Mechanistic insights into anti-inflammatory and immunosuppressive effects of plant secondary metabolites and their therapeutic potential for rheumatoid arthritis.

The anti-inflammatory and immunosuppressive activities of plant secondary metabolites are due to their diverse mechanisms of action against multifarious molecular targets such as modulation of the complex immune system associated with rheumatoid arthritis (RA). This review discussed and critically analyzed the potent anti-inflammatory and immunosuppressive effects of several phytochemicals and their underlying mechanisms in association with RA in experimental studies, including preliminary clinical studies of some of them. A wide range of phytochemicals including phenols, flavonoids, chalcones, xanthones, terpenoids, alkaloids, and glycosides have shown significant immunosuppressive and anti-inflammatory activities in experimental RA models and a few have undergone clinical trials for their efficacy and safety in reducing RA symptoms and improve patient outcomes. These phytochemicals have potential as safer alternatives to the existing drugs in the management of RA, which possess a wide range of serious side effects. Sufficient preclinical studies on safety and efficacy of these phytochemicals must be performed prior to proper clinical studies. Further studies are needed to address the barriers that have so far limited their human use before the therapeutic potential of these plant-based chemicals as anti-arthritic agents in the treatment of RA is fully realized.

Inhibition of nitric oxide and prostaglandin E2 production by pyrrolylated-chalcones: Synthesis, biological activity, crystal structure analysis, and molecular docking studies.

In search of potent anti-inflammatory agents, twenty-four chalcone derivatives including seven new compounds (13 - 17, 21 and 23) containing pyrrole moiety were designed, synthesized, and assessed for their nitric oxide (NO) and prostaglandin E2 (PGE2) suppression ability on IFN-γ/LPS-induced RAW 264.7 macrophage cells. Results showed that none of the synthesized compounds were PAINS-associated molecules, with 3-(2,5-dimethoxyphenyl)-1-(1H-pyrrol-2-yl)-prop-2-en-1-one (compound 16) exhibiting remarkable inhibition activity towards PGE2 and NO production with IC50 values of 0.5 ±â€¯1.5 µM and 12.1 ±â€¯1.5 µM, respectively. Physicochemical and ADMET studies showed that majority of the compounds obey to Lipinski's rule of five (RO5) having high blood brain barrier (BBB) penetration, human intestinal absorption (HIA), P- glycoprotein (PgP) inhibition and plasma binding protein (PPB) inhibition. The obtained atomic coordinates for the single-crystal XRD of 16 were then applied in a molecular docking simulation, and compound 16 was found to participate in a number of important binding interactions in the binding sites of ERK and mPGES-1. Based on these results, we have observed the potential of compound 16 as a new hit anti-inflammatory agent, and these findings could serve as a basis for further studies on its mechanism of action.

Development of diarylpentadienone analogues as alpha-glucosidase inhibitor: Synthesis, in vitro biological and in vivo toxicity evaluations, and molecular docking analysis.

A series of aminated- (1-9) and sulfonamide-containing diarylpentadienones (10-18) were synthesized, structurally characterized, and evaluated for their in vitro anti-diabetic potential on α-glucosidase and DPP-4 enzymes. It was found that all the new molecules were non-associated PAINS compounds. The sulfonamide-containing series (compounds 10-18) selectively inhibited α-glucosidase over DPP-4, in which compound 18 demonstrated the highest activity with an IC50 value of 5.69 ± 0.5 µM through a competitive inhibition mechanism. Structure-activity relationship (SAR) studies concluded that the introduction of the trifluoromethylbenzene sulfonamide moiety was essential for the suppression of α-glucosidase. The most active compound 18, was then further tested for in vivo toxicities using the zebrafish animal model, with no toxic effects detected in the normal embryonic development, blood vessel formation, and apoptosis of zebrafish. Docking simulation studies were also carried out to better understand the binding interactions of compound 18 towards the homology modeled α -glucosidase and the human lysosomal α -glucosidase enzymes. The overall results suggest that the new sulfonamide-containing diarylpentadienones, compound 18, could be a promising candidate in the search for a new α-glucosidase inhibitor, and can serve as a basis for further studies involving hit-to-lead optimization, in vivo efficacy and safety assessment in an animal model and mechanism of action for the treatment of T2DM patients.

Assessing Parent Perceptions of Physical Activity in Families of Toddlers With Neurodevelopmental Disorders: The Parent Perceptions of Physical Activity Scale (PPPAS).

PURPOSE: The purpose of this study was to examine a new tool (PPPAS = Parent Perceptions of Physical Activity Scale-Preschool) developed to study parental perceptions of physical activity (PA) among parents of toddler and preschool age children. METHOD: 143 children (mean age 31.65 months; 75% male) and their parents were recruited from a neurodevelopmental clinic. Parents completed questionnaires, and both a psychologist and a physician evaluated the children. Eighty-three percent of the children received a diagnosis of Autism Spectrum Disorder; 20% of the children had a BMI > 85th percentile. Analyses were conducted to evaluate the reliability, concurrent validity, discriminant validity, and predictive validity of PPPAS scores. RESULTS: Results supported a two-factor structure: Perceptions of the Benefits of PA and the Barriers to PA. The internal consistency of scores was good for both PPPAS subscales, derived from the two factors. Parent perceptions of barriers to PA were significantly correlated with delays in overall adaptive functioning, daily living skills, socialization, and motor skills. When a child's motor skills were delayed, parents were less likely to believe PA was beneficial and perceived more barriers to PA. Parent perceptions of barriers to PA predicted parent-reported weekly unstructured PA and ratings of how physically active their child was compared with other children. CONCLUSION: We present the PPPAS-Preschool for use in pediatric exercise research and discuss potential applications for the study of parent perceptions of PA in young children.

Detection of hepatitis viruses in suspected cases of Viral Haemorrhagic Fevers in Nigeria.

There have been several Viral Hemorrhagic Fever (VHF) outbreaks in Nigeria which remains a public health concern. Despite the increasing number of suspected cases of VHF due to heightened surveillance activities and growing awareness, only a few cases are laboratory-confirmed to be VHF. Routinely, these samples are only tested for Lassa virus and Yellow fever virus with occasional testing for Dengue virus when indicated. The aetiology of the disease in these VHF suspected cases in Nigeria which are negative for Lassa, Yellow fever and Dengue viruses remains a puzzle. Since the clinical features exhibited by suspected VHF cases are like other endemic illnesses such as Hepatitis, there is a need to investigate the diversity and co-infections of hepatitis viruses as differentials and possible co-morbidity in suspected cases of VHFs in Nigeria. A total of three hundred and fifty (350) blood samples of 212 (60.6%) males and 138 (39.4%) females, aged <1-70 years with a mean age of 25 ±14.5, suspected of VHFs and tested negative for Lassa, Yellow fever and Dengue viruses were investigated for Hepatitis A, B, C and E viruses at the Centre for Human and Zoonotic Virology (CHAZVY), College of Medicine, University of Lagos (CMUL) using serologic and molecular techniques. The serologic analysis of these VHF suspected cases samples revealed that 126 (36%) were positive for at least one hepatitis virus. Individual prevalence for each of the hepatitis virus screened for showed that 37 (10.6%), 18 (5.1%) and 71 (20.3%) were positive for HBV, HCV and HEV respectively. All the samples were negative for HAV. A co-infection rate of 11.9% was also observed, with HCV/HEV co-infections being the most prevalent and the Northern region having the greatest burden of infection. The evidence of hepatitis virus infections in suspected cases of VHF was documented. Thus, their associations as co-morbidities and/or mortalities in this category of individuals require further investigations in endemic countries such as Nigeria. Therefore, the possible inclusion of screening for hepatitis viruses and other aetiologic agents that could mimic infections in suspected cases of VHFs in Nigeria should be thoroughly evaluated to guide informed policy on the diagnosis and management of these cases.

A review on Mitragyna speciosa (Rubiaceae) as a prominent medicinal plant based on ethnobotany, phytochemistry and pharmacological activities.

Mitragyna speciosa Korth (kratom) is a tropical indigenous tree of Southeast Asia. It is commonly consumed by the people due to its various pharmacological properties. The leaves of this plant are traditionally used for the treatment of several diseases including pain, fever, cough, anxiety, depression, obesity, diarrhoea, wound healing, diabetes, hypertension as well as for the prevention of cancer and improvement of sexual performance. Phytochemical investigations have confirmed the presence of more than forty alkaloids along with the presence of other bioactive secondary metabolites. Among the alkaloids isolated, mitragynine and 7-hydroxymitragynine along with their derivatives have been widely evaluated and reported to possess various pharmacological effects. Hence, the aim of this review is to shed light on the traditional uses of kratom and the scientific studies to justify the folkloric claims and active principles responsible for the various medicinal effects associated with the leaves of this plant. This review highlights the potential benefits and toxicities associated with M. speciosa leaves along with the phytochemistry. Moreover, the existing gaps in the field of M. speciosa study have been identified along with the future directions to further avail the benefits of this plant species.

Does theory of mind performance differ in children with early-onset and regressive autism?

A deficit in theory of mind (ToM), or the ability to infer the mental states of others, has been implicated as one of the major characteristics of Autism Spectrum Disorder (ASD); however, little attention has been devoted to possible differences in ToM ability within ASD. The current study examined ToM performance in children with early-onset autism and regressive autism in comparison to typically developing children. Results indicated that children in the regressive autism group performed significantly better than the early-onset autism group on the non-verbal appearance-reality task. Additionally, Fisher's exact tests indicated a pattern of lowest scores in the early-onset group and highest scores in the typically developing group, whereas the regressive autism group tended to score in between the early-onset and typically developing groups. The apparent heterogeneity in ToM performance within ASD could account for the lack of universality in ToM ability found in previous studies.

Recent advances in remotely controlled pulsatile drug delivery systems.

Pharmaceutical technology is drastically developing to enhance the efficacy and safety of drug therapy. Pulsatile delivery systems, in turn, gained attraction for their ability to deliver the right drug amount to the right body site, at the right time which is advantageous over conventional dosage forms. Their use is associated with increased patient compliance and allows on-demand drug delivery as well as customizable therapy. Recent technologies have been implemented to further develop pulsatile delivery systems for more precise determination of the dosage timing and duration as well as the location of drug release. Great interests are directed towards externally regulated pulsatile release systems which will be the focus of this review. The recent advances will be highlighted in remotely controlled delivery systems. This includes electro responsive, light-responsive, ultrasound responsive, and magnetically induced pulsatile systems as well as wirelessly controlled implantable systems. The current status of these technologies will be discussed as well as the recent investigations and future applications.

Saliva sample for detection of SARS-CoV-2: A possible alternative for mass testing.

Molecular diagnostic testing has played a critical role in the global response to the novel Coronavirus disease (COVID-19) pandemic, since its first outbreak in late 2019. At the inception of the COVID-19 pandemic, nasopharyngeal swab sample analysis for COVID-19 diagnosis using the real-time polymerase chain reaction (RT-PCR) technique was the most widely used. However, due to the high cost and difficulty of sample collection, the number of available sample types for COVID-19 diagnosis is rapidly increasing, as is the COVID-19 diagnostic literature. The use of nasal swabs, saliva, and oral fluids as viable sample options for the effective detection of SARS-CoV-2 has been implemented successfully in different settings since 2020. These alternative sample type provides a plethora of advantages including decreasing the high exposure risk to frontline workers, enhancing the chances of home self-sampling, reducing the cost, and significantly increasing testing capacity. This study sought to ascertain the effectiveness of Saliva samples as an alternative for COVID-19 diagnosis in Nigeria. Demographic data, paired samples of Nasopharyngeal Swab and Drooling Saliva were obtained from 309 consenting individuals aged 8-83 years presenting for COVID-19 testing. All samples were simultaneously assayed for the detection of SARS-CoV-2 RdRp, N, and E genes using the GeneFinder™ COVID-19 Plus RT-PCR test kit. Out of 309 participants, only 299 with valid RT-PCR results comprising 159 (53.2%) males and 140 (46.8%) females were analyzed in this study using the R Statistical package. Among the 299 samples analyzed, 39 (13.0%) had SARS-CoV-2 detected in at least one specimen type. Both swabs and saliva were positive in 20 (51.3%) participants. Ten participants (25.6%) had swab positive/saliva-negative results and 9 participants (23.1%) had saliva positive/swab-negative results. The percentage of positive and negative agreement of the saliva samples with the nasopharyngeal swab were 67% and 97% respectively with positive and negative predictive values as 69% and 96% respectively. The findings indicate that drooling saliva samples have good and comparable diagnostic accuracy to the nasopharyngeal swabs with moderate sensitivities and high specificities.

Efficacy of mindfulness-based intervention for the treatment of chronic headaches: A systematic review and meta-analysis.

Background: Mindfulness-based stress reduction/cognitive therapy has attained popularity as an adjunctive treatment for a plethora of medical and psychiatric conditions, however, its impact on chronic headaches is inconclusive. This review aims to assess the impact of MBSR/MBCT in alleviating the symptoms of chronic headaches. Data sources and data selection: PubMed and Cochrane CENTRAL were searched from inception till 1st May 2021. Randomized Control Trials evaluating mindfulness-based stress reduction/cognitive therapy with either passive comparators (usual care) or active comparators (e.g., Health education or cognitive behavioral therapy) for chronic headaches (Migraine, Tension-type, or cluster headaches), which evaluated either headache frequency, pain intensity or headache duration as primary outcome were eligible for inclusion. The Risk of Bias was evaluated using the Cochrane Collaboration's Risk of Bias Tool. Results: A total of ten Randomized Controlled Trials (five on migraine; three on tension-type; two with mixed samples) were evaluated. In comparison to usual care, mindfulness-based stress reduction/cognitive therapy did not illustrate significant changes in headache frequency (MD = -0.14; 95% CI -1.26 to 0.97; P = 0.80; Moderate Certainty), headache duration (MD = -0.27; 95% CI -3.51 to 2.97, P = 0.87; Low Certainty) or pain intensity (MD = -0.19; 95% CI -0.46 to 0.07; P = 0.15; Moderate Certainty). Conclusion: The results found are insignificant for the three primary outcomes, which may be due to the low number of participants and often a high or unclear risk of bias in the randomized control trials included. Perhaps more aggressive clinical trials with a larger sample size effectively demonstrate differences in outcomes before and after therapy for MBSR/MBCT could provide a more significant change.

A Review on Biological Properties and Synthetic Methodologies of Diarylpentadienones.

Medicinal chemists have continuously shown interest in new curcuminoid derivatives, diarylpentadienones, owing to their enhanced stability feature and easy preparation using a one-pot synthesis. Thus far, methods such as Claisen-Schmidt condensation and Julia- Kocienski olefination have been utilised for the synthesis of these compounds. Diarylpentadienones possess a high potential as a chemical source for designing and developing new and effective drugs for the treatment of diseases, including inflammation, cancer, and malaria. In brief, this review article focuses on the broad pharmacological applications and the summary of the structure-activity relationship of molecules, which can be employed to further explore the structure of diarylpentadienone. The current methodological developments towards the synthesis of diarylpentadienones are also discussed.

Are parental depressive symptoms related to the sleep quality and physical activity of their children with developmental disabilities?

BACKGROUND: Parenting young children with developmental disabilities presents unique opportunities and challenges. Parents can experience meaningful priority shifts in and appreciation for their lives, but they can also be at greater risk for diminished emotional health. Physiological child factors warrant further investigation as correlates for parent risk of or protection from depression. AIM: This study examined the relations between parental depressive symptoms and the (1) sleep quality and (2) physical activity in their children with developmental disabilities adjusting for parent- and child-level factors. METHODS AND PROCEDURES: Children and parents were recruited for participation in this study from a university-based neurodevelopmental clinic. Parents completed questionnaires about themselves including measures of depressive symptoms and about their children including measures of sleep quality and physical activity. Researchers administered developmental measures to the children and physicians completed children's diagnostic evaluations. Participants were 147 children (32 ± 4 months old) mostly with autism spectrum disorder (ASD) and their parents (mostly mothers). Factors associated with parent-reported depressive symptoms were analyzed with a generalized linear model. OUTCOMES AND RESULTS: An R2deviance value of 43 % confirmed that there was a substantial, moderate-to-large sized, improvement in the proportion of variance explained by the final model when compared with a null, or intercept-only, model. Depressive symptoms were approximately two times higher for parents of children with above average sleep disturbances and one and half times higher for parents whose children engaged in above average physical activity. CONCLUSION AND IMPLICATIONS: Our study demonstrates the importance of considering children's sleep and physical activity in supporting children's developmental disabilities because they may offer pathways to enhanced family resilience and well-being.

Psychological Determinants of Physical Activity and Development in Early Childhood Among Children With Developmental Delays: The Role of Parent Beliefs Regarding the Benefits of Physical Activity.

Among the various psychological determinants of physical activity (PA) in early childhood, relatively little attention has been paid to the role of parent beliefs in the benefits of PA for their child. Believing that PA is beneficial may impact parent behavior, resulting in more opportunities for PA in early childhood, particularly among children with neurodevelopmental disabilities (NDs) who may face more barriers to PA. Greater opportunity for PA may promote the development of motor skills and healthy body composition. This study examined the association between parental beliefs about PA and children's weight status in a sample of 147 children (32 ± 4 months old) with NDs. The proportion of parents with below average (mean - 1SD) perceptions of the benefits of PA whose children were overweight or obese was approximately was 2.5 times (proportion ratio, 2.35; 95% CI, 1.05-5.27) larger than it was for parents with above average (mean + 1SD) perceptions (after adjusting for the confounding effects of ethnicity, marital status, and mothers' self-reported depressive symptoms). Mothers' self-reported depressive symptoms was the only other covariate that was significantly associated with the weight status of these children, though, these data also signal possible (p = 0.07) differences in proportions between Hispanic/Latinx and White children in the sample who were classified as overweight and obese. Our study demonstrates the importance of considering parental or caregiver beliefs in the value of PA as another risk factor that may predict risk for overweight and obesity. Future studies should include parental beliefs in the benefits of PA as a potential psychological determinant of PA and associated health outcomes.

The Relative Utility of Concurrent Sources of Information for Diagnosis of Autism Spectrum Disorder in Early Childhood.

The development of effective screening methods for Autism Spectrum Disorder (ASD) in early childhood remains a public health priority for communities around the world. Little is known regarding the concurrence between parent concerns about ASD and formal ASD diagnostic methods. This study aimed to examine the relationships among a priori parental ASD concern, ADOS classification, and a physician specialist's diagnosis. One hundred and thirty-four toddlers (74% male; mean age = 31.8 months, SD 4.4) received an evaluation at a university center specializing in ASD and neurodevelopmental disorders. Correspondence between a priori parental ASD suspicion and physician diagnosis of ASD was 61% (p = 0.028). Correspondence between a priori parental suspicion of ASD and ADOS ASD classification was 57% (p = 0.483). Correspondence between ADOS classification and physician diagnosis of ASD was 88% (p = 0.001). Our results have implications for evaluations in low resource regions of the world where access to physician specialists may be limited; the high correspondence between ADOS classification and a physician specialist's diagnosis supports the use of trained ADOS evaluators, such as field health workers or early childhood educators, in a tiered screening process designed to identify those most in need of a specialist's evaluation. Our results also have implications for public health efforts to provide parent education to enable parents to monitor their child's development and share concerns with their providers. Parent awareness and expression of concern coupled with timely responses from providers may lead toward earlier identification of ASD, and other neurodevelopmental disorders, and hence, generate opportunities for earlier and more personalized intervention approaches, which in turn may help improve long-term outcomes. Empowering parents and community members to screen for ASD may be especially important in regions of the world where access to formal diagnosis is limited.

The Role of Animal Assisted Intervention on Improving Self-Esteem in Children With Attention Deficit/Hyperactivity Disorder.

Attention Deficit/Hyperactivity Disorder (ADHD), the most ubiquitous mental health problem in children, has been associated with poor self-esteem. Psychosocial interventions have aimed to improve self-esteem among this group, with the aim of reducing the development of comorbid depression and anxiety. The present study implemented a randomized control design to examine the possibility of Animal Assisted Interventions (AAI) as a viable approach to improving self-esteem among children with ADHD. Children's self-esteem across multiple domains as measured by the Self-Perception Profile for Children was evaluated (n = 80, ages 7-9, 71% male). To test the hypothesis that AAI improves self-esteem, stratified Wilcoxon Signed-Rank Tests (SAS NPAR1WAY procedure) were used to compare pre- to post-treatment ratings. Analyses indicated that scores of children's self-perceptions in the domains of behavioral conduct, social, and scholastic competence, were significantly increased from baseline to post-treatment in the AAI group (z = 2.320, p = .021, z = 2.631, p = .008, and z = 2.541, p = .011, respectively), whereas pre-post-treatment differences in self-perceptions were not found for the children in the control group without AAI. Findings suggest that AAI is a viable strategy for improving ratings of self-perceived self-esteem in children with ADHD.

Cortisol circadian rhythms and response to stress in children with autism.

BACKGROUND: Autism is a severe neurodevelopmental disorder characterized by impairment in communication, social interaction, repetitive behaviors and difficulty adapting to novel experiences. The Hypothalamic-Pituitary-Adrenocortical (HPA) system responds consistently to perceived novel or unfamiliar situations and can serve as an important biomarker of the response to a variety of different stimuli. Previous research has suggested that children with autism may exhibit dysfunction of the HPA system, but it is not clear whether altered neuroendrocrine regulation or altered responsiveness underlies the differences between children with and without autism. In order to provide preliminary data concerning HPA regulation and responsiveness, we compared circadian rhythms and response to a non-social, environmental stressor in children with and without autism. METHODS: Circadian rhythms of cortisol were estimated in children with (N=12) and without (N=10) autism via analysis of salivary samples collected in the morning, afternoon and evening on 2 consecutive days. HPA responsiveness was assessed by examining the time course of changes in salivary cortisol in response to a mock MRI. RESULTS: Both groups showed expected circadian variation with higher cortisol concentration in morning than in the evening samples. The children with autism, but not typical children, showed a more variable circadian rhythm as well as statistically significant elevations in cortisol following exposure to a novel, nonsocial stimulus. CONCLUSIONS: The results suggest that children with autism process and respond idiosyncratically to novel and threatening events resulting in an exaggerated cortisol response.

Biosafety level-2 laboratory diagnosis of Zaire Ebola virus disease imported from Liberia to Nigeria.

INTRODUCTION: Global travel is an efficient route of transmission for highly infectious pathogens and increases the chances of such pathogens moving from high disease-endemic areas to new regions. We describe the rapid and safe identification of the first imported case of Ebola virus disease in a traveler to Lagos, Nigeria, using conventional reverse transcription polymerase chain reaction (RT-PCR) in a biosafety level (BSL)-2 facility. CASE PRESENTATION: On 20 July 2014, a traveler arrived from Liberia at Lagos International Airport and was admitted to a private hospital in Lagos, with clinical suspicion of Ebola virus disease. METHODOLOGY AND OUTCOME: Blood and urine specimens were collected, transported to the Virology Unit Laboratory at the College of Medicine, University of Lagos, and processed under stringent biosafety conditions for viral RNA extraction. RT-PCR was set-up to query the Ebola, Lassa and Dengue fever viruses. Amplicons for pan-filoviruses were detected as 300 bp bands on a 1.5% agarose gel image; there were no detectable bands for Lassa and Dengue viral RNA. Nucleotide BLAST and phylogenetic analysis of sequence data of the RNA-dependent RNA polymerase (L) gene confirmed the sequence to be Zaire ebolavirus (EBOV/Hsap/NGA/2014/LIB-NIG 01072014; Genbank: KM251803.1). CONCLUSION: Our BSL-2 facility in Lagos, Nigeria, was able to safely detect Ebola virus disease using molecular techniques, supporting the reliability of molecular detection of highly infectious viral pathogens under stringent safety guidelines in BSL-2 laboratories. This is a significant lesson for the many under-facilitated laboratories in resource-limited settings, as is predominantly found in sub-Saharan Africa.

Heavy metal in children's tooth enamel: related to autism and disruptive behaviors?

To examine possible links between neurotoxicant exposure and neuropsychological disorders and child behavior, relative concentrations of lead, mercury, and manganese were examined in prenatal and postnatal enamel regions of deciduous teeth from children with Autism Spectrum Disorders (ASDs), high levels of disruptive behavior (HDB), and typically developing (TD) children. Using laser ablation inductively coupled plasma mass spectrometry, we found no significant differences in levels of these neurotoxicants for children with ASDs compared with TD children, but there was marginal significance indicating that children with ASDs have lower manganese levels. No significant differences emerged between children with HDB and TD children. The current findings challenge the notion that perinatal heavy metal exposure is a major contributor to the development of ASDs and HDB.