain several challenges that may delay or hamper the widespread use of AI in the field.

Pro and Con: How Important Is the Exact Location of Adductor Canal and Femoral Triangle Blocks?

In this Pro-Con commentary article, we debate the importance of anterior thigh block locations for analgesia following total knee arthroplasty. The debate is based on the current literature, our understanding of the relevant anatomy, and a clinical perspective. We review the anatomy of the different fascial compartments, the course of different nerves with respect to the fascia, and the anatomy of the nerve supply to the knee joint. The Pro side of the debate supports the view that more distal block locations in the anterior thigh increase the risk of excluding the medial and intermediate cutaneous nerves of the thigh and the nerve to the vastus medialis, while increasing the risk of spread to the popliteal fossa, making distal femoral triangle block the preferred location. The Con side of the debate adopts the view that while the exact location of local anesthetic injection appears anatomically important, it has not been proven to be clinically relevant.

The expression of tuftelin 1 as a new theranostic marker in early diagnosis and as a therapeutic target in hepatocellular carcinoma.

Currently, many challenges are associated with hepatocellular carcinoma (HCC) as the failure of early diagnosis, and the lack of effective therapy. This study aimed to investigate the possible role of tuftelin 1 (TUFT 1) in the early diagnosis of HCC and evaluate the potential contribution of the TUFT 1/Ca+2 /phosphinositol 3 kinase (PI3K) pathway in dantrolene sodium (Dan) therapeutic outcomes. The study was performed on two sets of rats, the staging (30 rats) and treatment sets (80 rats). HCC was induced by a single dose of diethylnitrosamine (DENA). The hepatic content of TUFT 1 protein was assayed via western blot and immunohistochemistry (IHC), while PI3K, vascular endothelial growth factor (VEGF), Cyclin D1, and matrix-metalloproteinase-9 (MMP-9) contents were assessed using enzyme-linked immunosorbent assay. Hepatic and serum calcium were measured colorimetrically. Furthermore, the nuclear proliferation marker, (Ki-67), (Kiel [Ki] where the antibody was produced in the University Department of Pathology and the original clone number is 67)-expression was assessed by IHC. TUFT 1/Ca+2 /PI3K signaling pathway was progressively activated in the 3 studied stages of HCC with subsequent upregulation of angiogenesis, cell cycle, and metastasis. More interestingly, Dan led to TUFT 1/Ca+2 /PI3K pathway disruption by diminution of the hepatic contents of TUFT 1, calcium, PI3K, VEGF, Cyclin D1, and MMP-9 in a dose-dependent pattern. TUFT 1 can serve as a theranostic biomarker in HCC. Moreover, Dan exerted an antineoplastic effect against HCC via the interruption of TUFT 1/Ca+2 /PI3K pathway.

Preparation and characterization of low-cost nano-particle material using pomegranate peels for brilliant green removal.

A low-cost nano-particle material was successfully prepared using waste pomegranate peels. Batch adsorption experiments were carried out to investigate the effect of different operating conditions on the removal of brilliant green (BG) dye from an aqueous solution. SEM images of pomegranate peels nano-particles (PPNP) declared roughness of the surfaces and TEM images indicated a spheroid shape with an average particle size of 37 nm. The specific surface area of the PPNP was 354.46 m2/g and the particle size had a mean diameter of 613.4 nm. The active nano-particle suspension showed a net negative charge (-29 mV) at natural pH. The XRD pattern of PPNP displayed an average crystallite size of 13.50 nm and EDS analysis shows that the PPNP consists of 83% carbon. The experimental work showed that the removal of BG had optimum removal efficiency at 20 min, 0.3 g adsorbent mass, 25 °C, and pH 8. The kinetic data can be described well with the pseudo-second-order model and the isotherm data was found to fit the Dubinin model. The thermodynamic study proved that BG adsorption on PPNP was physisorption (ΔG = -5.949 kJ/mol) and spontaneous at low temperature (ΔH = -17.193 kJ/mol, ΔS = -0.0382 kJ/mol. k)This study used an agriculture waste (pomegranate peels) to prepare an environmentally friendly and low-cost adsorbent within the nano-scale by thermal activation. The nano-particles prepared were shown to be a promising adsorbent, demonstrating high surface area and well-developed porosity. The prepared adsorbent will have a great impact on wastewater treatment technology and possible applications at a large scale.

Deep Learning Computer-aided Polyp Detection Reduces Adenoma Miss Rate: A United States Multi-center Randomized Tandem Colonoscopy Study (CADeT-CS Trial).

BACKGROUND & AIMS: Artificial intelligence-based computer-aided polyp detection (CADe) systems are intended to address the issue of missed polyps during colonoscopy. The effect of CADe during screening and surveillance colonoscopy has not previously been studied in a United States (U.S.) population. METHODS: We conducted a prospective, multi-center, single-blind randomized tandem colonoscopy study to evaluate a deep-learning based CADe system (EndoScreener, Shanghai Wision AI, China). Patients were enrolled across 4 U.S. academic medical centers from 2019 through 2020. Patients presenting for colorectal cancer screening or surveillance were randomized to CADe colonoscopy first or high-definition white light (HDWL) colonoscopy first, followed immediately by the other procedure in tandem fashion by the same endoscopist. The primary outcome was adenoma miss rate (AMR), and secondary outcomes included sessile serrated lesion (SSL) miss rate and adenomas per colonoscopy (APC). RESULTS: A total of 232 patients entered the study, with 116 patients randomized to undergo CADe colonoscopy first and 116 patients randomized to undergo HDWL colonoscopy first. After the exclusion of 9 patients, the study cohort included 223 patients. AMR was lower in the CADe-first group compared with the HDWL-first group (20.12% [34/169] vs 31.25% [45/144]; odds ratio [OR], 1.8048; 95% confidence interval [CI], 1.0780-3.0217; P = .0247). SSL miss rate was lower in the CADe-first group (7.14% [1/14]) vs the HDWL-first group (42.11% [8/19]; P = .0482). First-pass APC was higher in the CADe-first group (1.19 [standard deviation (SD), 2.03] vs 0.90 [SD, 1.55]; P = .0323). First-pass ADR was 50.44% in the CADe-first group and 43.64 % in the HDWL-first group (P = .3091). CONCLUSION: In this U.S. multicenter tandem colonoscopy randomized controlled trial, we demonstrate a decrease in AMR and SSL miss rate and an increase in first-pass APC with the use of a CADe-system when compared with HDWL colonoscopy alone.

Ameliorative effect of nanocurcumin and Saccharomyces cell wall alone and in combination against aflatoxicosis in broilers.

BACKGROUND: The adverse effect of aflatoxin in broilers is well known. However, dietary supplementation of Saccharomyces cell wall and/or Nanocurcumin may decrease the negative effect of aflatoxin B1 because of the bio-adsorbing feature of the functional ingredients in Yeast Cell Wall and the detoxification effect of curcumin nanoparticles. The goal of this study was to see how Saccharomyces cell wall/Nanocurcumin alone or in combination with the aflatoxin-contaminated diet ameliorated the toxic effects of aflatoxin B1 on broiler development, blood and serum parameters, carcass traits, histology, immune histochemistry, liver gene expression, and aflatoxin residue in the liver and muscle tissue of broilers for 35 days. Moreover, the withdrawal time of aflatoxin was measured after feeding the aflatoxicated group an aflatoxin-free diet. Broiler chicks one day old were distributed into five groups according to Saccharomyces cell wall and/or nanocurcumin with aflatoxin supplementation. The G1 group was given a formulated diet without any supplements. The G2 group was supplemented with aflatoxin (0.25 mg/kg diet) in the formulated diet. The G3 group was supplemented with aflatoxin (0.25 mg/kg diet) and Saccharomyces cell wall (1 kg/ton diet) in the formulated diet. The G4 group was supplemented with aflatoxin (0.25 mg/kg diet) and nanocurcumin (400 mg/kg) in the formulated diet. The G5 group was supplemented with aflatoxin (0.25 mg/kg diet) and Saccharomyces cell wall (1 kg/ton diet) in combination with nanocurcumin (200 mg/kg) in the formulated diet. RESULTS: According to the results of this study, aflatoxin supplementation had a detrimental impact on the growth performance, blood and serum parameters, carcass traits, and aflatoxin residue in the liver and muscle tissue of broilers. In addition, aflatoxin supplementation led to a liver injury that was indicated by serum biochemistry and pathological lesions in the liver tissue. Moreover, the shortening of villi length in aflatoxicated birds resulted in a decrease in both the crypt depth ratio and the villi length ratio. The expression of CYP1A1 and Nrf2 genes in the liver tissue increased and decreased, respectively, in the aflatoxicated group. In addition, the aflatoxin residue was significantly (P ≤ 0.05) decreased in the liver tissue of the aflatoxicated group after 2 weeks from the end of the experiment. CONCLUSION: Saccharomyces cell wall alone or with nanocurcumin attenuated these negative effects and anomalies and improved all of the above-mentioned metrics.

Effects of Wii Fit Rehabilitation on Lower Extremity Functional Status in Adults With Severe Burns: A Randomized Controlled Trial.

OBJECTIVES: To investigate the effects of the Wii Fit rehabilitation program in addition to a standard physical therapy program (SPTP) on lower extremity functional status and functional mobility in adults with severe burns after hospital discharge. DESIGN: A single-blinded, parallel groups, randomized controlled trial. SETTINGS: Outpatient rehabilitation center. PARTICIPANTS: Thirty-four patients (N=34), aged 31.3±7.3 years old, with lower extremity deep partial-thickness and full-thickness burn and total body surface area of more than 40% were allocated randomly into 2 equal groups. INTERVENTIONS: The Wii Fit group received the Wii Fit program for 30 minutes in addition to SPTP for 60 minutes, whereas the SPTP group received SPTP only. The intervention was 3 sessions a week for 12 weeks. MAIN OUTCOME MEASURES: The primary outcome measurements were the functional status and functional mobility, which were assessed by the high mobility assessment tool, Lower Limb Functional Index, and timed Up and Go test. The secondary outcomes included exercise capacity, muscle strength, and balance measured by the 6-minute walk test, isokinetic muscle strength assessment, and stability index. All the outcome measures were collected at the baseline and after 12 weeks of intervention. RESULTS: After 12 weeks of intervention, there were statistically significant differences between groups in all outcome measures in favor of the Wii Fit group (P<.001). Also, statistically significant differences were found in all the measured outcomes after 12 weeks of intervention in each group (P<.05). CONCLUSIONS: Patients with lower extremity burns who received the Wii Fit program in addition to the SPTP had better improvements in lower limb functional status, functional mobility, exercise capacity, muscle strength, and balance than patients who received SPTP alone. The Wii Fit program was a useful adjunctive therapy in rehabilitating adults with lower extremity burn injury.

New method of screening for COVID-19 disease using sniffer dogs and scents from axillary sweat samples.

BACKGROUND: Early screening for COVID-19 is needed to limit the spread of the virus. The aim of this study is to test if the sniffer dogs can be successfully trained to identify subjects with COVID-19 for 'proof of concept' and 'non-inferiority' against PCR. We are calling this method, Dognosis (DN). METHODS: Four hundred and fifty-nine subjects were included, 256 (Group 'P') were known cases of COVID-19 (PCR positive, some with and some without symptoms) and 203 (Group 'C') were PCR negative and asymptomatic (control). Samples were obtained from the axillary sweat of each subject in a masked fashion. Two dogs trained to detect specific Volatile Organic Compounds for COVID-19 detection were used to test each sample. RESULTS: [DN] turned out positive (+) in all the cases that were PCR positive (100% sensitivity). On the other hand, [DN] turned positive (+) in an average of 12.5 cases (6.2%) that were initially PCR negative (apparent specificity of 93.8%). When the PCR was repeated, true specificity was 97.2%. These parameters varied in subgroups from 100% sensitivity and 99% specificity in symptomatic patients to 100% sensitivity and 93% specificity in asymptomatic patients. CONCLUSION: DN method shows high sensitivity and specificity in screening COVID-19 patients.

Cavitation and radiofrequency versus cryolipolysis on leptin regulation in central obese subjects: A randomized controlled study.

BACKGROUND AND OBJECTIVE: To investigate the efficacy of adding ultrasound cavitation and radiofrequency versus cryolipolysis to weight reduction program on leptin, insulin, waist circumference, skinfold, body weight in central obese subjects. MATERIAL AND METHODS: Sixty centrally obese participants were randomly allocated into three equal groups. Subjects in the study group (I) received cavitation and radiofrequency plus dietary regimen, subjects in the second study group (II) received cryolipolysis in conjunction with the same diet program, and subjects in the control group (III) received the same dietary regimen only. Leptin, insulin level, waist circumference, skinfold, body weight, and body mass index were measured shortly before intervention techniques and 3 months afterward. RESULTS: There were no statistically significant differences between cavitation plus radiofrequency and cryolipolysis on leptin and insulin levels after 3 months of intervention. However, statistically significant differences were found in waist circumference, skinfold, weight reduction, and body mass index in favor of the cavitation group (p < 0.05). In addition, both cavitation-radiofrequency and cryolipolysis were statistically significantly different than the diet alone in favor of the study groups (p < 0.05) in all the outcome measures. Furthermore, there were statistically significant differences in all outcome measures (p < 0.05) when comparing the baseline and postintervention results in each group except for leptin level in the diet group (p = 0.14). CONCLUSION: Subjects who underwent cavitation plus radiofrequency had better improvement on waist circumference, skinfold, and body mass index than subjects who received cryolipolysis. However, no differences were found between cavitation plus radiofrequency and cryolipolysis on leptin and insulin levels.

Clinicoradiological and prognostic features of COVID-19-associated acute disseminated encephalomyelitis.

INTRODUCTION: The Covid-19 pandemic has resulted in a spark in interest in the subject given the high exposure rate to viral antigens in the form of infections and vaccines. It is expected that acute disseminated encephalomyelitis (ADEM) cases see a rise in incidence during this period. Given the plethora of Covid-19-related central nervous system (CNS) involvement, it is important to be aware of the varied presentations of ADEM. CASE REPORTS: In this paper, we report 3 cases of ADEM following Covid-19 infection. Patients presented with polyfocal neurological symptoms 6 to 18 days after respiratory symptoms onset. The diagnosis of Covid-19 was made based on nasal swab reverse transcriptase-polymerase chain reaction (RT-PCR) and chest computerized tomography (CT). DISCUSSION: These cases illustrate both classic and atypical presentations requiring exclusion of a spectrum of CNS conditions to be able to retain the diagnosis of ADEM. Consequently, we stress the importance of context, clinical examination and MRI findings in the differentials. In addition, we discuss workup, and particularly, the indication of brain biopsy. Also, the paper discusses options in therapy and the prognosis. The prognosis of covid-associated ADEM is dependent on the extent of pathology intrinsic to ADEM and the intrication of the prognosis of Covid-19 infection. CONCLUSION: The key message in these 3 cases is that clinicians should have a low threshold of suspicion of ADEM in the Covid-19 context, adopt appropriate workup strategies, and initiate adequate treatment for better outcomes.

Mentoring in Times of Crisis and Beyond.

During the global crisis triggered by the COVID-19 pandemic, university programs, meetings, and conferences have moved to virtual settings, with consequent erosion of mentorship opportunities for students and early-career professionals. This calls for mentorship platforms that are adapted to the new landscape in order to bring about a positive change. Our Viewpoint Article shares the perspective of the Transformative Education program and Mentorship Talks initiative at the American University of Beirut in Lebanon, with the aim of providing insights that could stimulate other mentorship platforms.

Combined effects of a ketogenic diet and exercise training alter mitochondrial and peroxisomal substrate oxidative capacity in skeletal muscle.

Ketogenic diets (KDs) are reported to improve body weight, fat mass, and exercise performance in humans. Unfortunately, most rodent studies have used a low-protein KD, which does not recapitulate diets used by humans. Since skeletal muscle plays a critical role in responding to macronutrient perturbations induced by diet and exercise, the purpose of this study was to test if a normal-protein KD (NPKD) impacts shifts in skeletal muscle substrate oxidative capacity in response to exercise training (ExTr). A high fat, carbohydrate-deficient NPKD (16.1% protein, 83.9% fat, 0% carbohydrate) was given to C57BL/6J male mice for 6 wk, whereas controls (Con) received a low-fat diet with similar protein (15.9% protein, 11.9% fat, 72.2% carbohydrate). After 3 wk on the diet, mice began treadmill training 5 days/wk, 60 min/day for 3 wks. The NPKD increased body weight and fat mass, whereas ExTr negated a continued rise in adiposity. ExTr increased intramuscular glycogen, whereas the NPKD increased intramuscular triglycerides. Neither the NPKD nor ExTr alone altered mitochondrial content; however, in combination, the NPKD-ExTr group showed increases in PGC-1α and markers of mitochondrial fission/fusion. Pyruvate oxidative capacity was unchanged by either intervention, whereas ExTr increased leucine oxidation in NPKD-fed mice. Lipid metabolism pathways had the most notable changes as the NPKD and ExTr interventions both enhanced mitochondrial and peroxisomal lipid oxidation and many adaptations were additive or synergistic. Overall, these results suggest that a combination of a NPKD and ExTr induces additive and/or synergistic adaptations in skeletal muscle oxidative capacity.NEW & NOTEWORTHY A ketogenic diet with normal protein content (NPKD) increases body weight and fat mass, increases intramuscular triglyceride storage, and upregulates pathways related to protein metabolism. In combination with exercise training, a NPKD induces additive and/or synergistic activation of AMPK, PGC-1α, mitochondrial fission/fusion genes, mitochondrial fatty acid oxidation, and peroxisomal adaptations in skeletal muscle. Collectively, results from this study provide mechanistic insight into adaptations in skeletal muscle relevant to keto-adaptation.

Patient Involvement in Anesthesia Decision-making: A Qualitative Study of Knee Arthroplasty.

BACKGROUND: Calls to better involve patients in decisions about anesthesia-e.g., through shared decision-making-are intensifying. However, several features of anesthesia consultation make it unclear how patients should participate in decisions. Evaluating the feasibility and desirability of carrying out shared decision-making in anesthesia requires better understanding of preoperative conversations. The objective of this qualitative study was to characterize how preoperative consultations for primary knee arthroplasty arrived at decisions about primary anesthesia. METHODS: This focused ethnography was performed at a U.S. academic medical center. The authors audio-recorded consultations of 36 primary knee arthroplasty patients with eight anesthesiologists. Patients and anesthesiologists also participated in semi-structured interviews. Consultation and interview transcripts were coded in an iterative process to develop an explanation of how anesthesiologists and patients made decisions about primary anesthesia. RESULTS: The authors found variation across accounts of anesthesiologists and patients as to whether the consultation was a collaborative decision-making scenario or simply meant to inform patients. Consultations displayed a number of decision-making patterns, from the anesthesiologist not disclosing options to the anesthesiologist strictly adhering to a position of equipoise; however, most consultations fell between these poles, with the anesthesiologist presenting options, recommending one, and persuading hesitant patients to accept it. Anesthesiologists made patients feel more comfortable with their proposed approach through extensive comparisons to more familiar experiences. CONCLUSIONS: Anesthesia consultations are multifaceted encounters that serve several functions. In some cases, the involvement of patients in determining the anesthetic approach might not be the most important of these functions. Broad consideration should be given to both the applicability and feasibility of shared decision-making in anesthesia consultation. The potential benefits of interventions designed to enhance patient involvement in decision-making should be weighed against their potential to pull anesthesiologists' attention away from important humanistic aspects of communication such as decreasing patients' anxiety.

Effects of bovine lactoferrin and chitosan nanoparticles on serum biochemical indices, antioxidative enzymes, transcriptomic responses, and resistance of Nile tilapia against Aeromonas hydrophila.

The present study was carried out to investigate the effects of dietary bovine lactoferrin (BLF) or chitosan nanoparticles (CHN) alone or in combinations on serum biochemical indices, antioxidative capacity, transcriptomic responses, non-specific immunity, and resistance of Nile tilapia (Oreochromis niloticus) against challenge with Aeromonas hydrophila. Fish were fed on the basal diet with no supplements and served as control (CTR), and six other experimental diets containing different levels of BLF (800 and 1200 mg per kg diet), CHN (500 and 1000 mg per kg diet), and their combinations (400 mg BLF plus 250 mg CHN per kg diet, and 600 mg BLF plus 500 mg CHN per kg diet) for 45 days. At the end of the experiment, serum, and tissue specimens (liver and kidney) were collected, fish in all groups were challenged with A. hydrophila and then observed for another ten days to calculate the RPS. Compared to the CTR group, no significant differences were recorded in TP, ALB, GLO, BUN, and CREAT values among all treatments. Serum LYZ, ALT, AST, and ALP enzyme activities were significantly increased in all experimental groups over the CTR (P < 0.05), and their highest values were recorded in the combined treatments. Moreover, dietary supplementation with CHN (1000 mg/kg) and combined treatments significantly increased the SOD, CAT, and GSH-Px enzyme activities compared to other groups (P < 0.05). The highest mRNA expression levels of IGF-1 gene in liver, and IL-1ß, and IFN-γ genes in kidneys were found in CHN (1000 mg/kg) group and combined treatments more than other groups. Interestingly, no, or mild histopathological alterations were noticed in the hepatopancreas and posterior kidney of the treated groups. A significantly higher RPS was identified in the combined treatments challenged with A. hydrophila compared with the CTR group. This study exemplifies the positive impacts of dietary supplementation with BLF or CHN alone or combinations on the antioxidative status, immunity, and disease resistance of Nile tilapia.

Matrix metalloproteinase contribution in management of cancer proliferation, metastasis and drug targeting.

Matrix metalloproteinases (MMPs) or matrixins, are members of a zinc-dependent endopeptidase family. They cause remodeling of the extracellular matrix (ECM) leading to numerous diseases. MMPs subfamilies possess: collagenases, gelatinases, stromelysins and membrane-type MMPs (MT-MMP). They consist of several domains; pro-peptide, catalytic, linker peptide and the hemopexin (Hpx) domains. MMPs are involved in initiation, proliferation and metastasis of cancer through the breakdown of ECM physical barriers. Overexpression of MMPs is associated with poor prognosis of cancer. This review will discuss both types of MMPs and current inhibitors, which target them in different aspects, including, biosynthesis, activation, secretion and catalytic activity. Several synthetic and natural inhibitors of MMPs (MMPIs) that can bind the catalytic domain of MMPs have been designed including; peptidomimetic, non-peptidomimetic, tetracycline derivatives, off-target MMPI, natural products, microRNAs and monoclonal antibodies.