Seeing the forest through the trees: characterizing the glycoproteome.

Post-translational modifications (PTMs) immensely expand the diversity of the proteome. Glycosylation, among the most ubiquitous PTMs, is a dynamic and multifarious modification of proteins and lipids that generates an omnipresent foliage on the cell surface. The resulting protein glycoconjugates can serve important functions in biology. However, their vast complexity complicates the study of their structures, interactions, and functions. There is now a growing appreciation of the need to study glycans and proteins together as complete entities, as the sum of these two components can exhibit unique functions. In this review, we discuss the growing forestry toolbox to characterize the structure, interactions, and biological functions of protein glycoconjugates, as well as the potential payouts of understanding and controlling these enigmatic biomolecules.

Chemical editing of proteoglycan architecture.

Proteoglycans are heterogeneous macromolecular glycoconjugates that orchestrate many important cellular processes. While much attention has focused on the poly-sulfated glycosaminoglycan chains that decorate proteoglycans, other important elements of their architecture, such as core proteins and membrane localization, have garnered less emphasis. Hence, comprehensive structure-function relationships that consider the replete proteoglycan architecture as glycoconjugates are limited. Here we present an extensive approach to study proteoglycan structure and biology by fabricating defined semisynthetic modular proteoglycans that can be tailored for cell surface display. The expression of proteoglycan core proteins with unnatural amino acids permits bioorthogonal click chemistry with functionalized glycosaminoglycans for methodical dissection of the parameters required for optimal binding and function of various proteoglycan-binding proteins. We demonstrate that these sophisticated materials can recapitulate the functions of native proteoglycan ectodomains in mouse embryonic stem cell differentiation and cancer cell spreading while permitting the analysis of the contributing architectural elements toward function.

Stereoselective synthesis of photoactivatable Man(ß1,4)GlcNAc-based bioorthogonal probes.

We report an operationally facile protocol to prepare photoactivatable probes of the bioactive mammalian disaccharide, Man(ß1,4)GlcNAc. Using conformationally restricted mannosyl hemi-acetal donors in a one-pot chlorination, iodination and glycosylation sequence, ß-mannosides were generated in excellent diastereoselectivities and yields. Upon accessing the disaccharide, we generated the corresponding photoactivatable probes by appending a diazirine-alkyne equipped linker via a condensation reaction between a diazirine-containing linker and C-1 and C-2 derivatized mannosylamines to furnish the desired C-1 and C-2 modified Man(ß1,4)GlcNAc-based probes. This new synthetic protocol greatly simplifies the preparation of this important bioactive disaccharide to enable future work to identify its protein binding partners in cells.

Normative Data and Conversion Equation for Spectral-Domain Optical Coherence Tomography in an International Healthy Control Cohort.

BACKGROUND: Spectral-domain (SD-) optical coherence tomography (OCT) can reliably measure axonal (peripapillary retinal nerve fiber layer [pRNFL]) and neuronal (macular ganglion cell + inner plexiform layer [GCIPL]) thinning in the retina. Measurements from 2 commonly used SD-OCT devices are often pooled together in multiple sclerosis (MS) studies and clinical trials despite software and segmentation algorithm differences; however, individual pRNFL and GCIPL thickness measurements are not interchangeable between devices. In some circumstances, such as in the absence of a consistent OCT segmentation algorithm across platforms, a conversion equation to transform measurements between devices may be useful to facilitate pooling of data. The availability of normative data for SD-OCT measurements is limited by the lack of a large representative world-wide sample across various ages and ethnicities. Larger international studies that evaluate the effects of age, sex, and race/ethnicity on SD-OCT measurements in healthy control participants are needed to provide normative values that reflect these demographic subgroups to provide comparisons to MS retinal degeneration. METHODS: Participants were part of an 11-site collaboration within the International Multiple Sclerosis Visual System (IMSVISUAL) consortium. SD-OCT was performed by a trained technician for healthy control subjects using Spectralis or Cirrus SD-OCT devices. Peripapillary pRNFL and GCIPL thicknesses were measured on one or both devices. Automated segmentation protocols, in conjunction with manual inspection and correction of lines delineating retinal layers, were used. A conversion equation was developed using structural equation modeling, accounting for clustering, with healthy control data from one site where participants were scanned on both devices on the same day. Normative values were evaluated, with the entire cohort, for pRNFL and GCIPL thicknesses for each decade of age, by sex, and across racial groups using generalized estimating equation (GEE) models, accounting for clustering and adjusting for within-patient, intereye correlations. Change-point analyses were performed to determine at what age pRNFL and GCIPL thicknesses exhibit accelerated rates of decline. RESULTS: The healthy control cohort (n = 546) was 54% male and had a wide distribution of ages, ranging from 18 to 87 years, with a mean (SD) age of 39.3 (14.6) years. Based on 346 control participants at a single site, the conversion equation for pRNFL was Cirrus = -5.0 + (1.0 × Spectralis global value). Based on 228 controls, the equation for GCIPL was Cirrus = -4.5 + (0.9 × Spectralis global value). Standard error was 0.02 for both equations. After the age of 40 years, there was a decline of -2.4 µm per decade in pRNFL thickness ( P < 0.001, GEE models adjusting for sex, race, and country) and -1.4 µm per decade in GCIPL thickness ( P < 0.001). There was a small difference in pRNFL thickness based on sex, with female participants having slightly higher thickness (2.6 µm, P = 0.003). There was no association between GCIPL thickness and sex. Likewise, there was no association between race/ethnicity and pRNFL or GCIPL thicknesses. CONCLUSIONS: A conversion factor may be required when using data that are derived between different SD-OCT platforms in clinical trials and observational studies; this is particularly true for smaller cross-sectional studies or when a consistent segmentation algorithm is not available. The above conversion equations can be used when pooling data from Spectralis and Cirrus SD-OCT devices for pRNFL and GCIPL thicknesses. A faster decline in retinal thickness may occur after the age of 40 years, even in the absence of significant differences across racial groups.

Ethnobotanical, Phytochemistry, and Pharmacological Activity of Onosma (Boraginaceae): An Updated Review.

The genus Onosma belongs to the Boraginaceae family and contains over 230 species. The present review sheds light on the ethnopharmacology, phytoconstituents, bioactivity, and toxicology of the Onosma species from previous investigations. Furthermore, the paper also highlights the unresolved issues for the future investigations. The review included previous studies of the genus Onosma available from Google Scholar and Baidu Scholar, Science Direct, SciFinder, Wiley Online Library, and Web of Science. Until now, more than 200 chemical compounds have been detected from the genus Onosma, including naphthoquinone (33), flavonoids (30), hydrocarbon (23), phenolic (22), ester (17), alkaloids (20), aromatics (12), carboxylic acid (11), fatty acids (9), terpenoids (10), while the most important ones are rosmarinic, ferulic, protocatechuic, chlorogenic, caffeic, p-coumaric acids, and apigenin. The Onosma species are reported as traditional medicine for wound healing, heart disease, and kidney disorders, while the pharmacological investigations revealed that the extracts and the phytochemicals of Onosma species have different therapeutic properties including antioxidant, enzyme inhibitory, antitumor, hepatoprotective, antiviral, anti-inflammatory, and antimicrobial actions. The summarized knowledge in this review provides valuable ideas for the current and future drug discovery and a motivation for further investigation on the genus Onosma.

Exploring associations between oral health measures and oral health-impacted daily performances in 12-14-year-old schoolchildren.

BACKGROUND: Oral health-related quality of life, a prominent topic in dentistry, has been studied extensively. However, the comparison between various self-perceived and clinical oral health measures still needs to be explored. The purpose of the current study is; first, to report the self-perceived and clinically examined oral health measures that are associated with the oral impacts on daily performances. Second, to identify the oral health measure that best predicts greater oral impact scores. Third, to investigate the difference in findings related to the disease experience measures and the treatment measures. METHODS: A cross-sectional study was carried out on children aged 12-14 years. The prevalence, frequency, and oral impact scores of each daily performance were calculated. Thirteen self-perceived OH conditions were assessed. Clinically examined oral health measures included gingival health, oral hygiene status, DMFT, DT, MT, and FT scores and, one or more decay (1 + D), missing (1 + M) and filled (1 + F) teeth. Simple linear and multiple linear regressions were carried out to report the associations. RESULTS: At least one oral health impacted daily performance was reported by 40% of the total sample of schoolchildren (N = 700). Based on the magnitude and precision of adjusted regression coefficients (RC), decay severity (DT) was identified as a better predictor of a greater oral impact score with regression coefficient values ranging between 0.3 (social contact) and 2.4 (1 + performance). Contrariwise, MT and FT components of DMFT were associated with lower oral impact scores. The self-perceived measures were also associated with oral impact scores and presented similar findings to that of the clinical oral health measures. CONCLUSIONS: Untreated decay significantly impacted daily performances, especially eating, sleeping, studying, and social contact. The findings are of importance to public health practitioners for reporting, treating, and preventing oral health problems in children, and eventually contributing to better oral health-related quality of life.

Facile anomer-oriented syntheses of 4-methylumbelliferyl sialic acid glycosides.

As part of a program to find new sialidases and determine their enzymatic specificity and catalytic activity, a library of 4-methylumbelliferyl sialic acid glycosides derivatised at the C-5 position were prepared from N-acetylneuraminic acid. Both α- and ß-4-methylumbelliferyl sialic acid glycosides were prepared in high yields and stereoselectivity. α-Anomers were accessed via reagent control by utilising additive CH3CN and TBAI, whereas the ß-anomers were synthesised through a diastereoselective addition reaction of iodine and the aglycone to the corresponding glycal followed by reduction of the resulting 3-iodo compounds. Both anomer-oriented synthetic pathways allow for gram-scale stereoselective syntheses of the desired C-5 modified neuraminic acid derivatives for use as tools to quantify the enzymatic activity and substrate specificity of known sialidases, and potential detection and investigation of novel sialidases.

Novel Homozygous Missense Variant in GJA3 Connexin Domain Causing Congenital Nuclear and Cortical Cataracts.

Congenital cataracts (CC) are responsible for approximately one-tenth of childhood blindness cases globally. Here, we report an African American family with a recessively inherited form of CC. The proband demonstrated decreased visual acuity and bilateral cataracts, with nuclear and cortical cataracts in the right and left eye, respectively. Exome sequencing revealed a novel homozygous variant (c.563A > G; p.(Asn188Ser)) in GJA3, which was predicted to be pathogenic by structural analysis. Dominantly inherited variants in GJA3 are known to cause numerous types of cataracts in various populations. Our study represents the second case of recessive GJA3 allele, and the first report in African Americans. These results validate GJA3 as a bona fide gene for recessively inherited CC in humans.

Optimal intereye difference thresholds by optical coherence tomography in multiple sclerosis: An international study.

OBJECTIVE: To determine the optimal thresholds for intereye differences in retinal nerve fiber and ganglion cell + inner plexiform layer thicknesses for identifying unilateral optic nerve lesions in multiple sclerosis. Current international diagnostic criteria for multiple sclerosis do not include the optic nerve as a lesion site despite frequent involvement. Optical coherence tomography detects retinal thinning associated with optic nerve lesions. METHODS: In this multicenter international study at 11 sites, optical coherence tomography was measured for patients and healthy controls as part of the International Multiple Sclerosis Visual System Consortium. High- and low-contrast acuity were also collected in a subset of participants. Presence of an optic nerve lesion for this study was defined as history of acute unilateral optic neuritis. RESULTS: Among patients (n = 1,530), receiver operating characteristic curve analysis demonstrated an optimal peripapillary retinal nerve fiber layer intereye difference threshold of 5µm and ganglion cell + inner plexiform layer threshold of 4µm for identifying unilateral optic neuritis (n = 477). Greater intereye differences in acuities were associated with greater intereye retinal layer thickness differences (p ≤ 0.001). INTERPRETATION: Intereye differences of 5µm for retinal nerve fiber layer and 4µm for macular ganglion cell + inner plexiform layer are robust thresholds for identifying unilateral optic nerve lesions. These thresholds may be useful in establishing the presence of asymptomatic and symptomatic optic nerve lesions in multiple sclerosis and could be useful in a new version of the diagnostic criteria. Our findings lend further validation for utilizing the visual system in a multiple sclerosis clinical trial setting. Ann Neurol 2019;85:618-629.

Updates in diagnosis and management of Ebola hemorrhagic fever.

Ebola hemorrhagic fever is a lethal viral disease transmitted by contact with infected people and animals. Ebola infection represents a worldwide health threat causing enormous mortality rates and fatal epidemics. Major concern is pilgrimage seasons with possible transmission to Middle East populations. In this review, we aim to shed light on Ebola hemorrhagic fever as regard: virology, transmission, biology, pathogenesis, clinical picture, and complications to get the best results for prevention and management. We also aim to guide future research to new therapeutic perspectives to precise targets. Our methodology was to review the literature extensively to make an overall view of the biology of Ebola virus infection, its serious health effects and possible therapeutic benefits using currently available remedies and future perspectives. Key findings in Ebola patients are fever, hepatic impairment, hepatocellular necrosis, lymphopenia (for T-lymphocyte and natural killer cells) with lymphocyte apoptosis, hemorrhagic manifestations, and complications. Pathogenesis in Ebola infection includes oxidative stress, immune suppression of both cell-mediated and humoral immunities, hepatic and adrenal impairment and failure, hemorrhagic fever, activation of deleterious inflammatory pathways, for example, tumor necrosis factor-related apoptosis-inducing ligand, and factor of apoptotic signal death receptor pathways causing lymphocyte depletion. Several inflammatory mediators and cytokines are involved in pathogenesis, for example, interleukin-2, 6, 8, and 10 and others. In conclusion, Ebola hemorrhagic fever is a serious fatal viral infection that can be prevented using strict health measures and can be treated to some extent using some currently available remedies. Newer treatment lines, for example, prophetic medicine remedies as nigella sativa may be promising.

Levofloxacin-Induced Toxic Epidermal Necrolysis.

Toxic epidermal necrolysis (TEN), also known as Lyell's syndrome, is a severe episodic mucocutaneous reaction that is usually brought on by oral medications and/or sporadically by infections. We report a case of a 19-year-old male with the presenting complaint of generalized skin blistering over the previous seven days at the dermatology outpatient clinic. The patient has had epilepsy since he was 10 years old. Due to an upper respiratory tract illness, a local healthcare facility recommended oral levofloxacin to him seven days ago. Levofloxacin-induced toxic epidermal necrolysis (TEN) was suspected based on the patient's medical history, physical examination, and research. On the basis of histological investigations and clinical correlation, the diagnosis of TEN was determined. The mainstay of treatment after diagnosis was made was supportive care. The best methods for treating TEN involve stopping any potential causal agents and providing supportive care. The patient received care in the intensive care unit.

Low intensity mechanical signals promote proliferation in a cell-specific manner: Tailoring a non-drug strategy to enhance biomanufacturing yields.

Biomanufacturing relies on living cells to produce biotechnology-based therapeutics, tissue engineering constructs, vaccines, and a vast range of agricultural and industrial products. With the escalating demand for these bio-based products, any process that could improve yields and shorten outcome timelines by accelerating cell proliferation would have a significant impact across the discipline. While these goals are primarily achieved using biological or chemical strategies, harnessing cell mechanosensitivity represents a promising - albeit less studied - physical pathway to promote bioprocessing endpoints, yet identifying which mechanical parameters influence cell activities has remained elusive. We tested the hypothesis that mechanical signals, delivered non-invasively using low-intensity vibration (LIV; <1g, 10-500Hz), will enhance cell expansion, and determined that any unique signal configuration was not equally influential across a range of cell types. Varying frequency, intensity, duration, refractory period, and daily doses of LIV increased proliferation in CHO-adherent cells (+79% in 96h) using a particular set of LIV parameters (0.2g, 500Hz, 3x30 min/d, 2h refractory period), yet this same mechanical input suppressed proliferation in CHO-suspension cells (-13%). Exposing these same CHO-suspension cells to distinct LIV parameters (30Hz, 0.7g, 2x60 min/d, 2h refractory period) increased proliferation by 210%. Particle image velocimetry combined with finite element modeling showed high transmissibility of these signals across fluids (>90%), and LIV effectively scaled up to T75 flasks. Ultimately, when LIV is tailored to the target cell population, its highly efficient transmission across media represents a means to non-invasively augment biomanufacturing endpoints for both adherent and suspended cells, and holds immediate applications, ranging from small-scale, patient-specific personalized medicine to large-scale commercial bio-centric production challenges.

Association Between Risk for Prediabetes and Type 2 Diabetes Mellitus Prevention Among Faculty Members and Administrative Staff of a Saudi University.

BACKGROUND: Diabetes mellitus prevalence continues to rise globally, causing disability and decreased productivity among patients, a significant strain on healthcare systems, and a burden on national economies. In 2021, diabetes will affect approximately 537 million adults. The rising prevalence of prediabetes worldwide also poses a significant public health threat, as it is estimated that by 2030, more than 470 million individuals will be prediabetic. OBJECTIVE: This study aimed to determine the association between the risk of prediabetes and the level of Type 2 Diabetes Mellitus (T2DM) prevention among faculty members and administrative staff of a Saudi university. METHODS: An analytic cross-sectional study design was utilized. The prediabetes risk of respondents was assessed using a risk test developed by the CDC, while the participants' diabetes prevention practices were determined using a researcher-developed questionnaire. Data were collected from 360 selected faculty members and administrative staff of three randomly selected health colleges and three non-health colleges at King Faisal University, Hofuf, Al-Ahsa, Saudi Arabia, between September 25 and October 13, 2022. The collected data were subjected to estimation of proportion and logistic regression analyses using Epi InfoTM version 7. RESULTS: Nearly 40% of respondents (39.72%, 95% CI: 34.80, 44.86) were found to be at high risk for prediabetes. The majority of university faculty and administrative staff consistently practiced T2DM preventive measures related to the limitation of processed food consumption, smoking cessation, and regular checking of weight and the nutritional value of food. However, there was poor T2DM prevention practice in terms of exercise, consumption of sweetened beverages, and stress reduction. Those who had a high prediabetes risk were 1.17 times more likely to engage in T2DM prevention practices. However, they were found to be 19% less likely to perform T2DM prevention practices when sociodemographic variables were held constant. CONCLUSION: Prediabetes risk was prevalent among Saudi university faculty and administrative staff. T2DM prevention was not consistently practiced by those who had a high risk for prediabetes. High prediabetes risk was negatively associated with the level of T2DM prevention.

Chemoproteomic mapping of human milk oligosaccharide (HMO) interactions in cells.

Human milk oligosaccharides (HMOs) are a family of unconjugated soluble glycans found in human breast milk that exhibit a myriad of biological activity. While recent studies have uncovered numerous biological functions for HMOs (antimicrobial, anti-inflammatory & probiotic properties), the receptors and protein binding partners involved in these processes are not well characterized. This can be attributed largely in part to the low affinity and transient nature of soluble glycan-protein interactions, precluding the use of traditional characterization techniques to survey binding partners in live cells. Here, we present the use of synthetic photoactivatable HMO probes to capture, enrich and identify HMO protein targets in live cells using mass spectrometry-based chemoproteomics. Following initial validation studies using purified lectins, we profiled the targets of HMO probes in live mouse macrophages. Using this strategy, we mapped hundreds of HMO binding partners across multiple cellular compartments, including many known glycan-binding proteins as well as numerous proteins previously not known to bind glycans. We expect our findings to inform future investigations of the diverse roles of how HMOs may regulate protein function.

Rare pathogenic mutation in the thymidine phosphorylase gene (TYMP) causing mitochondrial neurogastrointestinal encephalomyelopathy.

Background: Mitochondrial neurogastrointestinal encephalopathy (MNGIE) disease is a rare multisystem disorder that mainly affects the digestive and nervous systems. Key features of the disease include cachexia, ptosis, external ophthalmoplegia, peripheral neuropathy and leucoencephalopathy. Symptoms most often begin by age 20 and overlap several other Metabolic and endocrine disorders making the diagnosis challenging. It has been determined that MNGIE is caused by mutations in the gene-encoding thymidine phosphorylase (TP; previously known as endothelial cell growth factor 1). Case: We herein present the clinical, neuroimaging and molecular findings in a patient with MNGIE caused by a novel homozygous variant of TYMP gene c.1048C>T, which is predicted to result in a premature protein termination (p.Gln350*). TYMP is a gene on chromosome 22q13.33 that encodes TP. Conclusion: This case highlights the importance of good understanding and early recognition of a rare condition like MNGIE, so that the suffering from unnecessary interventional procedures can be avoided and better multidisciplinary care can be implemented for the symptomatic management of the patient.

A novel chest CT severity score in COVID-19 and its correlation with severity and prognosis of the lung disease: A retrospective cohort study.

Background: HRCT chest has a high sensitivity in the diagnosis of patients with COVID-19 infection. Through our study, we intend to evaluate the diagnostic accuracy and inter-reader variability of a semi-quantitative CT severity score, a novel parameter designed for risk stratification and prognostication of COVID-19 pneumonia with clinical staging of disease. Methods: It was a single-center retrospective analysis performed on an original cohort of 4180 symptomatic patients with the suspicion of SARS-CoV-2 interstitial pneumonia. Out of 4180, a total of 4004 patients with COVID-19 were confirmed by an RT-PCR. We used an HRCT chest severity score (CT-SS) to evaluate the COVID-19 disease burden on the initial scan obtained at admission. The data were analyzed with IBM SPSS Statistics Version 22.0 Release 2013. Results: Our study subjects demonstrated the most common clinical features fever, cough, dyspnea, and body aches. Raised CRP levels (CRP >0.5 mg/dL) were found in 81.86% and increased D-dimer levels (>500 ng/mL) were found in 92.3% of patients. The most common radiological findings of the disease included ground-glass opacities, observed in 98.8%. Our study has a sensitivity of 89.2%, a specificity of 94.8%, a positive predictive value (PPV) of 90.6%, and a negative predictive value (NPV) of 94%. Conclusion: As per our findings, this novel CT scoring system might aid in the risk stratification and the short-term prognostication of patients suffering from COVID-19 pneumonia. This will eventually help in curtailing the extensive burden on the healthcare system amid the current pandemic.

Anabolic-androgenic steroid use in a young body-builder: A case report and review of the literature.

Introduction: Anabolic-androgenic steroid (AAS) abuse is routine in athletes to enhance their overall physique. It often leads to detrimental effects, including cardiovascular diseases, hormonal imbalances, and cancer. Our case presentation emphasizes two important aspects: the first is the importance of thorough history taking in correctly diagnosing diseases with multiple etiologies. The second one relates to the reversible and preventable hazards of the increasing incidence of usage of illicit drugs, mainly androgenic anabolic steroids in young adults. Case presentation: We present a case of a 30-year-old male bodybuilder with presenting complaints of increased anxiousness, excessive anger, and dyspnea on minimal exertion. Echocardiogram showed a dilated cardiomyopathy with left ventricular ejection fraction (LVEF) of 20%. The patient was counseled for quitting AAS and symptomatically treated on heart failure management guidelines. He responded well to the management plan and now enjoying a healthy life. Conclusion: It is imperative to raise awareness regarding the substantial adverse effects of AAS abuse that might precipitate severe cardiovascular system complications leading to morbidity and eventual mortality. Most of the times, the pathological changes due to AAS abuse are reversible. This shows a good prognosis and better compliance with the management plan advised to the patients.

Surgical and mediastinal emphysema in critically ill COVID-19 patients: A multicentric experience.

INTRODUCTION: Coronavirus illness 2019, commonly referred to as COVID-19, is a highly infectious disease brought on by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 was declared a universal pandemic in March 2020 by the World Health Organization and is a severe health issue with unprecedented morbidity and mortality rates. Both surgical and mediastinal emphysema have been seen in cases of critically ill COVID-19 patients in several hospitals in the Eastern Province of Saudi Arabia. METHODS: This was a retrospective, cross-sectional, multicentric study involving several hospitals in the Saudi Arabian Eastern Province. Data were collected from intensive care units (ICUs) in these hospitals from March 2 to August 2, 2020. The inclusion criteria consisted of all patients who tested positive for SARS-CoV-2 and were admitted to a critical care unit. RESULTS: Thirty patients required thoracic consultation and management, including 26 males (81.3%) and 4 females (12.5%) (1:0.15) who developed surgical and mediastinal emphysema requiring thoracic surgery intervention. Most of the patients were on high ventilation settings, and the mean duration of ventilator support was 16.50 ± 13.98 days. Two patients (6.3%) required reintubation. The median positive end-expiratory pressure (PEEP) was 12 ± 2.80 cmH2O with a median FiO2 of 70% ± 19.73. On average, thoracic complications occurred on day 3 (±6.29 days) postintubation. Ten patients (33.33%) experienced a pneumothorax associated with surgical emphysema (SE), 1 patient (3.33%) presented with only mediastinal emphysema; 17 patients (56.66%) with only SE, and 1 (3.33%) had mediastinal emphysema associated with SE. We noted a correlation between the duration of ventilator support, the length of ICU stay (P < 0.001), and the total length of stay (LOS) in the hospital (P < 0.001). Total length of hospital stay showed significant association with the onset of complications (P = 0.045) and outcomes (P = 0.006). A significant association between PEEP and the duration of ventilator support was also evident with a P value = 0.009 and the onset of complications (P = 0.043). In addition, we found a significant association between the group with pneumothorax in combination with SE, and their outcomes, with a P = 0.002. CONCLUSION: Surgical and mediastinal emphysema in the critically ill patients are usually attributed to barotrauma and high ventilations settings. During COVID-19 pandemic, these entities were seen and the pathogenesis was revisited and some attributed its presence to the disease process and destruction on lung parenchyma. The associated with extended LOS and delayed recovery in addition to poor prognosis were seen. Their presence is an indicator to higher morbidity and mortality.

The Role of Optical Coherence Tomography Criteria and Machine Learning in Multiple Sclerosis and Optic Neuritis Diagnosis.

BACKGROUND AND OBJECTIVES: Recent studies have suggested that intereye differences (IEDs) in peripapillary retinal nerve fiber layer (pRNFL) or ganglion cell + inner plexiform (GCIPL) thickness by spectral domain optical coherence tomography (SD-OCT) may identify people with a history of unilateral optic neuritis (ON). However, this requires further validation. Machine learning classification may be useful for validating thresholds for OCT IEDs and for examining added utility for visual function tests, such as low-contrast letter acuity (LCLA), in the diagnosis of people with multiple sclerosis (PwMS) and for unilateral ON history. METHODS: Participants were from 11 sites within the International Multiple Sclerosis Visual System consortium. pRNFL and GCIPL thicknesses were measured using SD-OCT. A composite score combining OCT and visual measures was compared individual measurements to determine the best model to distinguish PwMS from controls. These methods were also used to distinguish those with a history of ON among PwMS. Receiver operating characteristic (ROC) curve analysis was performed on a training data set (2/3 of cohort) and then applied to a testing data set (1/3 of cohort). Support vector machine (SVM) analysis was used to assess whether machine learning models improved diagnostic capability of OCT. RESULTS: Among 1,568 PwMS and 552 controls, variable selection models identified GCIPL IED, average GCIPL thickness (both eyes), and binocular 2.5% LCLA as most important for classifying PwMS vs controls. This composite score performed best, with area under the curve (AUC) = 0.89 (95% CI 0.85-0.93), sensitivity = 81%, and specificity = 80%. The composite score ROC curve performed better than any of the individual measures from the model (p < 0.0001). GCIPL IED remained the best single discriminator of unilateral ON history among PwMS (AUC = 0.77, 95% CI 0.71-0.83, sensitivity = 68%, specificity = 77%). SVM analysis performed comparably with standard logistic regression models. DISCUSSION: A composite score combining visual structure and function improved the capacity of SD-OCT to distinguish PwMS from controls. GCIPL IED best distinguished those with a history of unilateral ON. SVM performed as well as standard statistical models for these classifications. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that SD-OCT accurately distinguishes multiple sclerosis from normal controls as compared with clinical criteria.

Association of quality of life, anxiety, and depression with restless leg syndrome in the hemodialysis patients.

OBJECTIVES: Restless Legs Syndrome (RLS) is commonly known to cause morbidity in patients on hemodialysis, making them prone to chronic mental health illnesses such as depression and anxiety, and also adversely impact quality of life. In this study, we examined the association of quality of life, anxiety, and depression with restless leg syndrome in the hemodialysis patients at Karachi Institute of Kidney Diseases. RESULTS: About 26.7% of the participants reported RLS among the sample size Presence of RLS was not associated with quality of life, depression, and anxiety. However, p-values < 0.05 were significant for body-mass index (BMI), diabetes mellitus as a cause of end-stage renal disease, and serum albumin levels. Majority (82.5%) of the RLS-diagnosed patients had moderate to severe symptoms with 16 (40%) and 17 (42.5%) clients, respectively.