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Highlights Convalescent plasma is adjunct treatment in COVID-19 moderate and severe disease. Clinical improvement is noticed in COVID-19 disease after convalescent plasma. Mortality is significantly reduced after COVID-19 convalescent plasma treatment.

Autism spectrum disorder is a neurodevelopmental disorder marked by repetitive behaviour, challenges in verbal and non-verbal communication, poor socio-emotional health, and cognitive impairment. An increased level of signal transducer and activator of transcription 3 (STAT3) and a decreased level of peroxisome proliferator-activated receptor (PPAR) gamma have been linked to autism pathogenesis. Guggulsterone (GST) has a neuroprotective effect on autistic conditions by modulating these signalling pathways. Consequently, the primary objective of this study was to examine potential neuroprotective properties of GST by modulating JAK/STAT and PPAR-gamma levels in intracerebroventricular propionic acid (ICV PPA) induced experimental model of autism in adult rats. In this study, the first 11 days of ICV-PPA injections in rats resulted in autism-like behavioural, neurochemical, morphological, and histopathological changes. The above modifications were also observed in various biological samples, including brain homogenate, CSF, and blood plasma. GST was also observed to improve autism-like behavioural impairments in autistic rats treated with PPA, including locomotion, neuromuscular coordination, depression-like behaviour, spatial memory, cognition, and body weight. Prolonged GST treatment also restored neurochemical deficits in a dose-dependent manner. Chronic PPA administration increased STAT3 and decreased PPAR gamma in autistic rat brain, CSF, and blood plasma samples, which were reversed by GST. GST also restored the gross and histopathological alterations in PPA-treated rat brains. Our results indicate the neuroprotective effects of GST in preventing autism-related behavioural and neurochemical alterations.

Summary Background Pain and discomfort are main concerns at the commencement of orthodontic treatment. It may have negative impact on compliance or even discourage patients from being treated. Orthodontic pain can be alleviated by paracetamol or use of chewing gum. However, studies comparing their effectiveness are scarce. Objectives To compare the effectiveness of paracetamol versus chewing gum for pain alleviation and to investigate the frequency of bracket loss during the first day of fixed orthodontic treatment. Trail design Prospective randomized multicentre clinical trial. Methods Sixty patients (28 boys and 32 girls), between 12 and 18 years of age were randomly allocated either to take paracetamol (31 patients) or to use chewing gum (29 patients). After one arch bonding and insertion of the initial archwire, the patients rated the sensation of pain on a visual analogue scale with the jaw at rest and when biting after 6 hours (T1), at bedtime (T2), and the next morning (T3). Paracetamol (1000 mg) was taken 1 hour and chewing gum was used 10 minutes prior to pain rating at T2 and T3. A simple method of randomization was used in this study, and blinding of subjects and the operators to the type of intervention was not possible because of the nature of the treatments. Results There was no detectable difference in pain sensation between the groups at T1. At T2 and T3 the chewing gum group displayed higher mean values than the paracetamol group but when adjusting for age, gender, and mode of pain registration, there was no significant difference between the groups. There was no bracket loss in the chewing gum group, whereas two patients in the paracetamol group lost two brackets. Conclusions The effect of chewing gum and paracetamol for initial orthodontic pain relief seems equivalent. Short term use of chewing gum is not a risk factor for bracket loss. Trial registration This study was not registered.

Enterococcus species are an emerging group of bacterial pathogens that have a significant role in hospital-associated infections and are associated with higher mortality and morbidity rates. Among these pathogens, Enterococcus mundtii is one of the causative agents of multiple hospital associated infections. Currently, no commercially available licensed vaccine is present, and multi-drug resistant strains of the pathogen are prominent. Due to several limitations of experimental vaccinology, computational vaccine designing proved to be helpful in vaccine designing against several bacterial pathogens. Herein, we designed a multi-epitope-based vaccine against E. mundtii using in silico approaches. After an in-depth analysis of the core genome, three probable antigenic proteins (lytic polysaccharide monooxygenase, siderophore ABC transporter substrate-binding protein, and lytic polysaccharide monooxygenase) were shortlisted for epitope prediction. Among predicted epitopes, ten epitopes—GPADGRIAS, TTINHGGAQA, SERTALSVTT, GDGGNGGGEV, GIKEPDLEK, KQADDRIEA, QAIGGDTSN, EPLDEQTASR, AQWEPQSIEA, QPLKFSDFEL—were selected for multi-epitope vaccine construct designing. The screened B- and T-cell epitopes were joined with each other via specific linkers and linked to the cholera toxin B subunit as an adjuvant to enhance vaccine immune protection efficacy. The designed vaccine construct induced cellular and humoral immune responses. Blind docking with immune cell receptors, followed by molecular dynamic simulation results confirms the good binding potency and stability of the vaccine in providing protection against the pathogen.

Mucormycosis in patients who have COVID-19 or who are otherwise immunocompromised has become a global problem, causing significant morbidity and mortality. Infection is debilitating and fatal, leading to loss of organs and emotional trauma. Radiographic manifestations are not specific, but diagnosis can be made through microscopic examination of materials collected from necrotic lesions. Treatment requires multidisciplinary expertise, as the fungus enters through the eyes and nose and may even reach the brain. Use of the many antifungal drugs available is limited by considerations of resistance and toxicity, but nanoparticles can overcome such limitations by reducing toxicity and increasing bioavailability. The lipid formulation of amphotericin-B (liposomal Am-B) is the first-line treatment for mucormycosis in COVID-19 patients, but its high cost and low availability have prompted a shift toward surgery, so that surgical debridement to remove all necrotic lesions remains the hallmark of effective treatment of mucormycosis in COVID-19. This review highlights the pathogenesis, clinical manifestation, and management of mucormycosis in patients who have COVID-19.

Objective To investigate the effects of dental/skeletal malocclusion and orthodontic treatment on four main objective parameters of chewing and jaw function (maximum occlusal bite force [MOBF], masticatory muscle electromyography [EMG], jaw kinematics, and chewing efficiency/performance) in healthy children. Materials and methods Systematic searches were conducted in MEDLINE (OVID), Embase, and the Web of Science Core Collection. Studies that examined the four parameters in healthy children with malocclusions were included. The quality of studies and overall evidence were assessed using the Joanna Briggs Institute and GRADE tools, respectively. Results The searches identified 8192 studies; 57 were finally included. The quality of included studies was high in nine studies, moderate in twenty-three studies, and low in twenty-five studies. During the primary dentition, children with malocclusions showed similar MOBF and lower chewing efficiency compared to control subjects. During mixed/permanent dentition, children with malocclusion showed lower MOBF and EMG activity and chewing efficiency compared to control subjects. The jaw kinematics of children with unilateral posterior crossbite showed a larger jaw opening angle and a higher frequency of reverse chewing cycles compared to crossbite-free children. There was a low to moderate level of evidence on the effects of orthodontic treatment in restoring normal jaw function. Conclusions Based on the limitations of the studies included, it is not entirely possible to either support or deny the influence of dental/skeletal malocclusion traits on MOBF, EMG, jaw kinematics, and masticatory performance in healthy children. Furthermore, well-designed longitudinal studies may be needed to determine whether orthodontic treatments can improve chewing function in general. Clinical relevance Comprehensive orthodontic treatment, which includes evaluation and restoration of function, may or may not mitigate the effects of malocclusion and restore normal chewing function.

Enterobacter hormaechei is involved in multiple hospital-associated infections and is resistant to beta-lactam and tetracycline antibiotics. Due to emerging antibiotics resistance in E. hormaechei and lack of licensed vaccine availability, efforts are required to overcome the antibiotics crisis. In the current research study, a multi-epitope-based vaccine against E. hormaechei was designed using reverse vaccinology and immunoinformatic approaches. A total number of 50 strains were analyzed from which the core proteome was extracted. One extracellular (curlin minor subunit CsgB) and two periplasmic membrane proteins (flagellar basal-body rod protein (FlgF) and flagellar basal body P-ring protein (FlgI) were prioritized for B and T-cell epitope prediction. Only three filtered TPGKMDYTS, GADMTPGKM and RLSAESQAT epitopes were used when designing the vaccine construct. The epitopes were linked via GPGPG linkers and EAAAK linker-linked cholera toxin B-subunit adjuvant was used to enhance the immune stimulation efficacy of the vaccine. Docking studies of the vaccine construct with immune cell receptors revealed better interactions, vital for generating proper immune reactions. Docked complexes of vaccine with MHC-I, MHC-II and Tool-like receptor 4 (TLR-4) reported the lowest binding energy of −594.1 kcal/mol, −706.7 kcal/mol, −787.2 kcal/mol, respectively, and were further subjected to molecular dynamic simulations. Net binding free energy calculations also confirmed that the designed vaccine has a strong binding affinity for immune receptors and thus could be a good vaccine candidate for future experimental investigations.