Validation of LittlEARS® Early Speech Production Questionnaire in Arabic-speaking children with normal hearing

Objectives:To validate an Arabic version of the LittlEARS^® Early Speech Production Questionnaire (LEESPQ), which assesses the early development of speech and language in infants between 0 and 18 months, in Arabic-speaking children with normal hearing in Saudi Arabia.Methods:This is a cross-sectional study conducted in the city of Riyadh, Saudi Arabia between September and December 2020. Parents completed the LEESPQ regarding their child’s speech production development. To assess the ability of normal hearing children aged 0-18 months in developing speech and language production, a norm curve has been generated based on the standardized values that were calculated from the Arabic normal-hearing data set.Results:A total of 198 questionnaires were analyzed. The total score on the LEESPQ correlated with age, gender, and bilingualism. A norm curve for early speech production in children with normal hearing was created.Conclusion:The Arabic version of LEESPQ appears to be a valid questionnaire that can be used in the assessment of early language and speech development of Arabic-speaking children with normal hearing in the age range of 0-18 months. The Arabic version of the LEESPQ might also be a useful tool to detect developmental delays and hearing disorders in young children.     

Investigation of inflammation related gene polymorphism of the mannose-binding lectin 2 in schizophrenia and bipolar disorder

Objectives:To investigate the association between mannose-binding lectin 2 (MBL2) codon 54 polymorphism and clinical features of patients diagnosed with schizophrenia (SCZ) or bipolar disorder (BD).Methods:One hundred and eighteen patients with SCZ, 100 patients with BD, and 100 healthy volunteers were included in the case-control study. The patients consecutively admitted to the outpatient clinic in December 2017-May 2018 and were evaluated with some scales for clinical parameters. Polymerase chain reaction and RFLP were used to determine MBL2 polymorphism in DNA material.Results:The MBL2 gene polymorphism distributions in SCZ or BD patients were significantly different from the control group. The heterozygous genotype percentages were significantly higher in the control group than in the SCZ or BD patients (OR: 0.450; 95% Cl: 0.243-0.830; p=0.010; OR: 0.532; 95%Cl: 0.284-0.995; p=0.047, respectively), and there were statistically significant differences in the MBL2 polymorphism distributions between treatment-responsive SCZ or BD patients and treatment-resistant patients diagnosed with SCZ or BD. The heterozygous genotype percentages were also significantly higher in the treatment-responsive group than in the treatment-resistant group in SCZ or BD patients (OR: 7.857; 95% Cl: 1.006-61.363; p=0.023; OR: 8.782; 95% Cl: 1.114-69.197; p=0.016, respectively).Conclusion:The presence of a heterozygous MBL2 genotype seems to be favorable both in terms of the absence of SCZ and BD in the healthy population and treatment response for Turkish patients.

Schizophrenia (SCZ) and bipolar disorder (BD) are chronic psychiatric disorders that cause substantial disruptions in psychosocial capacity and occur in approximately 1% of the world population.¹ Genome-wide association studies (GWAS) of Psychiatric Genomics Consortium for SCZ recognized more than a hundred common single nucleotide polymorphisms (SNPs) with minor individual effects presenting susceptibility to the SCZ.² A similar mega-analysis for BD, although including a more moderate sample, identified common risk variants specific to BD.³ The long-lasting alterations in gene expression patterns after environmental exposures imply that epigenetic mechanisms might also play a critical role in chronic psychiatric disorders.⁴ Again, previous researches have constantly reported shared genetic etiology between SCZ and BD. Researches showing the genetic overlap between SCZ and BD have improved from studying family and twin inheritance to determine genetic correlation and performing polygenic risk score analysis from GWAS data in large case-control samples.⁵ Despite these researches with large sample size, the cause of both disorders is still relatively unknown; recent studies have shown that uncontrolled activity of microglia and excessive inflammatory responses caused by pro-inflammatory cytokines are among the factors that play a role in the development of SCZ and BD based on genetic susceptibility.^1,6 A relationship between SCZ and many autoimmune diseases and an increase in the prevalence of an autoimmune disease occurrence by about 45% have been found. Moreover, infections of embryonic and early childhood periods lead to delays in fetal brain development and excessive synaptic pruning during adolescence, are among the possible risk factors of psychosis.^7,8 Systemic inflammation and central inflammation are thought to be associated with episodes, remission, and prognosis of BD. Neuroendocrine irregularities, neurotransmitter abnormalities, and glial cell dysfunctions cause plastic alterations in the mood-regulating brain areas. The high rate of comorbid autoimmune diseases also supports this claim.⁹Mannose-binding lectin (MBL) has a vital function in the innate immune system by stimulating the complement system’s lectin pathway. Therefore, it is the only collectin that binds to microorganisms, serves as an opsonin, promotes phagocytosis, and stimulates macrophages. MBL2 gene, which consists of 4 exons in the q11.2-q21 region of the long arm of chromosome 10, encoded MBL. Mutation at codon 54 follows in a replacement of glycine to aspartic acid (allele B), and the normal MBL2 allele is defined by allele A.^10-12 In heterozygous mutants, serum MBL decreases almost 10-fold, whereas, in homozygous mutants, the level decreases to an undetectable level. MBL deficiency is the most common immune defect in humans, affecting approximately 5-7% of individuals.¹³ A decrease in serum MBL level can cause recurrent spontaneous miscarriage,¹⁴ premature birth,¹⁵ and exacerbation of chronic diseases such as ischemic heart disease,¹⁶ and severe infections such as sepsis and systemic inflammatory response syndrome (SIRS).¹⁷ Besides, previous studies suggested that MBL plays an essential role in the pathogenesis of autoimmune diseases.^12,18 We believe that this is the first case-control study comparing MBL2 genotype distributions in patients with SCZ or BD according to treatment resistance, clinical characteristics, and scale scores in detail.Aims of the studyWe aimed to examine whether MBL2 codon 54 polymorphism was involved in the etiopathogenesis and treatment response of SCZ and BD compared with healthy controls.     

In silico identification of potential SARS COV-2 2′-O-methyltransferase inhibitor: fragment-based screening approach and MM-PBSA calculations

In the present era, there are many efforts trying to face the emerging and successive waves of the COVID-19 pandemic. This has led to considering new and unusual targets for SARS CoV-2. 2′-O-Methyltransferase (nsp16) is a key and attractive target in the SARS CoV-2 life cycle since it is responsible for the viral RNA protection via a cap formation process. In this study, we propose a new potential inhibitor for SARS COV-2 2′-O-methyltransferase (nsp16). A fragment library was screened against the co-crystal structure of the SARS COV-2 2′-O-methyltransferase complexed with Sinefungin (nsp16 – PDB ID: 6WKQ), and consequently the best proposed fragments were linked via a de novo approach to build molecule AP-20. Molecule AP-20 displayed a superior docking score to Sinefungin and reproduced the key interactions in the binding site of 2′-O-methyltransferase. Three molecular dynamic simulations of the 2′-O-methyltransferase apo structure and its complexed forms with AP-20 and Sinefungin were performed for 150 nano-seconds to provide insights on the dynamic nature of such setups and to assess the stability of the proposed AP-20/enzyme complex. AP-20/enzyme complex demonstrated better stability for the ligand–enzyme complex compared to Sinefungin in a respective setup. Furthermore, MM-PBSA binding free energy calculations showed a better profile for AP-20/enzyme complex compared to Sinefungin/enzyme complex emphasizing the potential inhibitory effect of AP-20 on SARS COV-2 2′-O-methyltransferase. We endorse our designed molecule AP-20 to be further explored via experimental evaluations to confront the spread of the emerging COVID-19. Also, in silico ADME profiling has ascribed to AP-20 an excellent safety and metabolic stability profile.

The identification of AP-20 as a potential SARS COV-2 2′-O-methyltransferase inhibitor: fragment-based screening approach and MM-PBSA calculations.     

Colonoscopy in patients with psoriasis before the initiation of treatment with biological agents

Psoriasis may lead to subsequent colorectal cancer, since chronic systemic inflammation is the common etiologic factor in both psoriasis and colorectal cancer. It is a matter of dispute whether biological agents used in the treatment of psoriasis cause predisposition to colorectal cancer as a result of their immunosuppressive effect. Medical records of psoriasis patients who underwent colonoscopy before biological agents were reviewed. Colonoscopy was performed in all patients who were aged 50 years and older and in patients younger than 50, if they had positive fecal occult blood test results. The study included 95 patients between the age of 34 to 84. Colonoscopy results revealed tubular adenoma in 16 (16.8%) patients, hyperplastic polyps in 7 (7.4%) patients, villous adenoma in 1 (1.1%) patient, and tubulovillous adenoma in 1 (1.1%) patient. Two patients were diagnosed with colon cancer detected by a former colonoscopy, which was recommended by their dermatologist before the biological agent treatment plan. These results revealed that adenomatous polyps which can evolve to colon adenocarcinoma were the most frequent polyp type in patients with psoriasis. We suggest that routine colonoscopy should be performed before the initiation of biological therapy in psoriasis patients who are aged 50 years old and over.     

Extensive calcification of the mitral valve annulus in transcatheter aortic valve implants

 Open in a separate windowOBJECTIVESThis study sought to report the calcification pattern of the mitral valve annulus and its implications for procedural and safety outcomes in transcatheter aortic valve implantation.METHODSBetween November 2018 and September 2019, a total of 305 patients had transcatheter aortic valve implants at our institution. The extent of calcification of the mitral valve annulus was analysed, and the impact on safety outcomes was evaluated.RESULTSThe prevalence of mitral annular calcification (MAC) was 43%. Calcification of the mitral valve annulus was either less than or at least one-third of the posterior annulus (34% and 32%), the whole posterior annulus (28%) or the extension to the attachment of the anterior leaflets (7%). Severe circumferential MAC revealed moderate paravalvular leaks in 5/8 (63%) patients and was associated with right branch bundle block [odds ratio (OR) 2.01 (0.39–3.06); P = 0.098] and low cardiac output [OR 3.12 (1.39–7.04); P = 0.033]. Subannular calcification at the anterolateral trigonum represented a risk factor for left ventricular outflow tract injury [OR 3.54 (1.38–8.27); P = 0.001] in balloon-expandable valves, associated with relevant rhythm disorders [OR 2.26 (1.17–5.65); P = 0.014] and female gender (7/8, 88%). The 30-day all-cause mortality in circumferential MAC reaching into the anterior annulus (grade IV) compared to patients with less MAC (grade I–III) was 13% vs 2% with a mean valve size of 24.6 vs 25.7 mm.CONCLUSIONSExtensive MAC was associated with moderate paravalvular leaks, with implications for the prosthesis size and survival in transcatheter aortic valve implants. In severe MAC, we recommend implanting oversized self-expandable prostheses, the goal being to reduce the risk of right branch bundle block and paravalvular leaks.Subj collection122, 125     

Total versus subtotal thyroidectomy for the management of benign multinodular goiter in an endemic region

BACKGROUND: Because controversy still continuous to surround use of total thyroidectomy for the management of benign multinodular goiter, the present study aims to prospectively compare the safety and efficacy of total thyroidectomy with subtotal thyroidectomy. METHODS: A total of 200 consecutive patients with benign multinodular goiter were assigned to have either total thyroidectomy (n = 105) or subtotal thyroidectomy (n = 95) based on preoperative evaluation, intraoperative macroscopic findings and nodular dissemination. The patients with no healthy tissue or nodules localized in the dorsal part of the gland, which are usually left during normal subtotal resection, were assigned to the total thyroidectomy group. Demographic details, biochemical findings, indications for operation, operating time, specimen weight, complications and hospital stay were noted. RESULTS: There was no significant difference in the sex, hormonal status or duration of goiter between the two groups (P = 0.74, P = 0.59 and P = 0.59, respectively). The mean operating time was longer (148.52 min +/- 51.10 vs 135.10 min +/- 32.47, P = 0.03), and the mean weight of the specimens was greater (228.40 g +/- 229.91 vs 157.01 g +/- 151.23, P = 0.01) for total rather than subtotal thyroidectomy. Either temporary recurrent laryngeal nerve (RLN) palsy or hypoparathyroidism occurred in 10 (9.3%) or 12 (11.4%) of the patients undergoing total compared with six (6.3%) or nine (9.5%) of the patients undergoing subtotal thyroidectomy (P = 0.40 and P = 0.65, respectively). Either permanent RLN palsy or hypoparathyroidism was observed in one patient undergoing total thyroidectomy (P = 0.34 for each comparison). The mean hospital stay was longer in the total thyroidectomy group (2.24 days +/- 1.18 vs 1.89 days +/- 0.72 for subtotal thyroidectomy, P = 0.01). CONCLUSIONS: The present study shows that total thyroidectomy can be performed without increasing risk of complication, and it is an acceptable alternative for benign multinodular goiter, especially in endemic regions, where patients present with a huge multinodular goiter.     

Serum endostatin levels and regenerative capacities of normal and cirrhotic livers following partial hepatectomy in mice: the response to different resection sizes

BACKGROUND: Angiogenesis has an important role in liver regeneration. Antiangiogenic response in remnant liver following resection and its relationship to regeneration is not well known. The aim of this study was to investigate the effect of hepatectomy size on serum endostatin levels, and the effect of endostatin levels to liver regeneration after partial hepatectomy in normal and cirrhotic mice. MATERIALS AND METHODS: Sixty noncirrhotic and 36 carbon tetrachloride-induced cirrhotic mice were included in the study. Noncirrhotic mice were randomly divided into four main groups: sham, 20%, 40%, and 70% hepatectomy groups. Similarly, cirrhotic mice were randomly divided into three main groups: sham, 20%, and 40% hepatectomy groups. The mice in each group were further divided into two subgroups to compare serum endostatin levels and liver regeneration indexes on days 1 and 14. Liver regeneration was evaluated by the proliferating cell nuclear antigen-labeling index. Serum endostatin level was measured to evaluate antiangiogenic response. RESULTS: Serum endostatin levels on the first day and 14th day increased significantly in correlation with the hepatectomy size, both in normal mice and cirrhotic mice (P < 0.05). In normal mice with high regeneration indexes that underwent 40% and 70% hepatectomies, there was a significant increase in serum endostatin levels on the 14th day compared with the first day (P < 0.05). However, the increase in mice that underwent 20% hepatectomies was not significant. After 20% and 40% hepatectomies, first day serum endostatin levels were significantly higher in cirrhotic mice compared with normal mice (P < 0.05), which was independent of regeneration. Nevertheless, after 40% hepatectomies, 14th day serum endostatin levels were significantly lower in cirrhotic mice compared with normal mice, attributable to the limited regeneration capacity of cirrhotic liver (P < 0.05). Regeneration capacity of cirrhotic liver was low at all times. CONCLUSIONS: The current study suggests that there is a significant relationship between serum endostatin levels and regeneration capacity after hepatectomy in normal mice. On the other hand, following resection of cirrhotic liver, regeneration capacity is depressed and high endostatin levels are independent of hepatic regeneration.     

Endovascular management of isolated iliac artery aneurysms

OBJECTIVE: We reviewed our experience with endovascular treatment of isolated iliac artery aneurysms (IAAs). METHODS: Medical records for consecutive patients undergoing endovascular IAA repair from 1995 to 2004 were reviewed. Computed tomography (CT) angiograms were used to assess IAA location, size, and presence of endoleaks after endovascular repair. Rates of primary patency and freedom from secondary interventions were estimated using the Kaplan-Meier life-table method. RESULTS: From July 1995 to November 2004, 45 patients (42 men), with a mean age of 75 years, underwent endovascular repair of 61 isolated IAAs: 41 common iliac, 19 internal iliac, and one external iliac. Five patients (11%) were symptomatic, although none presented with acute rupture. The mean preoperative IAA diameter was 4.2 +/- 1.7 cm. Fifteen patients (33%) had prior open abdominal aortic aneurysm repair. Local or regional anesthesia was used in 28 cases (62%). Thirty-four patients (75%) were treated with unilateral iliac stent-grafts, eight (18%) with bifurcated aortic stent-grafts, and three (7%) with coil embolization alone. Perioperative major complications included one early graft thrombosis that eventually required conversion to open repair and one groin hematoma that required operative evacuation. On follow-up, late complications included one additional graft thrombosis and one late death after amputation. No late ruptures occurred after endovascular repair, with a mean follow-up of 22 months (range, 0 to 60 months). The mean postoperative length of stay was 1.3 +/- 1.0 days. On postoperative CT scans obtained at 1, 6, 12, 24, and 36 months, aneurysm shrinkage was noted in 18%, 29%, 57%, 67%, and 83% of IAAs, respectively, compared with the baseline diameter. One hypogastric aneurysm enlarged in the presence of a later identified type II endoleak. Five endoleaks were noted (4 type II, 1 indeterminate) at 1 month, with four other endoleaks (1 type II, 1 type III, 2 indeterminate) identified on later CT scans. At 2 years, primary patency was 95%, and freedom from secondary interventions was 88%. CONCLUSIONS: Endovascular repair of isolated IAAs appears safe and effective, with initial results similar to those after endovascular abdominal aortic aneurysm repair.     

Lisfranc injury: how frequently does it get missed? And how can we improve?

Lisfranc injuries are sometimes easily missed especially if they present in a subtle form. In this study, we have tried to measure the level of accuracy of plain radiographs in detecting this type of injury. We have selected 30 sets of foot radiographs with various diagnoses. Eighteen of them had a Lisfranc type of injury which was confirmed by operative findings or further imaging. These radiographs, together with a small diagnostic questionnaire, were presented to nine senior clinicians. We found that only 11 of the 18 cases (61%) were detected by all the readers. Eight of nine readers (90%) missed one particular case of subtle Lisfranc injury in a diabetic neuropathic foot. One case of a divergent injury was missed by five readers (56%). Another case with a coexistent Frieberg's disease was missed by three readers (33%). The mean accuracy for all injuries was 87% (95% confidence interval (CI) 84.6-89.9%). The mean accuracy level for detection of Lisfranc injury among the whole series was 92% (CI 89-95%). We think that the presence of a strong clinical index of suspicion or the presence of impaired pain sensation, further imaging is a must to avoid missing this type of injury at early presentation, and consequently the long term poor prognosis.     

Leakage evaluation of three different root canal obturation techniques using electrochemical evaluation and dye penetration evaluation methods

The aim of this study was to compare the apical sealing ability of three different obturation techniques using an electrochemical evaluation and evaluating dye penetration. One hundred and thirty-two maxillary anterior teeth were randomly divided into six groups. There were 20 teeth in each group. The teeth were obturated as follows: Groups 1 and 4 with Thermafil, Groups 2 and 5 with System B, and Groups 3 and 6 with cold lateral condensation (CLC). The apical leakage in these groups was evaluated using an electrochemical method for Groups 1, 2, 3 and a dye penetration method for Groups 4, 5 and 6. In both methods, the lowest mean leakage values were observed for Thermafil and the highest were observed for the CLC groups. The difference between Thermafil and CLC was statistically significant (P < 0.05). In both groups, System B fillings showed moderate leakage and the difference was not significant with Thermafil and CLC groups.