Gastrointestinal symptoms and gut dysbiosis may occur before the onset of motor symptoms in Parkinson's disease (PD). Prediagnostic and prodromal features, such as constipation and α-synuclein ...pathology, can be detected several years before the clinical diagnosis of PD and have the potential to develop as early PD biomarkers. Environmental toxins and gut dysbiosis may trigger oxidative stress and mucosal inflammation, and initiate α-synuclein accumulation in the enteric nervous system, early in PD. Chronic gut inflammation can lead to a leaky gut and systemic inflammation, neuro inflammation, and neuro degeneration via gut–vagus–brain signaling or through blood–brain barrier permeability. Concepts regarding the gut–brain signaling in PD pathogenesis are changing rapidly and more investigation is required. The gut microbiota interacts with the human body by modulating the enteric and central nervous systems, and immune activity. Understanding the immune responses between gut microbiota and human body might help in elucidating the PD pathogenesis. As changes in gut microbiota composition might be associated with different clinical phenotypes of PD, gut microbiota-modulating interventions, such as probiotics and fecal microbiota transplantation (FMT), have the potential to restore the gut dysbiosis, reduce inflammation, and possibly modulate the clinical PD phenotype.
An experiment was conducted at the research farm of Assam Agricultural University, Jorhat, Assam during 2020–22 to assess the genetic variability among 50 rice (Oryza sativa L.) genotypes with ...respect to ratooning ability and perennation. Out of 50 genotypes, only 30 genotypes showed different degree of ratoon production and ratoon yield. All the genotypes showing better ratooning ability mainly belonged to photo-insensitive group and only few were slightly photosensitive. True perenniation as expressed by formation of rhizome (O. longistaminata) was not observed in any of the genotypes. However, stolen formation as in O. rufipogon was observed only in 1 genotype Terabali. ANOVA result suggested the presence of statistically significant variability among all the genotypes in both main and ratoon crop. Genotypes, viz. Binadhan-11, Sayjihari and IR-64 were found to be best performing for all the desirable ratoon crop traits. High heritability coupled with high genetic advance was estimated for all the ratoon crop traits except for days to ratoon maturity indicating the involvement of additive gene action in the expression of the traits.
Abstract
Advanced Parkinson’s Disease (APD) is complicated by the emergence of motor and non-motor fluctuations, which are initially predictable and eventually become unpredictable, in part due to ...erratic gastric absorption and short half of oral levodopa. Attempts to manage such fluctuations with oral dopaminergic drugs often lead to disabling dyskinesias. Continuous Subcutaneous Apomorphine Infusion (CSAI), despite being approved for the treatment of APD since 1993, was approved in India only in 2019. We studied the safety, tolerability and efficacy of CSAI in Indian patients with APD in a registry design to raise local awareness of this important treatment. We conducted a prospective registry-based observational audit at 10 centers across different states of India. Patients with APD, not responding to or with significant side effects from oral dopaminergic therapy, were assessed at baseline and at month 6 and 12 following CSAI infusion. Fifty-one patients completed the study, CSAI significantly reduced the functional impact of dyskinesia (p < 0.01 at 6 months and p < 0.001 at 12 months). There was a significant improvement in the OFF-state from baseline (p < 0.01 at 6 months and p < 0.001 at 12 months) No discernible side effects were observed apart from mild site reaction (n = 7), nausea (n = 7) skin nodules (n = 2). CSAI demonstrated safety, efficacy, tolerability and improved quality of life in patients with APD, as shown in previous studies. Our study highlighted current existing inequalities in treatment availability, lack of awareness, knowledge gap, affordability and cost remains a concern regarding apomorphine use in Indian PD population.
Growing evidence suggests that non-motor symptoms (NMS) in Parkinson's disease (PD) have differential progression patterns that have a different natural history from motor progression and may be ...geographically influenced. We conducted a cross-sectional analysis of 1607 PD patients of whom 1327 were from Europe, 208 from the Americas, and 72 from Asia. The primary objective was to assess baseline non-motor burden, defined by Non-Motor Symptoms Scale (NMSS) total scores. Other aims included identifying the factors predicting quality of life, differences in non-motor burden between drug-naïve and non-drug-naïve treated patients, and non-motor phenotypes across different geographical locations. Mean age was 65.9 ± 10.8 years, mean disease duration 6.3 ± 5.6 years, median Hoehn and Yahr stage was 2 (2-3), and 64.2% were male. In this cohort, mean NMSS scores were 46.7 ± 37.2. Differences in non-motor burden and patterns differed significantly between drug-naïve participants, those with a disease duration of less than five years, and those with a duration of five years or over (p ≤ 0.018). Significant differences were observed in geographical distribution (NMSS Europe: 46.4 ± 36.3; Americas: 55.3 ± 42.8; Asia: 26.6 ± 25.1; p < 0.001), with differences in sleep/fatigue, urinary, sexual, and miscellaneous domains (p ≤ 0.020). The best predictor of quality of life was the mood/apathy domain (β = 0.308, p < 0.001). This global study reveals that while non-motor symptoms are globally present with severe NMS burden impacting quality of life in PD, there appear to be differences depending on disease duration and geographical distribution.
The research was conducted at Instructional cum Research (ICR) farm in Assam Agricultural University, Jorhat, Assam for the year 2019–21 with the objective to determine the crossability of wild rice ...species O. longistaminata and O. rufipogon with O. sativa and observe the inheritance of rhizome. In first year of experiment, varieties having good ratooning ability were identified. Out of them, five varieties namely Ranjit, Ranjit sub-1, IR-64, Binadhan-11 and Bahadur were crossed with both of the wild species. Crossablity of O. longistaminata with O. sativa ranged from 11.1% (Ranjit sub-1 × O. longistaminata) to 22.2% (Binadhan11 × O. longistaminata) while O. rufipogon with O. sativa ranged from 13.3% (Ranjit sub-1 × O. rufipogon) to 30% (Ranjit × O. rufipogon). All the hybrids except for IR64 × O. longistaminata were photoinsensitive as that of their female parent. Hybrids from O. sativa/O. longistaminata exhibited various distinguishing characters which can be used as morphological marker in order to identify true interspecific hybrids in further breeding programme. The pollen viability of these interspecific hybrids were found lower than both the parents. However, rhizome formation could not be observed in any hybrid.
Parkinson's disease (PD) is a major neurological disorder that requires lifelong treatment, and the combined presence of Helicobacter pylori (H. pylori) infection can increase the required anti-PD ...medications. We aim to investigate the effect of H. pylori infection in Indian PD patients.
We prospectively recruited 36 PD patients from December 2007 to January 2011. All patients underwent a detailed neurological evaluation and serological examination for H. pylori infection. Seropositive and seronegative patients were considered to be the cases and controls, respectively. All patients who were seropositive received triple therapy for 2 weeks. Outcome measures of the mean 'off' Unified Parkinson's Disease Rating Scale (UPDRS)-III score, mean 'on' UPDRS-III score, mean onset time, mean 'on' duration, and mean daily 'on' time were measured at baseline and at a 3-week follow-up.
H. pylori-IgG positivity was present in 18 (50%) PD patients. The prevalence of men (72.2% vs. 33.3%), mean duration of disease (13.8 vs. 12.5) and mean levodopa equivalent daily dose (824 mg vs. 707 mg) were significantly higher among H. pylori positive patients than in controls (p<0.0001). Controls had a significantly longer 'on' duration and daily 'on' time, and better 'on' UPDRS-III scores. Seropositive patients took a significantly longer time to turn 'on' after a levodopa challenge. At the 3-week follow-up, H. pylori eradication significantly improved the mean 'on' UPDRS-III score, onset time, 'on' duration, and daily 'on' time.
H. pylori infection was present in 50% of Indian PD patients. H. pylori seropositivity was associated with a poor response to levodopa and increased medication usage, while eradication therapy was associated with better patient outcomes.
Dystonia deafness syndrome (DDS) is a rare syndrome characterized by childhood onset sensorineural deafness followed by adult-onset dystonia. We here report the first case of DDS from India caused by
...ACTB
gene mutation presented with deafness, generalized dystonia and scoliosis who showed improvement after Deep brain stimulation.
The presence of dyskinesia is the most common side effect of chronic administration of levodopa in Parkinson’s disease (PD) subjects. Genetic polymorphisms in levodopa metabolizing gene, ...catechol-O-methyl transferase (COMT), is shown to influence the inter-individual variability in drug response and adverse events. In the present study, the association of COMT rs6269, rs4633, rs4818, and rs4680 polymorphisms and haplotypes on pharmacokinetics and adverse events with levodopa was investigated in 150 PD patients. The age of onset of PD was 58.00 ± 10 yrs. The most common side effect faced by 78% of the subjects was dyskinesia. The AUC of levodopa was found to be significantly higher in subjects with dyskinesia (1695 ± 113 ng/ml/hr,
p
< 0.0001) than those without dyskinesia (1550 ± 122 ng/ml/hr). We found that the frequency of subjects presenting dyskinesia was significantly higher in subjects carrying variant genotype of COMT rs6269, rs4633, and rs4680 than that with wild genotype and these subjects presented higher AUC of levodopa. In addition, in subjects with dyskinesia, the AUC of levodopa was found to be significantly higher with low COMT (ACCG) haplotype. The association of COMT rs6269, COMT rs4633, COMT rs4818, and COMT rs4680 variant genotypes with the risk of dyskinesia due to levodopa therapy showed an ROC AUC of 0.67 indicating the moderate prediction of dyskinesia (
p
= 0.0021) with these COMT variants. In conclusion, PD subjects carrying the variant genotypes of COMT strongly influence high levodopa-induced dyskinesia. Hence the genotyping of COMT before the levodopa therapy will be useful to reduce the adverse events associated with the chronic levodopa treatment.