Comparison of systemic lupus international collaborating clinics 2012 classification criteria and European league against rheumatism/American college of rheumatology 2019 classification criteria for early detection of childhood onset systemic lupus erythematosus (multi-center study).

OBJECTIVE: To assess the performance of the new EULAR/ACR criteria, particularly for early detection of cSLE, in comparison to the SLICC criteria among the pediatric population in multiple centers in Saudi Arabia. METHODS: We conducted a retrospective study that enrolled pediatric patients up to the age of 14 years who've been diagnosed with SLE and followed in pediatric rheumatology clinics at 9 multi-tertiary hospitals in Saudi Arabia from 2010 to 2021 as a case group and were compared to a similar group of pediatric patients who've had defined rheumatological diseases other than SLE with a positive ANA titer (≥1:80) as controls. In total, 245 patients were included and distributed as 129 cases (diagnosed by expert pediatric rheumatologists) versus 116 patients in the control group. All relevant clinical information, including history, physical examination findings, and laboratory tests, was documented at the initial presentations. Then, the two sets of SLE classification criteria were applied to both groups to define who's going to meet both or either one of them. The exclusion criteria included those who had insufficient data or had overlapping or undifferentiated diseases. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), receiver operating curve (ROC), and accuracy were calculated for SLICC 2012 and EULAR/ACR 2019 criteria (total scores≥ 10 and ≥ 13). We performed a Chi-squared test to compare sensitivity and specificity of SLICC 2012 and EULAR/ACR 2019. RESULTS: For SLICC (cut-off ≥4 criteria), the sensitivity was found to be 96.9% (95% CI 92.6%-99.4%) and the specificity was 94.8% (95% CI 89.6%-98.32%), with PPV and NPV of 95.4% and 96.5%, respectively. The ROC for it was 0.96 (95% CI 0.93-0.99), and this criterion had an accuracy of 95%. Regarding EULAR/ACR (total score ≥ 10), the performance measure showed a sensitivity of 99.2% and a specificity of 86.2%. Similarly, PPV was 88.9%; while NPV was a little higher (99.0%) than SLICC. The ROC for EULAR/ACR (total score ≥ 10) was 0.93 (95% CI 0.89-0.96), and this criterion had an accuracy of 93%. However, there was no statistically significant difference between the sensitivity and specificity of either using SLICC or EULAR/ACR (total score ≥ 10), as reflected by a p-value of 0.86 using the Chi-squared test. Although applying the EULAR/ACR with a total score of ≥ 13 revealed lower sensitivity (93.8%) than both the SLICC and the EULAR/ACR (total score ≥ 10), the specificity for it was found to increase up to 91.4% (85.7-96.2%) compared to the (86.2%) specificity of the EULAR/ACR (total score ≥ 10). CONCLUSION: In this cohort among the Saudi population with childhood-onset SLE, the new EULAR/ACR 2019 criteria efficiently enable early detection of SLE, although a more frequent rate of false positives was observed with them. Escalating the total score from ≥ 10 to ≥ 13 in the cSLE population improved the specificity close to that of SLICC 2012. Further prospective studies in pediatrics need to be done for the validation of a cut- off score of ≥ 13 in cSLE rather than the traditional score of ≥ 10 in aSLE.

Monogenic interferon-mediated diseases: novel phenotype and genotype characteristics from a Saudi population.

OBJECTIVES: IFN-mediated diseases are mendelian innate immunodysregulatory disorders that present early in life with fevers, sterile organ inflammation, and a high type-I IFN-response gene signature in peripheral blood cells. To date, monumental discoveries of novel genetic variants with various phenotypic features have been recognised. We aimed to describe the genotype and phenotype findings in Saudi children diagnosed with autoinflammatory interferonopathy and to report novel findings. METHODS: This is a descriptive retrospective cohort study of children with genetically confirmed type I interferonopathies. Medical records were reviewed for demographic, family history, clinical and laboratory data. All patients underwent genetic testing. RESULTS: A total of 20 patients (11 females) were included in the study. Sixteen patients (80%) presented within the first 2 years. The median age of disease onset was 0.87 years (IQR: 0.5-2) and the median age of diagnosis was 4.5 years (IQR: 2-7.5). The rates of consanguinity and family history of affected members were high (88% and 47%, respectively). Among the cohort of patients, whole exome sequencing was conducted for 15 patients. Three patients underwent targeted gene tests, and 2 patients had a leukoencephalopathy genetic panel. Eight patients were diagnosed with Aicardi-Goutières syndrome, attributed to variants in the RNASEH2A, RNASEH2C, and IFIH1 genes. Additionally, 2 patients were identified with STING-associated vasculopathy with onset in infancy linked to the TMEM173 variant. One patient exhibited chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature due to PSMB8, and another patient had DNase II. Moreover, 8 patients presented with rare interferonopathy conditions, including three with ISG15, 3 with ZNFX1, 1 with the SOCS1 variant, and 1 the STAT1 variant. Of 12 variants, six (50%) found to have novel genetic variants. The most frequent features were fever (75%), neurology (70%), mucocutaneous (60%), gastrointestinal (50%), and pulmonary (50%). Hypogammaglobinaemia and recurrent infections were seen in (45%) and (20%), respectively. Fifteen patients (75%) had elevated inflammatory markers. The majority of patients received intensive treatment, including corticosteroids, JAK inhibitors, IVIG, and various immunosuppressive agents. Despite these interventions, a partial response to treatment was observed, and cumulative disease damage primarily manifested as growth failure and developmental delay. CONCLUSIONS: Our findings support the previous reports; early-onset fever, neurology, and respiratory features should raise the suspicion of interferonopathies. However, there is eminent evidence of phenotypic variability. Our data also expanded the spectrum of clinical findings in relation to novel genetic variants.

Molecular dynamics exploration of Lupenone: therapeutic implications for glioblastoma multiforme and alzheimer's amyloid beta pathogenesis.

Neuro-oncological and neurodegenerative disorders, represented paradigmatically by glioblastoma and Alzheimer's disease, respectively, persist as formidable challenges in the biomedical realm. The interconnected molecular underpinnings of these conditions necessitate rigorous and novel therapeutic examinations. This comprehensive research was anchored on the premise of unveiling the therapeutic potential and specificity of Lupenone, a potent phytoconstituent, in targeting the molecular pathways underpinning both glioblastoma and Alzheimer's amyloid beta pathology. This was gauged through its interactions with key protein structures, 5H08 and 2ZHV. An integrative approach was adopted, marrying advanced proteomics and modern computer-aided drug design techniques. Molecular docking of Lupenone with 5H08 and 2ZHV was meticulously executed, with subsequent molecular dynamics simulations providing insights into the stability, viability, and intricacies of these interactions. Lupenone demonstrated profound binding affinities, evidenced by robust docking scores of -9.54 kcal/mol for 5H08 and -10.59 kcal/mol for 2ZHV. These interactions underscored Lupenone's eminent therapeutic potential in mitigating glioblastoma and modulating the amyloid beta pathology inherent to Alzheimer's. The introduction of Proteolysis Targeting Chimeras (PROTACs) further magnified the therapeutic prospects, accentuating Lupenone's efficacy. The findings of this study not only underscore the therapeutic acumen of Lupenone in addressing the challenges posed by glioblastoma and Alzheimer's but also lay a strong foundation for its consideration as a leading candidate in future neuro-oncological and neurodegenerative research endeavors. Given the compelling in-silico data, a clarion call is made for its empirical validation in holistic in-vivo settings, potentially pioneering a new therapeutic epoch in both glioblastoma and Alzheimer's interventions.

A homozygous truncating mutation of FGL2 is associated with immune dysregulation.

BACKGROUND: The type II transmembrane protein fibrinogen-like protein 2 (FGL2) plays critical roles in hemostasis and immune regulation. The C-terminal immunoregulatory domain of FGL2 can be secreted and is a mediator of regulatory T (Treg) cell suppression. Fgl2-/- mice develop autoantibodies and glomerulonephritis and have impaired Treg cell function. OBJECTIVE: Our aim was to identify the genetic underpinning and immune function in a patient with childhood onset of leukocytoclastic vasculitis, systemic inflammation, and autoantibodies. METHODS: Whole-exome sequencing was performed on patient genomic DNA. FGL2 protein expression was examined in HEK293 transfected cells by immunoblotting and in PBMCs by flow cytometry. T follicular helper cells and Treg cells were examined by flow cytometry. Treg cell suppression of T-cell proliferation was assessed in vitro. RESULTS: The patient had a homozygous mutation in FGL2 (c.614_617del:p.V205fs), which led to the expression of a truncated FGL2 protein that preserves the N-terminal domain but lacks the C-terminal immunoregulatory domain. The patient had an increased percentage of circulating T follicular helper and Treg cells. The patient's Treg cells had impaired in vitro suppressive ability that was rescued by the addition of full-length FGL2. Unlike full-length FGL2, the truncated FGL2V205fs mutant failed to suppress T-cell proliferation. CONCLUSIONS: We identified a homozygous mutation in FGL2 in a patient with immune dysregulation and impaired Treg cell function. Soluble FGL2 rescued the Treg cell defect, suggesting that it may provide a useful therapy for the patient.

Outcome of Colorectal Robotic Surgery in Newly Established Robotic Surgery Center: A Case Series.

INTRODUCTION: The robotic platform compared to laparoscopy has proven to have similar postoperative outcomes, however its adoption in the Middle East has been slow and there is limited data regarding outcomes with its use in small newly established robotic colorectal programs. Our aim was to report our experience and outcomes of robotic colorectal surgery performed by fellowship-trained robotic colorectal surgeons and compare them to larger, more experienced centers. METHODS: This is retrospective review of data collected between November 2021 and March 2023 from a tertiary health care referral center. The series included 51 patients who had elective or urgent robotic colorectal surgery. Patients who had emergency surgery were excluded. The outcomes were overall morbidity, serious morbidity, mortality, conversion to open, length of hospital stay, and quality of oncological specimen. RESULTS: The overall morbidity was 31.4% (n = 16 patients). Only 9.8% (n = 5) had serious morbidity of which three required interventions under general anesthesia. The median length of hospital stay was 6 days (IQR = 4), and there was no mortality. Of 17 rectal cancer resections, 88% had complete mesorectal excision, 15 of them were R0 resections, median lymph node harvested was 14 (IQR = 7) and two cases were converted to open. All the colon cancer resections had R0 resection, median lymph nodes harvested was 21 (IQR = 4) and none were converted to open. CONCLUSIONS: The implementation and integration of robotic colorectal surgery at a newly established center in a small country, when led by fellowship trained robotic colorectal surgeons, is safe and effective in terms of morbidity, mortality, conversion to open and specimen pathological quality.

Validation of the PEDiatric Behçet's Disease classification criteria: an evidence-based approach.

OBJECTIVES: to validate the PEDiatric Behçet's Disease classification criteria (PEDBD) with an evidence-based approach. METHODS: 210 pediatric patients (70 Behçet's disease (BD), 40 Periodic Fever, Aphthous stomatitis, Pharyngitis, Adenitis, 35 familial Mediterranean fever, 26 hyper-IgD syndrome, 22 TNF-Receptor associated Periodic fever Syndrome, 17 undefined recurrent fevers) were randomly selected from the Eurofever Registry. A set of 11 experienced clinicians/researchers blinded to the original diagnosis evaluated the patients. Using the table consensus as gold standard (agreement ≥ 80%), the PEDBD, ISG and ICBD criteria were applied to BD patients and to confounding diseases with other autoinflammatory conditions in order to define their sensitivity, specificity and accuracy. RESULTS: At the end of the third round, a consensus was reached in 139/210 patients (66.2%). The patients with a consensus ≥80% were classified as confirmed-BD (n = 24), and those with an agreement of 60-79% as probable-BD (n = 10). When comparing these patients with the confounding diseases group, an older age at disease onset, the presence of oral and genital ulcers, skin papulo-pustular lesions, a positive pathergy test and posterior uveitis were BD distinctive elements. The ISG, ICBD and PEDBD criteria were applied to confirmed-BD and to the confounding disease group, showing a sensitivity of 0.50, 0.79 and 0.58, a specificity of 1.00, 0.97, 0.99, and an accuracy of 0.91, 0.94 and 0.92, respectively. CONCLUSIONS: the PEDBD criteria were very specific, while the ICBD resulted to be more sensitive. The complexity of childhood BD suggests larger prospective international cohorts to further evaluate the performance of the criteria.

Comparison of EULAR/PRINTO/PReS Ankara 2008 and 2022 ACR/EULAR Classification Criteria for Granulomatosis with Polyangiitis in Children.

OBJECTIVE: Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibody-associated vasculitis. The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR)-endorsed classification criteria for GPA was derived using data only from adult patients. We aimed to assess the performance of the ACR/EULAR classification criteria for GPA in pediatric patients and compare it with the EULAR/Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology European Society (PReS)-endorsed Ankara 2008 criteria for GPA. METHODS: Retrospective data of pediatric patients with GPA in 20 centers from 9 countries were evaluated. The diagnosis of GPA was made according to the expert opinion. The sensitivity, specificity, positive predictive value, and negative predictive value of the criteria sets were evaluated. RESULTS: The study included 77 patients with GPA and 108 controls (immunoglobulin A vasculitis (n = 44), Takayasu's arteritis (n = 20), microscopic polyangiitis (n = 16), polyarteritis nodosa (n = 14), Behçet's disease (n = 12), eosinophilic granulomatosis with polyangiitis (n = 1), and Cogan's syndrome (n = 1)) with a median age of 17.8 and 15.2 years, respectively. Of patients with GPA, constitutional symptoms (85.7%) and ear-nose-throat involvement (79.2%) were the most common presentations. In the GPA group, 73 patients fulfilled the Ankara 2008 criteria and 69 the ACR/EULAR classification criteria. Sensitivities of the Ankara 2008 criteria and the ACR/EULAR classification criteria were 94.8% and 89.6%, while specificities were 95.3% and 96.3%, respectively. No significant difference was found between sensitivities and specificities of both classification criteria (p= 0.229 and p= 0.733, respectively). CONCLUSION: In children, both the ACR/EULAR and EULAR/PRINTO/PReS Ankara 2008 classification criteria for GPA perform well and similarly.

Phenotype and disease course differences in monogenic and sporadic childhood lupus.

OBJECTIVE: To report the differences in phenotypic characteristics, disease course, and outcome in monogenic and sporadic childhood lupus (SC-lupus) from a single tertiary childhood lupus clinic. METHODS: A descriptive, observational, cross-sectional study was conducted. Data were retrospectively collected at the last follow-up visit on patients with monogenic lupus proven by genetic variants and SC-lupus seen between June 1997 and July 2022. SC-lupus patients were selected by systematic sampling from lupus patients presenting to our lupus clinic; the first patient was chosen randomly, and the subsequent patients were chosen at intervals of three. Data comprised the clinical and laboratory findings, disease activity using the SLEDAI, and damage measured by the pSDI. RESULTS: A total of 54 patients with a median disease duration of 6.8 (IQR 3.5-10.5) years were included. There were 27 patients with monogenic lupus and 27 patients with SC-lupus, with a median age at disease onset of 3.5 (IQR 1.0-6.0), and 9.5 (IQR 7.0-11.8), respectively. (p < 0.05). The rate of consanguinity and family history of lupus were higher in monogenic lupus patients. The two groups were comparable. However, monogenic lupus patients showed more gastrointestinal tract symptoms, and failure to thrive (p < 0.05). They also had more infections. The frequency of the autoantibody profile was higher in monogenic lupus patients. Belimumab was more frequently used in monogenic lupus while rituximab in SC-lupus patients. Monogenic lupus patients had a higher mean SLEDAI, but statistically, it was insignificant. Patients with monogenic lupus had greater disease damage, with a higher mean pSDI and a higher mortality rate (p < 0.05). CONCLUSION: Patients with monogenic lupus are likely to have an early disease onset and a strong family history of lupus, as well as a guarded prognosis, which is likely due to the disease's severity and frequent infections. These differences may be related to the high consanguinity rate and underlying genetic variants.

New insights on genetic variants and phenotypic features of childhood large-vessel vasculopathy: a systematic review and single-centre series.

OBJECTIVES: To describe the phenotypic, genetic, and outcome characteristics of large-vessel vasculopathy (LVV) in childhood associated with genetic variants. Additionally, a systematic literature review was conducted to delineate the differences between LVV with and without genetic variants. METHODS: The medical records of all children with LVV seen between January 2000 and September 2022 at our institution were retrospectively reviewed for demographic, clinical and genetic data, and outcomes at the last follow-up visit. In addition, we systematically reviewed the literature for the clinical features and known variants of previously reported cases. RESULTS: Eleven patients with childhood LVV were identified; five (three males) of them had proven genetic variants (two DOCK8variants, one FOXP3, one DiGeorge syndrome, and one ZNF469 variant), while six patients had sporadic childhood LVV. Remarkably, patients with genetic variants were younger and had early-onset disease. However, the diagnosis of LVV was delayed compared to those without genetic variants. All patients with genetic variants were treated with corticosteroids, and three patients required sequential immunosuppressive drugs. Four patients underwent surgical intervention, and one received a haematopoietic stem-cell transplant (HSCT). Three patients achieved clinical remission, and two died. Furthermore, data from 20 previously published cases was extracted from the literature. All patients had inherited disorders. Of those, 14 patients had a genetically proven diagnosis. Most of them are treated with corticosteroids and immunosuppressive drugs, with partial responses. Two patients underwent HSCT. There were four deaths. CONCLUSIONS: This study demonstrates that a variety of inherited disorders may contribute to childhood LVV. Strong genetic evidence and the preponderance of autosomal-recessive inheritance may allow us to propose that monogenic LVV is a distinct entity.

Approaches through effects of Hall current, nanoparticle radius, inter-particle spacing and multiple slips on the suspension of copper-water nanofluid with gyrotactic microorganisms.

In this comprehensive study, the dynamic behavior of a copper-water nanofluid infused with gyrotactic microorganisms, focusing on the effects of Hall current, nanoparticle radius, inter-particle spacing, and multiple slip mechanisms is investigated. Through advanced numerical simulations and rigorous analysis, intricate relationships between the parameters and the suspension's characteristics are uncovered. Comparison of the present results show a good agreement with the published results. The research findings unveil the potential for fine-tuning transport processes, manipulating thermal properties, and controlling dispersion and aggregation in nanofluids. These insights hold promise for a wide array of applications, from enhancing heat exchangers and cooling systems to pioneering biomedical devices utilizing gyrotactic microorganisms for targeted drug delivery and sensing. This study not only advances the fundamental understanding of nanofluid dynamics but also paves the way for innovative developments across various scientific and engineering domains.

LEPREL1 -RELATED GIANT RETINAL TEAR DETACHMENTS MIMIC THE PHENOTYPE OF OCULAR STICKLER SYNDROME.

PURPOSE: To describe the features of retinal detachments and high myopia in patients with novel pathogenic variants in LEPREL1 and report a possible association with nephropathy. METHODS: Retrospective study of 10 children with biallelic LEPREL1 pathogenic variants. Data included ophthalmic features, surgical interventions, and genetic and laboratory findings. RESULTS: 10 patients (8 females) from three families with homozygous (2) or compound heterozygous (1) variants in LEPREL1 were included. At presentation, mean age was 9.9 ± 2.6 years. Mean axial length was 28.9 ± 1.9 mm and mean refraction was -13.9 ± 2.8 diopters. Bilateral posterior subcapsular cataracts were present in eight patients (80%), with lens subluxation in five eyes of three patients (30%). Rhegmatogenous retinal detachments (RRD), associated with giant retinal tears (GRT), developed in seven eyes of five patients (50%) at a mean age of 14.14 ± 5.9 years. Six were successfully reattached with mean Snellen best-corrected visual acuity improving from 20/120 preoperatively to 20/60 at last follow-up. Urinalysis in nine patients revealed microhematuria and/or mild proteinuria in six patients (67%). CONCLUSION: LEPREL1 -related high myopia confers a high risk of early-onset GRT-related RRD. The ocular phenotype may be confused with that of ocular Stickler syndrome if genetic testing is not performed. Further investigations into a potential association with renal dysfunction are warranted.

Super pulsed thulium fiber laser outcomes in retrograde intrarenal surgery for ureteral and renal stones: a systematic review and meta-analysis.

BACKGROUND: Laser lithotripsy using a thulium fiber laser (TFL) has become an effective treatment option for small renal stones with low complication rates. TFL has a higher absorption coefficient, smaller fibers, and better pulse rate capability. METHODS: We conducted a systematic review and meta-analysis to evaluate the published evidence regarding TFL's lithotripsy performance in retrograde intrarenal surgery (RIRS), for which we primarily assessed the outcomes of stone-free rate, operation time, and complications. We searched different databases from inception to April 2023. We assessed the methodological quality and risk of bias using the Cochrane Risk of Bias tool for randomized trials and the ROBINS-I tool for non-randomized studies. We used a random-effects model for meta-analysis and assessed heterogeneity using the I2 statistic. RESULTS: Twelve published studies evaluated the efficacy of RIRS using a TFL for treating renal and ureteral stones. The meta-analysis revealed a predicted stone-free rate of 89.37% (95% CI: 83.93% to 93.12%), indicating that, on average, approximately 89.37% of patients achieved a stone-free state after treatment. The substantial heterogeneity among the studies was evident, as shown by a Q-value of 33.1174 and a p-value of 0.0003. The I2 value of 69.80% (95% CI: 25.91% to 92.02%) highlighted the proportion of variability attributed to genuine heterogeneity across the studies. Moreover, the H2 value 3.31 (95% CI: 1.35 to 12.53) indicated significant heterogeneity beyond random chance. The estimated overall effect size (logit-transformed) of 2.1289 was highly statistically significant (z = 8.7648, p < 0.0001) with a confidence interval of 1.6528 to 2.6049. The reported complications varied across studies, encompassing Clavien grade I-II complications in most cases, with a subset experiencing more severe Clavien grade III-V complications. Additionally, other studies noted a range of complications, such as haematuria, fever, transient creatinine elevation, and postoperative issues like bleeding, pain, and sepsis. CONCLUSION: This meta-analysis suggests that RIRS using TFL is an effective and safe treatment option for renal and ureteral stones, with high stone-free and low complication rates. The included studies exhibited a low risk of bias and were of high quality. However, more extensive randomized controlled trials with extended follow-up periods are needed to investigate this technique's efficacy and safety.

Targeted Drug Administration onto Cancer Cells Using Hyaluronic Acid-Quercetin-Conjugated Silver Nanoparticles.

Quercetin (QtN) displays low systemic bioavailability caused by poor water solubility and instability. Consequently, it exerts limited anticancer action in vivo. One solution to increase the anticancer efficacy of QtN is the use of appropriate functionalized nanocarriers that preferentially target and deliver the drug to the tumor location. Herein, a direct advanced method was designed to develop water-soluble hyaluronic acid (HA)-QtN-conjugated silver nanoparticles (AgNPs). HA-QtN reduced silver nitrate (AgNO3) while acting as a stabilizing agent to produce AgNPs. Further, HA-QtN#AgNPs served as an anchor for folate/folic acid (FA) conjugated with polyethylene glycol (PEG). The resulting PEG-FA-HA-QtN#AgNPs (further abbreviated as PF/HA-QtN#AgNPs) were characterized both in vitro and ex vivo. Physical characterizations included UV-visible (UV-Vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), particle size (PS) and zeta potential (ZP) measurements, and biopharmaceutical evaluations. The biopharmaceutical evaluations included analyses of the cytotoxic effects on the HeLa and Caco-2 cancer cell lines using the MTT assay; cellular drug intake into cancer cells using flow cytometry and confocal microscopy; and blood compatibility using an automatic hematology analyzer, a diode array spectrophotometer, and an enzyme-linked immunosorbent assay (ELISA). The prepared hybrid delivery nanosystem was hemocompatible and more oncocytotoxic than the free, pure QtN. Therefore, PF/HA-QtN#AgNPs represent a smart nano-based drug delivery system (NDDS) and could be a promising oncotherapeutic option if the data are validated in vivo.

Echocardiographic Left Ventricular Hypertrophy and Geometric Patterns in Patients with Sickle Cell Anaemia.

BACKGROUND: Left ventricular hypertrophy (LVH) is a common complication in patients with sickle cell anaemia (SCA), and it has been associated with systolic and diastolic dysfunction, and sudden death. There is a wide variation in the reported prevalence of LVH in patients with SCA, partly due to the varying criteria applied, and the impact of small weight and body surface area (BSA) in SCA patients. We used four different criteria to determine echocardiographic LVH and geometric patterns in patients with steady-state SCA. Left ventricular hypertrophy was defined by LVM, LVM indexed to BSA, LVM indexed to height and LVM indexed to height2.7 using gender-specific reference values. Left ventricular geometry was determined using LVH and relative wall thickness. RESULTS: Eighty-two patients with steady-state SCA, aged 18years and above were studied from January 2018 to April 2018. The median [IQR] age of the patients was 23 [10] years. Forty-seven (57.3%) were females. The prevalence of LVH was highest when LVM was indexed to BSA (80.5%), followed by LVM indexed to height (73.2%). Comparable prevalences of 68.3% and 69.5% were observed using LVM and LVM indexed to height2.7, respectively. The prevalence of LVH was similar in males and females for all the criteria. CONCLUSION: The prevalence of LVH is high among patients with steady-state SCA irrespective of the criteria applied. The most prevalent geometric pattern was eccentric LVH. Indexing to BSA might result in over-estimation of LVH given the relatively small BSA in patients with SCA. Indexing to height 2.7 might give a more accurate estimate of LVH.

CONTEXTE: L'hypertrophie ventriculaire gauche (HVG) est une complication fréquente chez les patients atteints d'anémie falciforme (ACS), et elle a été associée à un dysfonctionnement systolique et diastolique, ainsi qu'à une mort subite. La prévalence de l'HVG chez les patients atteints d'anémie falciforme varie considérablement, en partie à cause des différents critères appliqués et de l'impact du petit poids et de la surface corporelle (BSA) des patients atteints d'anémie falciforme. Nous avons utilisé quatre critères différents pour déterminer l'HVG échocardiographique et les schémas géométriques chez les patients atteints d'ACS à l'état stable. L'hypertrophie ventriculaire gauche a été définie par la MVL, la MVL indexée sur la surface corporelle, la MVL indexée sur la taille et la MVL indexée sur la taille2,7 en utilisant des valeurs de référence spécifiques au sexe. La géométrie du ventricule gauche a été déterminée en utilisant l'HVG et l'épaisseur relative de la paroi. RÉSULTATS: Quatre-vingts deux patients atteints d'ACS à l'état stable, âgés de 18 ans et plus ont été étudiés de janvier 2018 à avril 2018. L'âge médian [IQR] des patients était de 23 [10] ans. Quarantesept (57,3 %) étaient des femmes. La prévalence de l'HVG était la plus élevée lorsque la MVL était indexée sur la BSA (80,5 %), suivie de la MVL indexée sur la taille (73,2 %). Une prévalence comparable de 68,3 % et 69,5 % a été observée en utilisant la MVL et la MVL indexée sur la taille2,7, respectivement. La prévalence de l'HVG est similaire chez les hommes et les femmes pour tous les critères. CONCLUSION: La prévalence de l'HVG est élevée chez les patients atteints d'ACS à l'état stable, quel que soit le critère appliqué. Le modèle géométrique le plus répandu est l'HVG excentrique. L'indexation à la BSA pourrait entraîner une surestimation de l'HVG étant donné la BSA relativement faible chez les patients atteints d'ACS. L'indexation à la taille 2,7 pourrait donner une estimation plus précise de l'HVG. Mots clés: Hypertrophie ventriculaire gauche; Géométrie ventriculaire gauche; Drépanocytose ; Échocardiographie.

The ameliorative effect of bergamot oil nano-emulsion in stressed rabbit bucks: Influence on blood biochemical parameters, redox status, immunity indices, inflammation markers, semen quality, testicular changes and the expression of HSPs genes.

This work explored the activities of bergamot oil nano-emulsion (NBG) in modulating blood biochemical parameters, redox status, immunity indices, inflammation markers, semen quality, testicular changes and the expression of HSPs genes in stressed rabbit bucks. Twenty-four mature rabbit bucks (5 months) were randomly divided into three groups; control group (NBG0) received 1 ml of distilled water, while the other two groups received NBG orally at doses of 50 and 100 mg/kg (bw) twice a week. The present study's findings revealed that treated groups had lower values of total and direct bilirubin, triglyceride, lactate dehydrogenase, and creatinine compared with NBG0 group (p < 0.05). NBG100 group recorded the greatest of total protein, albumin, GPx, T3 and T4 values as well as the lowest values of uric acid, MDA, and indirect bilirubin. Both treated groups showed significantly reduced 8-OhDG, Amyloid A, TLR 4, while significantly increased nitric oxide, IgA, IgM, TAC, and SOD levels. Semen characteristics such as volume, sperm count, sperm motility, normal sperm, and vitality were significantly higher in the NBG100 group compared to the NBG50 and NBG0 groups, whereas sperm abnormalities and dead sperm were significantly reduced. HSP70, HSP72, and HSPA9 gene overexpression showed that testicular integrity was maintained after buck received oral doses of 50 or 100 mg/kg of NBG. Existing findings indicate that oral administration of NBG improves heat tolerance in rabbit bucks primarily as e result of its antioxidant and anti-inflammatory effects.

Diagnostic usefulness of serum procalcitonin in patients with bacterial sepsis.

Background: The Sequential Organ Failure Assessment (SOFA) score is used for the diagnosis of sepsis and involves clinical and laboratory parameters that may not be readily and/or timely available in most resource-poor settings. Procalcitonin (PCT) has its level changed in response to bacterial sepsis and its measurement costs only a fraction of the total cost of investigations required to calculate SOFA score. This study aims to determine the diagnostic usefulness of PCT in bacterial sepsis. Materials and Methods: Ninety-nine participants were studied, divided into three groups: apparently healthy volunteers, those with bacterial infection without sepsis (SOFA score <2), and patients with bacterial sepsis (positive culture and SOFA ≥2). PCT level of each participant was measured and median group levels compared. Pearson's correlation was used to determine the correlation between serum PCT levels and SOFA scores in the sepsis group using a significance level of 5 percent (P < 0.05). Diagnostic usefulness of PCT was assessed using receiver operating characteristic (ROC). Result: Positive correlation was found between serum PCT levels and SOFA scores among patients with sepsis r = 0.42, P = 0.016. At a concentration of ≥4.25 ng/ml, serum PCT as a surrogate for SOFA score had a sensitivity and specificity of 57.60% and 84.80%, respectively, for indicating sepsis. The area under the ROC curve (AUC) was 0.74 (95% CI {0.62 to 0.86}, P = 0.001). Conclusion: Serum PCT concentration was significantly higher in bacterial sepsis compared to bacterial infection without sepsis and healthy state. PCT concentration demonstrated positive correlation with SOFA score in bacterial sepsis and can be used as surrogate for sepsis screening/monitoring in resource-poor settings.

Emerging contaminants of high concern for the environment: Current trends and future research.

Wastewater is contaminated water that must be treated before it may be transferred into other rivers and lakes in order to prevent further groundwater pollution. Over the last decade, research has been conducted on a wide variety of contaminants, but the emerging contaminants are those caused primarily by micropollutants, endocrine disruptors (EDs), pesticides, pharmaceuticals, hormones, and toxins, as well as industrially-related synthetic dyes and dye-containing hazardous pollutants. Most emerging pollutants did not have established guidelines, but even at low concentrations they could have harmful effects on humans and aquatic organisms. In order to combat the above ecological threats, huge efforts have been done with a view to boosting the effectiveness of remediation procedures or developing new techniques for the detection, quantification and efficiency of the samples. The increase of interest in biotechnology and environmental engineering gives an opportunity for the development of more innovative ways to water treatment remediation. The purpose of this article is to provide an overview of emerging sources of contaminants, detection technologies, and treatment strategies. The goal of this review is to evaluate adsorption as a method for treating emerging pollutants, as well as sophisticated and cost-effective approaches for treating emerging contaminants.

The impact of ABO blood groups on clinical outcomes and susceptibility to COVID-19: A retrospective study in an unselected population.

BACKGROUND: ABO blood groups have been linked to susceptibility to infection with certain microorganisms, including coronaviruses. We examined the relationship between blood group and clinical outcomes in individuals infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and compared their blood group distribution with the general population. METHODS: At the inception of the pandemic, all individuals testing positive for SARS-CoV-2 in Kuwait were admitted to one designated coronavirus disease 2019 (COVID-19) hospital and enrolled in a prospective registry. Patients admitted from February 24 to May 27, 2020, were stratified according to blood group. As a control, blood groups of 3,730,027 anonymized individuals representing almost Kuwait's entire population were obtained from a national database. RESULTS: Of 3305 SARS-CoV-2-positive patients, 37.1%, 25.5%, 28.9%, and 8.5% were groups O, A, B, and AB, respectively. Univariate analysis revealed no significant differences in severe clinical outcomes or death among the blood groups. However, multivariable analysis demonstrated that group A individuals had higher odds of developing pneumonia compared with non-group A (adjusted odds ratio 1.32, 95% confidence interval 1.02-1.72, p < .036). Compared with the general population, the COVID-19 cohort had a lower frequency of group O, equivalent frequency of A, and higher frequency of B and AB. No significant difference in the RhD group was found. CONCLUSION: This study supports potential involvement of the ABO blood group system in predisposing to infection with SARS-CoV-2 in an unselected population. Examination of the mechanistic link between blood group and COVID-19 and its implications on controlling the current pandemic is warranted.

Fatal automobile accident due to airbag misdeployment.

The purpose of this case report was to demonstrate a fatal motor vehicle accident in which a 33-year-old man died at the scene immediately after his car collided with the roadside curbstone at a normal speed. The autopsy of the deceased body revealed a penetrating injury on the neck as he was struck by the deployed airbag. Pathological examination showed the offending material to be a fractured cylinder-shaped metal piece, which had settled within the fourth cervical vertebral body. Further forensic engineering investigation of the airbag unit found that the metal fragment originated from a defective airbag gas generator, which had exploded upon deployment. These findings reflect on the increasing popularity of airbag-associated trauma across the globe in recent years. We suggest an effective management plan for the evaluation and mitigation of the complications associated with airbag-related incidents.

Familial Clustering of Juvenile Psoriatic Arthritis Associated with a Hemizygous FOXP3 Mutation.

PURPOSE OF REVIEW: We describe the clinical and genetic findings in four patients from a single family who presented with refractory psoriatic arthritis and were hemizygous in the forkhead box protein 3 (FOXP3) gene (c.1222G>A). RECENT FINDINGS: We report four siblings with hemizygous mutation in the FOXP3 gene (c.1222G>A) who presented with type 1 diabetes mellitus and psoriatic arthritis poorly responsive to treatment. Our findings expand the phenotype spectrum of FOXP3 mutations. Immune dysregulation, polyendocrinopathy, and enteropathy, X-linked (IPEX) syndrome is a rare disorder caused by mutations in FOXP3 gene, which lead to early onset of constellation of autoimmune manifestations. This report highlights the influence of immune dysregulation in juvenile arthritis.