RESUMEN

Speech is the most common means of communication in humans. Any defect in accurate speech production ability results in the development of speech sound disorder (SSD), a condition that can significantly impair an individual's academic performance, social interactions, and relationships with peers and adults. This study investigated the genetic basis of SSD in three Pakistani families. We performed family-based genome-wide parametric linkage analysis and homozygosity mapping in three consanguineous families with SSD from the Punjab province of Pakistan. The Test for Assessment of Articulation and Phonology in Urdu (TAAPU) was used to analyze the speech articulation data and determine the Percentage Correct Consonants (PCC) score. The PCC score defined the affected and unaffected individuals in each family. Parametric linkage analysis revealed a linkage to chromosome 5 (5q21.3-5q23.1) with a significant logarithm of the odds (LOD) score of 3.13 in a Pakistani family with specific language impairment-97 (PKSLI-97) under an autosomal recessive mode of inheritance. The other two families showed a suggestive linkage at 6p22.1, 14q12, and 16q12.1 under the recessive mode of inheritance. Interestingly, homozygosity mapping showed a loss of heterozygosity in the linkage region at 5q15-5q23.1, shared among seven affected (mostly in the younger generation) and one unaffected individual of PKSLI-97. Our analysis identified the 6p22 locus previously implicated in dyslexia, childhood apraxia of speech (CAS), and language impairment, confirming the role of KIAA0319 and DCDC2 in this locus. These findings provide statistical evidence for the genomic regions associated with articulation disorder and offer future opportunities to further the role of genes in speech production.

Asunto(s)

Consanguinidad , Ligamiento Genético , Linaje , Trastorno Fonológico , Humanos , Masculino , Femenino , Trastorno Fonológico/genética , Niño , Pakistán , Cromosomas Humanos Par 5/genética , Adulto , Adolescente , Cromosomas Humanos Par 16/genética , Escala de Lod , Cromosomas Humanos Par 14/genética , Estudio de Asociación del Genoma Completo , Mapeo Cromosómico

RESUMEN

Various metals have been complexed with drugs to improve their cellular impact. Inflammatory diseases like rheumatoid arthritis (RA) are characterized by unbalanced production of proinflammatory cytokines (PICs) and prostaglandins with decreased levels of vitamin D and calcium. The inflammation can be suppressed through targeting the formation of PICs or related enzymes by various treatment strategies that involve the use of corticosteroids, disease-modifying antirheumatic drugs and NSAIDs. We present a detailed review on the impact of calcium complexes of oxicams as an advanced treatment strategy for RA. The calcium complexes demonstrate promising capabilities to cure the disease, improve the strength of bones and suppress PICs in RA.

Asunto(s)

Antirreumáticos , Artritis Reumatoide , Humanos , Calcio , Artritis Reumatoide/tratamiento farmacológico , Inhibidores de la Ciclooxigenasa , Antiinflamatorios no Esteroideos/uso terapéutico , Antirreumáticos/farmacología , Antirreumáticos/uso terapéutico , Citocinas

RESUMEN

Emerging evidence suggests that impaired speech may be related to reduced working memory (WM). The current study aimed to validate and compare the influence of articulation, short-term memory (STM), WM, and receptive vocabulary abilities of Pakistani children with speech sound disorder (SSD; N = 50) versus typically developing (TD; N = 30) children aged 7-13 years. Assessments included the Test for Assessment of Articulation and Phonology in Urdu (TAAPU), Peabody Picture Vocabulary Test-4, translated to Urdu (U-PPVT-4), and Digit Memory Test (DMT) used to determine speech articulation, receptive vocabulary, and memory abilities respectively. The percentage correct consonants (PCC) score was used to divide the SSD group further into SSD severity groups. The TD and SSD groups significantly differed in performance on all tasks (p < 0.05). Moreover, the SSD severity groups showed significant differences (p < 0.0001) in performance on different components of TAAPU (total errors and substitution errors) and DMT tasks. However, the SSD severity groups did not show significant differences in performance on the U-PPVT-4. Correlational analyses indicate statistically significant correlations of PCC with STM, WM, and receptive vocabulary. Regression analyses suggested that both WM and STM contribute to speech intelligibility in children with SSD. Our findings in Urdu-speaking children support previous results in English-speaking children suggesting the articulation skills, receptive vocabulary, STM, and WM were less developed in children with SSD than in TD children.

Asunto(s)

Trastorno Fonológico , Niño , Humanos , Trastorno Fonológico/diagnóstico , Memoria a Corto Plazo , Vocabulario , Lenguaje , Fonética , Habla

RESUMEN

Drug development on basis of coordination compounds provides versatile structural and functional properties as compared to other organic compounds. In the present study, a new Ca(II) complex of meloxicam was synthesized and characterized by elemental analysis, FT-IR, UV-Vis, 13C NMR, SEM-EDX, powder XRD and thermal analysis (TGA). The Ca(II) complex was investigated for its in vitro, in vivo biological activities and in silico docking analysis against COX-1 and COX-2. The spectral analysis indicates that the meloxicam acts as a deprotonated bidentate ligand (coordinated to the metal atom through the amide oxygen and the nitrogen atom of the thiazolyl ring) in the complex. SEM-EDX and powder XRD analysis depicted crystalline morphology of Ca(II) complex with a crystalline size of 32.86 nm. The in vitro biological activities were evaluated by five different antioxidant methods and COX inhibition assay, while in vivo activities were evaluated by carrageenan-, histamine- and PGE2-induced paw edema methods and acetic acid-induced writhing test. The Ca(II) complex showed prominent antioxidant activities and was found to be more selective toward COX-2 (43.77) than COX-1 as compared to meloxicam. It exhibited lower toxicity (LD50 1000 mg/Kg) and significantly inhibited carrageenan- and PGE2-induced inflammation at 10 mg/Kg (P < 0.05), but no significant effect was observed on histamine-induced inflammation. Moreover, Ca(II) complex significantly reduced the number of writhes induced by acetic acid (P < 0.05). The in silico molecular docking data revealed that Ca(II) complex obstructed COX-2 (dock score 6438) more effectively than COX-1 (dock score 5732) as compared to meloxicam alone.

RESUMEN

Currently, the pandemic coronavirus disease 2019 (COVID-19) has unprecedentedly captivated its human hosts by causing respiratory illnesses because of evolution of the genetic makeup of novel coronavirus (CoV) known as severe acute respiratory syndrome coronavirus-2 (SARS CoV-2). As much as the researchers are inundated for the quest of effective treatments from available drugs, the discovery and trials of new experimental drugs are also at a threshold for clinical trials. There has been much concern regarding the new and targeted drugs considering the comprehensive ambiguity regarding the mechanism and pathway of the drug action with respect to the new and unpredictable structural and nonstructural proteins (NSPs) of SARS CoV-2. This study was aimed to discuss functional pathways related to NSPs in CoVs with updated knowledge regarding SARS CoV-2, mechanisms of action of certain approved and investigational drugs for correct orientation regarding the treatment strategies, including nucleotide analog mechanism, receptor analog mechanism, and peptide-peptide interactions, along with the impact of COVID-19 on a global scale. Although there is a dire need for targeted drugs against SARS CoV-2, the practical achievement of its cure is possible by only using effective drugs with appropriate mechanisms to eliminate the disease.

RESUMEN

Objective: To explore potential inhibitors of viral enzymes of SARS CoV-2.Methods: The in-silico docked potential of anti-viral, antibiotic, and analgesic drugs were studied for inhibition of the nonstructural protein (NSP) 9, NSP3, and NSP15 of SARS CoV-2 using recent structural peculiarities of these enzymes, 3D optimized structures of drugs and algorithm-based ligand inhibitory potential. Results: Teicoplanin, azithromycin, and remdesivir potentially inhibited NSP9 (Dock-score 9?620, 5?472 and 6?252, respectively), NSP3 (Dock-score 9?846, 5?604 and 5?548, respectively) and NSP15 (Dock-score 10?960, 6?414 and 6?002, respectively). Conclusions: Teicoplanin acts as a significant receptor antagonist and potentially inhibits the SARS CoV-2 enzymes.