Tryptophan interferes with the quorum sensing and cell surface hydrophobicity of Staphylococcus aureus: a promising approach to inhibit the biofilm development.

Staphylococcus aureus, a Gram-positive bacterium has been implicated in a plethora of human infections by virtue of its biofilm-forming ability. Inhibition in microbial biofilm formation has been found to be a promising approach towards compromising microbial pathogenesis. In this regard, various natural and synthetic molecules have been explored to attenuate microbial biofilm. In this study, the role of an amino acid, L-tryptophan was examined against the biofilm-forming ability of S. aureus. The compound did not execute any antimicrobial characteristics, instead, showed strong antibiofilm activity with the highest biofilm inhibition at a concentration of 50 µg/mL. Towards understanding the underlying mechanism of the same, efforts were given to examine whether tryptophan could inhibit biofilm formation by interfering with the quorum-sensing property of S. aureus. A molecular docking analysis revealed an efficient binding between the quorum-sensing protein, AgrA, and tryptophan. Moreover, the expression of the quorum-sensing gene (agrA) got significantly reduced under the influence of the test compound. These results indicated that tryptophan could interfere with the quorum-sensing property of the organism thereby inhibiting its biofilm formation. Further study revealed that tryptophan could also reduce the cell surface hydrophobicity of S. aureus by downregulating the expression of dltA. Moreover, the tested concentrations of tryptophan did not show any significant cytotoxicity. Hence, tryptophan could be recommended as a potential antibiofilm agent to manage the biofilm-associated infections caused by S. aureus. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02924-3.

1,4-Naphthoquinone accumulates reactive oxygen species in Staphylococcus aureus: a promising approach towards effective management of biofilm threat.

Staphylococcus aureus, a Gram-positive opportunistic microorganism, promotes pathogenicity in the human host through biofilm formation. Microorganisms associated with biofilm often exhibit drug-resistance property that poses a major threat to public healthcare. Thus, the exploration of new therapeutic approaches is the need of the hour to manage biofilm-borne infections. In the present study, efforts are put together to test the antimicrobial as well as antibiofilm activity of 1,4-naphthoquinone against Staphylococcus aureus. The result showed that the minimum bactericidal concentration (MBC) of this compound was found to be 100 µg/mL against Staphylococcus aureus. In this regard, an array of experiments (crystal violet, biofilm protein measurement, and microscopic analysis) related to biofilm assay were conducted with the sub-MBC concentrations (1/20 and 1/10 MBC) of 1,4-naphthoquinone. All the results of biofilm assay demonstrated that these tested concentrations (1/20 and 1/10 MBC) of the compound (1,4-naphthoquinone) showed a significant reduction in biofilm development by Staphylococcus aureus. Moreover, the tested concentrations (1/20 and 1/10 MBC) of the compound (1,4-naphthoquinone) were able to reduce the microbial motility of Staphylococcus aureus that might affect the development of biofilm. Further studies revealed that the treatment of 1,4-naphthoquinone to the organism was found to increase the cellular accumulation of reactive oxygen species (ROS) that resulted in the inhibition of biofilm formation by Staphylococcus aureus. Hence, it can be concluded that 1,4-naphthoquinone might be considered as a promising compound towards biofilm inhibition caused by Staphylococcus aureus.

Degradation of low-density poly ethylene (LDPE) by Enterobacter cloacae AKS7: a potential step towards sustainable environmental remediation.

Plastics composed of polyethylene are non-biodegradable and are mostly harmful to the environment. Literature studies documented that the extent of microbial degradation of low-density polyethylene (LDPE) seems to be insufficient and the underlying mechanisms of such degradation remain unexplored. In the present study, efforts were given to degrade LDPE by a recently isolated bacteria Enterobacter cloacae AKS7. Scanning electron microscopic (SEM) image, tensile strength, and weight loss analysis confirmed the efficient degradation of LDPE by AKS7. To investigate the mechanism, it was observed that with the progression of time, the extent of microbial colonization got increased considerably over the LDPE surface. It was also observed that the organism (AKS7) gradually increased the secretion of extracellular polymeric substances (EPS) suggesting the formation of efficient biofilm over the LDPE surface. Furthermore, to comprehend the role of cell-surface hydrophobicity towards biofilm formation, two mutants of AKS7 were screened that showed a considerable reduction in cell-surface hydrophobicity in contrast to its wild type. The result showed that the mutants revealed compromised LDPE degradation than wild-type cells of AKS7. Further investigation revealed that the mutant cells of AKS7 were incapable of adhering to LDPE in contrast to wild-type cells. Thus, the results demonstrated that the cell-surface hydrophobicity of AKS7 favors the development of microbial biofilm over LDPE that leads to the enhanced degradation of LDPE by AKS7. Therefore, the organism holds the assurance to be considered as a promising bio-remediating agent for the sustainable degradation of polythene-based hazardous waste.

Free tryptophan residues inhibit quorum sensing of Pseudomonas aeruginosa: a potential approach to inhibit the development of microbial biofilm.

Microbial biofilm reveals a cluster of microbial population aggregated on a surface. Pseudomonas aeruginosa, a strong biofilm forming organism, often causes several human diseases. Microorganism-based diseases become more difficult to manage when the causative organism develops biofilm during the course of disease progression as the organism attains alarming drug resistance in biofilm form. Agents inhibiting microbial biofilm formation could be considered as a potential tool to weaken the extent of microbial pathogenesis. Tryptophan has already been reported as a promising agent against the biofilm development by P. aeruginosa. In the current study, we had focused on the underlying mechanism of microbial biofilm inhibition of P. aeruginosa under the influence of tryptophan. The expression level of the mRNA of the genes (lasR, lasB and lasI) associated with quorum sensing was compared between tryptophan treated and untreated cells under similar conditions using real time polymerase chain reaction (RT-PCR). The results showed that the tested concentrations of tryptophan considerably reduced the expression of those genes (lasR, lasB and lasI) that are required during the occurrence of quorum sensing in P. aeruginosa. Molecular docking also revealed that tryptophan can interact with the proteins responsible for the occurrence of quorum sensing in P. aeruginosa. The cytotoxicity assay was carried out wherein we observed that the tested concentration of tryptophan did not show any considerable cytotoxicity against the RAW 264.7 macrophage cell line. From this study, it may be concluded that the tryptophan-mediated inhibition of biofilm formation is associated with interference of quorum sensing in P. aeruginosa. Hence, tryptophan could be used as a potential agent against the microbial biofilm mediated pathogenesis.

Injected corticosteroids for treating plantar heel pain in adults.

BACKGROUND: Plantar heel pain, commonly resulting from plantar fasciitis, often results in significant morbidity. Treatment options include nonsteroidal anti-inflammatory drugs (NSAIDs), orthoses, physical therapy, physical agents (e.g. extracorporeal shock wave therapy (ESWT), laser) and invasive procedures including steroid injections. OBJECTIVES: To assess the effects (benefits and harms) of injected corticosteroids for treating plantar heel pain in adults. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials (the Cochrane Library), MEDLINE, Embase, CINAHL, clinical trials registries and conference proceedings. Latest search: 27 March 2017. SELECTION CRITERIA: Randomised and quasi-randomised trials of corticosteroid injections in the treatment of plantar heel pain in adults were eligible for inclusion. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected studies, assessed risk of bias and extracted data. We calculated risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcome measures. We used a fixed-effect model unless heterogeneity was significant, when a random-effects model was considered. We assessed the overall quality of evidence for individual outcomes using the GRADE approach. MAIN RESULTS: We included a total of 39 studies (36 randomised controlled trials (RCTs) and 3 quasi-RCTs) that involved a total of 2492 adults. Most studies were small (median = 59 participants). Participants' mean ages ranged from 34 years to 59 years. When reported, most participants had heel pain for several months. The trials were usually conducted in outpatient specialty clinics of tertiary care hospitals in 17 countries. Steroid injection was given with a local anaesthetic agent in 34 trials. Follow-up was from one month to over two years. With one exception, trials were assessed at high risk of bias in one or more domains, mostly relating to lack of blinding, including lack of confirmation of allocation concealment. With two exceptions, we rated the available evidence as very low quality, implying in each case that we are 'very uncertain about the estimate'.The 39 trials covered 18 comparisons, with six of the seven trials with three or four groups providing evidence towards two comparisons.Eight trials (724 participants) compared steroid injection versus placebo or no treatment. Steroid injection may lead to lower heel pain visual analogue scores (VAS) (0 to 100; higher scores = worse pain) in the short-term (< 1 month) (MD -6.38, 95% CI -11.13 to -1.64; 350 participants; 5 studies; I² = 65%; low quality evidence). Based on a minimal clinically significant difference (MCID) of 8 for average heel pain, the 95% CI includes a marginal clinical benefit. This potential benefit was diminished when data were restricted to three placebo-controlled trials. Steroid injection made no difference to average heel pain in the medium-term (1 to 6 months follow-up) (MD -3.47, 95% CI -8.43 to 1.48; 382 participants; 6 studies; I² = 40%; low quality evidence). There was very low quality evidence for no effect on function in the medium-term and for an absence of serious adverse events (219 participants, 4 studies). No studies reported on other adverse events, such as post-injection pain, and on return to previous activity. There was very low quality evidence for fewer treatment failures (defined variously as persistent heel pain at 8 weeks, steroid injection at 12 weeks, and unrelieved pain at 6 months) after steroid injection.The available evidence for other comparisons was rated as very low quality. We are therefore very uncertain of the estimates for the relative effects on people with heel pain of steroids compared with other interventions in:1. Tibial nerve block with anaesthetic (2 trials); orthoses (4 trials); oral NSAIDs (2 trials); and intensive physiotherapy (1 trial).2. Physical modalities: ESWT (5 trials); laser (2 trials); and radiation therapy (1 trial).3. Other invasive procedures: locally injectable NSAID (1 trial); platelet-rich plasma injections (5 trials); autologous blood injections (2 trials); botulinum toxin injections (2 trials); cryopreserved human amniotic membrane injection (1 trial); localised peppering with a needle (1 trial); dry needling (1 trial); and mini scalpel needle release (1 trial).We are also uncertain about the estimates from trials testing different techniques of local steroid injection: ultrasonography-guided versus palpation-guided (5 trials); and scintigraphy-guided versus palpation-guided (1 trial).An exploratory analysis involving pooling data from 21 trials reporting on adverse events revealed two ruptures of plantar fascia (reported in 1 trial) and three injection site infections (reported in 2 trials) in 699 participants allocated to steroid injection study arms. Five trials reported a total of 27 participants with less serious short-term adverse events in the 699 participants allocated steroid injection study arms. Reported treatments were analgesia, ice or both. Given the high risk of selective reporting for these outcomes and imprecision, this evidence was rated at very low quality. AUTHORS' CONCLUSIONS: We found low quality evidence that local steroid injections compared with placebo or no treatment may slightly reduce heel pain up to one month but not subsequently. The available evidence for other outcomes of this comparison was very low quality. Where available, the evidence from comparisons of steroid injections with other interventions used to treat heel pain and of different methods of guiding the injection was also very low quality. Although serious adverse events relating to steroid injection were rare, these were under-reported and a higher risk cannot be ruled out.Further research should focus on establishing the effects (benefits and harms) of injected steroids compared with placebo in typical clinical settings, subsequent to a course of unsuccessful conservative therapy. Ideally, this should be preceded by research, including patient involvement, aimed to obtain consensus on the priority questions for treating plantar heel pain.

Cognitive Impairment and Rehabilitation Strategies After Traumatic Brain Injury.

Traumatic brain injury (TBI) is among the significant causes of morbidity and mortality in the present world. Around 1.6 million persons sustain TBI, whereas 200,000 die annually in India, thus highlighting the rising need for appropriate cognitive rehabilitation strategies. This literature review assesses the current knowledge of various cognitive rehabilitation training strategies. The entire spectrum of TBI severity; mild to severe, is associated with cognitive deficits of varying degree. Cognitive insufficiency is more prevalent and longer lasting in TBI persons than in the general population. A multidisciplinary approach with neuropsychiatric evaluation is warranted. Attention process training and tasks for attention deficits, compensatory strategies and errorless learning training for memory deficits, pragmatic language skills and social behavior guidance for cognitive-communication disorder, meta-cognitive strategy, and problem-solving training for executive disorder are the mainstay of therapy for cognitive deficits in persons with TBI. Cognitive impairments following TBI are common and vary widely. Different cognitive rehabilitation techniques and combinations in addition to pharmacotherapy are helpful in addressing various cognitive deficits.

Effect of ultrahigh diluted homeopathic medicines on the electrical properties of PVDF-HFP

In an effort to improve the electrical properties of the electroactive Poly(vinylidene fluoridehexafluoropropylene) (PVdF-HFP), we introduced a novel and simple approach to synthesize PVDFHFP composite films by incorporating ultrahigh dilutions of two homeopathic medicines Ferrum metallicum (FM) and Zincum oxidatum (ZO) in different potencies. The homeo-PVDF-composite films (HPCF) were synthesized by simple solution casting technique. XRD, FESEM, FTIR studies were performed to check the presence of nanoparticles in the film. The electrical properties of the HPCF samples get enhanced significantly due to the incorporation of the medicines and the effect increases with the increase in potency of the medicines. (AU)

Effect of ultrahigh diluted homeopathic medicines on the electrical properties of PVDF-HFP

In an effort to improve the electrical properties of the electroactive Poly(vinylidene fluoride-hexafluoropropylene) (PVdF-HFP), we introduced a novel and simple approach to synthesize PVDFHFP composite films by incorporating ultrahigh dilutions of two homeopathic medicines Ferrum metallicum (FM) and Zincum oxidatum (ZO) in different potencies. The homeo-PVDF-composite films (HPCF) were synthesized by simple solution casting technique. XRD, FESEM, FTIR studies were performed to check the presence of nanoparticles in the film. The electrical properties of the HPCF samples get enhanced significantly due to the incorporation of the medicines and the effect increases with the increase in potency of the medicines.

A rare presentation of subacute progressive ascending myelopathy secondary to cement leakage in percutaneous vertebroplasty.

Percutaneous vertebroplasty is used to manage osteoporotic vertebral body compression fractures. Although it is relatively safe, complications after vertebroplasty ranging from minor to devastatingly major ones have been described. Cement leakage into the spinal canal is one such complication. Subacute progressive ascending myelopathy is an infrequent neurologic complication after spinal cord injury, typically presenting as ascending neurologic deficit within weeks after the initial insult. The precise cause of subacute progressive ascending myelopathy still remains an enigma, considering the rarity of this disorder. The authors present the case of a 62-yr-old woman with osteoporotic vertebral fracture who underwent percutaneous vertebroplasty and developed T6 complete paraplegia because of cement leakage. A few weeks later, the neurologic level ascended to higher cervical level (C3). To date, no case of subacute progressive ascending myelopathy secondary to cement leakage after percutaneous vertebroplasty has been reported. Literature is reviewed regarding subacute progressive ascending myelopathy, and the rehabilitation challenges in the management of this patient are discussed.

Traumatic brachial plexus injury: electrodiagnostic findings from 111 patients in a tertiary care hospital in India.

OBJECTIVE: The study aims to characterise the electrodiagnostic findings of patients with traumatic brachial plexus injuries (BPIs) in India and to analyse the association between aetiologies and levels of injuries. METHODS: A total of 111 consecutive electrodiagnostic studies done between January 2009 and June 2011 on persons with traumatic BPI were retrospectively analysed. SETTING: Electrodiagnostic Laboratory, Department of Physical Medicine and Rehabilitation in a tertiary care university teaching hospital in South India. MAIN OUTCOME MEASURES: Nerve conduction velocities and electromyography (EMG) to locate the level of BPI, Dumitru and Wilbourne scale to assess the severity of BPI. RESULTS: We studied 106 males and five females, ranging from 11 to 59 years of age. All but one had unilateral BPI. Motorcycle crashes were the most frequent cause (n=64, 58%). Isolated supraclavicular injury was found in 98 arms (88%) and infraclavicular injury in seven arms (6%). Root-level injuries were more common in motorcycle crashes and occupation-related trauma, while trunk-level injuries were more often found in automobile crashes, falls, bicycle-related trauma and penetrating wounds. Pan root (C5-T1) involvement was more common in the motorcycle trauma group (74%). There was no significant association between aetiologies and levels of BPIs. A total of 73 (65%) plexus injuries were of 'severe' category as per Dumitru and Wilbourn scale. CONCLUSIONS: Motorcycle crash is the most common cause of traumatic BPIs. Supraclavicular injury is the rule in most cases. Proper attention needs to be given to differentiate the mild to moderate injuries from the severe injuries with EMG techniques since most of the cases are severe. There was no significant association found between aetiologies and levels of injury.