A Peculiar Case of Isolated Bilateral Tympanic Plate Fractures.

Tympanic plate fractures are uncommon injuries and carry the risk of external auditory canal stenosis. These injuries are often associated with fractures of adjacent bones like the mandible, maxilla, and temporal bone. Isolated bilateral tympanic bone fractures have rarely been reported. The most frequently advocated treatment for these injuries is surgical to prevent canal stenosis in the future. The effectiveness of non-operative management has been seldom reported. In the current case report, we present an uncommon injury with isolated bilateral tympanic plate fractures secondary to trauma to the mandible with no associated mandible or condylar fractures that were treated non-operatively. The functional outcomes were favorable at one year of follow-up.

A Bis(Aquated) Mn(II)-Based MRI Contrast Agent with a Rigid Hydroquinazoline Unit: Synthesis, Characterization, and in Vivo MR Imaging Study.

Since the finding of nephrogenic systemic fibrosis (NFS) in patients with renal impairment and the long-term accumulation of Gd(III) ions in the central nervous system, the search for nongadolinium ion-based MRI contrast agents made of nutrient metal ions has drawn paramount attention. In this context, the development of Mn(II)-based MRI contrast agents has been a subject of interest for the last few decades. Herein, we report a pentadentate ligand (Li2[BenzPic2]) composed of two picolinate moieties and a rigid 1,2,3,4-tetrahydroquinazoline unit and the corresponding bis(aquated) Mn(II) complex (Complex 1). The complex exhibited high thermodynamic stability (log Kcond = 11.62) and kinetic inertness similar to that of the clinically approved Gd(III)-based contrast agent Magnevist. Complex 1 exerted longitudinal relaxivity (r1) of 5.32 mM-1 s-1 at 1.41 T, 37 °C, pH 7.4, and it increased by 3.6-fold in the presence of serum albumin protein, confirming a substantial rigidifying interaction (albumin association constant KA = 1.66 × 103 M-1) between the protein and the amphiphilic (log P = -0.45) contrast agent. An intravenous dose of 0.08 mmol/kg in a healthy mouse, excellent MRI signal intensity enhancement in the vasculature of the mouse liver, and brightened images of the gallbladder, kidney, and liver were realized.

Investigating the Effects of a Kinematic Gait Parameter-Based Haptic Cue on Toe Clearance in Parkinson's Patients.

Recurrent falls pose a significant challenge for Parkinson's disease (PD) patients and are a leading cause of disability in this population. One contributing factor to these recurring falls is the reduced minimum toe clearance (mTC). Preventing such falls by enhancing mTC has become an important goal in gait training among PD patients. In this paper, we propose a wearable cueing-based novel gait training device in anticipation of improved mTC. The cueing device records the foot strike angle (FSA) and cues the participants if the FSA is observed above a threshold. The patients with PD (n = 8) were recruited and asked to walk under two conditions: (a) with cue and (b) without cue at a self-selected speed during the ON medication state. Kinetic and kinematic gait parameters such as vertical ground reaction force, center of pressure, toe clearance, and FSA were recorded. A Mann-Whitney U test showed a significant increase (p < 0.001) in the toe clearance (within 34% to 64% of the swing phase from the toe-off instance) and FSA, from 87.60 mm and - 5.43degrees respectively during without cue to 94.29 mm and 2.93degrees respectively during with cue walking condition except in one subject. These findings support the potential incorporation of an FSA-based cueing device for toe clearance improvement among PD patients. In addition, the wearable setup supports the cueing device applicability outside laboratory and home settings.

A Novel Kinematic Gait Parameter-Based Vibrotactile Cue for Freezing of Gait Mitigation among Parkinson's Patients: A Pilot Study.

Auditory and visual cues have been efficacious in laboratory-based freezing of gait (FoG) mitigation in Parkinson's disease (PD). However, real-life applications of these cues are restricted due to inconvenience to the users. Closed-loop vibrotactile cues based on temporal gait events have overcome the shortcomings of auditory and visual cueing. However, kinematic gait parameter-driven vibrotactile cueing has not been explored yet. Kinematic gait parameter-driven cueing is more effective than temporal cueing, according to FoG pathophysiology studies. Therefore, we developed and pilot-tested a novel cueing scheme in which the foot-to-ground angle at heel strike (FGA_HS) is estimated using indigenous instrumented shoes to drive vibrotactile cueing. Ten PD freezers underwent a 6-meter timed walk test in the off-medication state with and without the cue and after medication without the cue. The proposed system potentially mitigated FoG, quantified by a reduction in the ratio of time spent freezing to the total walking time and the number of FoGs. The FoG mitigation potential of the cue was further supported by increased anteroposterior center of pressure progression and FGA_HS. With a future comprehensive validation in a larger number of participants, the novel cue could likely be used in practice and commercialized.

De Novo Movement Disorders Associated with COVID-19- A Systematic Review of Individual Patients.

Background: COVID-19 infection is associated with neurological manifestations, including various types of movement disorders (MD). A thorough review of individual patients with COVID-19-induced MD would help in better understanding the clinical profile and outcome of these patients and in prognostication. Objective: We conducted an individual patient-systematic review to study the clinical and imaging profile and outcomes of patients with COVID-19-associated MD. Methods: A systematic literature search of PubMed, EMBASE, and Cochrane databases was conducted by two independent reviewers. Individual patient data COVID from case reports and case series on COVID-19-associated MD, published between December 2019 and December 2022, were extracted and analyzed. Results: Data of 133 patients with COVID-19-associated MD from 82 studies were analyzed. Mean age was 55 ± 18 years and 77% were males. A mixed movement disorder was most commonly seen (41%); myoclonus-ataxia was the most frequent (44.4%). Myoclonus significantly correlated with age (odds ratio (OR) 1.02 P = 0.03, CI 1-1.04). Tremor had the longest latency to develop after SARS-CoV-2 infection [median (IQR) 21 (10-40) days, P = 0.009, CI 1.01-1.05]. At short-term follow-up, myoclonus improved (OR 14.35, P value = 0.01, CI 1.71-120.65), whereas parkinsonism (OR 0.09, P value = 0.002, CI 0.19-0.41) and tremor (OR 0.16, P value = 0.016, CI 0.04-0.71) persisted. Conclusion: Myoclonus-ataxia was the most common movement disorder after COVID-19 infection. Myoclonus was seen in older individuals and usually improved. Tremor and parkinsonism developed after a long latency and did not improve in the short-term.

Effect of rTMS at SMA on task-based connectivity in PD.

BACKGROUND: Transcranial magnetic stimulation (TMS) can aid in alleviating clinical symptoms in Parkinson's disease (PD). To better understand the neural mechanism of the intervention, neuroimaging modalities have been used to assess the effects of rTMS. OBJECTIVE: To study the changes in cortical connectivity and motor performance with rTMS at supplementary motor area (SMA) in PD using clinical assessment tools and task-based functional MRI. METHODOLOGY: 3000 pulses at 5 Hz TMS were delivered at the left SMA once a week for a total of 8 consecutive weeks in 4 sham sessions (week 1-4) and 4 real sessions (week 5 to week 8) in 16 subjects with PD. The outcomes were assessed with UPDRS, PDQ 39 and task-based fMRI at baseline, after sham sessions at week 4, and after real sessions at week 8. Visuo-spatial functional MRI task along with T1 weighted scans (at 3 Tesla) were used to evaluate the effects of rTMS intervention. Multivariate pattern analysis (MVPA) was used to analyse task-based fMRI using Conn toolbox. RESULTS: Improvements (p < 0.05) were observed in UPDRS II, III, Mobility and ADL of PDQ39 after real sessions of rTMS. MVPA of task-based connectivity revealed clusters of activation in right hemispheric precentral area, superior frontal gyrus, middle frontal gyrus, thalamus and cerebellum (cluster threshold pFDR=0.001). CONCLUSIONS: Weekly rTMS sessions at SMA incurred clinical motor benefits as revealed by an improvement in clinical scales and dexterity performance. These benefits could be attributed to changes in connectivity remote brain regions in the motor network.

Mechanisms of 1 Hz Inhibitory and 5 Hz Excitatory Repetitive Transcranial Magnetic Stimulations in Parkinson's Disease: A Functional Magnetic Resonance Imaging Study.

Background: Parkinson's disease (PD) is a progressive disorder with alterations in cortical functional activity. Transcranial magnetic stimulation is known to incur motor benefits in PD by inducing motor activity through cortical connectivity, although the mechanisms are unclear. Objective: The effects of repetitive transcranial magnetic stimulation (rTMS) (at three cortical sites) on functional and structural plasticity were studied in PD to understand inhibitory or excitatory rTMS-induced motor improvement. Methodology: The study was a single blind, randomized, sham-controlled type involving three groups. Three thousand rTMS pulses of frequency 1 Hz were given at primary motor area (in 13 patients of Group A) or premotor area (in Group B, n = 18) and a frequency 5 Hz at supplementary motor area in Group C (n = 19). Clinical rating scores (Unified Parkinson's Disease Rating Scale [UPDRS], Parkinson's Disease Questionaire-39 [PDQ-39]) and motor dexterity were assessed at baseline, after sham and real rTMS sessions. Visuospatial functional magnetic resonance imaging task along with T1-weighted scans (at three Tesla) were used to evaluate the motor execution and planning post rTMS intervention. Results: Improvements (p < 0.05) in UPDRS II, III, Mobility, and activities of daily living of PDQ-39, Purdue Pegboard were observed. Increased blood oxygen level-dependent (BOLD) activations (family-wise error [FWE]-corrected P-value [pFWE] <0.01) were observed in motor cortices, parietal association areas, and cerebellum in groups C and decrease in group A and B after real TMS as compared with sham. Conclusions: Repetitive TMS at motor (1 Hz) and supplementary motor (5 Hz) areas resulted in significant clinical benefits by inducing cortical plasticity. Impact statement TMS daily protocols have been commonly employed to modulate cortical connectivity in Parkinson's disease (PD). This study uses functional magnetic resonance imaging to assess rTMS-related effects in PD. Repetitive TMS protocol at higher pulses (3000/session) in primary and supplementary motor cortices administered weekly was clinically effective and safe. The results revealed functional restoration along with cortical plasticity mechanisms of externally generated movement in PD in response to noninvasive brain stimulation.

Zonisamide add-on in tremor-dominant Parkinson's disease- A randomized controlled clinical trial.

INTRODUCTION: and objective: Tremor is a disabling symptom of PD that usually responds poorly to available standard pharmacological agents. This study aimed to assess the effect of Zonisamide 25 mg on tremor in tremor-dominant PD patients as compared to placebo. METHODS: This was a randomized, placebo-controlled, double-blind study. Parkinson's disease patients were allocated either to the intervention group (standard treatment along with Zonisamide 25 mg add-on) or the placebo group (standard treatment along with placebo). Baseline Unified Parkinson's Disease Rating Scale (UPDRS) and Tremor Research Group Essential Tremor Rating Scale (TETRAS) scores, as well as accelerometric tremor analysis were done and follow-up assessments of the same were done after 12 weeks of intervention. Percentage change from baseline in the UPDRS tremor score was the primary outcome whereas percentage change from baseline of total UPDRS score, UPDRS rigidity and bradykinesia scores, TETRAS score, and accelerometric tremor analysis values were the secondary outcomes. RESULTS: There was no significant difference in the percentage change from baseline UPDRS tremor scores between the two groups (placebo: 8.33 [-19.89-23.86] vs drug: 26.14 [-35.58 to -16.07], p-value: 0.164, CI: 0.157-0.171). Best-case analysis for missing values showed a significant improvement in the drug group, compared to the placebo group (p-value: < 0.001, CI: <0.001 - <0.001). CONCLUSION: Zonisamide at a dose of 25 mg per day did not improve tremor in tremor-dominant PD patients, however, a positive trend was seen as compared to Placebo in the UPDRS tremor score. Larger studies are required to confirm this finding.

Enhancing Quality of Life in Indian Parkinson's Disease Patients with Improved Measurement of Psychological Domains: A Perspective.

Parkinson's disease (PD) is the second most common progressive neuro-degenerative disorder. Research in PD is gradually increasing in India due to increased clinical cases, which could double by 2030 worldwide. Although its prevalence is low in India as compared to other countries, the total burden is much higher due to the large population size. PD is progressively debilitating, with pronounced motor and nonmotor symptoms (NMSs) that severely affect the quality of life (QoL) of patients and their caregivers. The progressive nature of the disease lays great emphasis on doctors to focus on the patients' QoL. As a consequence, Health-related QoL (HRQoL) has gradually become one of the main indicators for assessing health-related outcome. There is a growing need to pay attention to the NMSs and a pressing need to look at the QoL of Indian patients with PD through a culture and value specific lens. Research into the holistic QoL assessment with emphasis on psychological domains may allow for the early evaluation and intervention of depressive and cognitive symptoms in PD. This could result into increased productivity, reduced morbidity, and healthcare cost, which would in turn result into better QoL of Indian PD patients.

Expression of Bacillus licheniformis chitin deacetylase in E. coli pLysS: Sustainable production, purification and characterisation.

Chitosan obtained by enzymatic deacetylation of chitin using chitin deacetylase (CDA) holds promise primarily due to the possibility to yield chitosan with non-random patterns of acetylation and more environmentally friendly process compared to chemical deacetylation. In the present study, a sustainable bioprocess is reported for over-expression of a bacterial CDA in E. coli pLysS cells. A Bacillus licheniformis CDA gene is identified in the genome of the bacterium, cloned, and expressed, yielding enzymatically active recombinant protein. For enzyme production, a growth medium is formulated using carbon and nitrogen sources, which do not compete with the human food chain. The maximum enzyme activity of 320 ±â€¯20 U/mL is achieved under optimized conditions. The CDA productivity is improved by about 23 times in shake flask culture by optimizing operating conditions and medium components. The CDA is purified and the enzyme kinetic values i.e. Km, Vmax and Kcat are reported. Also the effect of cofactors, temperature, and pH on the enzyme activity is reported. Further, economic yield is proposed for production of CDA through this bioprocess.

Antimicrobial peptide (Cn-AMP2) from liquid endosperm of Cocos nucifera forms amyloid-like fibrillar structure.

Cn-AMP2 is an antimicrobial peptide derived from liquid endosperm of coconut (Cocos nucifera). It consists of 11 amino acid residues and predicted to have high propensity for ß-sheet formation that disposes this peptide to be amyloidogenic. In the present study, we have examined the amyloidogenic propensities of Cn-AMP2 in silico and then tested the predictions under in vitro conditions. The in silico study revealed that the peptide possesses high amyloidogenic propensity comparable with Aß. Upon solubilisation and agitation in aqueous buffer, Cn-AMP2 forms visible aggregates that display bathochromic shift in the Congo red absorbance spectra, strong increase in thioflavin T fluorescence and fibrillar morphology under transmission electron microscopy. All these properties are typical of an amyloid fibril derived from various proteins/peptides including Aß.

Cortico-hippocampal salvage in chronic aluminium induced neurodegeneration by Celastrus paniculatus seed oil: Neurobehavioural, biochemical, histological study.

OBJECTIVE: To investigate the effects of Celastrus paniculatus seed oil in preventing the onset of chronic aluminum induced cortico-hippocampal neurodegeneration and oxidative stress. MATERIALS AND METHODS: An animal model of senile dementia of Alzheimer's type was produced by administering aluminum as aluminum chloride (4.2 mg/kg) intraperitoneally to male Wistar rats for 60 days and results compared to untreated control. Neurobehavioral investigations of Morris water maze tests, passive avoidance test, rotarod test and biochemical estimations of acetylcholineterase, malondialdehyde, glucose-6-phosphate dehydrogenase, superoxide dismutase, and hemoglobin in blood were performed fortnightly which gauged the extent of global oxidative stress and progressive neural damage. Findings were fortified by the above enzyme assays and histology of brain at necropsy. Prophylactic oral C. paniculatus in two doses 0.5 ml and 1 ml, were given to animals and the results were analyzed in comparison to a similar rodent model with standard drug donepezil (0.5 mg/kg) intraperitoneally. RESULTS: C. paniculatus showed a significant prevention in onset of aluminum induced neural insult and overall systemic oxidative stress which was corroborated by the enlisted neurobehavioral, biochemical, and histological evidence. CONCLUSION: C. paniculatus is a putative decelerator of Al-mediated Alzheimer's like pathobiology.

Evaluation of the effect of Ferula asafoetida Linn. gum extract on learning and memory in Wistar rats.

OBJECTIVE: Memory loss is universal and is the first symptom to manifest in majority of the patients suffering from Alzheimer's disease. This study is designed to investigate the effect of Ferula asafoetida linn. (F. foetida) extract on learning and memory in rats. MATERIALS AND METHODS: Learning and memory were evaluated using elevated plus maze and passive avoidance paradigm after the oral administration of two doses (200 mg/kg and 400 mg/kg) of F. foetida aqueous extract with rivastigmine as positive control. Brain cholinesterase activity, serum thiols and cholesterol were also estimated. RESULTS: Extract produced significant improvement in memory score i.e. step through latency at 400 mg/kg dose in passive avoidance model (P< 0.05) and dose-dependent improvement of transfer latency in elevated plus maze model (P< 0.001). Dose-dependent inhibition of brain cholinesterase (P< 0.001) and significant improvement in antioxidant levels (P< 0.05) were also noted. CONCLUSIONS: Memory enhancing potential of F. foetida can be attributed to acetylcholinesterase inhibiting and antioxidant properties. Hence, dietary usage of F. foetida is beneficial and can also be employed as an adjuvant to existing anti-dementia therapies.

Signalled roads to memory and its degeneration.

Brain is concerned with the thoughts, feelings, perception, learning, memory and behaviour. The present review discusses some of the prominent molecular pathways governing memory acquisition, storage and subsequent consolidation.